EFFICACY OF CHOLECALCIFEROL (VITAMIN D3)THERAPY IN CORRECTING VITAMIN D INSUFFICIENCY AND SECONDARY HYPERPARATHYROIDISM IN PATIENTS WITH CHRONIC KIDNEY DISEASE: A RANDOMISED, PLACEBO CONTROLLED STUDY Prakash Chandra‡, Thomas R. Ziegler*‡ Lynn E. Schlanger*, Wenli Wang*, James T Someren*, and Vin Tangpricha*‡

Departments of * Medicine, and ‡ Graduate Program in Nutrition and Health Sciences, Emory University, Atlanta, GA, USACorrection of vitamin D insufficiency by vitamin D supplementation in chronic kidney disease (CKD) stages 3 & 4 patients has been recommended by the National Kidney Foundation; however, limited data are available to determine its effectiveness in treating secondary hyperparathyroidism. This randomized, controlled, double-blinded pilot study investigated the efficacy of cholecalciferol to raise serum 25-hydroxyvitamin D (25(OH) D) levels and reduce parathyroid hormone (PTH) levels in subjects with CKD. Subjects with CKD stage 3 and 4 (GFR 15-59 ml/min/1.73 m2), vitamin D insufficiency (serum 25(OH)D <30 ng/mL) and serum PTH > 70 pg/mL were randomized to either 50,000 IU of cholecalciferol or placebo once a week for 12 weeks. 20 subjects finished the study, 10 subjects in both the placebo and cholecalciferol groups. Baseline racial distribution, age, GFR, PTH, and 25(OH)D concentrations were comparable in both study groups. After 12 weeks of therapy, all except one cholecalciferol-treated subject in the active treatment group became vitamin D sufficient. The mean serum 25(OH)D concentrations increased significantly from 17.3 [95% CI: (11.8,25.2)] to 49.4 [95% CI: (33.9,72.0)] ng/mL (+213%, p<0.0001) in cholecalciferol-treated subjects (baseline to week 12). In contrast, no significant change occurred in serum 25(OH)D values in placebo treated subjects over time. PTH levels in cholecalciferol treated subjects decreased by 31% from baseline values as compared to only 7% decrease in placebo treated subjects (p=0.14). Weekly supplementation of cholecalciferol is an effective method to correct vitamin D status in CKD stage 3 and 4 patients, and may be effective in reducing PTH levels.

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METABOLIC CONTROL AND SOLUTE CLEARANCE USING COMMERCIALLY AVAILABLE SOLUTIONS IN CVVHDF. Himabindu Chaparala, Yasmin Brahmbhatt, Sheng Kuo, Sunil George, Heesuck Suh, Nand K Wadhwa, Stony Brook University Medical Center, Stony Brook, NY, USA. CVVHDF is being increasingly used in critically ill patients with acute renal failure. The CVVHDF protocol should provide optimal metabolic control and solute clearance. At the same time the protocol should be simple for implementation. In the current study, we investigated the use of commercially available solutions for CVVHDF. Data was collected in 29 patients with acute renal failure undergoing CVVHDF using Prismasate (Gambro, USA) and ACD-A solution. All patients received CVVHDF using the Prisma M 100 set with AN69 dialyzer. The mean age of the patients was 57+11 years (range 34-76). Prismasate BGK2/0 or BGK 4/0 was delivered as replacement fluid at 1500 ml/hr and Prismasate BGK4/2.5 was delivered as dialysate at 500 ml/hr. Calcium Chloride was administered as continuous intravenous infusion through central venous catheter to maintain iCa between 4.0 -4.5 mg/dl. Anticoagulant Citrate Dextrose –Formula A (ACD-A) was initiated at 150 ml/hr. The rate was adjusted to maintain post filter ionized Calcium between 1-1.4 mg/dl. Data (mean+SD) are summarized below.

Variable 0 hour 48 hours 96 hours Pvalue

Sodium 139.5+6.3 139.5+4.0 139.3+3.4 NSPotassium 4.71+0.97 4.07+0.48 4.15+0.56 <0.01 Chloride 104.06+8.9 100.96+5.7 101.76+5.4 <0.05 Bicarbonate 22.03+5.40 26.13+4.53 27.76+5.26 <0.001 Anion gap 13.37+8.5 12.34+7.2 9.81+9.5 NSPH 7.30+0.09 7.40+0.09 7.40+0.09 <0.001 BUN 63.62+25.74 43.27+19.15 41.69+22.80 <0.001 Creatinine 3.85+1.84 2.50+1.29 2.0+1.14 <0.001 Serum citrate

_ 3.82+1.98 3.68+1.92 NS

The use of commercially available solutions is simple and provides adequate metabolic control and solute clearance in CVVHDF.

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ASSESSING THE USE OF THE CALCIMIMETIC CINACALCET WITH LOW DOSE VITAMIN D VERSUS ESCALATING DOSES OF VITAMIN D ALONE IN THE TREATMENT OF SECONDARY HYPERPARATHYROIDISM (HPT)—THE ACHIEVE STUDY C Charytan1, D Corry2, M Roppolo3, X Ling4, J Droge4, S Fishbane5.1NY Hosp Med Ctr Queens, Flushing, NY; 2Olive View UCLA-Med Ctr, Sylmar, CA; 3Renal Assoc. of Baton Rouge, Baton Rouge, LA; 4Amgen Inc, Thousand Oaks, CA; 5Winthrop Univ Hosp, Mineola, NY. The calcimimetic cinacalcet effectively lowers parathyroid hormone (PTH) and improves mineral metabolism in hemodialysis (HD) patients with secondary HPT, independent of vitamin D (vit D) use. The ACHIEVE study compared the treatment regimens of cinacalcet plus low-dose vit D (paricalcitol/doxercalciferol) to escalating doses of vit D without cinacalcet and the relative efficacy in achieving simultaneous control of iPTH and Ca x P (as described by KDOQITM goals) in HD subjects with secondary HPT. Mean iPTH increased while Ca x P decreased after a 3 wk vit D washout period. (Table 1)

Mean (SD) Pre-Washout (n =173) Post-Washout (n =173) iPTH, pg/mL 440.6 (157.3) 651.5 (234.8) Ca, mg/dL 9.9 (0.7) 9.6 (0.6) P, mg/dL 5.7 (1.6) 5.3 (1.7) Ca x P, mg2/dL2 56.6 (15.9) 50.8 (15.7)

After washout, subjects were randomly assigned to cinacalcet plus low dose vit D or vit D alone. Key mean baseline variables were similar between treatment groups. (Table 2)

cinacalcet +vit D (n=87) vit D only (n=86) iPTH, pg/mL 643.1 (231.7) 660.0 (239.0) Ca, mg/dL 9.6 (0.6) 9.7 (0.5) P, mg/dL 5.3 (1.7) 5.3 (1.7) Ca x P, mg2/dL2 50.2 (15.1) 51.4 (16.4) P-binder use 98 % 98 % Pre-washout vit D 99 % 99 %

Vit D washout increased PTH, and lowered Ca x P and serum P levels. This suggests that a treatment approach suppressing PTH while reducing the need for large doses of vit D may be optimal for the management of secondary HPT.

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DEVELOPMENT OF AN ACUTE TUBULAR NECROSIS CAST SCORING INDEX: A PILOT STUDY Lakhmir Chawla¹ ², Aaron Dommu³, Lana Burr², and Samir Patel² ¹Department of Critical Care Medicine and Anesthesiology, George Washington University Medical Center, Washington D.C., U.S.A. ²Division of Renal Diseases and Hypertension, Department of Medicine, George Washington University Medical Center, Washington D.C., U.S.A. ³Department of Medicine, George Washington University Medical Center, Washington D.C., U.S.A. Urine microscopy is a valuable tool when making a diagnosis of acute tubular necrosis (ATN), however, the manner in which nephrologists prepare, examine, and report urinary sediment findings is quite variable. The presence of granular and renal tubular epithelial (RTE) casts on urinalysis is known to be helpful in making a diagnosis of ATN, but a simple system to score the amount of casts is lacking. We developed an ATN Cast Scoring Index (CSI) as a framework to grade the degree of granular and RTE casts found on urinalysis. Further, we sought to assess the precision of this scoring system. Urine samples from 30 patients with the clinical syndrome of ATN were collected at the George Washington University Hospital in Washington, DC. Sample preparation was uniform, and based on a combination of recommendations from various nationwide acute kidney injury (AKI) experts. A panel of 3 blinded nephrologists was instructed to view and grade each slide using the ATN CSI. Grade 0 refers to no evidence of granular or RTE casts, while grade 1 signifies rare granular or RTE casts (at least one seen on the entire slide, but less than 10% of low power fields), grade 2 refers to a moderate amount of casts (many granular or RTE casts, but not seen on every low power field), and grade 3 signifies sheets of muddy brown casts (granular or RTE casts seen in 100% of low power fields). The scores of the three reviewers completely matched for 14 of 30 slides (46.7%), and all three reviewers agreed within one grade in 29 of 30 instances (96.7%). Intercorrelation coefficient was 0.787. We conclude that the ATN CSI is a simple, novel, reliable scoring system to grade the degree of granular and RTE casts present on urine microscopy. A standardized ATN CSI has the potential to incorporate urinary cast analysis into the advancing field of AKI diagnostics.

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NKF 2007 Spring Clinical Meetings AbstractsA34