lab methods / biomarkers

LABMETHODS / BIOMARKERS

SP122 COMPARISON OF ATHEROMATOUS DISEASE IN HIGH RISKPOPULATIONS REVEALS A DISTINCTASOCIATION OF RISKFACTORS AMONG PATIENT POPULATIONS AND ASTRICKING RELEVANCE FORGLYCEMIC CONTROL INDIABETIC NEPHROPATHY

Mercé Borras1, Jorge Roig1, Angels Betriu2, Ana Vilar1, Marta Hernandez3,Marisa Martin1 and Elvira D. Fernandez11Renal Division Hospital Universitari Arnau de Vilanova de Lleida Lleida Spain, 2IRBLleida UDETMA Unit Lleida Spain, 3Endocrinology Service Hospital UniversitariArnau de Vilanova de Lleida Lleida Spain

Introduction and Aims: Patients with Chronic Kidney Disease (CKD) and/orDiabetes are at a high risk for cardiovascular (CV) disease. Improved outcomes requirea better understanding of specific risk factors that distinctly modulate the incidence ofatheromatous disease. Herein. we compared the distinct and combined impact of CKDand of diabetes (DM) on the development of atheromatous disease, and prevalent riskfactors per condition.Methods: Cross sectional study in 2088 asymptomatic patients categorized as: 1)General Population (2 CV risk factors, no DM, estimated glomerular filtration rate(eGFR )>60 ml/min); 2) CKD,no DM; 3) DM, eGFR>60 ml/min, proteinuria<300mg/dl; 4) Established diabetic nephropathy (DN). Carotid ultrasound of left andright carotid arteries evaluated intima-media thickness (IMT) in the common, bulb,internal and external carotid. Carotid plaque (CP) was defined as IMT>1.5mm.Multivariate Logistic Regression analysis examined the variables independentlyassociated with the presence of CP, including glycosylated haemoglobin (HbA1c) indiabetics.Results: Table 1 shows the percent of patients with CP among the 4 populations ofpatients categorized by age.Table 2 shows the results of the multivariate analyses.There is a distinct association between classical risk factors and CP among the 4subpopulation of patients. In DN, age and Triglycerydes are the only classical riskfactors independently associated with CP. Also, exclusively in DN, HbA1 isindependently associated with the presence of CP.Conclusions: Our findings confirm the high prevalence of atheromatous disease inasymptomatic high CV risk patients with a distinct association of risks factors amongpatient populations. Importantly, in diabetic nephropathy, HbA1C emerges as a mainrisk factor independently associated with the presence of carotid plaques.

SP123 PREDICTIVE VALUE OF TRADITIONAL AND NOVEL RISKFACTORS FORCARDIOVASCULAR DISEASE AND END STAGERENAL DISEASE IN PATIENTSWITH CHRONIC KIDNEYDISEASE

Evangelia Dounousi1, Vasiliki Kiatou2, Aikaterini Papagianni3, Xanthi Zikou1,Kostas Pappas1, Efthymios Pappas1, Athina Tatsioni1, Dimitrios Tsakiris2 andKostas C. Siamopoulos11Department of Nephrology University Hospital of Ioannina Ioannina Greece,2Department of Nephrology General Hospital of Thessaloniki PapageorgiouThessaloniki Greece, 3Department of Nephrology University Hospital ofThessaloniki Hippokration Thessaloniki Greece

Introduction and Aims: Up to 25% of mild to moderate chronic kidney disease (CKD)patients die from cardiovascular (CV) disease before entering dialysis, whereas controlof CKD progression risk factors remains a bet to be won by nephrologists. Thepredictive value of traditional and novel risk factors is important because theidentification of «the best predictor» is of obvious importance for risk stratification inCKD patients. Mortality and non-fatal CV events (myocardial ischemia, stroke andperipheral vascular event) along with initiation of dialysis were the major end points.Methods: Two hundred thirty consecutive CKD outpatients of stages 1-4 (52% men)with mean age 65±12 years were prospectively followed up to 3 years. Patients lost ofFU (17.5%) were excluded. Estimated glomerular filtration rate (eGFR, MDRD-6variables) was 52.4±28.7 ml/min at recruitment. Demographic, somatometric, clinicalcharacteristics, routine laboratory parameters and specific inflammatory markers,along with drug therapy were assessed at study entry. Echocardiograms wereundertaken and left ventricular mass index (LVMI) was calculated. Cox regressionproportional hazard models were used to determine factors that best predicted theoccurrence of a CV event/death or initiation of dialysis. Models included traditionaland novel risk factors: sex, age, smoking, body mass index, mean BP, diabetes mellitus(DM), CV disease history, eGFR, urine protein (UPR, mg/24h), serum cholesterol,albumin (sAlb), uric acid and phosphorus, Hb, fibrinogen, CRP, IL-6, TNF-α,ICAM-1, VCAM-1 and LVMI.Results: During the follow up 31 (16%) CV events and 7 CV deaths (3%) occurredwith a mean time to the event of 21±12.5 months. Twenty one (11%) patients starteddialysis in a mean time of 20±9 months. The statistically important predictive factorsfor the CV outcome were: DM (RR: 0.455, 95%CI: 0.22-0.932, p=0.03), sAlb (RR:0.296, 95%CI: 0.113-0.773, p=0.013), LVMI (RR: 1.0, 95% CI: 1.009-1.001, p=0.021)and VCAM-1 (RR: 1.0007 95% CI: 1.00-1.0013, p=0.026). For the renal outcomesignificant factors were: eGFR (RR: 0.894, 95%CI: 0.844-0.947, p<0.001), UPR (RR1.0005, 95% CI: 1.0002-1.0007, p<0.001). A limitation of our study was the relativelysmall number of patients.Conclusions: The predictive value of traditional risk factors resulted to be superior tothat of novel risk factors with regards to CV disease and end stage renal disease in longterm CKD 1-4 stage patients.

SP124 CAROTID INTIMA-MEDIATHICKNESS AND PLAQUES AREINDEPENDENTLY ASSOCIATEDWITH RATE OF RENALFUNTION DECLINE IN PATIENTSWITH CHRONIC KIDNEYDISEASE

Jwa-Kyung Kim1, Youngsu Kim1, Sung Gyun Kim1 and Hyung Jik Kim1

1Department of Internal Medicine & Kidney Research Institute Hallym UniversitySacred Heart Hospital Anyang-si/Gunggi-do Republic of Korea

Introduction and Aims: Increased carotid intima-media thickness (cIMT) and thepresence of plaques are surrogate markers of systemic atherosclerosis and closelyassociated with adverse cardiovascular outcomes. Whether cIMT and plaques arerelated to renal decline rate and progression to dialysis remains to be determined inchronic kidney disease (CKD) patients.Methods: This longitudinal observational study enrolled 413 CKD stage 3 and 4patients. All patients performed carotid ultrasonography at their first visit tonephrologist. We classified patients into CKD stage 3a, 3b and 4 based on estimatedglomerular filtration rate (eGFR), and the decline of renal function was measured byeGFR slope. The renal endpoint was defined as commencement of dialysis.Results:Mean age was 69.7 years and mean eGFR slope was -1.90 ± 1.08 mL/min/1.73m2/yr. The cIMT values and plaque prevalence was significantly elevated withincreasing severity of CKD stages (p<0.001). During the 2.5-year follow-up, 11.4%started dialysis therapy. Patients with cIMT ≥1.0 mm had a worse dialysis-free survivalthan those with cIMT <1.0 mm [hazard ratio 2.17, 95% confidence interval (CI) 1.21 to3.88, p = 0.008]. Statistically significant variables associated with more rapid renalprogression rate were diabetes mellitus, wide pulse pressure, lower baseline eGFR, loweralbumin, greater proteinuria, and increased cIMT and the presence of carotid plaque.

SP122

2 CV Risk Factor(n=1315)

CKD no DM (n= 552 )

DM no CKD (n= 110 )

DN (n =111 )

<52 y 28,2 % 16,4 % 28,6 % 37,5 %52-60 y 43,9 % 53,4 % 86,4 % 65,6 %61-66 y 62,5 % 72,3 % 70 % 72,2 %> 67 y 75,8 % 83,3 % 90,5 % 80,5 %

SP122

2 CV risk factors CKD no DM DM no CKD DN

Age (y) <0.001 <0.001 <0.001 0.001Gender 0.003 0.033Tobacco <0.001SBP (mm Hg) 0.001 0.052DBP (mm Hg) 0.033 0.094Serum creat (mg/dl) 0.013MDRD -4 (ml/mn) 0.012Calcium (mg/dl) 0.080Phosphorus (mg/dL) 0.001Total cholesterol 0.008HDL- cholesterol 0.001 0.002LDL- cholesterol 0.010Triglycerides 0.002 0.014Hb A1c 0.027UAE (mg/dL) 0.006

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Nephrology Dialysis Transplantation 28 (Supplement 1): i117–i139, 2013doi:10.1093/ndt/gft108

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In multivariate analysis, cIMT was the strongest determinant for renal progression rate(change in slope –6.05, 95% CI -9.35 to -2.69).Conclusions: Increased cIMT and carotid plaque were associated with rapid decline ofrenal function and progression to dialysis in CKD stage 3 and 4 patients. MeasuringcIMT and detecting carotid plaque may help identify high-risk patients with rapidprogression of renal dysfunction.

SP125 THE EFFECTS OF THE CKD-MBD (CHRONIC KIDNEYDISEASE-MINERAL AND BONE DISORDERS) PARAMETERSON LEFT VENTRICULAR (LV) GEOMETRY IN PRE-DIALYSISCKD

Shin Young Ahn1, Ho Jun Chin1,2, Kook-Hwan Oh2, Curie Ahn2 andDong-Wan Chae1,21Internal Medicine, Devision of Nephrology Seoul National University BundangHospital Seongnam-si Gyeonggi-do Republic of Korea, 2Internal Medicine SeoulNational University College of Medicine Seoul Republic of Korea

Introduction and Aims: The biochemical parameters of CKD-MBD such serumphosphorus (P), iPTH (intact parathyroid hormone), and FGF (fibroblast growthfactor)-23 have been reported to have strong effects on the mortality of CKD patients.Left ventricular hypertrophy has also known to be a strong risk factor for the death ofCKD patients. Hence we investigated the effects of the parameters of CKD-MBD on theLV geometry in pre-dialysis CKD.Methods: KNOW-CKD is an on-going, prospective, university hospital basedobservational cohort study under the sponsorship of Korean Center for DiseaseControl and Prevention. Cross-sectional analysis of echocardiography data and otherclinical data was performed in 1231 participants of KNOW-CKD. LV muscle indexedby body surface area (LVMI) and relative wall thickness were used to define LVhypertrophy (LVH) and LV geometry according to recommendation by the AmericanSociety of Echocardiography. As paramaters of CKD-MBD, serum calcium (Ca), P,25-(OH) vitamin D, 1,25(OH)2 vitamin D, and FGF23 were measured.Results: The number of patients with CKD 1 & 2, CKD 3, and CKD 4 & 5 was 310(25.8%), 489 (40.7%) and 402 (33.5%) persons respectively and LVMI increased alongwith progression of CKD (87.5±24.0, 92.1±24.1, and 108.2±73.3g/m2 in each group,p<0.001). Along with the progression of CKD stage, the frequency of normal LVgeometry decreased and those of eccentric and concentric LVH increased (normal;43.2%, eccentric LVH; 21.7%, concentric remodeling; 13.6%, concentric LVH; 21.4% inCKD 4 & 5). Linear regression models showed that LVMI was positively associated withFGF-23 in whole patients (r2=0.014, p=0.002). This relationship was more pronouncedin patients with proteinuria ≥ 0.2g/day (r2=0.025, p<0.001). Multivariable analysis fullyadjusted by age, sex, FGF23, and other significant variables in univariate analysis revealedthat age, female, systolic blood pressure (SBP), body mass index (BMI), eGFR < 30ml/min/1.73m2 were risk factors for eccentric and concentric LVH, respectively. Among theparameters of CKD-MBD, serum Ca was related to eccentric and concentric LVH.Conclusions: Along with the progression of CKD stage, LVMI and frequency ofeccentric and concentric LVH increased. Although serum FGF23 level was positivelyrelated to LVMI in CKD patients, and more prominently in presence of protienuria,serum FGF23 was not independent risk factor for LVH in our cohort. Serum calciumwas related to eccentric and concentric LVH in Korean CKD patients.

SP126 ARTERIAL STIFFNESS IN PATIENTWITH DECREASED RENALMASS

Raziye Yazici1, Lutfullah Altintepe1, Suleyman Bakdik2, Ibrahim Guney1,Sevket Arslan1, Mustafa Topal1 and Ali Karagoz11Nephrology Konya Education and Research Hospital Konya Turkey, 2RadiologyKonya Education and Research Hospital Konya Turkey

Introduction and Aims: In the presence of hypoplastic kidney or a residue of kidneyafter nephrectomy some compensatory alterations take place. In this study, we aimed toinvestigate whether any alteration take place in arterial stiffness in patients withdecreased renal mass and if alteration is present to evaluate the relation of thisalteration with renal functions and ambulatory blood pressure.Methods: One hundred and thirty five patients who had one sided nephrectomy due todifferent causes or with congenital single kidney (mean age 43.4±8.5) and 44 healthyindividual with similar age and gender (mean age 42.5±7.1) as control group wereenrolled to this prospective study. Of these cases 44 had unilateral nephrectomy, 69 hadcongenitally single kidney, and 17 had renal agenesis.Cases with diabetes mellitus, withknown coronary artery disease, with previous cerebrovascular disease, having heartfailure, peripheral artery disease and receiving hemodialysis were excluded from thestudy.The serum hemogram and biochemical parameters of the patients were studied.By collecting 24 hours of urine, glomerular filtration rate and microalbuminuria valueswere measured. With Portabl compact digital recorder Mobil-O-Graph NG (I.E.MGmbH Stolberg Germany) device arterial stiffness parameters, pulse wave velocity(PWV) and augmentation index were determined with ossilometric method noneinvasively. With the same device, also 24 hours ambulatory blood pressure parameterswere detected.Results: There was no significant difference between study and control group withrespect to age, gender, body mass index, ambulatory systolic (116±10 and 113±10,

p=0.088) and diastolic (75±9 and 72±10, p=0.146) blood pressure. Among the arterialstiffness parameters of the cases, PWV value was significantly higher compared tocontrols (6.72±1.11 vs 6.29±0.75, p=0.018). Although augmentation index (Ai) of caseswas higher than control group, it was not statistically different (26.5±13.1 vs 23.5±13.2,p=0.187). In correlation analysis, there was correlation between PWV and age, bloodpressure (BP), GFR, calcium and uric acid levels. Also there was correlation between Aiand age, BMI, pulse pressure, hemoglobin value and GFR. In Lineer regressionanalysis, there was correlation between PWV and age (β=0.737, p=0.000) and 24 hoursmean systolic BP (β=0.349, p=0.000), and between Ai and age (β=0,314, p=0.001) andhemoglobin values (β=-0,203, p=0,026).Conclusions: Arterial stiffness increases in cases with renal mass loss. In these casesarterial stiffness increase is related to age, mean systolic blood pressure and hemoglobinlevel.

SP127 IS ABDOMINAL AORTIC CALCIFICATION RELATED TO RENALRESISTIVE INDEX?

Gabriel Stefan2, Gabriel Mircescu1,2, Cristina Capusa1,2, Simona Stancu1,2,Ligia Petrescu1,2, Silvia Alecu2 and Dana Nedelcu31Nephrology “Carol Davila” University of Medicine and Pharmacy BucharestRomania, 2“Dr Carol Davila” Hospital of Nephrology Bucharest Romania, 3DeltaHospital Bucharest Romania

Introduction and Aims: In chronic kidney disease (CKD), abdominal aortacalcification (AAC) is frequent and correlates with cardiovascular (CV) risk. Renalresistive index (RRI) predicts both renal and CV outcome. Therefore, we aimed toevaluate the relationship between AAC and RRI in non-dialysis CKD patients.Methods: This cross-sectional, single-center study prospectively enrolled 77 clinicallystable CKD patients (49% male, 70 [65-73] years, eGFR 33.5 [30.1-36.9] ml/min) witha positive history for systemic atherosclerosis. Exclusion criteria were end-stage renaldisease, obstructive nephropathy and valvular heart disease. RRI and carotidintima-media thickness (IMT) were assessed by Doppler sonography, AAC wereevaluated on a plain lateral lumbar X-ray (Kauppila score - AACs), cardio-anklevascular index (CAVI) and ankle-brachial index (ABI) were measured with anautomatic waveform analyzer (VaSera). CKD etiology, cardiovascular traditional (age,smoking, arterial hypertension, diabetes mellitus, lipid profile) and non-traditional(serum calcium, phosphate, C-reactive protein – CRP) risk factors were also assessed.Two groups were defined based on a AACs cut-off >5: AACs>5 (n=37) and AACs≤5(n=40). This value was obtained by ROC curve analysis considering the reportedcut-off for RRI>0.7 (area under the curve 0.69 [0.56-0.81], p=0.001). Spearman test wasused to assess correlations.Results: Vascular nephropathies (50%), diabetic nephropathy (26%) and primaryglomerulonephritis (8%) were the main causes of CKD. The eGFR was similar in thetwo groups (30.2 [28-35.2] vs. 33.7 [30.3-39]). Patients with AACs>5 were older (71.8[68.8-74.8] vs. 66.7 [64-69.5], p=0.006), had higher serum cholesterol (193 [175-211]vs. 167 [160-182], p=0.006), and more pronounced inflammation (CRP: 6 [4-12] vs. 3[2-7], p=0.01). No other investigated CV risk factors differed between the two groups.Lower ABI (0.92 [0.84-1.0] vs. 1.08 [1.04-1.21], p<0.001) and higher IMT (0.08[0.08-0.09] vs. 0.07 [0.07-0.08], p=0.006), but similar CAVI were found in AACs>5group. Moreover, AACs was negatively correlated with ABI (rs=−0.51, p<0.001) andpositively with IMT (rs=0.27, p=0.01), underlining the relationship of AACs with theextension of atherosclerosis in other territories rather than with arterial stiffness. RRIwas significantly higher in subjects with AACs>5 (0.73 [0.70-0.75] vs. 0.68 [0.64-0.69],p<0.001), and showed a significant direct correlation with AACs (rs=0.35, p<0.001).Conclusions: Assessment of AACs could predict advanced atherosclerosis, since it wasassociated with carotid plaques (IMT) and vascular artery disease (ABI). Moreimportant, AACs could be used as a fast, available and inexpensive tool for estimation ofRRI and consequently of the intrarenal vascular status, but further research is warranted.

SP128 DEVELOPMENTOF A NOVEL ELISATEST KIT FOR THEDETECTION OF DESPHOSPHO-UNCARBOXYLATEDMATRIXGLA PROTEIN

Alexandra H.L. Bennett1, Heather Pham1, Martha Garrity1, Elke Magdeleyns2 andCees Vermeer21Immunodiagnotic Systems (IDS) Ltd. Boldon, Tyne and Wear United Kingdom,2VitaK BV Maastricht The Netherlands

Introduction and Aims:Matrix Gla-protein (MGP) is regarded as the strongestinhibitor of vascular calcification and produced by many cells, including vascularsmooth muscle cells. MGP can undergo gamma-glutamate carboxylation (vitamin Kdependent step) and serine phosphorylation. Circulating desphospho-uncarboxylated(dp-uc)MGP reflects the amount of uncarboxylated MGP produced in the arterialvessel wall and is a direct marker for the vascular vitamin K status. In CKD patientshigh levels of circulating dp-uc MGP have been associated with calcification and overallmortality risk. The purpose of this study is to develop an ELISA for the accuratedetection of dp-uc MGP.Methods: The ELISA measures dp-ucMGP in plasma samples by use of twomonoclonal antibodies: the capture antibody, anti-dpMGP, is coated onto a microtitreplate and the detection antibody, anti-ucMGP, is biotinylated. Standards, controls and

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samples (neat or diluted) are added to the microtitre plate followed by the addition ofthe biotinylated antibody and incubated overnight. The plate is washed and incubatedwith enzyme labelled avidin before a second wash step and the addition of achromogenic substrate. The absorbance of the stopped reaction is read at 450-650nmwhere the colour intensity is directly proportional to the concentrations of dp-ucMGP.Results: The assay range of the MGP ELISA is 100 to 700pM with an analyticalsensitivity of less than 50pM. The performance of the MGP ELISA kit displaysexcellent inter-assay precision with samples reading across the assay range showing lessthan 15% CV. The assay also displays excellent intra-assay precision with samplesreading from 127pM to 423pM showing an average precision on 10 replicates of 6.3%to 8.8%.The average recovery of samples spiked with synthetic material is 103%. Highsamples linearity shows excellent recovery when diluted in a low MGP sample acrossthe assay range with an average observed / expected value of 106%. The correlation ofthe newly developed ELISA to a research in house ELISA shows the assay to be fullycomparable with a slope of 0.755, intercept of 50.8 and R2 of 0.860. The assay shows apositive relationship between increasing dp-ucMGP levels and progressing CKD stageand shows the expected decrease in dp-ucMGP after vitamin K supplementation.Conclusions: This new and novel MGP ELISA test kit is an accurate device for thedetection of desphospho-uncarboxylated Matrix Gla Protein. The measurement ofdp-ucMGP is a useful risk marker for cardiovascular calcification in CKD patients.

SP129 HIGH LEVELS OF SERUM FIBROBLAST GROWTH FACTOR 23ARE ASSOCIATEDWITH CORONARY ARTERYCALCIFICATION AND ADVERSE CLINICALOUTCOMES INPATIENTSWITHMODERATE AND ADVANCED STAGECHRONIC KIDNEY DISEASE

Minfang Zhang1, Zhaohui Ni1, Minli Zhu1, Jiayi Yan1, Shan Mou1, Qin Wang1 andJiaqi Qian11Renal Division Renji Hospital, Shanghai Jiaotong University School of MedicineShanghai China

Introduction and Aims: Fibroblast growth factor 23 (FGF23) is a remarkable regulatorof mineral and bone metabolism which was discovered in the early 21st century. Anumber of studies reported the association of high levels of FGF23 with cardiovasculardisease (CVD) and mortality in patients with chronic kidney disease (CKD), howeverthey still have controversies. Thus, we aimed to elucidate the association of FGF23 withthe presence of coronary artery calcification and its prognostic value in patients withmoderate and advanced stage CKD.Methods: Serum intact FGF23 levels in 150 patients with CKD stage 3 to 5 and 25 ageand sex matched controls were measured by using ELISA. We made routinebiochemistry and assessed coronary calcification by multi-slice spiral computedtomography (MSCT) within the CKD patients. The relationship between FGF23 andthe presence of coronary artery calcification were studied. The occurrence ofcardiovascular events and deaths was recorded over 22±3 months.Results: Serum FGF23 levels in CKD patients were significantly higher than those inhealthy controls (P<0.01). The concentrations of FGF23 were positively related withduration of dialysis (r=0.288, P=0.007), serum calcium (r=0.377, P<0.001), serumphosphorus (r=0.576, P<0.001), calcium and phosphorus product (r=0.659, P<0.001),PTH (r=0.331, P<0.001) and CRP (r=0.266, P=0.001) levels, and negatively relatedwith hemoglobin (r=-0.222, P=0.004), 25(OH)VitD (r=-0.207, P=0.007) and 1,25(OH)2VitD (r=-0.187, P=0.023) levels. Serum FGF23 levels were significantly associatedwith coronary artery calcification score (CACS) (r=0.177, P=0.034). During thefollow-up, 19 cardiovascular events (12.7%) and 9 deaths (6%) were registered. Patientswere stratified to two groups by median FGF23 level (675.8pg/ml). Kaplan-Meiersurvival curves showed that patients with FGF23 levels≥675.8pg/ml had significantlyhigher cardiovascular event incidence rate (P<0.01) and all-cause mortality (P<0.05)than patients with FGF23 levels below the cut-off. Cox regression analysis showed thatFGF23≥675.8pg/ml (HR=3.534, 95%CI: 1.111∼11.246, P<0.05) and severe coronaryartery calcification(CACS>400) (HR=4.445, 95%CI: 1.554∼12.717, P<0.01) wereindependent risk factors for cardiovascular events in CKD patients, while FGF23 levels(HR=3.534, 95%CI: 1.167∼10.704, P<0.05) and severe coronary artery calcification(CACS>400) (HR=9.718, 95%CI: 1.790∼52.770, P<0.01) were independent risk factorsfor all-cause mortality in CKD patients.Conclusions: Serum FGF23 levels in patients with moderate and advanced stage CKDwere significantly higher than normal population. Serum FGF23 levels may beassociated with coronary artery calcification and adverse clinical outcomes in patientswith moderate and advanced stage CKD.

SP130 NUTRITIONAL EDUCATION FORMANAGEMENTOFOSTEODYSTROPHY (NEMO) TRIAL: IMPACTON QUALITYOF LIFE

Abboud Saade2, Mirey Karavetian1, Hafez ElZein3 and Nanne de Vries11Health Promotion Maastricht University Maastricht Netherlands Antilles,2Nephrology Department Universite Saint Esprit Kaslik Kaslik Lebanon,3Hypertension and Nephrology Society Lebanese National Renal Registry BeirutLebanon

Introduction and Aims: Hyperphosphatemia and poor Quality of Life (QOL) are 2common conditions highly prevalent among hemodialysis (HD) patients. Provision of

individualized nutritional counseling has shown to improve these 2 components. Theaim of this study is to measure the effect of advanced individualized nutritioneducation given to HD by renal dietitian on serum phosphorus (P) and QOL.Methods: The study is a randomized controlled trial with pre and post design. Patients(n=300) were recruited from 6 HD units in Lebanon. Each HD unit was divided to halfas per the HD shift and assigned to the 2 study groups: experimental or control.Patients in the experimental group received nutritional education of 2 hours per monthfor 6 months by dedicated renal dietitian. Both study groups continued to receive theroutine dietetic care by hospital dietitian. Outcome Measures :Serum P (mg/dl) andQOL measured by SF-36 questionnaire.Results: Serum P in the experimental group dropped significantly from 5.6±1.55 mg/dL to 5.0 ± 1.51 mg/dL, no significant change was seen in the control group. As forQOL, at baseline, study participants reported to have 48 - 75% of full health. Postintervention only 2 components of QOL changed, they significantly dropped frombetter to worse: social functioning (experimental: 85.19±27.68 to 58.46±32.26 ,Control:85.64±28.79 to 57.77±32.96) and bodily pain (experimental: 76.85±29.57 to56.62±36.65, Control: 77.77±27.44 to 61.22±33.71).Conclusions: The educational intervention proved to be effective in improving serumP in Lebanese HD patients, but it was not effective on QOL parameters. Among theproblems we faced in collecting QOL from patients was that most did not like tocomplain about their health, and instead thanked God for their current situation. Ourfindings suggest the need for developing a culturally sensitive QOL instrument thatwould be able to detect QOL in religious and oriental cultures.

SP131 CLINICAL EFFECTOF DIFFERENTALBUMIN ASSAYS ONCALCIUM AND PHOSPHATEMANAGEMENT IN CHRONICHEMODIALYSIS PATIENTS

Dinky E. de Haseth1, E. Lay Penne2, Bastiaan van Dam1, Willem A. Bax1,Michiel L. Bots3, Muriel P.C. Grooteman2, Rene A. van den Dorpel4,Peter J. Blankenstijn3, Menso J. Nube2 and Piet M. Wee21MCA Alkmaar The Netherlands, 2VUMC Amsterdam The Netherlands, 3UMCUtrecht The Netherlands, 4Maasstad Hospital Rotterdam The Netherlands

Introduction and Aims: For measurement of serum albumin two different assays aregenerally used: bromcresol green (BCG) and bromcresol purple (BCP). These assaysprovide different results, in particular in hemodialysis (HD) patients. Hence, whencalcium levels are corrected for albumin (adjusted calcium=[total calcium]+0.0246 x(40 –[albumin])) as recommended by guidelines, results depend on the type ofalbumin assay used. The objective of this study was to evaluate whether the type ofalbumin assay has clinical implications in HD patients, especially on prescription ofphosphate binding agents.Methods: In this cross-sectional study, 503 patients were analysed from 24 Dutchdialysis centers, at entry in the Convective Transport Study between 2004 and 2008(mean age 63.3 ± 14.1 yrs;62 % male). 9 centers used BCP [n=330]. 15 centers usedBCG [n=173]. Plasma phosphate, calcium levels, albumin and use of phosphatebinding agents were compared between the two albumin assays.Results: Plasma albumin was lower in the BCP as compared to the BCG group (34.5±4.2g/lvs.40.4±3.1 g/l; P = 0.000), while nutritional (normalized nitrogen appearance,creatinine, cholesterol and body mass index) and inflammatory (hsCRP) parameterswere similar. The measured calcium levels were similar in both groups (2.34±0.2mmol/l for BCP vs 2.32±0.18 mmol/l for BCG; P=0.25). Corrected calcium was higherin the BCP group (2.46±0.2 mmol/l vs 2.33±0.2 mmol/l, respectively; P<0.000). Morepatients in the BCP group were hypercalcemic after correction for albumin (28.8% vs13.3%; P<0.001). Phosphate levels were higher in the BCP group (1.70±0.5 mmol/l vs1.57±0.4 mmol/l, respectively; P=0.006), which was not explained by patient- ortreatment characteristics. Use of calcium-containing phosphate binders tended to behigher in the BCP group as compared to the BCG group (43.9% vs 50.9 %; P=0.137).No difference in use of calcium-free containing binders was found (75.2% for BCP vs75.1% for BCG; P=0.999).Conclusions: Calcium concentrations after correction for albumin were higher inpatients treated in centers using the BCP as compared to the BCG assay, in the BCPgroup patients were more likely to be hypercalcaemic. Despite higher calcium levels,after correction for albumin, more calcium containing binders tended to be prescribedin these patients, suggesting that calcium levels were not corrected for albumin. Inaddition, phosphate levels were higher in the BCP group. Keeping in mind these areobservational data, it may be hypothesized that the latter is explained by less restrictivedietary measures due to apparent hypoalbuminemia in these patients.

SP132 URINE PROTEIN, ALBUMIN CREATININE RATIO ESTIMATIONBY URINE DIPSTICK PROTEIN AND SPECIFIC GRAVITY

Jung Hwan Park1, Young-Il Jo1 and Jong Ho Lee11Division of Nephrology Konkuk University Seoul Republic of Korea

Introduction and Aims: Proteinuria is an evidence of kidney disease and patients withproteinuria have higher cardiovascular risk. Though random urine protein creatinineratio (PCR) and albumin creatinine ratio (ACR) are standard methods to detectproteinuric patients, urine dipstick test is commonly used for general practice. We useddipstick protein (DP) and specific gravity (SG) to increase sensitivity and specificity fordetecting microalbuminuria and overt proteinuria.

Nephrology Dialysis Transplantation Abstracts

Volume 28 | Supplement 1 | May 2013 doi:10.1093/ndt/gft108 | iDownloaded from https://academic.oup.com/ndt/article-abstract/28/suppl_1/i117/1838454by gueston 12 April 2018

Methods:We collected urine sample data from electronic medical records that weresubmitted simultaneously for urine chemistry and dipstick test. Urine samples werecollected from adult (Age 16-98) patients. Six thousands nine hundreds forty onerandom urine samples were tested for PCR and urine dipstick, and 3,874 samples forACR and dipstick.Results: The median values of PCR and UCR were higher in samples of high grade DPand low SG. When DP 2+(100 mg/dL) and over or 1+(30 mg/dL) with SG ≤1.010 ortrace with ≤1.005 were used as selection criteria, the sensitivity, specificity, positivepredictive value (PPV) and negative predictive value (NPV) for detection of overtproteinuria (PCR ≥500 mg/g) were 89.6%, 87.7%, 87.5% and 89.8% respectively. Whenmore than trace was used, the sensitivity, specificity, PPV and NPV for detection ofmicroalbuminuria (ACR ≥30mg/g) were 60.2%, 86.6%, 85.6% and 62.0% respectively.With negative results, especially if SG levels were lower, there were manymicroalbuminuria cases.Conclusions: Combination of DP and SG value is more useful to estimate PCR and todetect overt proteinuria cases than DP only.

SP133 IS ANTIPROTEINURIC EFFECTOF ACE-INHIBITORSCONSTANT THROUGHOUT THE DAY?

Paola Cianfrone1, Nicola Comi1, Gaetano Lucisano1, Valentina Piraina1,Roberta Talarico1 and Giorgio Fuiano11Nephrology Magna Graecia University Catanzaro Italy

Introduction and Aims: It has been demonstrated that a low dose of ACE-inhibitor(ACE-I) has the same effectiveness as a higher dose in lowering blood pressure, butwith a shorter duration of action, so that the patient is unprotected for a relevant partof the day. However, if the same occurs also for the antiproteinuric effectiveness is notknown. In our prospective study, we aimed to recognize if proteinuria variesthroughout the day with different doses of ACE-I administered once a day.Methods: Between the 1st of January 2012 and the 1st of September 2012 we enrollednormotensive patients with a 24-hours urinary protein excretion between 1 and 3grams/day, eGFR >30 ml/min. Patients should have discontinued any therapy withanti-angiotensin agents or immunosuppressive agents from at least 3 months. At thetime of enrollment, participants performed three consecutive timed urine collections (8a.m.- 2 p.m., 2 p.m.-0 8 p.m., and 8 p.m.- 8 a.m. of the following day), on whichurinary protein/creatinine ratio (UPC ratio) was calculated. A single daily dose oframipril 2.5 mg was administered at 8 a.m. for 10 days. At day 10 the timed collectionswere repeated and at day 11 the dosage was increased to 10 mg for other 10 days. At theday 20, a new timed collection was obtained. Our study was approved by the LocalEthical Committee, and all participants gave written informed consent.Results: Eleven patients (3 women) met the inclusion criteria and completed the study.ACE-I therapy was well tolerated, without significant variations of blood pressure,eGFR or plasma potassium. Mean eGFR at enrollment was 46.3 ± 16.6 ml/min, meanage 55 ± 19 years. In the first part of the study (without ramipril therapy), UPC ratiowas maintained quite stable throughout the 24 hours, without any significant differencebetween the three consecutive time-matched collections (Table in Figure). After theadministration of ramipril 2.5 mg/day, a non-significant reduction of the UPC ratioduring the 24 hours was observed, without significant differences between the threetimed collections. By contrast, after the administration of ramipril 10 mg/day we founda significant reduction of the UPC ratio, with lower levels during the evening and thenight collection as compared with the morning collection, (p=0.048 and 0.032,respectively).

Conclusions: Our findings show that administration of ACE-I induces dose dependentantiproteinuric effects only after several hours, and no residual effect lasts over the 24hours. Also, this finding suggests that an antiproteinuric effect lasing 24-hour could beobtained administering the drug in two daily doses and that higher dosage induceshigher effect.

SP134 AGE-RAGE SYSTEM AND TUBULOINTERSTITIAL INJURY IN AMOUSE REMNANT KIDNEYMODEL

Maki Toyonaga1, Kei Fukami1, Sho-ichi Yamagishi2, Yusuke Kaida1,Yosuke Nakayama1, Ryotaro Ando1, Nana Obara1, Seiji Ueda1 and Seiya Okuda11Division of Nephrology, Department of Medicine Kurume University School ofMedicine Kurume Fukuoka Japan, 2Department of Physiology and Therapeutics ofDiabetic Vascular Complications Kurume University School of Medicine KurumeFukuoka Japan

Introduction and Aims: Tubulointertstitial injury is one of the common features ofpatients with chronic kidney disease (CKD). Advanced glycation end products (AGEs)are elevated in patients with diabetes mellitus and end-stage renal failure (ESRD),whose serum and tissue levels are strongly associated with mortality in these patients.Further, binding of AGEs to receptor for AGEs (RAGE) induces reactive oxygenspecies (ROS) generation and subsequently evokes tubular injury in experimentaldiabetic model. However, whether and how AGEs-RAGE system could be regulated innon-diabetic CKD model such as remnant kidney model has not been elucidated.Therefore, we investigated whether serum AGEs and intrarenal RAGE expression wereincreased and associated with tubulointerstitial injury in a mouse of subtotalnephrectomy (Nx), as a non-diabetic CKD model.Methods: Ten week old C57BL/6J mice were assigned to 2 groups (Nx; n=18 or sham;n=10). 5/6Nx was performed by surgical resection. Four weeks after the Nx, mice wereeuthanized and sacrificed for analysis. Urinary albumin and neutrophilgelatinase–associated lipocalin (NGAL) excretionand serum N-carboxymethyl-lysine (CML), oneof the AGEs, were measured by enzyme-linked immunosorbent assay. RAGE andtype-IV collagen expression was evaluated by western blotting and real-time PCR.Tubulointetstitial fibrosis was examined by periodic acid-Schiffandmasson'strichromestaining, respectively.Results: Subtotal nephrectomy significantly increased the levels of blood urea nitrogenand creatinine (Cr), and decreased Cr clearance levels. Circulating CML and renalRAGE expression levels were significantly increased compared with those insham-operated (Ctrl) mice. (305.60 ± 54.58 vs 529.53± 50.31, p=0.083, 1.07 ± 0.11 vs4.2 ± 2.01, p=0.028, respectively) Urinary albumin and NGAL excretion weresignificantly higher than Ctrl mice (4.02 ± 0.11 vs 4.83 ± 0.26, p=0.030, 4.07 ± 0.66 vs5.71 ± 0.31, p=0.017, respectively). Furthermore, type-IV collagen mRNA expressionwas increased and tubulointerstitial fibrosis was exacerbated in the kidney of 5/6 Nxmice compared with Ctrl mice. (1.05 ± 0.01 vs 2.04 ± 0.58, p=0.037).Conclusions:We demonstrated that induction of renal dysfunction increasedcirculating AGEs levels, increased RAGE expression and tubulointerstitial injury in Nxmice. These observations suggest that AGEs-RAGE system and tubulointerstitial injurymay be correlated with each other, thereby being involved in the progression oftubulointerstitial fibrosis in CKD.

SP135 URINARY ALPHA-1 MICROGLOBULIN CORRELATESWITHTHE DEGREE OF SECONDARY RENALTUBULOINTERSTITIALFIBROSIS

Jana Granatova1, Martin Havrda2, Zdenka Hruskova3, Vladimir Tesar3,Ondrej Viklicky4, Romana Rysava3, Ivan Rychlik2, Karolina Kratka2, Eva Honsová4,Zdenka Vernerova2, Jana Maluskova4, Jana Vranova2, Milada Bolkova1,Klara Borecka1, Hana Benakova3 and Tomas Zima31Thomayer Hospital Prague 4 Czech Republic, 23rd Medical Faculty, CharlesUniversity Prague 10 Czech Republic, 31st Medical Faculty, Charles UniversityPrague 2 Czech Republic, 4Institute of Clinical and Experimental Medicine Prague4 Czech Republic

Introduction and Aims: Non-invasive testing of the kidneys has a limited ability todescribe the condition of the renal tissue. It is desirable that we are able to distinguishbetween patients with chronic, irreversible scarring of the kidneys from those withactive and potentially treatable lesions. We tested the ability of urinaryalpha-1-microglobulin (A1m) to distinguish among patients with different degree ofrenal tubulointerstitial fibrosis.Methods: In this multi-center study, we included patients who underwent diagnosticrenal biopsy, whose primary diagnosis was other than acute or chronictubulointerstitial nephritis, who had proteinuria (protein/creatinine ratio ≥15mg/mmol) and whose A1m/albumin ratio did not exceed 0,5 (to exclude patients who arelikely to have a primary tubulointerstitial disease). Urinary levels of A1m, albumin(alb) and creatinine (creat) were measured and urinary indexes A1m/alb and A1m/creat were calculated. Tubulointerstitial (TI) fibrosis was graded 1 (0-5%), 2 (5-25%), 3(25-50%) and 4 (>50%) in the renal biopsy samples. We tested if A1m/alb and A1m/creat differantiate among patients with different grades of TI fibrosis. We usednon-parametric tests: Mann-Whitney U test and KruskalWallis ANOVA, and weperformed ROC analysis to find the discriminating power of parameters.

SP132

SG DP ≤1.005 1.010 1.015 1.020 1.025 ≥1.030Negative 69/254 20/441 0/519 3/528 3/282 4/75Trace 42/56 42/106 15/140 6/174 3/109 2/501+ 81/83 188/234 137/302 30/246 11/164 8/672+ 104/104 448/455 482/514 271/385 140/281 38/1053+ 15/15 226/226 472/473 290/290 146/151 103/111

SP133



Results: 137 patients were included in the analysis. TI fibrosis was graded 1 in 16patients, 2 in 52 patients, 3 in 37 patients, 4 in 32 patients. A1m/creat differentiatedbetter among groups than A1m/alb. Statistically significant differences of A1m/creatwere found between grade 1+2 versus grade 3+4 (p=0,002), grade 4 versus grade 1(p=0,00005), and grade 4 versus grade 2 (p=0,01). Using the ROC analysis we foundthat the discriminating power of A1m/creat is good between grade 4 versus grade 1with the sensitivity 78,1% and specificity 82,6% (AUC 0,795, cut-off >28 mg/mmol),and between grade 4 versus grade 1+2+3 with the sensitivity 71,9% and specificity68,9% (AUC 0,718, cut-off >64,07 mg/mmol).Conclusions:We confirmed results of our small pilot study, that urinary A1m isstrongly associated with the grade of TI fibrosis. A1m/creat can be used as anon-invasive marker, which is particularly useful to identify patients with a high degreeof renal tubulointerstitial fibrosis.

SP136 ROLE OF THE FUNCTIONALTOLL-LIKE RECEPTOR-9PROMOTOR POLYMORPHISM (-1237T/C) IN THE INCREASEDRISKOF END-STAGE RENAL DISEASE: ACASE-CONTROLSTUDY

Kuo-Cheng Lu1, Hsin-Yi Yang2 and Sui-Lung Su21Department of Medicine Cardinal Tien Hospital, Fu-Jen Catholic University NewTaipei City Taiwan Republic of China, 2School of Public Health National DefenseMedical Center Taipei Taiwan Republic of China

Introduction and Aims: Inflammation is a universal response to infectious andnoninfectious triggers in the kidney that may progress to end stage renal disease(ESRD). Toll-like receptor 9 (TLR-9), a receptor for CpG DNA, is involved inactivation of immune cells in renal diseases and may contribute to chronicinflammatory disease progression. Previous studies indicate that -1237T/C confersregulatory effects on TLR-9 transcription. To date, the effect of TLR-9 polymorphismson ESRD remains unknown. Therefore we investigated the predictive value of TLR-9gene polymorphisms and further functional study on ESRD in a Han Chinesepopulation.Methods:We performed a case-control study and genotyped (-1237T/C, -1486T/Cand 1635G/A) of TLR-9 polymorphisms on 630 ESRD patients and 415 controlsanalyzed by real-time PCR assays. Plasma concentrations of interleukin-6 (IL-6) weredetermined by ELISA. A luciferase reporter assay and real-time PCR were used to testthe function of the associated promoter polymorphism. The genotype distributionswere tested for Hardy-Weinberg equilibrium. The odds ratios (OR) and corresponding95% confidence intervals (CI) for assessing the effect of the genotype distribution andallele frequencies on ESRD were calculated by logistic regression analysis withadjustment for relevant significant variables. Linkage disequilibrium and haplotypeanalyses were performed using Haploview software (http://www.broad.mit.edu/mpg/haploview/) and WHAP (http://pngu.mgh.harvard.edu/˜purcell/whap/), respectively.Results: A significant association between -1237T/C in TLR-9 and ESRD wasidentified. The frequency of TLR-9 polymorphism haplotype “TCA” was 27.8%in theESRD patients compared with 34.6% in the controls (OR = 0.73, 95% CI = 0.60-0.88,p= 0.001). In contrast, haplotype TTA and CCAwere more common in the ESRDpatients (6.5% and 2.5%, respectively) than in the controls (1.9% and 0.6%,respectively) (OR = 3.47 and 4.45, 95% CI = 2.02-5.97 and 1.70-11.67, p <0.001 and <0.001, respectively). ESRD patients carrying -1237TC had a higher mean plasma IL-6level when compared with -1237TT. The TLR-9 transcriptional activity of the variant-1237CC allele is higher than the -1237TT allele. In vitro studies demonstrate that-1237T/C may be involved in the development of ESRD through transcriptionalmodulation of TLR-9.Conclusions:We found that single nucleotide polymorphisms of the TLR-9gene,especially -1237T/C, were significantly associated with ESRD in the Chinesepopulation. The functional study showed that -1237T/C may be involved in thedevelopment of ESRD through transcriptional modulation of TLR-9. It could provide anew insight into the role of TLR-9 in disease that has the potential to provide newavenues for treatment and to also identify individuals at risk.

SP137 IDENTIFICATION OF COMBLINED URINARYMRNABIOMARKERS FOR RENAL FIBROSIS IN IGA NEPHROPATHYWITH PCR ARRAY

Yu-Han Cao1, Lin-Li Lv1 and Bi-Cheng Liu11Southeast University Institute of Nephrology Nanjing China

Introduction and Aims: Immunoglobulin A nephropathy (IgAN) is the mostcommon form of primary glomerulonephritis worldwide. Here we reported anapplication of real-time quantitative PCR (RT-PCR) array in profiling new urinarybiomarkers of IgAN.Methods: 32 biopsy-proven IgAN patients and 6 healthy controls (HF) were enrolledin this study with complete clinical data. To evaluate progression of IgAN, patientswere divided into four groups based on the semiquantitativly graded tubulointerstitialfibrosis area (%) as none (5%, n=7), mild (6 - 25%, n=11), moderate (26 -50%, n=7),and severe (>50%, n=5). Urinary cell pellet was collected from each study participantand the total RNAwere extracted and identified from the urinary sediment. The PCRarray contains 89 renal fibrosis related genes, 4 housekeeping genes and 3 quality

controls and its performance was evaluated. The relative expression of each genebetween IgAN patients and healthy controls (HC) was examined and the data wastreated with ΔΔC method. Correlation between differentially expressed mRNA andclinical parameters and the ROC-curve analysis of differentially expressed mRNAwerealso determined. Linear discriminant analysis was used to weight those differentiallyexpressed mRNA and derive composite biomarkers which make superb performancefor RF diagnosis to the single gene.Results: The array we fabricated displayed high sensitivity, specificity, andrepeatability. Compared with healthy controls, a total of 20 mRNAs varied significantlyin IgAN patients (>2-fold) (p<0.05). They are podocyte markers, renin angiotensinsystem related, EMT markers, tubular injury markers, cytokines, signal pathwayrelated, and apoptosis related, respectively. Among these 20 differentially expressedmRNAs, 6 ones (ACE, CD71, FN1, PODXL, CCL5, VIM) were positively correlatedwith both serum creatinine and fibrosis area (%), and negatively correlated with eGFR(P<0.05).ROC-curve analysis show 5 mRNAs (ACE, CD71, PODXL, CCL5, VIM ) outof 6 were effectively able to differentiate RF and non RF subjects (p<0.05), withcalculated area under the curve (AUC) above 0.7(p<0.05).Linear discriminant analysiswas used to weight variables and derive composite biomarkers that identified the levelof RF based on urinary mRNA level of ACE, CD71, PODXL, CCL5, and VIM. Thediscriminant function that described the most accurate composite biomarkers includedACE, CD71, and CCL5 as the independent variables. The composite biomarker showedsensitivity and specificity of 82% and 90%. The positive predictive value and negativepredictive value was 95% and 70% respectively.Conclusions: This study demonstrated that target mRNA array might serve as ahigh-throughput and sensitive tool for detecting mRNA expression in urinarysediment. The composite of urinary mRNA established in this study might serve as annovel biomarker for RF of IgAN .

SP138 COMBINATION OF PLASMA AND URINARYMETABOLOMICSON THE IgA NEPHROPATHY CONTRIBUTED TO EVALUATIONOF CLINICALTREATMENT

Rong Zeng1, Xian-Fu Gao1 and Yue-Yi Deng21Shanghai Institutes for Biological Sciences Shanghai China, 2Department ofNephrology Longhua Hospital Shanghai China

Introduction and Aims: IgA nephropathy (IgAN) is a most commonglomerulonephritis characterized by diffuse mesangial deposition of the IgA antibodyin the glomerulus. The evaluation of treatment of IgAN could be helpful for theselection of clinical therapy. This study aims to profile metabolic features and identifypotential marker metabolites for diagnosis and treatment evaluation of IgAN patients,based on GC/MS metabolomics.Methods: This work involved 30 IgAN patients with biopsy-proven grades III-V byLee's classification scheme and 15 healthy subjects. GC-MS was used to profile themetabolomcis of both plamsa and urine. The data analysis was performed according tothe qualitative and quantitative detection of metabolome.Results: Both principal component analysis (PCA) and partial least squarediscriminant analysis (PLS-DA) could well discriminate IgAN patients withouttreatment from healthy controls based on plasma samples, whereas only PLS-DA coulddo so for urine samples. We further analyzed the differential metabolites by binarylogistic regression, and resultantly the combination of plasma glucose and2,4-dihydroxybutyrate could classify IgAN patients from healthy subjects with accuracy99.4%, as well as an 100% classification accuracy by the combination of urinary citrate,3-hydroxyisovalerate, and glycerate. After treated by either Prednisone andPrednisone-TCM therapy, the plasma and urinary metabolomic profiles of IgAN groupwere significantly changed by treatment according to PLS-DA.Totally 11 plasma and 7urinary metabolites were identified with differential regulation by treatment, of which 4plasma metabolites (aconitate, succinate, aspartate, and proline), and 3 urinarymetabolites (3-(3-hydroxyphenyl)-3-hydroxypropionate, glycerate, and citramalate)recovered to the level of healthy controls (p > 0.3). The differences of treatment byPrednisone and Prednisone-TCM were further compared.Conclusions: In summary, combined metabolomics based on plasma and urine was apowerful approach to study metabolic diseases such as IgA nephropathy. Four plasmametabolites and 3 urinary metabolites may be served as potential small molecularmarkers when diagnosing IgAN and evaluating the effects of treatment.

SP139 NON-TARGETEDMETABOLOMICS IN THE STUDYOF CHRONIC KIDNEY DISEASE

Jente Boelaert1,2, Ruben t' Kindt3, Griet Glorieux2, Eva Schepers2, Lucie Jorge3,Nathalie Neirynck2, Frédéric Lynen1, Pat Sandra1,4, Koen Sandra3 andRaymond Vanholder21Separation Science Group, Department of Organic Chemistry Ghent UniversityGhent Belgium, 2Renal Division, Department of Internal Medicine UniversityHospital Ghent Ghent Belgium, 3Metablys Kortrijk Belgium, 4Research Institute forChromatography Kortrijk Belgium

Introduction and Aims: The progressive loss in renal function in chronic kidneydisease (CKD) results in the accumulation of potentially toxic compounds. Earlydetection of an impaired kidney function and biomarkers predictive for the progression



of the disease are primordial towards an improved disease management. To attain thisgoal there is a clear need for novel biomarkers. In recent years, the so-called omicsapproach emerged as a powerful tool for biomarker discovery. The objective of thiswork was to perform a proof-of-concept metabolomics discovery study for CKD.Methods: Serum samples from CKD patients at stage 3 (n = 20), at stage 5 onhemodialysis (n = 19) and from healthy controls (n = 20) were monitored on a holisticmetabolomics platform combining reversed-phase liquid chromatography coupled tohigh-resolution quadrupole time-of-flight mass spectrometry (LC-Q-TOF MS) in bothnegative and positive ionization mode and gas chromatography coupled to quadrupolemass spectrometry (GC-MS). The methodological validity was ensured by use ofquality control (QC) samples in the analytical setup, and by a thorough data analysisstrategy for both the GC-MS and the LC-MS part.Results: A substantial portion of the serum metabolome was covered. Ninety-sixmetabolites were identified. Forty-five metabolites were already known in the contextof CKD (6 downregulated and 39 upregulated) while 51 metabolites were yet unknown(16 downregulated and 35 upregulated). Of the latter, 5 metabolites were found to besignificantly increased (fold change ≥ 5) at CKD stage 3 compared to control. Thesemetabolites were the sulfate and glucuronide conjugate of 3-hydroxyhippuric acid or2-hydroxyhippuric acid (salicyluric acid) (p < 0.001), hydroxypyridine (p < 0.00005),methoxy-hydroxyphenylglycol glucuronide (p < 0.0005) and a hexose basedtetrasaccharide (C24H42O21) (p < 0.0005).Conclusions: Further targeted analysis in an increased study population will beperformed to validate and quantify these novel, potential biomarkers across all CKDstages.

SP140 MASS SPECTROMETRY- AND ANTIBODY-BASEDPROTEOMICS OF THE HUMAN KIDNEY AND URINE

Tadashi Yamamoto1, Masaaki Nameta1, Yutaka Yoshida1 and Mathias Uhlen21Structural Pathology Institute of Nephrology Niigata University Niigata Japan,2Science for Life Laboratory and Albanova University Center Royal Institute ofTechnology (KTH) Stockholm Sweden

Introduction and Aims: Functions of the kidney and nephron segments are obituaryknown, however, the precise details have not been clarified. Pathophysiologicalmechanisms of human kidney diseases have also not been disclosed yet. Proteomics is apowerful tool to analyze tissues or urine to understand the functions, proteininteractions (pathways) and pathophysiology.Methods: Normal parts of tissues (cortex, medulla and glomerulus) were obtainedfrom nephrectomized kidneys due to renal cancers. Urine samples were also collectedfrom healthy volunteers. Proteins were separated by gel electrophoresis and peptideswere prepared by in-gel trypsin digestion for mass spectrometry (MS). Sections ofnephron segments were taken by laser-microdissection from normal human kidneysections, which were immunostained with anti-AQP1, calbindin and AQP2 antibodies,for identification of each segment (proximal, distal tubules and collecting duct,respectively). Glomerular sections were also collected from kidney biopsy samples ofkidney disease patients (membranous nephropathy, IgA nephropathy and others). Thepeptides were prepared by direct digestion of these sections with trypsin (On-SiteDirect Digestion) method for MS. Antibody (Ab)-based analysis of human tissues havebeen carried out in the Human Protein Atlas (HPA) project and more than a half ofhuman proteins have been localized in the human body and in the kidney byimmunohistochemistry (IHC).Results:MS identified more than a thousand proteins with high confidence in eachcomponent of the normal human kidney. The Ab-based proteomics disclosedthousands of proteins in the kidneys. Comparison of the MS-based and Ab-basedglomerulus proteomes showed approximately one fourth of proteins, which wereidentified by MS or Ab, were detected by both MS- and Ab-based methods. About ahalf of urine proteins identified by MS were also found in human plasma proteomes.Urine proteins, which were not plasma proteins, were localized in the kidney and otherurinary tract by looking at the HPA IHC images. The localization of urine proteinswere summarized in a human urine proteome database. By MS analysis of humanglomerular sections of each kidney biopsy samples, approximately a thousand proteinswere identified and were further analyzed by bioinformatics to understandpathophysiology of kidney diseases.Conclusions: Proteomic analyses of human kidney tissues and urine providedfunction- and disease-related information. These data were combined in a kidney andurine proteome database for public use.

SP141 INFLUENCE OF CYP3A5, CYP2C8 AND ABCB1POLYMORPHISMS ON TACROLIMUS-INDUCEDNEPHROTOXICITY IN LIVER TRANSPLANT RECIPIENTS

Yunying Shi1, Jiangtao Tang2, Junlong Zhang2, Yunfei An2, Yun Liao2, Yi Li2,Ye Tao1 and Lanlan Wang2

1Department of Nephrology West China Hospital of Sichuan University ChengduSichuan China, 2Department of Laboratory Medicine West China Hospital ofSichuan University Chengdu Sichuan China

Introduction and Aims: The nephrotoxicity of calcinurin inhibitors (CNI) remainsthe dominant causative factor for kidney failure in nonkidney organ

transplantrecipients, especially in liver transplantrecipients.The possible influenceof single nucleotide polymorphisms (SNPs) including cytocrome P450 3A(CYP3A) subfamily, CYP2C8 and P-gp (ABCB1) on CNI induced renal injury inliver transplant recipients have recently been indicated as one of the mostimportant factors. The purpose of this study was to explore the associationbetween known ABCB1, CYP3A5 and CYP2C8 polymorphisms and the risk ofdeveloping tacrolimus (Tac) associated nephrotoxicity in liver transplantrecipients.Methods: A total of 136 living donor liver transplant recipients (107 males and29 females) and 150 healthy controls (120 males and 30 females) were enrolledin this study. All the recipients had normal renal function (normal Cystatin Cand normal urine micro-albumin) before transplantation and received Tac-basedimmunosuppressive regime (Tac+MMF+ prednisone) afterwards. CYP3A5,CYP2C8 and ABCB1 SNPs were assessed by polymerase chain reaction (PCR)and high-resolution melting curve analysis (HRM analysis). The troughconcentrations of Tac were measured by enzyme-multiplied immunoassaytechnique (EMIT). We also detected serum cystatin C (Cys-C) and urinemicroproteins including α1 microalbumin (α1M), microalbumin (MA),transferring (TRU) and IgG (IgU) among 136 allo-liver recipients to evaluatewhether they have early renal injury and the probable location of the renallesion.Results: We could clearly distinguish three genotypes of CYP3A5 and ABCB1,while only two genotypes of CYP2C8 were identified in 136 recipients included.The genotype frequencies of the recipients did not show significant deviationfrom the Hardy-Weinberg equilibrium (P>0.05). The levels of cystatin C as wellas all the four urine micro-proteins in the recipient group were significantlyhigher than those in the control group (P<0.05). There was a significantdifference in TRU concentration instead of other three microproteins amongpatients with different CYP3A5 genotypes (P<0.05). The concentrations of α1Mand Cys-C in recipients with CYP2C8*3*1 were significantly higher than that inthose with CYP2C8*1*1 allele (p<0.05). Regarding MDR1 SNPs C3435T andC1236T, no significantdifference was found In Cys-C and urine microproteinsamong patients with different genotypes.Conclusions: CYP2C8*3 and CYP3A5*3 might have predictive value on therisk of Tac-induced nephrotoxicity. CYP3A5*3 was associated with the riskof early glomerular injury, while CYP2C8*3*1 was associated with the riskof early tubulointerstitial injury. ABCB1 genotypes (both C3435T andC1236T) were irrelevant to the Tac-induced nephrotoxicity in liver transplantrecipients.

SP142 THE RISK FACTORS OFWORSENING RENAL FUNCTION BYVASOPRESSIN RECEPTOR 2 ANTAGONIST (TOLVAPTAN) INNON-DIALYSIS CHRONIC KIDNEY DISEASE PATIENTSWITHCHRONIC HEART FAILURE

Kiyoto Koibuchi1, Kentaro Tanaka2, Toshiyuki Aoki1, Moriatsu Miyagi1, Ken Sakai2

and Atsushi Aikawa21Department of Nephrology Saiseikai Yokohama-City Eastern Hospital YokohamaKanagawa Japan, 2Department of Nephrology Toho University School of MedicineOta-ku Tokyo Japan

Introduction and Aims: Tolvaptan is a selective vasopressin receptor 2 antagonist anddose-dependent drug used to treat chronic heart failure (CHF) as diuretics. It is knownthat tolvaptan increases excretion of excess fluids and improves blood sodium levels inpatients with heart failure without affecting renal function compared to conventionaldiuretics. However, it is pointed out the possibility that tolvaptan worsens renalfunction especially in non-dialysis chronic kidney disease (NDCKD) patients, and fewstudies examined the risk of worsening renal function about tolvaptan. The aim of thestudy is to investigate the risk factors of worsening renal function by tolvaptan inNDCKD patients with CHF.Methods:We administrated tolvaptan (Doses 10.7±3.9mg) for 120 NDCKD patients(male/female: 72/48, 76.8±11.9 years old, estimated glomerular filtration rate (eGFR):42.3±21.8 ml/min/1.73m2) with CHF in admission. Those of all patients have alreadytreated conventional diuretics. The patients who changed the dose of conventionaldiuretics in observation period were excluded. The following data were collected fromthe electric record at baseline: age, sex, presence of diabetes, blood pressure, urineoutput, body weight, eGFR, serum sodium concentration, hemoglobin, serum albumin,serum bicarbonate, brain natriuretic peptide (BNP), and cardiac ejection fraction. Wedefined reduction of eGFR in duration from administration of tolvaptan to dischargeas worsening renal function (WRF), and statistical analysis was used by logisticregression models.Results: 44 patients (36.7%) developed the WRF. In univariate analysis, age (Odds ratio1.43, 95%CI 1.11-1.65,p=0.003), serum albumin (0.87, 0.78-0.93, p=0.02), urine output(0.047,0.01-0.99, p=0.008), bicarbonate (0.92, 0.80-0.97, p=0.03), and cardiac ejectionfraction (0.68, 0.55-0.84, p=0.008) were associated with WRF. In multivariate analysis,age (1.16, 1.06-1.31, P=0.02), serum albumin (0.91, 0.83-0.95, p=0.03), cardiac ejectionfraction (0.88, 0.72-0.93, p=0.01) were remained significant after adjusted for age,eGFR, serum albumin, urine output, and bicarbonate. It suggests that diuresis bytolvaptan in condition of low serum albumin and cardiac ejection fraction causesdecrease of renal plasma flow especially in NDCKD and lead to WRF.Conclusions: Age, serum albumin, and cardiac ejection fraction were independent riskfactors of WRF by tolvaptan in NDCKD patients with CHF.



SP143 BARIATRIC SURGERY IN OBESE PATIENTS IS ASSOCIATEDWITH REDUCTION OF ALBUMINURIA ANDCARDIOVASCULAR RISK FACTORS

Ana R. Martins1, Patricia Q. Branco1, Filipa M. Serra2, Patricia J. Matias1,Carlos P. Lucas1, Teresa Adragão1, Joao Duarte2, Maria M. Oliveira2,Antonio M. Saraiva2 and Jose D. Barata11Nephrology Hospital Santa Cruz/CHLO Lisbon Portugal, 2EndocrinologiaHospital Egas Moniz Lisboa Portugal

Introduction and Aims: Obesity is a health problem with epidemic proportions andhas been shown to be associated with chronic kidney disease and albuminuria. Extremeobesity (body mass index [BMI] > or =40 kg/m2) is associated with cardiovasculardisease, type 2 diabetes, dyslipidemia, and hypertension. Bariatric surgery (BS) is aneffective means of achieving long-term weight loss. Improvement in albuminuria hasalso been reported. The objective was to evaluate, at a weight control center in acommunity hospital setting, the effect of weight loss after BS on blood pressure (BP),renal parameters and cardiovascular risk markers.Methods:We performed a prospective study in 71 obese adults who had undergonegastric bypass surgery. Clinical and laboratorial data were evaluated at baseline and 1, 6and 12 months after surgery.Results: Our cohort of 71 patients had a mean age of 46,11 ± 11,4 years, 84,7% femaleand 76,3% caucasian, with a mean BMI of 44,5±5,5 (33- 57,3) kg/m2. At baseline 55,6%had BP > or =140/90mmHg, and 45,8% had type 2 diabetes. During the 10±4,5 monthsof follow-up (postoperative), a decrease occurred in BMI (44,2± 5,6 kg/m2 to 30,7 ± 4,2kg/m; p<0,0001), excess body weight (113,6±19,5 kg to 78,9 ± 13,5 kg; p <0,0001),systolic BP (134±23,9 to 116±11,5 mmHg, p=0,01), diastolic BP (81±13,2 to 67±4,9mmHg; p=0,004), total cholesterol (182±39 to 169±36,3 mg/dl; p=0,004), triglycerides(136,4±64,6 to 97,7±40 mg/dl; p<0,0001), hypotensive medication (1,3±1,4 to 0,48±0,8;p<0,0001), oral antidiabetics (0,9±1,2 to 0,3±0,6; p<0,0001) and dyslipidemicmedication (0,6±0,7 to 0,5±0,4 p<0,0001). Five from the twelve patients treated withinsulin stopped this medication. The majority (53,3%) of the patients with significantpreoperative albuminuria lowered their albumin excretion levels [urinary albumin/creatinine ratio (UACr) from a median of 52,1 mg/g to a median of 12,3 mg/g;p<0,0001]. All parameters improved at 12 month after BS. There was no significantdifference in UACr reduction after BS between diabetics and non diabetics (pNS). Inmultivariate analysis (binary regression), there was a significant association betweenhigher percentage of weight reduction (> 18%) and higher UACr reduction at 6months (p=0,007, Exp(B): 3.0, CI: 0,41-7,24), even when adjusted for age, diabetesmellitus and hypertension.Conclusions: In this study of obese patients submitted to BS there was a significantreduction in UACr during the follow-up time. There was also an association betweenhigher percentage of weight reduction (> 18%) and higher UACr reduction at 6months. Simultaneously, this surgery had a positive impact in major cardiovascularrisk factors, such as BP, dyslipidemia and type 2 diabetes.

SP144 PROTEOGLYCANS AND GLYCOSAMINOGLYCANSTRANSCRIPTOMIC ANALYSIS SHOWED A SPECIFIC PROFILEIN CHRONIC KIDNEY DISEASE PATIENTS

Valentina Masola1, Gianluigi Zaza1, Simona Granata1, Marta Proglio1,Paola Pontrelli2, Cataldo Abaterusso3, Francesco Schena2, Loreto Gesualdo2,Giovanni Gambaro4 and Antonio Lupo11Renal Unit, Departement of Medicine, University-Hospital of Verona Verona Italy,2Renal, Dialysis and Transplant Unit -Department of Emergency andTransplantation, University of Bari Bari Italy, 3Renal and Dialysis Unit, CastelfrancoVeneto Hospital Castelfranco Veneto Italy, 4Division of Nephrology and Dialysis,Columbus-Gemelli Hospital Catholic University, School of Medicine Rome Italy

Introduction and Aims: Chronic kidney disease (CKD) patients, particularly in moreadvanced stages, have an increased risk of cardiovascular events compared to thegeneral population. However the systemic machinery associated to this condition andthe contribution of microinflammation to this complex event is still not completelydefined. Additionally, numerous reports have suggested a link between kidney disease,alteration of the immune system and endothelial dysfunction.Methods: To identify dysregulated elements possibly involved in this multifactorialprocess, we measured the expression level of 132 genes involved inglycosaminoglycans/proteoglycans metabolism in peripheral blood mononuclear cells(PBMCs) of 5 healthy subjects (HS), 9 chronic kidney disease II-III K/DOQI stage(CKD II-III), 10 peritoneal (PD) and 17 hemodialysis (HD) patients by microarrayanalysis.Results: Statistical analysis identified 67 genes discriminating HD/PD patients fromHS/CKD II-III subjects (p<0.001, FDR<5%). Thirty-four genes were up-regulated (e.g.,VEGFA, HPSE, VCAN, SOD1, CHSY1) and 33 down-regulated (e.g., IDS, HEXA,DMD, SNTB2) in HD/PD compared to HS/CKD II-III. We found only a slight and notsignificant difference in the transcriptomic profile between HS and CKD II–III(p=0.14) and PD and HD (p=0.16). Then, for the second part of the study, we focusedon 2 selected up-regulated genes in HD/PD: Heparanase (HPSE) and Vascularendothelial growth factor (VEGF). We measured the protein levels of HPSE and VEGFby ELISA in plasma of patients in an independent testing-group (11 HS, 7 CKD II-III,11 CKD IV-V, 17 PD and 18 HD). Both protein levels, were higher in CKD IV-V, PD

and HD patients compared to CKD II-III and HS (p<0.01). Additionally, HPSEactivity was significantly correlated with high-sensitive C reactive protein levels(R2=0.11, p=0.007). In vitro stimulation of PBMCs with Lipopolysaccharide caused astatistically significant up-regulation of HPSE mRNA level (p=0.04).Conclusions: Our results demonstrated an active and highly dynamic PBMCsbiological machinery involved in the GAGs/PGs metabolism in CKD and they add newinsights towards understanding the systemic molecular link betweenmicroinflammation, endothelial dysfunction and chronic kidney disease and it revealsnew potential diagnostic bio-markers and targets useful for innovative therapeuticinterventions.

SP145 RENALTISSUE OXYGENATION ASMEASUREDWITHBOLD-MRI IN PATIENTSWITH CHRONIC KIDNEY DISEASE INCOMPARISONWITH ARTERIAL HYPERTENSION ANDHEALTHY CONTROLS

Menno Pruijm1, Lucie Hofmann1, Matthias Stuber2, Carole Zweiacker1,Maciej Piskunowicz4, Marie-Eve Muller1, Bruno Vogt3 and Michel Burnier11Nephrology University Hospital Lausanne (CHUV) Lausanne Switzerland,2Radiology University Hospital of Lausanne (CHUV) Lausanne Switzerland,3Nephrology University Hospital of Bern Lausanne Switzerland, 4RadiologyUniversity Hospital of Gdansk Gdansk Poland

Introduction and Aims: Animal studies have suggested that renal tissue hypoxia playsan important role in the pathogenesis of chronic kidney disease (CKD), yet data inhumans are sparse. We are actually assessing cortical and medullary oxygenation inpatients with CKD using blood oxygenation level-dependent magnetic resonanceimaging (BOLD-MRI).Methods: Patients with CKD stage I-V (all causes except polycystic kidney disease)recruited at our outpatient clinic undergo BOLD-MRI under standardized hydrationconditions. Four coronal slices are selected over both kidneys, and a multi gradientecho sequence is used to acquire T2* weighted images. The mean cortical andmedullary R2* values (=1/T2*) based on a total of 16 regions of interest placed perkidney are calculated, a low R2* indicating a high tissue oxygenation. Healthynormotensive and hypertensive subjects are recruited as controls. Blood pressure is thereported as the mean of three office blood pressure measurements. Kidney function isestimated using the MDRD formula, and dietary sodium intake is estimated by 24hurinary sodium excretion.Results: So far, 75 CKD patients (69% male), 54 AHT patients (67% male), and 43controls (48% male) have been recruited, aged (mean±SD) respectively 57±15, 57±12and 46±13 years, with eGFR55±28, 91±16, and 93±16 ml/min/1.73m², and urinarysodium excretion of 172±94, 176±96, and 155±74 mmol/24h. Overall, cortical R2*(17.9±1.5, 17.4±1.2 vs 17.3±1.8 sec-1, p ANOVA=0.1) and medullary R2* values (29.3±2.0, 28.7±2.1 vs 29.3±2.5sec-1, p ANOVA =0.30) are not significantly differentbetween CKD, AHT and healthy subjects. In multivariate linear regression, adjusted forage, sex, smoking, hemoglobin level and 24h urinary sodium excretion, cortical andmedullary R2*were not associated with eGFR or blood pressure.Conclusions: In this interim analysis, R2* as a measure of kidney oxygenation is notaltered in CKD patients, suggesting that kidney oxygenation is tightly maintained overa broad range of kidney function.

SP146 PREDICTION OF DETERIORATION IN RENAL FUNCTION BYMRI AND URINARYMARKERS

Nobuhiko Togashi1, Tomohisa Yamashita1, Tomohiro Mita2, Yoshito Ohnuma2,Tohru Hasegawa2, Toshiaki Endo2, Akihito Tsuchida2, Toshiaki Ando2,Hideaki Yoshida3 and Tetsuji Miura31Nephrology JR Sapporo Hospital Sapporo Japan, 2Cardiology JR SapporoHospital Sapporo Japan, 3Second Department of Internal Medicine SapporoMedical University Sapporo Japan

Introduction and Aims: Recent studies have shown that magnetic resonance imaging(MRI) of the kidney can be useful for detecting renal dysfunction as well asmorphological abnormalities. However, how functional indices in MRI correlate withglomerular and tubular injuries in the kidney remain unclear. Here we examinedrelationship between decline in glomerular filtration rate (GFR), an index in renal MRIand urinary markers in patients with chronic kidney disease (CKD).Methods: Fifty-seven patients with CKD were consecutively recruited to this study anddivided into patients with estimated GFR (eGFR) 60 > ml/min/ 1.73 m2 (G1-2 group,n=31), patients with eGFR being 30˜59 ml/min/ 1.73 m2 (G3 group, n=12) andnon-hemodialysis patients with eGFR<30 ml/min/ 1.73 m2 (G4-5 group, n=14). Asurinary markers, we determined urinary protein, urinary N-acetyl-betaD-glucosaminidase (NAG), urinary alpha-1 microglobulin (A1MG), urinary beta-2microglobulin (B2MG). In MRI study, apparent diffusion coefficient (ADC), whichreportedly reflects tubulo-interstitial fibrosis, was calculated according to the methodby T. Inoue et al. with slight modifications.Results: In the study subjects, 91% and 18% of patients were hypertensive and diabetic,and the incidences were similar in the G1-2, G3 and G4-5 groups. ADC in the CKDG4-5 group was significantly lower than in the other two groups (1.38±0.18 in G4-5 vs.1.65±0.17 in G1-2 and 1.55±0.14 in G3, p<0.05). In the cross-sectional analyses using



all study subjects, eGFR was positively correlated with ADC (r=0.55, p<0.05) andnegatively correlated with A1MG (r=-0.68, p<0.05). On the other hand, there were nosignificant correlations between eGFR and levels of NAG, B2MG or urinary protein.ADC was negatively correlated with A1MG (r=-0.34, p<0.05), but not with NAG,B2MG or urinary protein. We could follow up 24 patients for more than 6 months (720days on average). In the longitudinal analyses of their data, change in eGFR duringfollow-up period (delta-eGFR, ml/min/ 1.73 m2 /year) was negatively correlated withurinary protein (r=-0.69, p<0.69) and with A1MG (r=-0.60, p<0.05). However,correlation between delta-eGFR and ADC did not reach statistical significance (r=0.36,p=0.09).Conclusions: Declined ADC in MRI indicates reduction in GFR. Of urinary markersexamined in the present study (NAG, A1MG, B2MG, urinary protein), only A1MG isuseful for detection of declining GFR. In prediction of renal prognosis, A1MG andurinary protein levels appear to be better markers than ADC.

SP147 A SIMPLE SCORING ALGORITHM USING SERUM FREE LIGHTCHAINS FOR THE RISK ASSESSMENTOF PROGRESSION OFCHRONIC KIDNEY DISEASE

Anne Bevins1,2, Lakhvir Assi1, James Ritchie3, Mark Jesky2, Stephanie Stringer2,Philip Kalra3, Colin Hutchison2,4, Stephen Harding1 and Paul Cockwell21The Binding Site Group Ltd Birmingham United Kingdom, 2Nephrology UniversityHospital Birmingham Birmingham United Kingdom, 3Vascular Research GroupSalford Royal NHS Foundation Trust Salford United Kingdom, 4Hawke's BayDistrict Health Board Hastings New Zealand

Introduction and Aims: There is a major need for accurate risk stratification forpatients with stage 4 CKD; although 30% of patients progress to end-stage kidneydisease (ESKD) as defined by a requirement for renal replacement therapy (RRT), themajority do not. Here we propose an algorithm utilising polyclonal combined serumfree light chains (cFLC; κFLC + λFLC), as a marker of kidney function and adaptiveimmunity, in combination with routinely measured laboratory data to optimise theidentification of those at no risk of progression to ESKD within 12 months.Methods: Baseline sera from 561 stage 4 CKD patients (University HospitalBirmingham [UHB] n=201, Chronic Renal Insufficiency Standards ImplementationStudy [CRISIS] n=205 and Renal Insufficiency in Secondary Care [RIISC] n=155) hadFLC measured using the Freelite® assay (The Binding Site Group Ltd, UK). Results wereused in combination with other laboratory assessments to develop the model (initiallyin UHB and validated in CRISIS and RIISC).Results: In the UHB population (median follow up 1483 days [range 22-2906]), cFLClevels were associated with reduced time to ESKD (HR=1.009, 95%CI 1.005-1.012,p<0.001). During this period 60 patients progressed to RRT. Univariate analysisidentified 7 risk factors (including cFLC, ACR, phosphate and eGFR) being associatedwith progression to RRT. An algorithm comprising cFLC>120mg/L, eGFR≤20ml/min/1.73m2, ACR>30mg/mmol, and phosphate>1.4mmol/L was developed. By 12 months7/201 patients progressed to RRT. 51/201 (25%) patients were negative for all riskfactors and none progressed to RRT. A further 61 patients were positive for 1 riskfactor; a single patient from this group progressed at 361 days. Individually, eachvariable had a poorer discrimination than the collective value. In the validationpopulations, 51/205 (25%) (CRISIS) and 36/155 (23%) (RIISC) patients had 0 riskfactors and no patients progressed to ESKD. 68/205 (33%) and 51/155 (33%) patientshad 1 risk factor respectively, of whom 4 progressed to ESKD. Combining the 3datasets, the algorithm identified 138/561 (25%) patients with no risk factors, with norisk of progression within 12 months and 180/561 (32%) patients with 1 risk factor anda 2.8% risk of progression who could be returned to primary care for 6-12 months.Conclusions: An algorithm for the risk stratification of stage 4 CKD that includescFLC identifies patients at no and very low risk of progression to ESKD in thesubsequent 12 month period. This approach has major potential benefits, both forpatients and the costs of health care in stage 4 CKD.

SP148 PLASMA PTH LEVELS MEASUREDWITH THE 3RD

GENERATION 1-84 PTH ASSAY IN PATIENTSWITHDIFFERENT STAGES OF CHRONIC KIDNEY DISEASE

Giuseppe Viccica1, Adamasco Cupisti1, Silvia Chiavistelli1, Simona Borsari1,Elena Pardi1, Roberta Centoni1, Giordano Fumagalli1, Filomena Cetani1 andClaudio Marcocci11Department of Clinical and Experimental Medicine University of Pisa Pisa Italy

Introduction and Aims: Previous guidelines derived from studies that used the Allegrointact PTH assay, which measures both the full 1-84 PTH molecule as well as the 7-84PTH inactive fragment,recommended that patients with different chronic kidneydisease (CKD) should be managed in order to maintain plasma PTH within a givenrange, which was fixed between 150 and 300 pg/ml in CKD stage 5 patients. Severalmethods of intact PTH assay are available and a wide inter-method variability in thePTH results has been shown and opposite therapeutic attitudes may be reached in asingle patient depending on the PTH assay used. A new 3rd generation PTH assay,which measures only the full length molecule, is currently available. Aim of the presentstudy was to define PTH ranges using this assay in patients with different stages ofCKD.

Methods: A series of 141 patients (65 females and 76 males, age 21-89 yr) with CKDstage 3-5 followed in a tertiary care center were enrolled in the study. Patients wereclassified according to the estimated GFR (eGFR, stage 3: n=46; stage 4: n= 42; stage 5:n=53). Plasma PTH was measured using the 3rd generation LIAISON® 1-84 PTH assay(DiaSorin; normal range 5-40 pg/ml). Serum bone specific alkaline phosphatase(BASP; normal range 16-26 ng/ml), serum C-terminal telopeptide (S-CTx; normalrange 0.07-1.43 ng/ml) and 25OH vitamin D (25OHD; normal range 4-64 ng/ml) werealso measured. Finally, in a subgroup of patients (n=80) plasma intact PTH wasmeasured using the 2nd generation LIAISON® N-tact™PTH (Diasorin).Results: Plasma 1-84 PTH was increased in the majority (72%) of our patients andthere was a significant negative correlation with the eGFR (r=-0.46, P<0.001).Conversely, a significantly positive correlation was found between plasma 1-84 PTHand BSAP (r= 0.23, P=0.008) and S-CTx (r=0.31, P=0.001), and a no correlation withserum 25OHD and age. A significantly high positive correlation was found betweenplasma 3nd generation 1-84 PTH and intact 2nd generation PTH concentrations(r=0.94, P<0.0001). The table summarizes our data for the whole group of patientssub-divided according to the different CKD classes. Results are expressed as mean±SD.Conclusions: The plasma PTH levels, measured by the 3rd generation 1-84 PTH assay,nicely segregate patients with different stages of CKD and could provide a referencepoint for managements of CKD patients across the various stages of CKD.

SP149 THIRD GENERATION BIO-INTACT PTH ASSAYS PRODUCERESULTSWHICH ARE BETTER CORRELATEDWITHBIOCHEMICAL AND SKELETAL PARAMETERS IN CKDPATIENTS THAN DO SECOND-GENERATION INTACT PTHASSAYS – NOW IS IT TIME TOMOVE ON AND CHANGE OVER?

Paul Scully1, Deidre O'Flaherty2, Arun Sankaralingam2, Geeta Hampson2 andDavid J. Goldsmith11Nephrology and Transplantation Guy's Campus King's Health Partners AHSCLondon United Kingdom, 2GSTS Chemical Pathology Guy's Campus King'sHealth Partners AHSC London United Kingdom

Introduction and Aims: As CKD becomes more severe, PTH levels in the bloodincrease. As well as PTH (1–84), PTH (7–84) – and many other fragments of PTH –accumulate in the bloodstream of patients with severe CKD, particularly thosereceiving dialysis. Using traditional assays, even "intact PTH" assays, the presence ofPTH (7–84) typically leads to an overestimation of concentrations of biologically activefull-length PTH, further compounded by the longer half-life of these fragments. True"biointact" PTH assays are now available for use. We wanted to compare analytical datafrom the Roche second generation (Roche Diagnostics, Basel) serum intact PTH assayswith Roche Elecsys EDTA-plasma biointact PTH (1-84) (Roche Diagnostics, Basel)assays using CKD and dialysis cohorts - splitting blood samples to record PTHconcentrations in parallel.Methods: Serum calcium, phosphate, creatinine, bone specific alkaline phosphatiae(BAP), Tartrate-resistant acid phosphatase-5b (TRACP-5b) were determined in 79healthy ambulant CKD (stage 2-4) patients. Bone mineral density (BMD) wasdetermined by DXA scan at the fore-arm (FARM), lumbar spine (LS), femoral neck(FN) and total hip (TH). PTH was analysed by both the second and third generationPTH assays. The relationship between the 2 PTH assays with the biochemicalparameters and BMD was compared.Results: 79 healthy ambulant CKD (stage 2-4) patients – 41M, 38F, mean[SD] age of53[15] years. Inter and intra- assay CVs were < 2% for both PTH assays at meanconcentrations of 41, 105, 131 pg/mL. The results from the two assays were closelycorrelated (r=0.958, p <0.001). The intact (second generation) PTH concentation wassignificantly higher 79[55] pg/mL compared to biointact (third generation) PTH 68[49] pg/mL (p < 0.001). Bland-Altmann plot revealed a significant average bias of-18%. Only the biointact PTH assay showed any significant correlation with serumcalcium concentrations (r = - 0.26, p < 0.05) and phosphate (r=0.25, p<0.05). BMD wasbetter correlated with biointact PTH than with intact PTH, especially so at the FARMand LS (Z score FARM r =– 0.33, p =0.009 cf r= 0.26, p = 0.040, LS : r=0.34, p=0.006 cfr=-0.29, p =0.02).Conclusions: PTH and calcium concentrations are normally very tightly coupled. Theinability of intact PTH assays to show a correlation with simultaneous plasma calcium,or phosphate, concentrations suggests that what it is measuring is not biologicallyrelevant. The improved correlations between plasma PTH (but only when measured bythe biointact assay) and bone mineral density also point to more relevant functional

SP148

CKDclass

Age(yr)

eGFR(ml/min/1.73m2)

1-84 PTH(pg/ml)

BSAP(ng/ml)

S-CTx(ng/ml)

25OHD(ng/ml)

3 (n=46) 61±14 42±9 a,b 46±26 a,b 17±9 b 0.76±0.50a,b

17±9

4 (n=52) 66±13 21±4 a,c 89±58 a,c 20±12 2.00±1.93a

16±7

5 (n=43) 64±14 8±3 b,c 134±103 b,

c23±10 b 2.56±2.18

b15±10

P<0.05:a CKD class 3 vs 4;b CKD class 3 vs 5;c CKD class 4 vs 5.



linkages. As a result, it is probably time to find ways to make a transition towards amore robust and reliable PTH assay methodology.

SP150 1H-NMR PROFILING OF URINARYMETABOLITES FOR ABETTER CHARACTERIZATION OF KIDNEY INJURIES: A PILOTSTUDY

Nicolas Pallet2, Sophie Chauvet1, Philippe Beaune2, Domonique Nochy1,Eric Thervet1, Alexandre Karras1 and Gildas Bertho31Nephrology HEGP Paris France, 2INSERM Paris France, 3CNRS Paris France

Introduction and Aims: Proton-Nuclear Magnetic Resonance (1H-NMR)-basedcharacterization of small molecules, including metabolites, in body fluids is apromising method to detect biomarkers and to drive hypothesis.Methods:We undertook a pilot study to generate the urinary metabolomic profiles ofpatients with various kidney diseases. In this monocentric prospective study, 24consecutive patients who underwent a diagnosis kidney biopsy were recruited andprovided an urinary sample for biochemical and NMR analysis. The NMR experimentswere run at 500.13 MHz for 1H on a Bruker AVANCE 500 spectrometer. Each NMRspectrum was reduced to 170 variables (buckets), obtained by integrating spectralregions of equal width (0.04 ppm). We applied a principal component analysis (PCA)to identify groups of patients based on their urinary profiles.Results: The PC discriminated two groups of patients, and explained 77% of thevariability. All patients in one group (A) had a diagnosis of glomerular nephropathy,whereas all but one the other patients (group B) had a tubular and/or interstitlal injury.Subesequently, the patients were assigned within group A or group B, and a supervisedmethod (Partial Least Squares Discriminant Analysis) was used to test whether somevariables (buckets) would separate the two groups. The model obtained has highlighteddiscriminating variables; most of them localized between the 8 and 8.3 ppm parts ofthe spectrum. Two buckets (on 170) with the minimal variance could effectivelyseparate groups A and B. Small molecules that provide a signal within this part of thespectrum are aromatic molecules, including nucleic acids (adenosine, ATP…).Conclusions: Our results suggest that 1H-NMR-based detection of urinary nucleicacids could discriminate patients with glomerular injury vs. tubular injury. Sincenucleic acids signal promote tissular inflammation through purinergic receptors, ourfindings provide a new hypothesis regarding the negative impact of proteinuria ontubulointerstitial inflammation and fibrosis.

SP151 ASYMMETRIC DIMETHYLARGININE CONTRIBUTES TO THEKIDNEY FUNCTION DECREASE VIA AGGRAVATION OFVASCULAR REMODELING IN OBESE PATIENTSWITH CKDI-IIIa

Marat G. Gallyamov1,3, Evgeniya A. Saginova1,2, Mariya M. Severova2, TatyanaN. Krasnova1,2 and Aleksandra A. Kopylova11Internal Medicine Lomonosov Moscow State University Moscow RussianFederation, 2I.M. Sechenov First Moscow State Medical University MoscowRussian Federation, 3Interteach Medical Assistance Almaty Kazakhstan

Introduction and Aims: Asymmetric dimethylarginine (ADMA) is well knownendogenous inhibitor of all types of NO-synthases. Endothelial dysfunction caused byelevated plasma ADMA leads to vascular alteration. Thickening of intima-mediacomplex is early marker of atherosclerotic remodeling. Endothelial dysfunction is oneof the main mechanisms in damage of kidney in obesity which is a trigger of metabolic,hemodynamic and inflammatory disturbances. Aim of our study was to define role ofADMA and vascular remodeling in the progression of early stage CKD in obesepatients.Methods: 86 obese patients (64M, 22F) were included in the study (age 44±11 yrs, BMI33.5±6.3 kg/m^2). Exclusion criteria were CKD IIIb-V, albuminuria >2 g/day,hematuria, glomerulonephritis, severe hypertension, coronary heart disease, braininsult, autoimmune diseases et al. GFR was estimated by MDRD4 equation. Allpatients were tested on common biochemical features of blood and urine includinginsulin, C-peptide, ADMA (by ELISA), urinary albumin excretion (UAE).Intima-media thickness (IMT) of common carotid artery was measured by duplexultrasonography.Results: CKD I-IIIa was at 27 (31%) patients. CKD individuals had higher BMI andwaist circumference as well as increased level of insulin, C-peptide, HOMA-indexwhich were linked to UAE rate. Patients with CKD IIIa had elevated plasma ADMA(0.77±0.19 umol/l vs. CKD I, 0.58±0.11, p=0.048; vs. CKD II, 0.61±0.13, p=0.071). Wefound significant correlations between ADMA and IMT (r=0.43), ADMA and highdensity lipoproteins (HDL) level (r=-0.52). IMT correlated with eGFR (r=-0.38).Independently from ADMA, serum uric acid (SUA) and blood pressure level werelinked to IMT as well (r=0.41 and r=0.45, respectively). Using of multiple linearregression analysis we found prognostic factors of eGFR decline in obese patients(p<0.003, R^2=0.64, standard estimation error 15): insulin (13.3+/-6.5 uU/ml; b =1.52; p=0.004), HOMA-index (3.3+/-1.7; b = -1.31; p=0.009), SUA (421+/-100 umol/l;b = -0.94; p<0.001) and ADMA (0.62+/-0.12; b = 0.44; p=0.038).Conclusions: In obese subjects progression of early stage CKD is tightly associatedwith endothelial dysfunction and vascular remodeling. We detected that ADMA cancontribute kidney function decrease mainly via aggravation of dyslipidemia and

vascular alteration. Additional factors influencing on thickening of intima-mediacomplex were elevation of serum uric acid and blood pressure.

SP152 EFFECTOF ACUTE KIDNEY INJURY EPISODES ONPROGRESSION OF CHRONIC KIDNEY DISEASE IN EARLYSTAGE CKD PATIENTS

Eunjung Cho1, Sang-Kyung Jo1, Myung-Gyu Kim1, Won-Yong Cho1and Hyung Kyu kim1

1Korea University Hospital Seoul Republic of Korea

Introduction and Aims: Although episodes of acute kidney injury (AKI) is awell-known risk factor for progression of chronic kidney disease (CKD), most studieshave been performed in in-hospital or intensive care unit settings. We designed thisstudy to assess the contribution of AKI episodes on progression of CKD in a stableambulatory, early stage CKD patient setting.Methods:We retrospectively assembled a cohort of 458 ambulatory patients with stage2 and stage 3 CKD and analyzed the risk of CKD progression as a function of AKIepisodes using acute kidney injury network (AKIN) criteria. Primary outcome(progression of CKD) was defined as more than 15 ml/min/1.73m2 decline ofestimated GFR (eGFR) from the baseline.Results: Over a median follow-up of 902 days, 134 (29.3%) patients had AKI episodes.We observed no mortality in our cohort during the follow-up period. Patients withAKI episodes were older and more likely to have diabetes and lower baseline eGFR.There was no difference in the proportion of gender and hypertension. Significantlymore patients with AKI episodes reached primary outcome than patients without AKIepisodes [29 (21.6%) vs. 15 (4.6%), p<0.001]. In multivariate-adjusted Coxproportional hazard model, age, baseline eGFR and episodes of AKI were independentpredictors of CKD progression. Among these, episodes of AKI was the most powerfulpredictor (hazard ratio, 3.517 vs. 1.031 for age vs. 1.037 for baseline eGFR). Subgroupanalysis including only patients with episodes of AKIN stage 1 AKI and patientswithout AKI episodes also revealed the important contribution of minor elevation ofserum creatinine on progression of CKD (hazard ratio, 2.852 for AKI episode vs. 1.046for age vs. 1.043 for baseline GFR).Conclusions: Even in stable stage 2 and stage 3 ambulatory patients, silent AKIepisodes are also thought to be a powerful risk factor for progression of CKD.Multi-sided approach to develop tools for prevention, early detection, or stratificationshould be continued to improve the ultimate prognosis.

SP153 HbA1c IS AN INDEPENDENT RISK FACTOR FORMORTALITYBUT NOT FOR END STAGE RENAL DISEASE IN NONDIABETIC CKD PATIENTS

Claire Trivin1, Marie Metzger2, Jean-Jacques Boffa3, Francois Vrtovsnik4,Pascal Houiller1, Jean-Philippe Haymann3, Martin Flamant4, Benedicte Stengel2and Eric Thervet11Physiology & Nephrology Hopital Europeen Georges Pompidou Paris France,2U1018 INSERM Centre for Research in Epidemiology and Population HealthVillejuif France, 3Physiology & Nephrology Hopital Tenon Paris France, 4Physiology& Nephrology Hopital Bichat Paris France

Introduction and Aims: Glycated hemoglobin (HbA1c) is used as a diagnostic test fordiabetes (DM) with an usual threshold of 6.5%. The association between higher HbA1cand progression for end-stage renal disease (ESRD) and mortality has beendemonstrated in the diabetic population. The aim of this study was to examine theassociation between HbA1c and these endpoints in a non diabetic chronic kidneydisease (CKD) population.Methods: In the NephroTest cohort study, we measured glomerular filtration rate(mGFR) by Cr-EDTA clearance and HbA1c in 1162 adult patients with non-dialysisCKD stages 1 to 5 and no DM (HbA1c value< 6.5%, fasting glycemia<7 mmol/L,absence of known DM or hypoglycemic treatment). Deaths and ESRD (initiation ofrenal replacement therapy) were retrieved using national registries. Cox models wereused to estimate hazard ratio (HR) of ESRD and mortality according to HbA1c [as acontinuous and a categorical variable using tertile cut-off (<5.2, 5.2-5.6, ≥5.7], withadjustment for mGFR, age, gender, race, BMI, elevated blood pressure, history ofcardiovascular disease, smoking, albuminuria, ARBs and ACE inhibitors and center.Results:Mean age was 56.6±16.0 years with a mean BMI of 25.4±4.6; 66% were men,12.8% black . The mean mGFR and HbA1c at inclusion were respectively 42.2±19.8mL/mn/1.73 m2 and 5.5±0.5%. HbA1c values were significantly associated with age,BMI, systolic blood pressure, mGRF, albuminemia, fasting blood glucose,insulinemia and orosomucoid. The risk of ESRD was significantly decreased inpatients with intermediate value of Hba1c even after adjusting for initial mGFR[middle tertile HR 95%CI=0.59(0.39,0.89) compared to the lowest tertile]. Afteradjustment for all other risk factors, Hba1c level was no more associated with abetter renal survival in this group [HR=0.67(0.43,1.04)]. Moratlity HR wasassociated with higher HbA1c analysed both as a continuous or categorical variables:for each increase of 1% in HbA1c HR=1.95(1.31,2.91).After adjustment for similarrisk factors, the HR associated with Hba1c remained significant (HR=1.69(1.10-2.59)). Consistent results were found when analyse was restricted to mortalitybefore ESRD.



Conclusions: In a CKD cohort, HbA1c within normal range in non diabetic patientsis associated with ESRD occurrence and mortality. The later persists even afteradjustment for known risk factors. Since HbA1c is correlated with insulinemia andorosomucoid, various hypothesis including metabolic or inflammatory pathwaymust be explore to better understand these results.

SP154 EFFECTS OF ZINC SUPPLEMENTATION ON PLASMAHOMOCYSTEINE LEVEL IN ESRD PATIENTS: A DOUBLEBLIND RANDOMIZED CLINICALTRIAL

Jamshid Roozbeh1, Vahideh Yavari2, Maryam Pakfetrat1 and Ali Asghar Zolghadr21Shiraz Nephro-Urology Research Center, Shiraz University of Medical SciencesShiraz Iran (Islamic Republic of ), 2Department of Internal Medicine, ShirazUniversity of Medical Sciences Shiraz Iran (Islamic Republic of )

Introduction and Aims: Increased homocysteine (hCys) level is considered as anindependent risk factor for cardiovascular complications in end sage renal disease(ESRD) patients. The aim of this study was to determine the effects of Zincsupplementation on serum hCys level in ESRD patients.Methods: One hundred ESRD patients with Zinc deficiency were enrolled in thisprospective, randomized, double blind study. They were randomly subdivided into twogroups and supplemented with 50 mg/day Zinc (Zinc treated group) or placebo(placebo treated group) for 6 weeks. Fasting plasma hCys and Zinc levels weremeasured before treatment, and 43 days after the start of the study. An enzymeimmunoassay (EIA) was used to measure total hCys. Serum plasma Zinc level wasmeasured with atomic absorption method. The data were analyzed using the SPSS 15.0and p < 0.05 was considered significant.Results: Serum Zinc levels increased significantly in Zinc treated group (56.9±13.9 μg/dl versus 120.8±26.9 μg/dl; p < 0.0001). There was no significant change in Zinc levelsin the placebo-treated group. Serum hCys levels were also significantly reduced in theZinc treated group (17.1±4.4 μmol/L versus 13.20 ± 3.7μmol/L; p<0.0001), while nosignificant change was observed in the placebo group. Mean percentage reduction ofhCys was 21.5±18.3 in Zinc treated group compared to 1.2±16.1 in placebo group(p<0.0001). Mean percentage reduction of hCys level positively related with baselinehCys (r=0.251; P<0.013), plasma Zinc level at 43 days(r=0.446; P<0.0001) and meanpercentage increase of Zinc (r=0.327; P<0.001).Conclusions: Zinc supplementation leads to a reduction in serum hCys levels in ESRDpatients with Zinc deficiency.

SP155 INFLUENCE OF RENAL DYSFUNCTION ON CLINICALOUTCOMES IN PATIENTSWITH CONGESTIVE HEARTFAILURE COMPLICATING ACUTEMYOCARDIAL INFARCTION

Chang Seong Kim1, Min Jee Kim1, Yong Un Kang1, Joon Seok Choi1, EunHui Bae1, Seong Kwon Ma1 and Soo Wan Kim1

1Department of Internal Medicine Chonnam National University Hospital GwangjuRepublic of Korea

Introduction and Aims: Renal dysfunction is one of the most important comorbiditiesassociated with congestive heart failure (CHF) complicating acute myocardialinfarction (AMI). However, the clinical course and treatment of patients with CHF arenot well established, especially in patients with concomitant renal dysfunction. Thisstudy aimed to examine the influence of renal dysfunction on clinical outcomes inpatients with CHF complicating AMI.Methods:We performed a retrospective analysis of the prospective Korean AcuteMyocardial Infarction Registry data to assess the treatments and clinical outcomes ofpatients with CHF (Killip classes II or III) complicated by AMI, in the presence orabsence of renal dysfunction. The main outcome measures were the major adversecardiac events (MACEs) and mortality rates during the 1-year follow-up period.Results: Of 13,498 patients with AMI, 2769 (20.5%) had CHF on admission.Compared to CHF patients with preserved renal function, patients with renal

dysfunction were older; more often female; and had a higher prevalence ofhypertension, diabetes, dyslipidemia, and multivessel disease. Patients with renaldysfunction were less likely to receive aspirin, beta-blockers, statins, andangiotensin-converting enzyme (ACE) inhibitors, but were more likely to receivediuretics, calcium channel blockers (CCBs), and angiotensin II receptor blockers(ARBs) during hospitalization or at discharge. Furthermore, renal dysfunction wasassociated with increased in-hospital mortality and MACEs both at 1 month and at 1year after discharge. In patients with renal dysfunction, in-hospital use of aspirin,statins, and ACE inhibitors or ARBs reduced 1-year mortalities, while diureticsincreased the risk of 1-year mortality in Cox proportional hazard analysis. Moreover,postdischarge use of aspirin, beta-blockers, CCBs, ACE inhibitors, or ARBs and statins,which had been prescribed at discharge, significantly reduced the 1-year mortality ratefor those with renal dysfunction; such reduction was not observed for those withoutrenal dysfunction, except in the case of aspirin, which did have a positive impact onmortality in both groups.Conclusions: Patients with CHF complicating AMI, which is accompanied with renaldysfunction, are at higher risk for adverse cardiovascular outcomes than patientswithout renal dysfunction. However, they receive fewer medications proven to reducemortality rates.

SP156 ARE GFR ESTIMATING FORMULAS INACCURATE IN OBESEPATIENTS?

Sandrine Lemoine1, Fitsum Guebre-Egziabher1, Laurence Dubourg1 andAoumeur Hadj-Aissa11Departments of Nephrology and Renal Function Investigations Hospices Civils deLyon and Université Claude Bernard Lyon1 Lyon France

Introduction and Aims: The increasing prevalence of obesity, especially in theWestern world is associated with the risk to develop renal disease or accelerate theprogression of renal disease. Adequate estimation of renal function in obeses is thusessential. Recently, CKD-EPI formula was recommended as the most reliable methodto estimate GFR, but this formula was not validated in patients with extreme variationsof weight, and especially in obese patients.In this study, we measured GFR in obesepatients and compared the performance of creatinine-derived equations with measuredGFR indexed or not to body surface area (BSA) and using either real or ideal bodyweight (BW).Methods: A total of 218 obese patients were included (126 men [57.8 %] aged 17 to 87years). They all had nephropathy of various origins and were selected according to thecriteria body mass index (BMI) ≥ 30 kg/m2. The mean BMI was 34.8 ± 4.6 kg/m2 (30to 67). Twenty-three patients have a BMI > 40. We determined GFR withcreatinine-derived equations, MDRD and CKD-EPI formulas (eGFRMDRD andeGFRCKD-EPI) (enzymatic assay of serum creatinine standardized to IDMS). Theseformulas were compared to the gold standard method inulin clearance not indexed toBSA (mGFR mL/min) or indexed with BSA either with actual body weight (BW)(mGFRrealmL/min/1.73m2) or ideal BW (mGFRidealmL/min/1.73m2). The idealweight was determined by Lorentz formula. The BSAwas determined by Dubois andDubois formula.Results:mGFRreal (51.8 ± 24.2) was significatly lower (p< 0.01) than mGFRideal (61.9±28.3) or mGFR not indexed to BSA (60.2±28.0). eGFRMDRD and eGFRCKD-EPI wererespectively 57.7±27 and 60.6±28.0. They were not statistically different. There was nosignificant difference between creatinine-derived formulas and mGFR not indexed toBSA or mGFRideal. But mGFRreal was significatly lower than the formulas (p < 0.01).Bias and accuracy are shown in the following table.Conclusions: As nephron mass depends on lean mass rather than fat mass, GFR inobese patients should be indexed to BSA using ideal BW. Since there was no differencebetween CKD-EPI formula and mGFRidealmeasured by inulin clearance and theperformance of this formula was better than MDRD in terms of accuracy and bias, werecommend the use of CKD-EPI in obese patients.

SP157 NUTRITION ASSESSMENTAND RISK PREDICTION INDIALYSIS OATIENT - A NEW INTEGRATIVE SCORE

Sara Blumberg1, Zeev Katzir1, Alexander Biro1, Relu Cernes1 and Zvi Barnea11Institute of Nephrology Wolfson Medical Center Holon Israel

Introduction and Aims:Malnutrition is common in patients with end-stage kidneydisease on hemodialysis, and is associated with poor outcome. A number of studieshave documented malnutrition as a powerful predictor of morbidity, mortality and anSP155

SP156

Accuracy30% Bias (mL/min/1.73m2)

mGFRreal mGFRideal mGFRreal mGFRidealMDRD 79.3 % 82.1 +5.9a -4.2CKD-EPI 72% 84.4 +9.1ab -1.3b

a = p < 0.01 vs mGFRidealb = p < 0.01 vs MDRD



increased hospitalization rate in ESRD. It is recognized that no single alternativeobjective test is able to determine the overall nutritional status in ESKD patients.Several methods of nutritional risk evaluation are known: the Subjective GlobalAssessment (SGA), the Malnutrition-Inflammation-Score (MIS), the Objective Scoreof Nutrition on Dialysis (OSND). We have developed a new score, Integrative ClinicalNutrition Dialysis Score (ICNDS). The score is based solely on biochemical parametersroutinely taken monthly from HD patients, as well as their weight change, in order toassess nutrition status and detect deterioration as early as possible, thus preventingfurther complications.Methods: In an attempt to develop a simple nutritional status score of HD patients, weused laboratory tests parameters, routinely taken monthly before starting dialysissession: Albumin, Creatinine, Urea, Cholesterol, CRP, Kt/V and the patient's Weightchange. Each of the above parameters was given a scoring value of 1-5. A score of fivefor each parameter value close to the NKF-K/DOQI Nutrition GuidelineRecommendations, and a lower score for sub-optimal values. Scoring results for allparameters were summed each month and a final result, a number between 0-100, wasgiven for each patient. A higher score indicates a tendency towards a good nutritionalstatus, a lower score represents malnutrition.Results: In 63 patients, score results were significantly correlated with nutritionevaluation by the SGAwithin the same month (r=0.842, P<0.01). In 179 patients,followed for 31 months, baseline score emerged as a significant inverse predictor ofmortality and hospitalization frequency: For every unit increase in baseline score, deathodds as well as hospitalization frequency were significantly decreased (mortality:HR=0.929,95% cl 0.88-0.974, p<0.002,hospitalization frequency: HR=0.799, 95% cl0.726-0.881, p<0.0001). A unit increase ofslope of 3 monthlyscores at beginning ofstudy significantly reduced mortality and hospitalization risk (mortality:HR=0.485,95% cl 0.278-0.847, p<0.011, hospitalization frequency: HR=0.77, 95% cl 0.726-0.881,p<0.0001). A threshold score level of 75 was found to be a significant outpoint: Scoregreater or equal to 75 significantly reduced mortality. Worsening nutrition status overtime indicated by both score and slope significantly increased death hazard.Conclusions:We have developed a convinient tool to address the need of a monthlyroutine follow up of nutrition status and identification of nutritional deterioration at itsbeginnig.The Model provides for a high resolution of various nutrition status and theirprognosis.

SP158 ESTIMATION OF THE PREVALENCE OF CKD IN HEALTHYSUBJECTS BY FOUR DIFFERENT EQUATIONS

Damaris Vasquez1, Raquel Gordillo1, Carmen Aller1, Beatriz Fernandez1,Najaty Jabary1, Vicente Perez1, Alicia Mendiluce1, Jesus Bustamante1 andArmando Coca11Nephrology Hospital Clinico Valladolid Spain

Introduction and Aims: To calculate the prevalence of CKD in a sample of healthyspanish individuals, we compared the 24h creatinine clearance rate corrected by bodysurface area (CCr), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)equation, Cockroft-Gault formula corrected by body surface area (CG), the abbreviatedModification of Diet in Renal Disease (MDRDa) equation and the Mayo Quadratic(MQ) formula to determine glomerular filtration rate (GFR) in patients from anephrolithiasis consultation.Methods: 1067 healthy patients were enrolled in the present study. Patients werecarefully instructed about the 24h urine output collection by the same nurse. GFR wasestimated using five methods: CCr, CKD-EPI, CG, MDRDa and MQ equations. Thestatistical analýsis was performed using SPSS Statistics 19.Results: Figure 1 summarizes the % of individuals with GFR <60 ml/min according tothe different equations:Figure 2 represents the correlation between Scr, CCr and theeGFR equations.We found a positive correlation (p=0,03) between urinary Na, Mg, Pand Ca and GFR measured by all equations, and a negative correlation (p=0,02)between all equations and SCr, serum glucose and age.Conclusions: The prevalence of CKD in the spanish population is 6.8%, according tothe results of the EPIRCE study. In our sample the percentage of patients classified asCKD varies widely depending on the method of evaluation used. ClCr provides thehighest average eGFR value, probably due to mistakes in the 24h urine recollection,followed by MQ equation, CG-BSA, CKD-EPI and MDRD. These differences are

statistically significant (p <0.001). GFR equations are a useful tool in clinical practice,although they should be carefully considered, especially in patients with extremeweights or age. MQ equation seems the most precise equation to assess GFR in healthypatients, although neither method has an accuracy of 100%.

SP159 NOVEL METABOLITES ASSOCIATEWITH IMPAIRED KIDNEYFUNCTION AND KIDNEY FUNCTION DECLINE IN THEGENERAL POPULATION

Oemer-Necmi Goek1, Peggy Sekula1, Cornelia Prehn2, Christine Meisinger2,Christian Gieger2, Karsten Suhre2,3, Jerzy Adamski2, Gabi Kastenmüller2 andAnna Köttgen11University Medical Center Freiburg Freiburg im Breisgau Germany, 2HelmholtzZentrum München, German Research Center for Environmental HealthNeuherberg Germany, 3Weill Cornell Medical College in Qatar Doha Qatar

Introduction and Aims: Small molecules are extensively metabolized and cleared bythe kidney and may also play a role in the pathophysiology of chronic kidney disease(CKD).Methods: Here we applied an untargeted metabolomics approach (GC/MS and LC/MS/MS assays by Metabolon) to measure the serum concentrations of a broadspectrum of more than 400 known and unknown molecules in the generalpopulation-based KORA study (maximal n=1735). Metabolites were then related inlinear or logistic regression analyses to both eGFR estimated from serum creatinine orcystatin C cross-sectionally, as well as to annual eGFR change based on serumcreatinine over a mean of 7 years, all adjusted for known kidney disease risk factors.Results: Significant cross-sectional associations with both creatinine- and cystatinC-based eGFR were identified for 114 metabolites accounting for multiple testing.Published cross-sectional associations of serum acylcarnitines with lower eGFR wereconfirmed. Most remarkably, higher serum concentrations of c-glycosyltryptophanwere associated cross-sectionally with lower eGFR (P= 8.9 x 10-89 for creatinine-basedeGFR, P= 1.0 x 10-163 for cystatin C-based eGFR) and presence of CKD (eGFR < 60 ml/min/1.73 m2, P= 1.1 x 10-22). It was also associated with longitudinal kidney functiondecline even after adjustment for baseline kidney disease risk factors andcreatinine-based eGFR (P= 8.7 x 10-6). The pair-wise Pearson correlation betweenserum c-glycosyltryptophan and creatinine-based and cystatin C-based eGFR was -0.61and -0.71, respectively. Serum c-glycosyltryptophan has previously been described asassociated with inulin clearance in smaller studies of humans and rats.Conclusions: In the general population, serum c-glycosyltryptophan was associatedwith kidney function impairment measured by cross-sectional eGFR, as well asSP158

SP158

Avg StDev

Age(y) 53,3 14,2Height(cm) 163,7 9,5Weight(kg) 72 13,2Hb(g/dl) 13,9 3,9Urea* 37,7 12,5SCr* 0,93 0,24Uric* 4,8 1,3PTH(pg/ml) 53,9 52,524hDiu(ml) 2464 1036CCr** 96,3 37,5MDRDa** 85,5 20,8CG** 90,7 24,2MQ** 96,1 22CKD-EPI** 85,6 19

* (mg/dl), ** (ml/min), SCr: Serum creatinine

SP158



longitudinal eGFR decline. Further studies are needed to validate the observedassociations externally and clarify the identity of all discovered molecules.

SP160 NEUTROPHILS ACTIVATION CORRELATESWITH INSULINRESISTANCE IN END-STAGE RENAL DISEASE (ESRD)PATIENTS

Marek Kuzniewski1, Danuta Fedak2, Paulina Dumnicka3, Bogdan Solnica2,Beata Kusnierz-Cabala2, Maria Kapusta2, Wladyslaw Sulowicz1 andRyszard Drozdz31Department of Nephrology Jagiellonian University Medical College CracowPoland, 2Chair of Clinical Biochemistry, Diagnostic Department JagiellonianUniversity Medical College Cracow Poland, 3Department of Medical DiagnosticsJagiellonian University Medical College Cracow Poland

Introduction and Aims: Insulin resistance is often associated with chronic kidneydisease, especially in ESRD patients requiring maintenance dialysis. Duringextracorporeal circulation at the time of hemodialysis procedure, activation of variouscells takes place, including chronic activation of neutrophils. In consequence,concentration of human leucocyte elastase/alpha 1 protease inhibitor complex (HLE/alpha1PI) increases in plasma. The endothelial dysfunction related to repeatedhemodialysis procedures may additionally exacerbate insulin resistance.Methods: Fasting pre-dialysis blood samples were collected from 68 patients with ESRD,29 women and 39 men, aged 60 +/- 12 years, treated with maintenance hemodialysis formedian period of 60 (IQR: 36-100) months using reprocessed polysulphone dialyzersand low molecular weight heparin as anticoagulant. Patients with diabetes and acuteinflammation were excluded. Control samples were collected from 35 healthy sex and agematched subjects. The concentrations of HLE/alpha1PI and insulin was measured byELISA, CRP by nephelometry and glucose by routine method. Homeostasis modelassessment index of insulin resistance (HOMA-IR) was calculated as [fasting glucoseconcentration (mmol/l) x fasting insulin concentration (μU/mL)]/22.5.Results: The concentration of HLE/alpha1PI in studied group was 50.81+/-16.50 ng/mLand was significantly higher than in controls (37.20+/-1.36 ng/mL; p<0.001). HLE/alpha1PI significantly correlated with insulin level (R=0.32; p=0.02) and HOMA-IR(R=0.35; p=0.009). In multiple models, these correlations were independent of CRPconcentration as a marker of inflammation.Conclusions: Chronic neutrophil activation in ESRD is connected with insulin resistanceindependently on chronic inflammation. The consequence of insulin resisitanceexpressed as increase insulin level and HOMA-IR are glucose metabolism disturbancesand the increase of cardiovascular morbidity.

SP161 RENAL FUNCTION, SUBCLINICAL ATHEROSCLEROSIS ANDC1METABOLISM IN APPARENTLY HEALTHY SUBJECTS

Adam M. Zawada1, Kyrill S. Rogacev1, Björn Hummel2, Danilo Fliser1,Jürgen Geisel2 and Gunnar H. Heine11Internal Medicine IV - Nephrology and Hypertension Saarland University MedicalCenter Homburg Germany, 2Clinical Chemistry and Laboratory Medicine/CentralLaboratory Saarland University Medical Center Homburg Germany

Introduction and Aims: Although homocysteine has been proposed as acardiovascular risk factor, no interventional trail on homocysteine lowering in CKDpatients demonstrated clinical benefit. Recent evidence suggested that thehomocysteine metabolite S-Adenosylhomocysteine (SAH) is a better marker forcardiovascular disease. Additionally, an association between elevated SAH and earlyCKD has been shown in preliminary studies. Of note, these studies estimatedglomerular filtration rate (GFR) according to the MDRD equation. This equation wasout-performed by the recent introduction of the 2012 CKD-EPIcreat-cys equation, whichallows a better estimation of GFR in apparently healthy subjects without overt CKD.We therefore set out to re-analyse the association between estimated GFR (eGFR),subclinical atherosclerosis and C1 metabolism among 420 participants of the I LIKEHOMe study.Methods: Homocysteine, SAH, SAM (S-adenosylmethionine), routine laboratoryparameters and intima media thickness (IMT) were measured among 420 apparentlyhealthy participants of the I LIKE HOMe study. GFR was estimated according to theMDRD and the 2012 CKD-EPIcreat-cys equation. The SAM/SAH ratio was calculatedfor assessing methylation capacity as a major determinant of epigenetic generegulation.Results: SAH levels inversely correlated with eGFR estimated with both the MDRD(r = -0.302, p < 0.001) and the 2012 CKD-EPIcreat-cys equation (r = -0.327, p < 0.001).Compared to SAH, homocysteine showed a weaker inverse correlation with eGFR(MDRD: r = -0.227, p < 0.001; 2012 CKD-EPIcreat-cys: r = -0.252, p < 0.001). TheSAM/SAH ratio positively correlated with eGFR (MDRD: r = 0.206, p < 0.001; 2012CKD-EPIcreat-cys: r = 0.213, p < 0.001). Finally, in contrast to homocysteine (r = 0.018,p = 0.720), SAH positively correlated with the IMT (r = 0.119, p = 0.017).Conclusions: In subjects from the general population, eGFR and subclinicalatherosclerosis are more strongly associated with SAH than with homocysteine.These associations are more evident when using the 2012 CKD-EPIcreat-cys equation.Interestingly, recent studies indicate that vitamin therapy for homocysteine reduction(comprising folate, vitamin B12 and B6) does not lower SAH levels. Thus, SAH should

be considered as a more promising target in cardiorenal syndrome thanhomocysteine.

SP162 BIOMARKERS OF TISSUE REMODELING, TISSUE INJURYRESPONSE AND INFLAMMATION IN CHRONIC KIDNEYDISEASE (CKD): CLINICAL AND PRECLINICAL DATA

Axel Kretschmer1, Michaela Volsek2, Thomas Krahn1, Peter Kolkhof3,Andreas Kribben2 and Heike Bruck21Clinical Sciences Bayer Pharma AG Wuppertal Germany, 2Nephrology UniversityHospital Essen Germany, 3Cardiovascular Res Bayer Pharma AGWuppertalGermany

Introduction and Aims: Biomarkers apart from proteinuria, serum creatinine orcystatin C, which correlate with CKD grade and which have the potential to indicateearlier and predictively progression of CKD are demanded for selecting therapyregimes that fit best to attenuate loss of kidney function in CKD patients. Biomarkersreflecting in particular renal tissue remodeling and renal tissue injury response havebeen analyzed to identify biomarkers of prognostic value.Methods: In a translational approach, circulating tissue remodeling biomarkers (e.g.osteopontin, tenascin C (C-domain and B-domain), MMP2, MMP9), tissue injurybiomarkers (NGAL, cystatin C, H-FABP) and inflammatory markers (e.g. MCP1,calprotectin, MPO, CRP) were determined in comprehensively characterized CKDpatients (n=125, NT-CVD Study) and compared to matching controls (n=84).Respective plasma proteins and mRNAwere measured in renal cortex obtained fromchronically pressure and volume overloaded rodents with gradually increasing loss ofrenal function (DOCA hyperaldosteronism; SHR-SP).Results: Biomarkers of tissue remodeling and tissue injury correlated highly significantwith loss of renal function as defined by eGFR. Plasma cystatin C levels differentiatedthe four groups: controls (0.73 +/- 0.23 μg/ml, n=84), CKD3 (1.1 +/-0.34 μg/ml, n=55),CKD4 (2.4+/-0.79 μg/ml, n=17), CKD5 (3.71 +/-0.99 μg/ml, n=52) by p<0.001 for eachgroup comparison. Similar differentiations of CKD grade groups were measured forother tissue injury markers like NGAL (controls: 61 +/-21 ng/ml, CKD3: 93+/-49 ng/ml, CKD4: 267 +/-118 ng/ml, CKD5: 587 +/-351 ng/ml) or H-FABP. Likewise, tissueremodeling markers osteopontin (controls:75.4 +/-25 ng/ml, CKD3: 90 +/-32 ng/ml,CKD4: 151.1 +/-93.1 ng/ml, CKD5: 227.9 +/-124.8 ng/ml), tenascin C or TIMP1showed a similar grade of significance in correlating with severity of CKD. In sharpcontrast, serum markers indicating inflammatory processes like myeloperoxidase(MPO), C-reactive protein (CRP) or MCP1 do not reach levels of significance todiscriminate the CKD-groups (p>0.05). A similar biomarker pattern was seen inplasma and mRNA expression in renal cortex obtained from rodent models of chronicrenal impairment (DOCA hyperaldosteronism; SHR-SP).Conclusions: Tissue remodeling biomarkers are being highly eleveted in CKD patientsand these markers differentiate severity of CKD significantly even at small group-sizes(n>20). In sharp contrast, inflammatory markers lack this relationship in clinical andpreclinical samples. Futher investigations are ongoing by monitoring the longitudinalcourse of these tissue remodeling markers in CKD patients (NT-CVD study) toevaluate the predictivity of these markers for disease progression.

SP163 LECITHIN:CHOLESTEROL ACYLTRANSFERASE (LCAT)ACTIVITY IN CHRONIC KIDNEY DISEASE

Eun Sil Koh1, Sungjin Chung1, Hye Eun Yoon1, Cheol Whee Park1,Yoon Sik Chang1 and Seok Joon Shin11Division of Nephrology, Department of Internal Medicine College of Medicine, TheCatholic University of Korea Seoul Republic of Korea

Introduction and Aims: The LCAT activities have been shown to decrease in ESRD,the corresponding plasma LCAT activities at the different CKD stages, however, are notknown. The aim of this study was to evaluate whether LCAT activities also decrease inmild to moderate renal dysfunction groups.Methods: The study included 186 patients whose plasma LCAT activities weremeasured by enzymetic method from 2011 to 2012 at a single center. Other parametersrelate to lipid profile, including apolipoprotein A-I, apolipoprotein B, and lipoprotein(a) were also evaluated in an observational cross-sectional study. We calculatedglomerular filtration rate (GFR) by CKD-EPI equation.Results: The mean of plasma LCAT activities among all individuals was 65.34 ±1.64 (Unmol/ml/hr/37'C). The LCAT activities of each CKD stage 1-5 were 77.49 ± 3.22, 77.24± 4.18, 65.59 ± 3.52, 60.05 ± 3.89, and 55.44 ± 2.45, respectively (U nmol/ml/hr/37'C).The present data showed that more advanced CKD stages tend to have lower LCATactivities, correlated with lower HDL cholesterol level, although it did not havestatistical significance. In more advanced CKD stages, plasma apoA-I level significantlydecreased, while apoB, and Lp(a) showed no differences. Multivariate regressionanalysis demonstrated that plasma LCAT activities were associated positively withestimated GFR (β=0.233, p=0.012), and negatively with age (β=-0.282, p=0.002), as wellas with the interaction between LCAT activities and the amount of microalbuminuria(β=0.289, p<0.001), independent of diabetes, hypertension and BMI.Conclusions: The plasma LCAT activities decreased at more advanced CKD stages,even after adjustment for other confounder factors. The present results support thatplasma LCAT activity is as potential therapeutic target for dyslipidemia in CKD.



SP164 SURVIVALON LOW-PROTEIN DIETS: RESULTS OF AMULTIPLE CHOICE APPROACH

Maria C. Deagostini1, Federica N. Vigotti1, Martina Ferraresi1, Valentina Consiglio1,Stefania Scognamiglio1, Irene Moro1, Roberta Clari1, Germana Daidola1,Elisabetta Versino2 and Giorgina B. Piccoli11Department of Clinical and Biological Sciences, University of Turin SS Nefrologia,ASOU san Luigi Gonzaga Orbassano Torino Italy, 2Department of Clinical andBiological Sciences, University of Turin Igiene e Sanità Pubblica Orbassano Torino Italy

Introduction and Aims: Concerns on the long-term safety of low-protein diets limittheir use in Nephrology. In the discussion on the “best moment” to start dialysis,attention switched from slowing of the kidney function decline to the effects of delayingdialysis on survival. The aim of the study was to analyse survival in a cohort of patientstreated by low-protein diets, followed in the same setting in December 2007-September2012, with regard to baseline clinical conditions and low-protein diet chosen.Methods: Two main diets were offered, both at 0.6 g/Kg/day of proteins: a simplifiedlow-protein supplemented diet (LPD-KA supplementation: Ketosteril 1/10 Kg) and alow-protein diet employing “aproteic” commercial food (LPD-ACF). Survival analysiswas performed according to Kaplan Meier; multivariate analysis employed Cox model.The analysis took into consideration the period on the diet (up to dialysis start), oralternatively 1 year after the start of dialysis or the discontinuation of follow-up.Results: 285 patients started a LPD (167 LPD-KA and 118 LPD-ACF); the two groupswere non homogeneous for age (median age LPD-KA: 68, LPD-ACF: 74 years p<0.0001)and GFR at start (LPD-KA: 18.8; LPD-ACF: 22.9 mL/min; p=0.0008); prevalence ofcomorbidity was high in both (68%, 94%) in line with the European population startingdialysis. No significant difference in patient survival was observed according to the diet(607 patient years; 353 on LPD-KA and 254 on LPD-ACF); patient survival wassignificantly influenced by age and comorbidity, not by gender or baseline GFR. Survivalequivalence was confirmed prolonging follow-up up to one year after dialysis start ordiscontinuation. As for “renal survival” a significant advantage of LPD-ACF was foundin univariate analysis; the effect is lost if the combined outcome of death-start of dialysisis analysed, underlining the differences between the two populations and suggesting asubstantial equivalence between the two diets. Mortality rates were 4 per 100 patientyears on LPD-KA and 7 per 100 patients years on LPD-ACF, without differences afteradjustment for age. The data compare favourably with mortality on dialysis, as reportedon 3 Registries (Italy, France, USRDS), both comparing the age-adjusted rates andconsidering only the follow-up of cases with GFR <15mL/min.Conclusions:Our data support the safety of LPDs, suggesting that the patients do nothave a survival disadvantage as compared to dialysis, and may on the contrary have anadvantage. The substantial equivalence between treatments supports the policy ofallowing patients choosing the preferred diet option.

SP165 ENDOTHELIAL DYSFUNCTION IN CARDIORENAL SYNDROME

Mehman Mammadrahim Agayev1, Irada Mehrali Mammadova2 and Shalala QaribIsmayilova21Centre of Efferent Therapy Azerbaijan Medical University Baku Azerbaijan,2Department of Internal Medicine VI Azerbaijan Medical University Baku Azerbaijan

Introduction and Aims: In cardiorenal syndrome endothelial dysfunction (ED)promotes the pathological process and influences its course. This study investigates thefeatures of the development of ED in cardiorenal syndrome.Methods:We observed 48 patients (27 female and 21 male) aged 42-68 years (averageage 54 ± 7.3 years). The cause of chronic kidney disease (CKD) in 18 cases was diabeticnephropathy, in 12 - chronic glomerulonephritis, in 8 - ischemic renal disease, in 7 -chronic pyelonephritis, in 3 - lupus nephritis, and in 2 - polycystic kidney disease. In 14cases was determined the 2nd stage of CKD, in 16 - 3rd and in 18 - the 4h stage ofCKD. All patients had 1-3 stages of heart failure (according to the NYHA). Functionalstate of endothelium was determined by the method of D.Celermajer (1992) bydetermining the change in brachial artery diameter after nitroglycerin and reactivehyperemia. Discovered disorders were more pronounced in patients with cardiorenalsyndrome compared to those without it. With increasing stage of CKD, increases thedegree of endothelial dysfunction, which can be explained by the increase of arterialhypertension, dyslipidemia, conducive to the development of atherosclerosis.Results: Along with the clinical picture of renal and heart failure, hypertension, weobserved hypoalbuminemia, hyperuricemia, dyslipidemia. The diameter of the brachialartery in patients with CKD was 4.41 ± 0.76 mm, which did not differ much from thatof the control group (4,3 ± 0.78). In healthy people, after the application ofnitroglycerin artery diameter increased by 10.23%, and the measurements were notsignificantly different from those obtained from patients (an increase by 10.21%).Along with this, endothelium-dependent vasodilation in healthy people increased by13.4 ± 0.9%, while the increase in examined patients was only 6.7 ± 0.6%. Discovereddysfunctions were more pronounced in patients with cardiorenal syndrome comparedto those without it. With the increase of CKD stage, we noted an increase in the degreeof endothelial dysfunction, which can be explained by the increase of arterialhypertension, dyslipidemia, contributing to the development of atherosclerosis andimpaired calcium-phosphorus metabolism.Conclusions: In CKD in the occurrence of complications in the cardiovascular system,the primary pathogenetic role belongs to the endothelial dysfunction that may occurdue to metabolic disorders. On the other hand, the decrease in the level of relaxing, and

the increase in the concentration of pressor agents in the body and decrease insensitivity to vasodilator stimuli also contribute to endothelial dysfunction. Endothelialdysfunction can be considered the main pathogenetic mechanism for the developmentof cardiorenal syndrome.

SP166 CIRCULATING ANGIOTENSIN-CONVERTING ENZYME 2 INCHRONIC KIDNEY DISEASE PATIENTSWITHOUT HISTORYOF CARDIOVASCULAR DISEASE

Lidia Anguiano1, Marta Riera1, Julio Pascual1, Clara Barrios1, Angels Betriu2, JoseM. Valdivielso2, Elvira Fernández2 and María José Soler11Department of Nephrology Hospital del Mar-IMIM Barcelona Spain, 2Departmentof Nephrology Hospital Arnau de Vilanova Lleida Spain

Introduction and Aims: Circulating ACE2 activity is increased in patients withcardiovascular (CV) disease and in experimental models of diabetes mellitus (DM).However, it has not been previously studied in patients with Chronic Kidney Disease(CKD) without history of CV disease.Methods: A total population of 834 patients without history of CV disease from theNEFRONA study was analyzed. Patients were distributed into two groups: non-dialysisCKD stage 3-5 patients (CKD3-5,n=288) and patients on dialysis (CKD5D,n=546)(haemodialysis or peritoneal dialysis). Variables analyzed were: gender, age, DM,dyslipidemia, hypertension, glycemic, renal, nutritional, lipid and anemia profiles,phosphorous-calcium metabolism and treatment with ACE inhibitors or angiotensin IIreceptor blockers (ARBs). Circulating ACE2 activity was measured using a modifiedfluorimetric assay for plasma samples.Results: Patients on dialysis had higher levels of ACE2 activity compared to CKD3-5patients (38.46±1.62RFU/μl/hour vs 28.22±1.13,p<0.05). Similar differences wereobserved when patients treated with ACE inhibitors were removed from the analysis.Assessing only CKD3-5, an increased ACE2 activity was observed in men compared towomen (31.86±1.58 vs 22.82±1.41,p<0.05), DM patients (33.49±2.41 vs 26.32±1.25,p<0.05) and dyslipidemic patients (28.90±1.32 vs 26.31±2.19,p<0.05). In concordance,limiting the analyses to CKD5D, ACE2 activity was increased in men (45.55±2.46 vs27.71±1.37,p<0.05) and in those with dyslipidemia (42.58±2.84 vs 33.93±1.30, p<0.05).A direct correlation between age and ACE2 activity (p<0.05) was found in bothCKD3-5 and CKD5D patients, but only in CKD3-5 patients HbA1c directly correlatedwith ACE2 activity (p<0.05).By multiple regression analysis, male gender, advancedage and DM were independent predictors of circulating ACE2 activity in CKD3-5patients. Predictors in CKD5D patients were male gender, age and ARBs treatment, butnot DM (Table). When all patients were included in the model, male gender, older age,ARBs treatment and CKD5D were predictors of elevated circulating ACE2.Conclusions: In CKD patients without history of CV disease, old age and male genderare significant predictors for elevated circulating ACE2 activity. Independent additionalpredictors are DM in CKD stages 3-5 and treatment with ARBs in CKD5D. Increasedcirculating ACE2 activity in CKD might indicate the CKD patients at risk fordeveloping CV disease.

SP167 PSYCHOLOGICAL EVALUATION OF CKD PATIENTS.ASSOCIATION OF DEPRESSION AND STRESSWITH RENALFUNCTION

Vasiliki Tsarpali1, Vassilios Liakopoulos2, Efharis Panagopoulou3,Dorothea Kapoukranidou4, Sofia Spaia1, Myrto Kostopoulou2,Aikaterini Michalaki2, Olga Nikitidou2 and Nicholas Dombros21Dialysis Unit Ag Pavlos General Hospital-Panagia Thessaloniki Greece, 2RenalUnit, 1st Department of Internal Medicine AHEPA Hospital Thessaloniki Greece,3Department of Biological Sciences and Preventive Medicine Aristotle University ofThessaloniki, Medical School Thessaloniki Greece, 4Department of PhysiologyAristotle University of Thessaloniki, Medical School Thessaloniki Greece

Introduction and Aims: Depression and psychological stress are both associated withadverse health outcomes, like hypertension and cardiovascular disease. Prevalence ofdepression in CKD reaches 20% of patients, even before initiation of dialysis. Increased

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Predictors of circulating ACE2 Standardized coefficient(β) p value

CKD3-5 patientsMale 0.30 <0.001Age 0.17 0.002DM 0.14 0.001CKD5D patientsMale 0.32 <0.001Age 0.12 0.003ARBs treatment 0.09 0.03All included in the modelMale 0.32 <0.001Age 0.14 <0.001ARBs treatment 0.08 0.011CKD5D(vs CKD3-5) 0.21 <0.001



psychosocial stressors have been linked with an augmented rate of renal functiondecline. However, the direct impact of psychological stress and depression on renalfunction has not yet been investigated.Methods: 41 patients (23 M and 18 F) with CKD stage 2-4,mean age 73±6 years, wereenrolled in the study. Participants were receiving optimal therapy and had controlledlevels of blood pressure and plasma glucose concentration. Hospital AnxietyDepression Scale (HADS) was used to evaluate stress and depression. Estimated GFRwas calculated using MDRD formula, at the time of the psychological evaluation(eGFR2) and 12 months before (eGFR1).Results: Psychological evaluation was normal in 16 (40%) individuals. Psychologicaldisorder was present in 25 (60%) participants. 15 suffered from both depression andstress, while 5 experienced either stress or depression. A major chronic stressor, such asloss of a child, was present in 20 patients. Participants with normal HADSmeasurement for stress improved their renal function, compared to the stressed ones(eGFR1=42.8 ± 18 vs eGFR2=48.3 ± 17, p=0.006). Absence of depression, using HADSscale, led to similar results (eGFR1=40.6 ± 16 vs eGFR2=45.8 ± 17, p=0.01). Patientssuffering from both stress and depression had a significant eGFR decline (eGFR1=43 ±18 vs eGFR2=39.8 ± 15, p<0.1). HADS measurements for stress and depression werepositively correlated with the rate of CKD progression (HADS stress: r=0.5, p=0.001,depression: r=0.4, p=0.01).Conclusions: Psychological disorders seem to be a common, though under diagnosedproblem in CKD patients. In the present study, normal values for stress and depressionin HADS scale were associated with eGFR increase, while affected individualspresented an augmented rate of renal function decline. These results suggest a possiblerelationship between psychological disorders and CKD progression. Furtherinvestigation is warranted into factors that mediate this relationship and its potentialclinical consequences.

SP168 WHATARE THEMAJOR FACTORS TODETERMINE SERUMCREATININE IN HEALTHY POPULATION?

Fansan Zhu1, Samer Abba1, Cesar Flores-Gama1, Caroline Williams1,Cassandra Cartagena1, Mary Carter1, Peter Kotanko1 and Nathan W. Levin11Renal Research Institute New York United States

Introduction and Aims:Measurement of serum creatinine (Cr_S) concentration isessential to estimate glomerular filtration rate (GRF) as in GFR-Epi. Understanding thefactors which can influence the concetration of Cr_S is important to reduce error inestimating GFR. The aim of the study was to investigate relationship of Cr_S and bodycomposition measured using whole body bioimpedance method in a healthypopulation.Methods: A group of healthy subjects with absence of hypertension and renal diseasewere studied. Body weight, blood pressure, serum and urine creatinine were measured.Whole body bioimpedance (Hydra4200, Xitron Technologies) measurement wasperformed with a supine position. Extracellular and intracellular resistances werecalculated by a program based on the Cole model. Whole body extracellular (wECV)and intracellular (wICV) fluid volume were estimated using a Xitron program. Linearregression analysis was performed to find correlations of Cr_S to wICV, and wECV . Amultiple linear regression model (Cr model) was used to analyze relationship betweenCr_S and wECV, wICV, and age.Results: Forty seven subjects (Age 53.9 ± 5.8 years, weight 76.1 ±14 kg, Sex 19 male,race 15 AA) were measured. Systolic blood pressure (SBP), diastolic blood pressure(DBP), heart rate (HR), wECV and wICV were 123.7±19 mmHg, 75.7±9.2 mmHg and

68±11 beats/min, 16.3±3 L and 21.9±5.6 L, respectively. Cr_U and Cr_S were 165.7±104 mg/dl and 0.97±0.22 mg/dl respectively. Fig.1 show the correlation of Cr_S towICV (R2=0.35, p<0.0001), wECV(R2=0.25, p<0.001), and Cr model(Cr_S=0.041*wICV-0.033*ECV+0.009*Age+0.001*Cr_U, R2=0.5, p<0.0001). Fig1 alsoshows a high correlation between wECV and wICV.Conclusions: Since wICV represents whole body muscle mass, the correlation betweenCr_S and wICV confirm that amount of muscle mass is the major source to produceserum creatinine with normal kidney function. Since wECV correlated with wICV,Cr_S also correlated with ECV. In addition, Cr_S might also relate to amount of fluidvolume independently from the relationship of ECV/ICV for example with excessivesalt and fluid intake. Age related decrease in kidney function in absence of kidneydisease may also afest serum creatinine levels. In summary, the major factorsdetermining the value of concentration of Cr_s are muscle mass content, extracellularfluid volume and age in subjects with apparently normal renal function.

SP169 HYPEROXALURIAMEDIATED RENAL INJURY IN WOMENWITH RECURRENT PYELONEPHRITIS

Mykola Kolesnyk1, Natalia Stepanova1, Victoria Driyanska1, Natalia Stashevska1

and Valery Kundin21Department of Nephrology and Dialysis State Institution «Institute of Nephrologyof the National Academy of Medical Sciences» Kyiv Ukraine, 2Department ofNuclear Medicine Cardiology Center Kyiv Ukraine

Introduction and Aims: Urinary oxalate excretion in healthy individuals ranges from28 mg/day to 43 mg/d; values over 43 mg/d generally are classified as clinicalhyperoxaluria. Hyperoxaluria often associates with recurrent pyelonephritis, whichmay be caused by destruction of the Oxalobacter formigenes colonies in the intestinaltract. Recent studies have suggested that oxalate and CaOx crystals may injure renaltubular cells. Many clinical studies have demonstrated that neutrophil gelatinaseassociated lipocalin (NGAL) is a specific, sensitive, early predictor of kidney injury.The present study was performed to evaluate the effect of hyperoxaluria on kidneyinjury in female with recurrent pyelonephritis.Methods: Recurrent pyelonephritis was defined as 2 urinary tract infections episodeswithin 6 months or 3 or more episodes during the previous 12 months. We evaluatedserum NGAL, creatinine, and estimated glomerular filtration rate (eGFR)in 44 whiteadult women, age 18-62 yrs (mean 32,9±11,7) with recurrent pyelonephritis. 31 ofexamined patients had hyperoxaluria (>43 mg in 24 hours). The average of urinaryoxalate excretion in this group was 91.9±22.7 mg/d. Moreover, we determined the levelof interleukins IL-17 and IL-23 as biomarkers of disease activity, given their importantrole in inflammation and immune response. Renal scarring was documented bydimercaptosuccinic acid (DMSA) scintigraphy scan. The GFR level was calculatedusing the MDRD formula. The serum levels of NGAL and IL-17, -23 were measuredusing an ELISA kit. For statistical analysis we used the Student's t-test for independentsamples and Pearson's rank correlation.Results:We identified a positive strong correlation between the levels of the urinaryoxalate excretion and serum NGAL (R=0.91, P<0.001), the presence of renal scars(R=0.87, P=0.005) and the serum levels of IL-17 (R=0.77, P<0.02). In contrast, wedetect inverse correlation betweenhyperoxaluria and serum concentration of IL-23(R=-0.95, P<0.001). GFR was also significantly lower in patients with hyperoxaluria:75.4±22 vs 88.1±16 ml/min/m2(P=0.004).Conclusions: Hyperoxaluria in female with recurrent pyelonephritis is associated withelevated levels of serum NGAL and IL-17 as well deterioration of IL-23. Further studiesare needed to determine the role of pro-inflammatory cytokines in the pathogenesis ofoxalate-induced renal damage.

SP170 DEVELOPMENTOF AVISUALTEST FOR COPPERDETERMINATION IN SERUMOF HEMODIALYSIS PATIENTS

Iryna Shifris1, Iryna Dudar1, Olga Zaporozhets2, Tetiana Keda2, Mykola Ishchenko2and Miroslava Khil11Efferent Technology Department Institute of Nephrology NAMS Kyiv Ukraine,2Analytical Chemistry Department Taras Shevchenko National University KyivUkraine

Introduction and Aims: Despite advances in the renal replacement therapy,particularly hemodialysis, a significant incidence of complications is an actual problemof modern clinical nephrology. A large number of studies suggest that inflammationand oxidative stress are associated with the adverse course of disease. The role ofessential trace elements, particularly copper, in modulation of the intensity of oxidativestress and immune processes in hemodialysis patients is being studied. Considerableprogress has recently been made in developing multi-ion sensitive techniques whichutilize analytical reagents immobilized on silica surface. This methodology is simpleand inexpensive yet sensitive and informative. It requires small sample amounts andcan be applied for express screening of biological fluids, particularly serum. The aim ofthis work was to develop a new visual test technique for the direct copperdetermination in serum and application of such laboratory technique fordetermination of copper in serum of hemodialysis patients.Methods: 1-(4-Adamantyl-2-thiasolylazo)-2-naphthol immobilized onto silica surfacehas been proposed as effective solid-phase reagent for the adsorptional extraction of

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copper for the successive determination in the solid phase by using visual testtechnique.The interface interaction has been investigated.The modified silicademonstrates significant color change from bright orange to dark purple due tointeraction with Cu(II) ions. The standard color scale range is0.50-7.50 μg/per sampleCu(II), sample volume - 4.0 mL, time of analysis is 5 min. Blood collection from 39patients with end stage renal failure was carried out before the first HD session of theweek.Results: The data was compared to the results obtained using standardatomic-absorption spectroscopy technique (AAS). The data obtained are listed inTable. Average concentration of Cu(II) in serum of HD patients (n=39, P=0.95)Dataobtained follows normal distribution. Paired t-test showed no significant (α=0.05)difference between results obtained by two methods (texp=1.476, tcrit(α/2=0.025,f=37)=2.026. Accuracy and precision of the results are satisfactory.Conclusions: Due to it simplicity and reliability the visual test technique on the base ofmodified silica can be used for the analysis of multiple biological samples providingvaluable analytical information. The developed visual test technique can berecommended for the rapid Cu(II) determination in serum in the clinic laboratories.

SP171 EXPRESSION PATTERN OF CALPONIN IN THE CAPSULAREPITHELIUM AND PERIGLOMERULAR AREAOF HUMANKIDNEY IS RELATED TO THE DEVELOPMENTOFGLOMERULOSCLEROSIS

Jae-Yeon Choe1, Sun-Ah Nam1, Jin Kim1 and Jung-Ho Cha11Department of Anatomy College of Medicine, The Catholic University of KoreaSeoul Republic of Korea

Introduction and Aims: Progressive glomerulosclerosis lead to a common histologicaland functional end point referred to as end-stage renal disease. We previously havereported that periglomerular calponin expression in two chronic nephropathy ratmodels, puromycin aminonucleoside nephropathy and subtotal nephrectomy. Inpresent study, we examined correlation between calponin-immunoreactivity in theperiglomerular area and development of glomerulosclerosis using specimens obtained(KT, n=9) from the recipients at the time of kidney transplantation, and normalspecimens (NS, n=4) from normal portions of kidney segments from patientsundergoing nephrectomy for a renal tumor.Methods: Analysis was performed on two serial 5-um paraffin sections stained withperiodic acid-Schiff (PAS) and calponin-specific antibody respectively. The degree ofglomerulosclerosis was assessed on a blinded basis by determining the sclerotic damageto glomeruli, and were graded as follows: G0+, no changes; G1+ injury involved <25%damage to the glomerulus; G2+, 25%-50%; G3+, 50%-75%; and G4+, 75%-100%damage. Data were represented as percentage of damaged glomeruli showing any levelof injury (scale G0 to G4+). Periglomerular coverage with calponin-positivity weregraded as follows: C0+, no calponin-positivity in periglomerular area, C1+, <30%, C2+,30 ˜ 80%, C3+, >80%. All the periglomerular calponin was detected in myofibroblastand glomerular parietal epithelium.Results: In NS, most glomeruli ( >95%; G0) showed no sclerotic damage,calponin-positivity at its periglomerular area ( >97%; C0). In KT, results was as follows:glomeruloscelrotic index; G0+ (14%), G1+ (49%), G2+ (24%), G3+ (9%), and G4+(4%); calponin index; C0+ (57%), C1+ (24%), C2+ (10%), and C3+ (9%).Conclusions: These results suggested that calponin-positive myofibroblasts andglomerular parietal epithelium may play a key role in the development ofglomerulosclerosis. (This research was supported by Basic Science Research Programthrough the National Research Foundation of Korea(NRF) funded by the Ministry ofEducation, Science and Technology(20120002683).

SP172 ADVANCES IN KIDNEY FOCAL LESIONS-USE OF CONTRASTENHANCED ULTRASONOGRAPHY

Mirela L. Gliga1,2, Carmen G. Irimescu2, Carmen D. Caldararu1, Mihai G. Gliga3,Lucian V. Toma1 and Adriana Gomotârceanu41Internal Medicine University of Medicine and Pharmacy Târgu Mures MuresRomania, 2Hiparionmed Dialysis Center Târgu Mures Mures Romania, 3PathologyUniversity of Medicine and Pharmacy Târgu Mures Mures Romania, 4TOPMEDMedical Center Târgu Mures Romania

Introduction and Aims: Kidney focal lesions are frequent. Although CT scan and MRIare widely used, ultrasonography is noninvasive and repeatable, but can be improvedusing contrast-enhanced ultrasonography (CEUS). It has few side effects and can besafely used in chronic kidney disease.Methods:We used CEUS in ten patients with different kidney focal lesions: threeatypical cysts, three benign lesions and four malignant lesions, one of them for

monitoring the treatment. Patients were examined with an ultrasound device withcontrast soft application. 2,6 ml of contrast agent SonoVue was injected intravenouslyin bolus. The vascular pattern within the kidney lesion was recorded immediately afterinjection for three minutes.Results: From all lesions, six appeared benign in standard, Doppler and CT scanexamination before contrast: three cysts and three angiolipomas. After contrast US thediagnosis was confirmed in all ten cases, and the results were confirmed byhistopathology. All three cysts sowed fine echoic signal of the wall that appeared highlyvascular in CEUS and RRC was confirmed.The histology of kidney tumors was renalcell carcinoma (RRC). CEUS had a specificity of 100% and sensibility of 100%, with aPPV of 100. RRC are vascular tumors and can be easily detected by CEUS, in caseswhen color Doppler has lower sensibility. In the atypical cysts there was a vascularsignal inside the cyst and the histopathology revealed malignancy.The benign lesionswere angiolipomas and they were confirmed by the similar pattern of vascularization asthe normal kidney cortical parenchyma. The three malign lesions were characterizedby the rapid wash-out phenomena. One malign lesion was a metastasis from renal cellcarcinoma and it was monitored after 6 months of treatment.Conclusions: CEUS is a noninvasive, harmless, high tech investigation of kidney focallesions, with an excellent positive predictive value and can be performed also in kidneyfailure.

SP173 SODIUM BICARBONATE THERAPYOF THEMETABOLICACIDOSIS OF CHRONIC KIDNEY DISEASE

Yongki Park1, Yangwook Kim2 and Jimin Jeon11Division of Nephrology, Department of Internal Medicine Dongrae Bong SengHospital Busan Republic of Korea, 2Division of Nephrology, Department of InternalMedicine Haeundae Paik Hospital Busan Republic of Korea

Introduction and Aims: The prevalence of metabolic acidosis increases with decliningrenal function. The authors in this study investigated correcting metabolic acidosis inchronic kidney disease(CKD) patients may preserve renal function and improvenutritional parameters.Methods:We assigned 49 adult patients with creatinine clearance (CrCl) 15-60 ml/min and serum bicarbonate 16-20 mmol/L to either supplementation with oral sodiumbicarbonate(the bicarbonate group, n=25) or standard care (the control group, n=24)for 12 months. At the primary end points CrCl, proteinuria, and serum creatinine

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Ion VT technique AAS

x±Δx, ppm SD x±Δx, ppm SDCu(II) 0,782±0,068 0,21 0,797±0,067 0,21

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showed changed, and at the secondary end points body weight, lean body mass(LBM),mid-arm muscle circumference (MAMC) and serum albumin showed changed.Results: Compared with the control group, the bicarbonate group was improved inCrCl (+7.19 vs -3.47ml/min/yr, p<0.05) [Figure 1], nutritional parameters, body weight(+3.0 vs -1.0kg, p<0.05), LBM (+1.0 vs -2.8kg, p<0.05), and MAMC (+1.1 vs -0.34cm,p<0.05).Conclusions: Correcting metabolic acidosis(via bicarbonate supplementation) maypreserve renal function and improve nutritional parameters in CKD patients.

SP174 URINARY SYNAPTOPODIN EXCRETION AS A PREDICTOROFGLOMERULAR DISEASE PROGRESSION

Soon Kil Kwon1, Seung Jung Kim1, Sun Moon Kim1 and Hye-Young Kim1

1Department of Medicine Chungbuk National University Hospital CheongjuChungbuk Republic of Korea

Introduction and Aims: Podocytes play an important role in maintaining glomerularfiltration barrier, and make slit diaphragm that is essential for preventing albumin lossand filtering water and solutes. Diabetic kidney disease is progressive kidney failurecaused by intraglomerular hypertension showing heavy proteinuria. Urinary podocyteloss is associated with diabetic kidney disease progression, but it is not clear that theamount of podocyte or podocyte slit diaphragm protein can reflect clinical significanceof glomerular damage. We investigated the correlation between the amount of urinaryslit diaphragm proteins and renal function and albuminuria.Methods: Total 40 patients with diabetic chronic kidney disease and glomerulardisease patients were enrolled, and the amount of urinary podocyte and slit diaphragmproteins were measured by Western blot analysis. Amount of urinary nephrin,podocalyxin, podocin, synaptopodin and beta actin were measured by Western blotband density. Each urine sample was loaded as same amount of total sample protein,

and adjusted by beta-actin band density in the setting of same beta-actin band density.We measured serum creatitine and sopt urine albumin/creatinine ratio as a marker ofrenal damage, and compared correlation of urinary podocyte protein between diseasegroups or renal disease progression.Results: 15 Patients were diabetes, 25 were glomerulonephritis and others wereunspecified chronic kidney disease. Mean age was 34±15.8 years old, mean serumcreatinine was 2.01±1.37 mg/dL, mean albumin/creatinine ratio was 4.65±3.60.Urine albumin excretion showed no difference between diabetes and non-diabetes(p=0.26), and that showed no correlation with serum creatinine level (p=0.81).The reference beta-actin band density showed no significant difference betweendiabetes and non-diabetes (p=0.60), and band density of podocalyxin/actin andnephrin/actin and showed no significant difference between patient group(p=0.31, 0.58). However, synaptopodin/actin and podocin/actin ratio betweendiabetes and non-diabetes showed remarkable difference (6.43±3.79 vs. 2.79±3.29,8.46±9.43 vs. 4.47±7.67, respectively, p<0.01). Serum creatinine level showedsignificant correlation only with urinary synaptopodin/actin ratio (r=0.58,p<0.001) in contrast to nephrin, podocalyxin and podocin showed no significantcorrelation.Conclusions: In conclusion, amount of urinary synaptopodin excretion isincreased in diabetic kidney disease comparing with glomerulonephritis, and itshowed significant correlation with serum creatinine elevation inglomerulonephritis. We suggest that urine synaptopodin level can be a predictorof glomerular damage regardless of urine albumin excretion.

SP175 URINE PROTEIN-TO-CREATININE RATIO CORRELATESWITH24-H URINE TOTAL PROTEIN EXCRETION BUT POORLY INNEPHROTIC RANGE PROTEINURIA

Nuria Montero1, Maria José Soler1, Clara Barrios1, Eva Márquez1, Ali Berrada1,Carlos Arias1, Jenny Alejandra Prada1, Maria A. Orfila1, Sergi Mojal2,Carles Vilaplana3 and Julio Pascual11Nephrology Hospital del Mar Barcelona Spain, 2Institut del Mar d' InvestigacionsMèdiques-IMIM Barcelona Spain, 3Laboratori Central de Referència de CatalunyaBarcelona Spain

Introduction and Aims:Measurement of the protein content of a timed 24 hour urinecollection is the definitive method of establishing the presence of abnormal proteinuria,however, the urine collection is cumbersome. The spot urine protein to creatinine (p/c)ratio seems to be a reliable diagnostic tool for urine protein measurement. Our aim isto evaluate the spot urine p/c ratio compared to 24-h urine total protein excretion indifferent proteinuria ranges.Methods: Observational, cross-sectional study of 1179 consecutive paireddeterminations of 24-h urine total protein excretion and the spot urine p/c ratio inrenal patients. The strength of the correlation was determined by calculating theintraclass correlation coefficient (ICC) and the Spearman correlation coefficient (SCC).Results: Among all groups, the ICC was 0.749 (CI 95% 0.660-0.809) and the SCC wasr=0.8 (p<0.01). As shown in the table, there is an excellent significant correlationbetween the spot urine p/c ratio and 24-hour urine total protein excretion whenproteinuria was more than 300 mg/24 hours. This correlation decreased when it wasmore than 3500 mg. When patients were stratified according to eGFR, the correlationsbetween the spot urine p/c ratio compared to 24-h urine total protein excretion weresimilar between groups.Conclusions: In summary, a strong correlation is observed between spot urine p/c ratioand 24-h urine total protein excretion when the level of proteinuria is less than 3500mg/day. In our experience, there is not enough correlation between spot urine p/c ratioand 24-h urine total protein excretion in nephrotic-range proteinuria.

SP176 WHATABOUT THE CHILDREN BORN TOMOTHERS ONVEGAN LOW-PROTEIN SUPPLEMENTED DIETS INPREGNANCY?

Federica N. Vigotti1, Rossella Attini2, Silvia Parisi2, Federica Fassio2,Maria C. Deagostini1, Sara Ghiotto1, Martina Ferraresi1, Roberta Clari1,Marilisa Biolcati2, Tullia Todros2 and Giorgina B. Piccoli11SS Nephrology S.Luigi Gonzaga Hospital, University of Turin Orbassano (TO)Italy, 2Materno-Fetal Unit OIRM-S. Anna Hospital, University of Turin Turin Italy

Introduction and Aims:Women with CKD increasingly choose to undergo thechallenges of pregnancy, but very few tools are available to counteract the effects of thehyperfiltration of pregnancy; experience with low protein diets in CKD in pregnancy islimited. Hence, we report the results obtained in pregnant women with severe CKDtreated by supplemented vegan low protein diets, focusing on intrauterine fetaldevelopment and on subsequent children growth.Methods: Diet group: CKD stages 3b and 4, or stage 3a in the presence of kidneytransplant, type 1 diabetes, collagen disease and/or proteinuria >1 g in the firsttrimester, or nephrotic later on. Controls: CKD stage 3a not included either for stable,less severe disease, or for late referral, cultural o linguistic barriers, other low-proteindiets, eating disorders, patient's choice. Diet: vegan, low-protein(0.6-0.7 g/Kg/day) withamino and chetoacid supplementation,1-3 free meals/week. Compliance, side effects,biochemical data recorded at least twice monthly. All mothers delivered in the same

SP173

SP173



Center. Small for gestational age (SGA) babies were defined as gestational-age adjusted<10percentile.Results: Out of over 350 CKD pregnancies referred between 2000 and 2012, 21 caseswere treated by the diet(median age 33 yrs (26-40), sCr 1.3 mg/dL (0.5-3.2), GFR 75(20-135), proteinuria 2.5 gr/24h (0.2-6.3) 8/21 diabetes-3/21 kidney graft-2/21interstitial-8/21 glomerular diseases). We identified 14 controls(median age 31 yrs(22-39), sCr 1.4 mg/dL (1.1-2.9), GFR 51 ml/min (24-60), proteinuria 0.6 gr/24h(0.1-2) 1/14 kidney graft-3/14 glomerular diseases-10/14 interstitial or malformative).In the diet group, 1 pregnancy was terminated (patient's choice); 1 was a twinpregnancy; 19 singletons babies were delivered. 1 twin child, affected by great vesseltransposition died after neonatal heart surgery. In the control group 14 singletons weredelivered. In the diet group, in spite of pre-term delivery in 20/21cases, 4/19singletonswere SGA (2 <5thcentile, 2 5-10thcentile). Conversely in the control group, withpre-term deliveries 9/14 cases, SGAwas recorded in7/14 (2 <5thcentile, 5 5-10thcentile).Mean follow up of the children born from mothers in the diet group was of 33 months(1-120); at the end of each observation period, none of the children had majordevelopmental problems, all attaining normal developmental targets for their age.Conclusions: Our report suggests considering vegetarian supplemented diets as anadditional and safe tool in the management of selected pregnant CKD patients, with arisk of SGA at least comparable (and potentially lower) than controls, and a goodauxologic profile in the long term.

SP177 DYSREGULATION OF HEPATIC FATTY ACIDMETABOLISM INCHRONIC KIDNEY DISEASE: EFFECTOF NIACINSUPPLEMENTATION

Kyubok Jin1,2 and Nosratola D. Vaziri11Division of Nephrology and Hypertension University of California, Irvine Irvine CAUnited States, 2Internal Medicine Inje University, Haeundae Paik Hospital BusanRepublic of Korea

Introduction and Aims: Chronic kidney disease (CKD) results inhypertriglyceridemia which is largely due to impaired clearance of triglyceride-richlipoproteins occasioned by down-regulation of lipoprotein lipase and VLDL receptorin the skeletal muscle and adipose tissue and of hepatic lipase and LDL receptor-relatedprotein (LRP) in the liver. However information on the effects of CKD and niacinadministration on fatty acid metabolism in the liver is limited and was investigatedhere.Methods: Expression of molecules involved in fatty acid metabolism in the liver weredetermined in untreated CKD (5/6 nephrectomized), niacin-treated CKD (50 mg/Kg/day in drinking water for 12 weeks) and control rats.Results: The CKD rats exhibited hypertension, proteinuria, hypertriglyceridemia,up-regulation of hepatic tissue carbohydrate-responsive element binding protein(ChREBP), fatty acid synthase (FAS), and acyl-CoA carboxylase (ACC), anddown-regulation of sterol responsive element binding protein-1 (SREBP-1), SREBP-2,HMG-CoA reductase, fatty acid binding protein (L-FABP), CPT1A, ATP synthase α,ATP synthase β, glycogen synthase, and diglyceride acyltransferase 1 (DGAT1),DGAT2. Niacin therapy attenuated hypertension, proteinuria, hypertriglyceridemia,reduced ChREBP, FAS, ACC abundance and raised SREBP-1, L-FABP, ATP synthaseα, and DGAT1.Conclusions: Advanced CKD results in carbohydrate responsive element bindingprotein driven upregulation of key enzymes involved in fatty acid synthesis anddown-regulation of the key enzymes involved fatty acid catabolism in the liver. Niacinadministration attenuates these abnormalities and improves plasma lipid profile in theCKD animals.

SP178 ALBUMIN INDUCED DOWN-REGULATION OF PGLYCOPROTEIN IN HK-2 HUMAN TUBULAR CELLS:INFLUENCE OF VARIOUS CHEMICALS

Gianfranco Tramonti1, Nadia Romiti2 and Elisabetta Chieli21Dipartimento di Medicina Clinica-Nefrologia University of Pisa Pisa Italy,2Dipartimento Traslazionale University of Pisa Pisa Italy

Introduction and Aims: Progressive renal failure has been closely linked to proteinuriaand tubulointerstitial involvement. Tubular reabsorption of filtered albumin maycontribute to the structural interstitial injury that has been associated withalbuminuria. Upon protein endocytosis, the tubules that reabsorb albumin

demonstrate increased expression of pro-inflammatory cytokines that promoteinflammation, tubular degeneration, and fibrosis. Furthermore, a large number ofgenes encoding membrane transporter proteins of tubular cells was found to be up- ordown-regulated by proteinuria. One membrane transporter is P-glycoprotein (Pgp), aglycoprotein involved in the ATP-dependent transmembrane efflux of a wide range ofcompounds leading to a decrease in drug concentration within the cell. In the kidneyPgp is mainly expressed in the proximal tubule. The influence of albumin onexpression and function of Pgp in HK-2 proximal tubular cells has previously beendemonstrated. Aim of this study was to assess the influence of various drugs on Pgpexpression in HK-2 cells exposed to albumin.Methods: Tubular cells were cultured in presence of albumin (15 mg/mL) for 72 hours.Mycophenolic acid (MPA, 100 mM), paracalcitol (PAR, 100 mM), and celecoxib (CEL,20 mM) were added to culture medium. Pgp protein expression was assessed byWestern Blot (WB). To study the ABCB1 Pgp encoding gene expressionsemi-quantitative RT-PCR was employed. Pgp transport function was evaluated byintracellular accumulation of rodhamine-123 test (R-123).Results: In cells exposed to albumin a reduction in Pgp expression to 33.9% respect tocontrols (Western blot) was found (p<0.001 t-test and 1-way ANOVA). ABCB1 geneexpression showed a reduction to 66 % of controls (p<0.02). Pgp mediated transportassessed by the R-123 test was also impaired. In fact, the fluorescence of HK-2 cellsresulted 1.5-fold higher than that of controls (p<0.05). MPA added to the mediumincreased Pgp expression to 56% of controls, while the fluorescence was reduced to1.37-fold. In presence of PAR Pgp expression increased to 44% of controls. Instead,CEL induced a reduction of Pgp expression to 19.6% of controls, higher than thatcaused by albumin alone.Conclusions: Tubular cells exposed to albumin present a reduction in both protein andgene expression of Pgp with ensuing impairment in the membrane transport function.The reduction of the transport function mediated by Pgp leads to intracellularaccumulation of drugs and toxic compounds resulting in increased tubular cellstoxicity. This could be a further factor of progression of kidney damage linked toproteinuria. The results of this study show that the albumin induced down-regulationof Pgp can be reversed by MPA and PAR and point out a perspective of limiting thenegative effect of albumin on tubular cells.

SP179 EVALUATION OF RENAL FUNCTION RESERVE IN HEALTHYVOLUNTEERS AND CKD PATIENTS BY DOPAMINE INFUSION

Adelya N. Maksudova1 and Lia A. Khusnutdinova11Hospital Medicine Kazan State Medical University Kazan Russian Federation

Introduction and Aims: It is generally accepted to use amino acid solutions or proteinload to establish renal function reserve (RFR). Oral meat production could havedifferent amount of protein and electrolytes and give different response type; moreoversodium could increase tubular-glomerular feedback mechanism. Thus, protein loadingmethods not only expensive, but may give false results. It is known, that othervasodilating factors could be used for RFR investigation, one of them is dopamine. Theaim of the study: to establish accuracy and safety of RFR definition after low dosedopamine load.Methods: Two groups of subjects were studied: 41 healthy volunteers (26,8±6,7 yearsold, BMI 21,5±2,9 kg/m2, GFR 109±21,7 ml/min/1,73m2) and 20 patients withhypertension and gout with CKD 3-4 stage (40,7±9,9 years old, BMI 26,3±4,6 kg/m2,GFR 48,9 ± 14 ml/min/1,73m2). To establish RFR we assessed baseline serumcreatinine and patients were asked to urinate. Than patients collected urine during two1-hour periods. In first period patients drink 200 ml of water, during second periodthey were infused dopamine 3 mkg/kg/min with same water amount. Creatinineclearance (CrCL) was calculated during both periods. RFR was calculated from usualformula: RFR(%)=CrCL2 - CrCL1) x 100/ CrCL1.Results: Dopamine load didn't show side effects in patients, but nausea in somevolunteers with low arterial blood pressure. After dopamine load in healthy peopleminute diuresis grow from 3,98±3,61 to 6,13±4,4 ml/min, GFR increased from 109±22,7 to 305±117,2 ml/min/1,73m2 ; accordingly RFR was 43,6 ± 67 % (95% CI 22,6 –64,6). In CKD patients RFR didn't increase, contrary decreased in most cases -19,8±27% (95%CI (-31,9) - (-7,8)). To establish normal value of RFR we have compareddifferent normal values of RFR: 5, 10 and 15%. Statistical analysis has showed, that inany of this normal values odds ratio to have normal RFR more large in healthy persons(p = 0,001), but the 10% value is best one.Conclusions: Dopamine infusion test is harmless. Test has showed positive result inhealthy volunteers and significantly lower result in patients with renal insufficiency.Low dose dopamine load test could be advised to evaluate RFR.

SP175

Proteinuria 24h (mg) All < 300 300-3499 < or =3500

Number 1179 387 680 112Age (mean +/- DT) 59,9 (+/- 16.25) 57.9 (+/- 16) 59.4 (+/- 16.2) 58.9 (+/- 14.54)Gender (Male/Female) 640/539 178/209 393/287 69/43Creatinine (mg/dl) (mean +/- DT) 1.91 (+/-1.55) 1.61 (+/-1.4) 2.04 (+/- 1.66) 2.15 (+/- 1.23)Intraclass correlation coefficient (Confidence interval 95%) 0.749 (0.660-0.809) 0.493 (0.378-0.592) 0.344 (0.199-0.462) 0.090 (-0.032-0.231)Spearman correlation coefficient (r) p 0.890 <0.001 0.459 <0.001 0.784 <0.001 0.416 <0.001



SP180 ASSOCIATION OF SERUMCYTOKINE PROFILESWITHTACROLIMUS-INDUCED CHRONIC NEPHROTOXICITYIN CHINESE LIVER TRANSPLANT RECIPIENTS

Jiangtao Tang1, Yunying Shi2, Junlong Zhang1, Yi Li1, Yunfei An1, Ye Tao2 andLanlan Wang11Department of Laboratory Medicine West China Hospital of Sichuan UniversityChengdu Sichuan China, 2Department of Nephrology West China Hospital ofSichuan University Chengdu Sichuan China

Introduction and Aims: Calcinurin inhibitors (CNI) associated chronicnephrotoxicity has become a serious problem which threatens the prognosis of livertransplant recipients. This study was aimed to find out the relationship between serumcytokines, chemokines and chronic tacrolimus (Tac) induced nephrotoxicity. Wedetected the posttransplant serum inflammatory cytokines and chemokines levels inliver transplant recipients to illuminate the correlations of inflammatory cytokines orchemokines withthe chronic renal injury.Methods: A total of 136 living donor liver transplant recipients (107 males and 29females) and 150 healthy controls (120 males and 30 females) were enrolled in thisstudy. All the recipients had normal Cystatin C (Cys-C) and normal urinemicroalbumin before transplantation and received Tac-based immunosuppressiveregime (Tac+MMF+ prednisone) afterwards. A human 10-plex antibody bead kit(BioSource, Camarillo,CA) was used to measure the levels of 10 cytokines andchemokines in 50 ml of serum from each transplant patient and controls. Aftertransplantation, serum Cys-C and urine microproteins including α1 microalbumin(α1M), microalbumin (MA), transferring (TRU) and IgG (IgU) were measured among136 allo-liver recipients to evaluate whether they had early renal injury and theprobable location of the renal lesion.Results: The levels of IL-6,IL-10, IFN-γ,IP-10 and MCP-1 in the recipients' group weresignificantly higher than those in the control group (P<0.05), while the levels of IL-8was onthecontrary (P<0.05). In early renal damage group (Cys-C>1mg/L), theconcentration of IP-10 was much higher compared to the group with normal renalfunction (Cys-C≤1mg/L), whereas the concentration of MCP-1 in early renal damagegroup was lower than the group with normal renal function. The concentration ofIP-10 in the group with tubulointerstitial injury (α1M >12.5 mg/L )was much highercompared with the group without such injury (α1M≤12.5 mg/L).Conclusions: IP10 may be the important cytokine leading to chronic CNI-inducednephrotoxicity, especially the tubulointerstitial injury. Allo-liver recipients with highserum IP10 posttransplant levels might develop severe chronic CNI-inducednephrotoxicity due to increased immune activation.

SP181 HIGH SENSITIVITY TROPONIN T IN CHRONIC KIDNEYDISEASE

Javier E. Reque1, Borja Quiroga1, Juan M. Lopez1, Ursula G. Verdallez1,Marisol Garcia de Vinuesa1, Marian Goicoechea1, Panizo G. Nayara1,David R. Arroyo1 and Jose Luño11Nephrology Hospital General Universitario Gregorio Marañon Madrid Spain

Introduction and Aims: Chronic kidney disease (CKD) is an independent risk factorfor developing coronary heart disease (CHD). The cardiac troponins are structuralproteins predictors of (CHD). It has been demonstrated that high sensitivity TroponinT (hs-TnT) has greater predictive value than conventional Troponin T in thedevelopment of CHD in the general population. However, its usefulness in patientswith CKD is unclear.Objectives: To study the influence that the degree of renal function has on levels ofhs-TnT and its possible association with other cardiovascular risk factors.Methods:We conducted a prospective study including 563 patients: 58% male, 32.5%diabetics, aged 64 ± 17 years, at different stages of CKD. We collected clinical history,routine laboratory parameters and hs-TnT. 20% had CHD history and 9.2% of acutemyocardial infarction (AMI). Glomerular filtration rate was 50 ± 29 ml/min/m2(MDRD-4) and 51 ± 29 mil/min/m2 (CKD-EPI). In 408 patients an echocardiogramwas performed simultaneously.Results: The mean hs-TnT was 18.5 ng/ml. Plasma concentrations of as-TnT weredirectly relate to age (r = 0.643, p <0.001) and inversely with the MDRD 4 (r = -0,674 p<0.001). The hs -TnT is higher in men than in women (20.4 vs 15.9 ng / ml, p <0.01), issignificantly higher in patients with history of CHD (p = 0.032) and especially inpatients with a history of myocardial infarction ( p <0.01). The mean hs-TnTaccording to stages of CKD was: Stage1: 3.97 ng / ml; stage 2: 6.03 ng /ml; stage 3: 18.94ng/ml; stage 4: 30.93 ng/ml; stage 5: 45.56 ng/ml, with a statistically significantdifference in the variance analysis (p <0.01). When we divided the patients with andwithout history of CHD, the differences remained significant (p <0.01 and p <0.001respectively), although the values were significantly higher in those with a history.19.1% of patients had left ventricular hypertrophy in this group, the values of hs-TnTwere higher (40.4 vs 13.8 ng / ml, p <0.001). In a multivariable model, remain aspredictors of high hs-TnT values the loss of renal function, history of CHD and LVH.Conclusions: Hs-TnT levels increased as the severity of CKD, even without evidence ofacute myocardial damage, so the value of this marker must be adjust according to thedegree of renal function. hs-TnT concentrations are higher as in men, patients withhistory of CHD and those with LVH.

SP183 HOW THE PATIENT KINETICS HAS ALTERED AFTER THEIMPLEMENTATION OF eGFR IN A NEPHROLOGYOUTPATIENT CLINIC

Hiroshi Tanaka11Division of Nephrology, Department of Internal Medicine Hiroshima Red CrossHospital and Atomic-bomb Survivors Hospital Hiroshima Japan

Introduction and Aims: Implementation of estimated GFR (eGFR) in the generalmedicine has massively changed the renal clinics. Those changes might include notonly the expansion of the renal patient numbers but an increase in number of patientssent back to general practitioners. This study was done in order to clarify whether theplacement of renal patients has been changed according to their renal function, beforeand after the eGFR measurement implementation.Methods: Two 6-month periods (from Jan 1 to Jun 30), in years 2005 and 2010, i.e.before and after the nationwide implementation of eGFR, were chosen for the analysis.All the new visits to a certified nephrologist in the Hospital were included and themedical charts were reviewed to find out the background clinical status and thedisposition of each patient 2 years after the initial visit. Patients already onmaintenance dialysis due to ESRD at the initial visit or those with no renal disease wereexcluded from the analysis.Results: In 2005 and 2010, 115 and 117 new patients were included in the analysis,respectively. Although the total number of new visits appeared close, the details in 2010differed from those in 2005 in many aspects. New patients with eGFR between 15 and45 mL/min/1.73m2 nearly doubled (35.2% in 2005 vs 64.8% in 2010, P<0.0001). Afterthe nephrologist's initial evaluation, more patient were asked to be followed in theoriginal non-nephrology clinic (9.6% vs 28.2%, P<0.001). The patients who continuedto be followed in the renal clinic had significantly lower eGFR (median, 56.7 vs33.8mL/min/1.73m2, P=0.016, Mann-Whitney); within 2 years, those with baselineeGFR between 15 and 45 mL/min/1.73m2 were more likely to be sent back tonon-nephrologists (9.6 vs 29.8% of all the followed patients, P<0.001), due to theoverwhelming renal clinic. Dropout patients (14.4% in 2005 and 26.2% in 2010) hadsignificantly lower eGFR in 2010 (median, 79.0 vs 35.0 mL/min/1.73m2, P=0.015,Mann-Whitney).

Conclusions: Implementation of eGFR has resulted in "backflow" of more severe renalpatients to non-nephrologists.

SP184 BODY COMPOSITION IN HEALTHY SUBJECTS ANDPATIENTS IN EARLY STAGES OF CHRONIC KIDNEY DISEASE

César Flores-Gama1, Samer R. Abbas1, Caroline Williams1,Cassandra Cartagena1, Mary Carter1, Sthephan Thijssen1, Peter Kotanko1,Nathan W. Levin1 and Fansan Zhu11Renal Research Institute New York NY United States

Introduction and Aims: Fluid balance and body composition are maintained inpatients with chronic kidney disease (CKD) until glomerular filtration rate (GFR) fallsbelow 15 ml/min. The aim of this study was to evaluate whether body compositiondiffers in healthy subjects and patients with moderate loss of kidney function.

SP183



Methods: Healthy subjects older than 40 years without previous diagnosis of diabetes,cardiovascular and chronic kidney disease were selected. Calf, segmental and wholebody bioimpedance spectroscopy (BIS) were performed using Hydra 4200.Extracellular (ECV), intracellular (ICV) fluid volume, total body water (TBW=ECV+ICV), and skeletal muscle mass (SMM) (model to predict SMM by[Kaysen et al inAm J Clin Nutr 2005) using segmental and whole body methods were calculated. Bloodpressure, serum creatinine and albumin were measured, eGFR was estimated using theCKD epidemiology collaboration equation (CKD-EPI). CKD stages (revised KDIGOclassification based on eGFR[Levey et al in Kidney Int 2011]) were compared byANOVA or Kruskal Wallis tests.Results: Forty five subjects were studied (age 52 [range 45-61] years, 60% women, bodymass index (BMI) 27.0±4.1 Kg/m2, eGFR 82.1±16.8 ml/min/1.73 m2). Subjects weredivided into three CKD stages: G1 ≥90 ml/min/1.73m2(n=16), G2 60-89 ml/min/1.73m2 (n=24) and G3a 59-45 ml/min/1.73m2(n=5) (Table 1). The ECV/ICV ratio washighest and the whole body and leg SMM measurements were lowest in the G3a group.Serum albumin, BMI, whole body, segmental and calf ECV, ICV and TBW wereidentical between groups.Conclusions: Already in subjects with moderate loss of kidney function fluiddistribution and muscle mass is altered. Our results show an increased fractional ECVand lower SMM in the leg. These finding suggests that loss of skeletal muscle massmight be an early event in the progression of CKD. ECV volume in the calf isunaffected in CKD stages 1 and 2.

SP185 BODY COMPOSITION EVALUATION BYMULTIFREQUENCYSPECTROSCOPIC BIOIMPEDANCE IN CHRONIC KIDNEYDISEASE PATIENTS AT DIFFERENTeGFR STAGING:1 to 5NON-D

Francois C. Berthoux1, Lynda Azzouz2, Aida Afiani2, Abdelaziz Ziane2,Christophe Mariat1 and Henri Fournier31Nephrology, Dialysis, and Renal Transplantation University Hospital ofSaint-Etienne Saint-Etienne France, 2Dialysis Unit ARTIC 42 Saint-Priest-en-JarezFrance, 3Strategy and Innovations Fresenius Medical Care France Fresnes France

Introduction and Aims: There is no precise information on body composition withhydration and nutritional status in non-dialyzed patients with chronic kidney disease(CKD) . So we decided to investigate ambulatory renal patients (P) at different levels ofrenal function: KDOQI-eGFR stage 1, 2, 3, 4, or 5-non D. The primary objective was toevaluate the hydration status of these P.Methods:We used the Body Composition Monitor® (from Fresenius Medical CareGermany Inc.), based on multifrequency (50 measurements from 5 to 1000 kHz)spectroscopic bioimpedance, which is already validated for corporal fluid compositionand nutritional parameters in dialyzed patients (hemodialysis or peritoneal dialysis).We strictly followed the procedure and used the Fluid Management Tool® software. Allmeasurements were made by the same senior nephrologist (FB). Overall, we enrolled152 P (82 men; mean age 61.6 years) with 28 P in stage 1, 30 in stage 2, 44 in stage 3, 37in stage 4, and 13 in stage 5 non-D. For each P, we recorded many parameters: height,weight, waist circumference, SBP, DBP, serum creatinine with eGFR calculation byaMDRD for staging and classification; plus basic renal parameters with diagnosis andincluding clinical grading of peripheral edema (0, +/-, 1+, 2+, and 3+).The calculatedparameters were water balance and distribution, plus lean and fat tissues.Results: At baseline the major difference was a stepwise increasing age from 46.4 instage 1 P to 73.1y in stage 5 (P<0.0001). Overall, BCM detected 35 P (23%) withover-hydration (excess > 1 Liter) affecting 7, 20, 16, 38, and 46% of P in stage 1, 2, 3, 4,or 5 respectively, while the clinic noted only 19 P with ≥1+ edema. The water (W)excess (liter, L) was respectively -0.15, +0.65, +1.25, +2.73, and 4.60 L for clinicaledema grading of 0, +/-, 1+, 2+, and 3+ respectively. In addition, we found 28 P (18%)with under-hydration (W deficit >-1 L) and clinically silent. Distribution of body Wshowed a significant (P<0.001) stepwise decreasing intracellular volume (L) accordingto GFR stages, but with age as a cofounder. Similarly, the lean tissue mass index (kg/m2) decreased stepwise from stage 1 to 5, also with age as a cofounder. These results

were independent of the aetiology of the CKD.Conclusions: The BCM with FMT is a utility tool in all CKD patients whatever thediagnosis; it allows the detection of over- and under-hydration with precisequantitation of W excess or deficit in P at different eGFR staging. The procedure takesonly 10 mn in a clinic and was superior to a senior clinician. We recommend toimplement the body composition monitoring in renal patients with significant chronicrenal failure: CKD-3 to 5.

SP186 DIFFERENT BODY FLUID VOLUMESMEASURED BY SINGLE-ANDMULTI-FREQUENCY BIOELECTRICAL IMPEDANCEANALYZERS IN OVERWEIGHT/OBESE RENAL PATIENTS

Mariusz Kusztal1, Przemyslaw Dzierzek1, Grzegorz Witkowski1, Michal Nurzynski1,Tomasz Golebiowski1, WaclawWeyde1 and Marian Klinger11Nephrology and Transplantation Medicine Wroclaw Medical University WroclawPoland

Introduction and Aims: Bioelectrical impedance analysis (BIA) is an affordable,non-invasive and fast alternative method to assess body composition. The purpose ofthis study was to compare two different tetrapolar bioimpedance (BIA) devices forestimating body fluid volumes and body cell mass (BCM) in clinical setting amongpatients with kidney failure.Methods: All double measurement were performed by multi-frequency andsingle-frequency BIA analyzers, a Body Composition Monitor-BCM (FreseniusMedical Care, Germany) and BIA-101 (Akern, Italy), respectively. All procedures wereconducted according to manufacturers instructions (dedicated electrodes,measurements sites, positions etc). Total body water (TBW), extracellular water(ECW), intracellular water (ICW) and BCM were compared. Thirty six patients withchronic kidney disease (stage III-V) with mean age 45,8±8 y, 19 men and 17 women,who had a wide range of BMI [17-34 kg/m(2) (mean 26,6 ±5)] participated in thisstudy.Results: In general measurement of ICW and BCM were similar (19 vs 18,6; p= 0,87;and 24,8 vs 20,7 kg; 0,08) in two devices. The Akern device gives higher mean estimatesof TBW and ECW compared to the Fresenius device (41 vs. 35,8 kg, p=0,04 and 22 vs.17,2; p=0,001, respectively). A comparison of results from patients with BMI <25 vs≥25 revealed significant discrepancy measurement between both BIA devices. Namelyin group with BMI <25 (n=16) acceptable correlations were obtained in TBW (r 0.99;p<0,01), ICW (0,95; p<0,01), BCM (0,84; p<0,01), ECW (0,81 p<0,05), but in groupwith BMI ≥25 (n=20) huge discrepancy (poor correlations) in TBW (r 0.54; p<0,05),ICW (0,32; p=ns), BCM (0,15; p=ns), ECW (0,81; p<0,01) were found. In thosepatients (BMI≥25) the Akern device gives significantly higher mean estimates of TBW(45,9 vs 40,1; p=0,03), ECW (24 vs 19,2; p<0,01) and BCM (28,7 vs 23 ;p=0,05) thanFresenius device.Conclusions: Since estimates of TBW, ICW BCM by the present BIA devices do notdiffer in patients with BMI <25, they might be interchangeable. This does not hold truefor overweight/obese renal patients. Because both BIA devices could over/underestimate BCM in obese patients an effort to reduce the bias (electrodes repositioning?)and finally comparison to gold standard should be undertaken.

SP187 APPLICABILITY OF A DIFFERENT ESTIMATION EQUATIONOFGLOMERULAR FILTRATION RATE IN TURKEY

Mehmet Riza Altiparmak1, Nurhan Seyahi1, Sinan Trabulus1, Murat Bolayirli2,Zeynep Gulnur Andican2, Gultekin Suleymanlar3 and Kamil Serdengecti11Department of Nephrology Cerrahpasa Medical Faculty, Istanbul UniversityIstanbul Turkey, 2Department of Biochemistry Cerrahpasa Medical Faculty,Istanbul University Istanbul Turkey, 3Department of Nephrology School ofMedicine, Akdeniz University Antalya Turkey

Introduction and Aims:We aimed to investigate the performance of variouscreatinine based glomerular filtration rate estimation equations that were widely usedin clinical practice in Turkey and calculate a correction coefficient to obtain a better

SP187

Formulae mL/min

Iohexol GFR 47.24 ± 34.05Cockroft-Gault 64.07 ± 43.29Jelliffe 2 61.04 ± 40.20Mawer 70.86 ± 54.45Bjornsson 67.54 ± 45.25Gates 57.73 ± 39.60Formulae mL/min/1.73m2

Iohexol GFR 45.60 ± 32.17MDRD 1 (6 variables) 47.83 ± 33.58MDRD 2 (4 variables) 47.36 ± 28.35IDMS-traceable MDRD 56.69 ± 39.03Jelliffe 1 54.42 ± 36.56CKD-EPI 54.58 ± 34.59

SP184

G1 (n=16) G2 (n=24) G3a (n=5)Pvalue

eGFR (ml/min/1.73 m2)

100.2±7.0 75.8±8.3 54.3±3.1 n/a

Age (years) 46.5 (43-53.5) 54.5 (47-62) 70 (69-74) 0.004SBP (mmHg) 119.2

(113-125.8)115.5

(110.8-131)154.2

(137.6-170.5)0.02

Whole body ECV/TBW

0.43±0.03 0.42±0.03 0.46±0.02 0.03

Whole body ECV/ICV

0.76±0.08 0.75±0.08 0.86±0.08 0.02

Leg ICV/TBW 0.41±0.03 0.41±0.03 0.46±0.02 0.007Leg ECV/ICV 0.70±0.09 0.69±0.09 0.84±0.08 0.004Whole body SMM

(Kg)24.27±4.07 24.92±5.94 20.01±3.91 0.16

Leg SMM (Kg) 7.90±0.83 8.48±0.83 7.54±0.93 0.03



estimate using the isotope dilution mass spectrometry (IDMS)-traceable Modificationof the Diet in Renal Disease (MDRD) formula.Methods: This cross-sectional study included adult (>18 years) outpatients and inpatients with chronic kidney disease as well as healthy volunteers. Iohexol clearancewas measured and the precisions and bias of the various estimation equations werecalculated. A correction coefficient for the IDMS-traceable MDRD was also calculated.Results: A total of 229 (113 male/116 female; mean age 53.9±14.4 years) subjects wereexamined. A median iohexol clearance of 39.21 mL/min/1.73 m2 (range: 6.01-168.47mL/min/1.73 m2) was found. We found that the Cockroft-Gault, Mawer, Bjornssonand Gates formulae overestimated the mean GFR by more than 10 mL/min. TheMDRD 2 equation overestimated the GFR by 11 mL/min / 1.73 m2.The largest andsmallest bias and random errors were recorded with the Mawer and MDRD 2formulae, respectively. The best precision and accuracy was also obtained with theMDRD 2 formula. Bias and random error for the IDMS-traceable MDRD equationwere 11.33±8.97 mL/min /1.73 m2and 14.21 mL/min / 1.73 m2, respectively. There wasa good agreement between iohexol-measured GFR and corrected MDRD, especially inpatients with GFR<60 mL/min/1.73 m2.Conclusions:MDRD formula seems to provide the best estimates. To obtain the bestagreement with iohexol clearance, a correction factor of 0.804 must be introduced toIDMS-traceable MDRD equation for our study population.

SP188 CKD PREVENTION IN PATIENTSWITH CAUDA EQUINASYNDROME, USING ALTERNATIVE THERAPEUTIC METHODS

Andrei Niculae1, Ionel-Alexandru Checherita1, Dan-Nicolae Neagoe2 andAlexandru Ciocalteu11Nephrology and Dialysis “Carol Davila” University of Medicine and Pharmacy,“St. John”; Emergency Clinical Hospital Bucharest Romania, 2“St. Pantelimon”Balneotherapy and Rest Center Constanta Romania

Introduction and Aims: Cauda equina syndrome (CES) is a severe complication oflumbar spinal disorders. It is known that CES represents one of the most importantcauses of repeated acute pyelonephritis that cause chronic pyelonephritis, and thenCKD. The aim of this study was to evaluate if electrotherapy and hydrothermal therapywith natural factors (mud) help in reducing acute pyelonephritis episodes in thesepatients.Methods:We conducted a prospective study on 48 patients with CES and repeatedacute pyelonephritis. 30 of the patients had catheters à demeure. The age of the patientsconsidered for the study was between 20 and 70. These patients underwent every 3months, for 1 year, electrotherapy with medium frequency current (nemectron)lombosuprapubian applied with variable frequency (0-100 hz), 20 minutes, 1 session/day, 20 days and overall mud bath at 37 degrees Celsius for 20 minutes, 1 session/day/20 days.Results: In 65% of patients that underwent this recovery plan, the number of acutepyelonephritis episodes decreased during the follow up period, compared to thefrequency of episodes before the beginning of treatment (p=0.0001). Out of those withcatheters à demeure, 59% (p=0,0001) didn't use them anymore. The number ofpyelonephritis episodes was lower in patients aged between 20 and 50, compared tothose aged 50-75 years (p=0.0001). There were no statistical significant differencesbetween male and female sex in regards to the number of pyelonephritis episodes aftertreatment.Conclusions: Applying alternative methods of treatment in the CES seems to have aneffect in reducing the number of acute pyelonephritis episodes, as well as in reducingthe permanent bladder catheterisation . Patients younger than 50 years seem to have abetter response to treatment than those over 50 years. By reducing acute pyelonephritis

episodes in these patients we help preventing chronic pyelonephritis and chronickidney disease.

SP189 THE CREATININE AND CYSTATIN C BASED CKD-EPIEQUATION IMPROVES RISK PREDICTION OF RENALOUTCOME IN CKD PATIENTS

Sarah Seiler1, Kyrill S. Rogacev1, John W. Pickering2, Insa Emrich1, Danilo Fliser1and Gunnar Heine11Department of Internal Medicine IV- Nephrology and Hypertension SaarlandUniversity Hospital Homburg Germany, 2Christchurch Kidney Research Group,Department of Medicine University of Otago Christchurch Christchurch NewZealand

Introduction and Aims: Plasma creatinine and cystatin C are markers used to estimateglomerular filtration rate (GFR). Cystatin C is less influenced by muscle mass or dietthan creatinine. Recently, the Chronic Kidney Disease Epidemiology Collaboration(CKD-EPI) validated an equation which integrates creatinine and cystatin C toestimate GFR (i.e. the CKD-EPIcreat-cysequation). We present the first comparison ofthe CKD-EPIcreat-cys equation with the more established MDRD equation forprediction of renal outcome.Methods:We recruited 420 CKD patients from our ongoing CARE FOR HOMe studyfor the present subanalysis. Baseline creatinine and cystatin C were measured and thenGFR estimated by the MDRD 4 and CKD-EPIcreat-cys equations. Patients were classifiedto 2013 KDIGO CKD stages (stage 2: eGFR 60-90 ml/min/1.73 m²; stage 3a: eGFR45-60 ml/min/1.73 m²; stage 3b: 30-45 ml/min/1.73 m²; stage 4: 15-30 ml/min/1.73m²) by the MDRD equation and then re-classified by CKD-EPIcreat-cys. Annualfollow-ups were performed. The predefined renal outcome was either a 50% decrease ineGFR, or initiation of renal replacement therapy, or death from any cause.Results: Out of 420 patients, CKD-EPIcreat-cys re-classified 49 to a less advanced CKDstage than MDRD, 59 to a more advanced CKD stage, and 312 to the same stage.During a mean follow-up of 2.4 ± 0.8 years 54 patients suffered a renal outcome eventof whom 13 (24%) had been re-classified; 12 to a more advanced CKD stage and only 1to a less advanced CKD stage. Among the remaining 366 patients not suffering anevent, 47 had been re-classified to a more advance and 48 to a less advancedCKD-stage. The net re-classification improvement was 20.4% (95% Confidenceinterval: 9.1% to 34.3%) for patients with the subsequent outcome event, and 0.3%(-4.9% to 5.5%) for patients without the event.Conclusions: Compared to the established MDRD 4 equation, the newCKD-EPIcreat-cys equation allows better stratification of CKD patients for prediction ofrenal outcome. This finding is consistent with recent the 2013 KDIGOrecommendation to use CKD-EPI to estimate GFR.

SP190 VALIDATION OF A NEW STANDARDIZED CYSTATIN CTURBIDIMETRIC ASSAY: EVALUATION OF THE THREE NOVELCKD-EPI EQUATIONS IN HYPERTENSIVE PATIENTS

Anne-Sophie Bargnoux1, Julien Obiols1, Nils Kuster1, Pierre Fessler2,Stéphanie Badiou1, Anne-Marie Dupuy1, Jean Ribstein2 and Jean-Paul Cristol11Laboratoire de Biochimie CHRU Montpellier Montpellier France, 2Service deMédecine Interne CHRU Montpellier Montpellier France

Introduction and Aims: The aim of this study was first to evaluate the analyticalperformances of a new standardized automated turbidimetric cystatin C assay usingDiasys reagents (DiaSys Diagnostic Systems GmbH, Holzheim, Germany) on OlympusAU2700® analyzer (Olympus, Rungis, France). Furthermore, the clinical relevance ofrenal function markers (enzymatic IDMS-traceable creatinine and standardizedcystatin C) was assessed by comparison of estimated GFR (eGFR) equations with theGFR measured (mGFR) by a reference isotope method (99mTc-DTPA) in a populationof hypertensive patients.Methods:We have studied imprecision, linearity, limit of detection and limit ofquantification of this new immunoassay. Method comparison was assessed bycomparing with results generated by the standardized Siemens- particle-enhancednephelometric immunoassay. In order to evaluate the clinical relevance of this assay,estimated glomerular filtration rate (GFR) was calculated using MDRD, CKD-EPIcreatinine, CKD-EPI cystatin C 2012 and CKD-EPI creatinine-cystatin C 2012 andcompared to GFR measured using urinary clearance of 99mTc-DTPA in 100hypertensive patients.Results: Cystatin C measurements using Diasys reagents have reliable analyticalperformances and is comparable to the standardized Siemens-PENIA method (bias of0.01 mg/L). The mean measured GFR was 90.0 ± 29.7 mL/min/1.73m². Bias andaccuracy of the three CKD-EPI equations were better than the MDRD. Both CKD-EPIcreatinine-based and cystatin C-based formulae had similar bias, precision andaccuracy. The combined creatinine-cystatin C equation was significantly more accurateand precise than the CKD-EPI creatinine equation, in particular for early stages ofchronic kidney disease.Conclusions: The use of cystatin C in a combined equation with creatinine couldimprove the accuracy of eGFR in patients with high GFR (stage 1) and served as aconfirmatory test in patient monitoring.

SP187



SP191 ESTIMATED GLOMERULAR FILTRATION RATE BASED ONSERUMCYSTATIN C PROVIDES PROGNOSTIC INFORMATIONBEYOND ITS ROLE AS AN INDEX OF KIDNEY FUNCTION

Naoki Yanagisawa1,2, Minoru Ando2,3, Atsushi Ajisawa1, Ken Tsuchiya2 andKosaku Nitta21Department of Infectious Diseases Tokyo Metropolitan Komagome HospitalTokyo Japan, 2Department IV of Internal Medicine Tokyo Women's MedicalUniversity Tokyo Japan, 3Department of Nephrology Tokyo MetropolitanKomagome Hospital Tokyo Japan

Introduction and Aims: Cystatin C elevation may reflect the wide spectrum ofabnormalities including predisposition to cardiovascular disease (CVD),accompanying renal dysfunction. Clinical significance of estimated glomerularfiltration rate based on serum cystatin level (eGFRcy) in predicting adverse outcomeshas not been tested in HIV subjects, comparing with eGFR based on serum creatinine(eGFRcr).Methods: A 3.5-year prospectivecohort study was conducted in 661 HIV-infectedindividuals (mean age, 46.4 ± 11.6 years old) to compare the ability to predict adverseoutcomes between eGFRcy and eGFRcr. Adverse outcomes included all-causemortality, CVD and a decrease in eGFR over 25% from baseline. The ability to predictincidence of adverse outcomes was evaluated using the area under the receiveroperating characteristic curves (Au-ROC).Results: All patients completed the follow-up. CD4 cell count was 411 ± 204 /μL and81.7% had undetectable HIV-RNA level. Prevalence of eGFRcr and eGFRcy <60 ml/min/1.73 m2 was 8.6% and 3.5%, respectively. Au-ROC for eGFRcy (0.604) wasmoderate yet significant (P = 0.0003), whereas one for eGFRcr (0.564) was notstatistically significant (P = 0.0950).Conclusions: The frequency of HIV individuals affected with renal dysfunctionmanifested a nearly 2.5-fold decrease, if it was assessed by eGFRcy, instead of eGFRcr.Furthermore, eGFRcy is likely superior to eGFRcr in predicting composite adverseoutcomes among HIV-infected individuals.

SP192 MDRD VERSUS CKD-EPI EQUATIONS TO ESTIMATEGLOMERULAR FILTRATION RATE IN OBESE PATIENTS

Antoine Bouquegneau1, Etienne Cavalier2, Jean-Marie Krzesinski1 andPierre Delanaye11Nephrology-Dialysis-Transplantation CHU Sart Tilman, University of Liège LiègeBelgium, 2Clinical Chemistry CHU Sart Tilman, University of Liège Liège Belgium

Introduction and Aims: Obesity is recognized as a risk factor both for thedevelopment and progression of chronic kidney disease (CKD). Estimating glomerularfiltration rate (GFR) is thus especially important to follow these patients. We havetested the performances of two creatinine-based equations, namely the MDRD andCKD-EPI equations, in an obese population.Methods: Patients with body mass index (BMI) higher than 30 kg/m² were included.The reference method for GFR measurement was 51Cr-EDTA (single injection method,two blood samples at 120 and 240 minutes). Serum creatinine was measured using theIDMS traceable compensated Jaffe method. When obese patients are considered, oneimportant issue is the question of BSA indexation. In this work, we will present theresult with non-indexed GFR. We calculated bias (defined as the mean differencebetween measured and estimated GFR), precision (defined as the SD around the bias)and accuracy 30% (defined as the percentage of estimations which are between ± 30%of measured GFR). Analyses were repeated in patients with measured GFR higher than60 mL/min.Results: The population included 93 patients (Liège, Belgium), 62 women and 31males. Mean age was 51 ± 14 years and mean BMI was 41 ± 9 kg/m². Mean measuredGFR was 94 ± 30 ml/min (11 patients had a GFR lower than 60 ml/min). In the globalpopulation, the bias was -11 and -6 mL/min for the MDRD and CKD-EPI equationsrespectively. Precision was 19 mL/min for both equations. Accuracy 30% was 86 and

80% for the MDRD and CKD-EPI equations, respectively (no significant difference). Inpatients with measured GFR higher than 60 mL/min, bias, precision and accuracy forthe MDRD and CKD-EPI equations were: -12 and -6 mL/min, 20 and 20 mL/min, and90 and 84%.Conclusions: Both in the global and subgroup analyses, the CKD-EPI equation did notoutperform the MDRD study equation. The performances of both equations wereworse in CKD patients. These two conclusions were still valid if indexed GFR wasconsidered.

SP193 SHORT-TERM EFFECTS OF TOLVAPTAN ADDED TOFUROSEMIDE IN PATIENTSWITH CONGESTIVE HEARTFAILURE AND ADVANCED STAGES OF CHRONIC KIDNEYDISEASE

Naoto Tominaga1, Yugo Shibagaki1, Keisuke Kida2, Fumihiko Miyake2 andKenjiro Kimura11Division of Nephrology and Hypertension, Department of Internal MedicineSt. Marianna University School of Medicine Kawasaki Japan, 2Division ofCardiology, Department of Internal Medicine St. Marianna University School ofMedicine Kawasaki Japan

Introduction and Aims: Increasing dose of furosemide (Furo) often leads to worseningrenal function (WRF) in patients with Furo-resistant congestive heart failure (CHF),especially when complicated with advanced chronic kidney disease (CKD). Add-on useof tolvaptan (Tol), a novel V2 receptor antagonist, may give better control of excessivebody fluid in CHF patients without increasing dose of Furo and WRF, however, it hasbeen unclear whether it may give similar effect in advanced stages of CKD patients.This study aimed to clarify the efficacy of add-on Tol in patients with CHF andadvanced stages of CKD.Methods: 23 patients with CHF and CKD stage G3b-5 who showed insufficient controlof excessive body fluid using 40-200 mg of oral Furo daily were included in this study.We assessed the changes of hemodynamic and renal functional parameters in 23patients given fixed doses of Furo with add-on Tol (15 mg daily) for 1 week.Results: Compared with the baseline, increasing of urine volume(ΔUV, mL/d) in stagesG3b, G4 and G5 were 696±1250(P=0.19), −38±736(P=0.87) and 678±474(P<0.05),respectively, which showed significant increment of UV in CKD stage 5 at the end ofthe study. Increment of serum creatinine levels(ΔsCr, mg/dL) in each stage were 0.02±0.14(P=0.79), 0.48±0.47(P<0.05) and −0.11±0.44(P=0.53), respectively, showing nosignificant WRF except in stage 4. Changes in blood pressure(ΔBP, mmHg) were notstatistically significant, and status of excessive body fluid improved clinically in eachstage.Conclusions:Without WRF and decreasing BP, add-on use of Tol not only showedapparent increase of UV, but improved clinical symptoms associated with excessivebody-fluid status in patients with Furo-resistant CHF and advanced stages of CKD.

SP194 THE EFFICACYOF COLCHICINE TREATMENT IN RENALAMYLOIDOSIS IN THE FRAMES OF FAMILIALMEDITERRANEAN FEVER

Alexandr Ayvazyan1, Vilen Rameev2, Lidia Kozlovskaya2 and Armine Simonyan11Internal Diseases Yerevan State Medical University, Hospital Complex “Muratsan”Yerevan Armenia, 2Internal Diseases Moscow Medical Academy after I.M.Sechenov Moscow Russian Federation

Introduction and Aims: The main objective of the study was to assess the results ofcolchicine treatment in renal amyloidosis in the frames of Familial MediterraneanFever (FMF) depending on colchicine daily dose and the stage of nephropathy in thebeginning of the treatment.Methods:We studied 41 FMF patients with amyloid nephropathy. All patients weretaking colchicine: 18 patients began the treatment in proteinuric stage (I subgroup), 15– in the stage of nephrotic syndrome /NS/ (II subgroup), and 8 – in the stage of initial(creatinine level 116-300 mcmol/l) renal failure /RF/ (III subgroup). The preparationdosage was adequate (1.8-2.0 mg/day) only in 11 of 41 investigated patients (26,8%).The essential inclusion criterion for the participation in the study was the duration ofcolchicine treatment not less than 2 consequent years.Results: In I subgroup colchicine efficacy, i.e. disappearance or decrease in intensity ofproteinuria, was detected only in 3 adequately treated patients. In the rest 15inadequately treated patients we detected persistence of proteinuria: with increasetendency – in 12, and increase in creatinine level – in 3 patients. 5 patients in IIsubgroup were treated adequately. In 3 of them cochicine was efficient, however the rest2 patient developed RF. In the majority (7) of inadequately treated patients in thissubgroup (10 patients) colchicine was not efficient, and 6 patients developed RF. Onlyin 3 of 10 inadequately treated patients we detected decrease in intensity of proteinuria.There were no cases of colchicine efficacy in III subgroup regardless of preparationdosage.Conclusions: Our investigation has shown that colchicine in the most efficient in theterms of early prescription (proteinuric stage of amyloid nephropathy) and in adequatedose. The efficacy of colchicine tends to decrease in NS, and even full colchicine dose isnot able to prevent the progression of amyloidosis. In the stage of RF colchicinetreatment has no influence on the course of disease.

SP191



SP195 EXTRACELLULAR MATRIX PROTEIN FIBULIN-1 PLASMALEVELS ARE ASSOCIATEDWITH INCREASEDCARDIOVASCULAR RISK IN CHRONIC KIDNEY DISEASE

Alexandra Scholze1,2,3, Peter Marckmann1, Martin Tepel1,2 andLars M. Rasmussen41Nephrology Odense University Hospital Odense Denmark, 2Institute of MolecularMedicine University of Southern Denmark Odense Denmark, 3Institute of ClinicalMedicine University of Southern Denmark Odense Denmark, 4Department ofClinical Biochemistry Odense University Hospital Odense Denmark

Introduction and Aims: Fibulin-1 is one of the few extracellular matrix proteinspresent in blood in high concentrations. We aimed to define the relationship betweenplasma fibulin-1 levels and risk markers of cardiovascular disease in patients withchronic kidney disease.Methods: Plasma fibulin-1 was determined in patients with chronic kidney disease(n=32; median age, 63 years; inter-quartile range, 51 to 73 years). Serologicalbiomarkers related to cardiovascular disease (fibrinogen, interleukin 6, C-reactiveprotein) were measured. Arterial applanation tonometry was used to determine centralhemodynamic and arterial stiffness indices.Results:We observed a positive correlation of fibulin-1 levels with age (r=0.38;p=0.033), glycated hemoglobin (r=0.80; p=0.003), creatinine (r=0.35; p=0.045), andfibrinogen (r=0.39; p=0.027). Glomerular filtration rate and fibulin-1 were inverselycorrelated (r=-0.57; p=0.022). There was a positive correlation between fibulin-1 andcentral pulse pressure (r=0.44; p=0.011) and central augmentation pressure (r=0.55;p=0.001). In a multivariable regression model, diabetes, creatinine, fibrinogen andcentral augmentation pressure were independent predictors of plasma fibulin-1.Conclusions: Increased plasma fibulin-1 levels were associated with impaired kidneyfunction and diabetes. Fibulin-1 levels were also associated with hemodynamiccardiovascular risk markers. We conclude, that fibulin-1 is involved in the pathogenesisof cardiovascular disease observed in chronic kidney disease.

SP196 INCIDENCE OF PROTEINURIA FOLLOWING GEMCITABINEADMINISTRATION IS A LIKELY SIGN OF POOROUTCOMEFOR CANCER PATIENTS

Masaki Hara1, Minoru Ando1, Ken Tsuchiya2 and Kosaku Nitta21Department of Nephrology Tokyo Metropolitan Komagome Hospital Bunkyo-Ku/Tokyo Japan, 2Department IV of Internal Medicine Tokyo Women's MedicalUniversity Shinjuku-Ku/Tokyo Japan

Introduction and Aims: Gemcitabine (Gem) is approved for treatment of a variety ofcancers, including pancreatic and biliary carcinomas. Clinical experience suggests thatGem administration may be associated with the emergence of proteinuria. This studywas undertaken to examine incidence of proteinuria following Gem administration,and an association of de novo proteinuria and mortality among Gem recipients.Methods: A retrospective cohort study was conducted in 53 pancreatic or biliarycancer patients (27 men, mean age, 67 years) who received the first mono-therapy ofGem and who had never manifested proteinuria before it. Proteinuria was defined asdipstick test ≥ 1+, persistent in at least two consecutive examinations within sixmonths following Gem administration. Cumulative mortality was analyzed by theKaplan-Meier method, stratified by presence or absence of proteinuria. MultivariateCox proportional hazards regression analysis was used to calculate hazard ratio (HR)with its 95% confidence interval (CI) for all-cause mortality, adjusted for age, gender,and stage of disease.

Results: Incidence of proteinuria was 20.7% (18 out of 53 patients), and totally 18patients died during the follow-up period (mortality, 33.9%). Mean follow-up timeafter initiation of Gem was 453 ± 196 days. Cumulative mortality was significantlygreater in patients who developed proteinuria than those who did not. In addition,the HR (95% CI) of incident proteinuria for mortality was 2.81 (1.09 - 6.78; P =0.0335).Conclusions: Proteinuria may be a harbinger of near-term death for cancer patientswho received Gem treatment. Periodic monitoring of urinary protein is stronglyrecommended for frontline oncologists.

SP197 CONVERSION FROM ALLOPURINOLTO FEBUXOSTAT ISBENEFIT FOR CKD PATIENTSWITH HYPERURICEMIA

Hidetoshi Kanai1, Kenji Harada1, Yasuhisa Tamura1 and Yasuhiro Kawai11Nephrology Kokura Memorial Hospital Kitakyushu City Fukuoka Japan

Introduction and Aims: Hyperuricemia is known not only as a laboratory finding inchronic kidney disease (CKD), but also as one of major risk factors for bothprogresses in CKD and cardio-vascular disease. In advanced CKD patients, xanthineoxidase inhibitor (XOI) such as allopurinol had been established foranti-hyperuricemic agent. However, allopurinol might be limited to use in advancedCKD patients due to severe side effects and pharmacological renal metabolism ofthis medicine. Febuxostat has been recently introduced as a novel XOI to reduceserum uric acid (sUA) markedly and safely. We investigated whether febuxostatpotentiates to suppress the progression of kidney dysfunction in CKD individualspre-treated with / without allopurinol.Methods: 139 CKD patients (70+/-11 (SD) yo, M/F=107/32, diabetes: 30%) weresubjected and administered 12.5+/-5.4 (10 – 40)mg/day of febuxostat for 10+/-5.6 (3- 19) months. Out of 139, 63 patients (0toF group) had not been treatment with anyOXI. 76 patients (AtoF group), administered 103+/-45 (50 – 200)mg/day ofallopurinol previously, were converted to febuxostat (13.9+/-11 mg/day). EGFR andsUA at -12, 6, 3, 1, 0, 1, 3, 6, 12 months after starting administration of febuxostatwere applied to evaluate the time-dependent changes.Results: At the start of febuxostat (0months), sUA and eGFR in all subjects were24.4+/-14 ml/min and 9.1+/-3.3 mg/dl, respectively. At 12 months, sUA wassignificantly reduced to 7.0+/-1.5 mg/dl (p<0.01). EGFR at 12 months was disclosed25.5+/-13 ml/min, with no significant change after administration of febuxostat.Before starting febuxostat, eGFR was decreased as -0.63+/-0.8 ml/min/month. Afterinitiating febuxostat, decline of eGFR was significantly diminished as 0.03+/-0.8 ml/min/month (p<0.01). In both 0toF and AtoF groups, eGFR was showed stableduring followed-up periods. There was no difference in changes of eGFR with thedose of febuxostat (10 vs 20mg/day), age (over 65yo), presence of diabetes.Conclusions: In conclusion, treatment of hyperuricemia by XOI partially improvedprognosis in CKD patients. Even in the patients already treated with allopurinol,converse from allopurinol to febuxostat may be benefit for maintain kidney functionthrough enhanced lowering sUA.

SP196

SP196

Univariate analysis Multivariate analysis

Variable HR (95% CI) P value HR (95% CI) P valueAge 0.98 (1.03 - 1.01) 0.6333 1.00 (0.96 - 1.05) 0.6907Gender, men 1.33 (0.68 - 2.64) 0.3924 1.03 (0.50 - 2.15) 0.9182Stage of disease 1.38 (0.76 - 12.38) 0.1294 1.41 (0.91 - 2.40) 0.1206Incidence of proteinuria 2.71 (1.13 - 5.86) 0.0270 2.81 (1.09 - 6.78) 0.0335

SP197

-12months

-6months

-3months

0month

+3months

+6months

+12months

sUA(mg/dl)0toF

8.4 8.6 8.8 9.8 6.9 6.8 6.9

sUA(mg/dl)AtoF

7.5 7.3 7.7 8.0 7.6 7.4 7.1

eGFR(ml/min)0toF

32.1 30.1 25.9 26.3 27.7 25.2 26.6

eGFR(ml/min)AtoF

31.7 28.4 26.1 24.0 24.8 24.6 25.2



SP198 THE EFFECTOF ENVIRONMENTAL AND PATIENT HISTORYON THE FORMATION OF RENAL STONE AND RELATEDSERUM IONS LEVELSWITH REFERENCE TO URINARYTRACT INFECTIONS

Mohemid M. Al-Jebouri1 and Salih A. Madash21Microbiology College of Medicine, University of Tikrit Tikrit Salahaldeen Iraq,2Clinical Laboratory Tikrit Teaching Hospital Tikrit Salahaldeen Iraq

Introduction and Aims: As the prevalence of renal stone is different in males andfemales,some studies have focused on the possible roles of hormones including sextypes and their recepters in renal calcium stone diseases.Environmental as well patienthistory,habits and habitats may also influence the formation of stones,ions metabolismand consequently urinary tract infections.The present study is an attempt to correlatebetween the relavent parameters including environmental as well patients criteria inrelation to formation of renal stones,serum ion balances,hormones and possibleurinary tract infections.Methods: This study was conducted in Tikrit Teaching Hospital on 160 patients withpost-shockwave lithotripsy during 2012.The causative agents of urinary tract infectionswere identified.One hundred stones were collected and analysed.Blood samples werecollected from patients for serum analysis of vitamin D,parathyroid and sex hormones,calcium,phosphorus,uric acid and magnesium.Types of diet,occupation,residence,drinking water,education and family history were recorded.Results: Eighty four percent of the patients were infected with Gram-negative bacteria.The male to female ratio of infection was 2:1.Ca-oxalate was the predominant(85%).which was either mixed or pure.More than a half of the urolithiasis patients had one ormore metabolic abnormalities like hypercalcemia and hyperuricemia.Hypermagnesemia related to hyperparathyroidism was recorded.Most of the patientsused raw drinking waters without food restrictions.Almost 37% of the patients testedwere having a history of renal stone.It was found a significant variations of serum ionswith respect to sex hormones.Conclusions: Increased incidence of renal stones among males was attributed toincreased dietry protein intake which increases urinary excretion of phosphates andmagnesium and reduced urinary citrate concentration.The recurrence rate amongurolithiasis patients was almost 37% which indicates insufficient treatment of theunderlying causes.Vitamin D,parathyroid and sex hormones were highly interrelatedwith ions metabolism, stone formation and urinary tract infections.

SP199 PREOPERATIVE MARKERS OF DECREASED KIDNEYFUNCTION AFTER SURGICALTREATMENTOFNEPHROLITHIASIS

Oksana Leonidovna Berezinets1 and Anton Nicolaevich Rossolovskiy1

1Department of Urology and Nephrology, Saratov Scientific Research Institute ofFundamental and Clinical Urology and Nephrology Saratov State MedicalUniversity of V.I.Razumovsky Saratov Russian Federation

Introduction and Aims: It is known, that patients with nephrolithiasis have theincreased risk of development of the chronic kidney disease (CKD). Among risk factorsof development of CKD in nephrolithias, it is possible to allocate the repeated operativeinterventions, accompanied by transient disturbances of microcirculation to thedevelopment of tubulointerstitial damage and endothelial dysfunction innephrofibrosis outcome. Mediators of tubulointerstitial damage and nephrofibrosisparticipating in the cellular response can be used to predict the outcome of kidneydamage in the surgical treatment of nephrolithiasis.Methods: Examined 340 patients of nephrolithiasis. All patients underwent assessmentof renal function by the formula MDRD; preoperative and 3 months after surgeryusing ELISA determined levels of some profibrotic cytokines (uIL-6, uIL-8, uMCP-1,uTGF-β) and mediators of endothelial dysfunction (VEGF , NO and ET-1) in urineand blood serum. The age of patients, body weight, anamnesis duration, saltcomposition of the stone, GFR, urea, serum creatinine also underwent the analysis.Results: Based on the results of 57 intraoperative nefrobiopsy received during PCNLand open surgical treatment, revealed changes tubulointerstitial tissues of varyingseverity. The nonparametric correlation analysis on Spirmen's method showed a strongcorrelation (r ≥ 0,5) between of laboratory and morphometric parameters in patientswith nephroIlithiasis (p ≤ 0,05). Diameter of tubules correlated with concentration ofIL-1 and IL-6 in urine (r=0,77; p=0,04), and also back correlated with the ET-1 level inblood serum (r=-0, 78, p=0,006). Indicators such as uIGF-1 (r = -0,75; p = 0,026),uIL-6 (r = 0,77; p = 0,04) and VEGF (r = -0,77 p = 0,036) is directly dependent onelevation changes tubular epithelial cells (p ≤ 0,05). Infiltration of the renalparenchyma of the brain substance was correlated with the levels of TGF-β (r = 0,76;p = 0,02) and MCP-1 (r = 0,86; p = 0,02) in the urine, the concentration of NO inblood serum ( r = 0,77; p = 0,036). Dimensions of the long axis of the glomerulus had astrong positive correlation with the concentration uIL-8 (r = 0,77; p = 0,036), andnegatively with the concentration of VEGF in serum (r = -0,9; p = 0,018). Based onmultivariate discriminant analysis and ROC-analysis (area under the curve of> 0.70) tothe factors predictive of the risk of decreased kidney function in postoperative periodinclude increasing uTGF-βmore than 498 pg / ml, VEGF more than 268 pg / ml, NOmore than 15.1 mmol / l, and age older than 50 years.Conclusions: Use of mediators nephrofibrosis as quantitative prognostic criteria riskof decreased kidney function after surgery in patients with nephrolithiasis canidentify risk patients with a high probability of progression of CKD in thepostoperative period, to choose the best algorithm for diagnostic and treatmentinterventions in these patients and to determine the appropriate target for renalprotection therapy.



lab methods / biomarkers

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