saturday the 6th of may 11:00 -...
TRANSCRIPT
Saturday the 6th of May 11:00 - 12:15
Experimental physiology and pathophysiology
Chairs: Niels Henrik Buus and Henrik Birn
Fibroblast growth factor 23 (FGF23) regulates PTH levels in normocalcemia through FGF
receptor signaling in vivo
Maria Mace1,2, Eva Gravesen2, Anders Nordholm1, Jacob Hofman-Bang2, Klaus Olgaard2 & Ewa
Lewin1
Departments of Nephrology, Herlev Hospital1 & Rigshospitalet2, University of Copenhagen,
Denmark
Reversibility of Uremic Vascular Calcification
Eva Gravesen1, Maria L. Mace1,2, Anders Nordholm1,2, Jacob Hofman-Bang1, Klaus Olgaard1 &
Ewa Lewin 1,2
University of Copenhagen, 1Nephrological Department P, Rigshospitalet and 2Nephrological
Department B, Herlev Hospital, Copenhagen, Denmark
Unilateral renal fibrosis and expression of pro-fibrotic factors in the contralateral kidney
Anders Nordholm1, Maria Mace1,2, Eva Gravesen2, Jacob Hofman-Bang2, Klaus Olgaard2 & Ewa
Lewin1
Departments of Nephrology, Herlev Hospital1 & Rigshospitalet2, University of Copenhagen;
Denmark
The effect of CPT1A inhibition in renal ischemia/reperfusion organ injury – studies in a rat
model of bilateral renal artery occlusion leading to acute kidney injury
Mads Vammen Damgaard1,2, Rikke Nørregaard1, Søren Nielsen3 and Jørgen Frøkiær2 1Department of Clinical Medicine, Health, Aarhus University, Aarhus Denmark. 2Department of
Nuclear Medicine, Aarhus University Hospital, Aarhus Denmark. 3Department of Health Science
and Technology, Aalborg University, Aalborg, Denmark.
Unilateral nephrectomy enhances perfusion in the renal medulla following ischemia-
reperfusion injury
Lassen, C.K. 1,2, Nielsen, P.M.2, 4, Qi, H.2, 4, Damgaard, M. 2, Laustsen, C. 4, Pedersen, M. 5, Birn,
H. 1, 3, Nørregaard, R. 2, Jespersen, B. 1, 2
1: Department of Renal Medicine, Aarhus University Hospital, Skejby; 2: Department of Clinical
Medicine, Aarhus University; 3: Department of Biomedicine, Aarhus University; 4: MR Research
Centre, Aarhus University; 5: Comparative Medicines Lab, Aarhus University
Preservation of glycocalyx in experimental kidney transplantation
Kunisch, J1,2; Moeslund, N1,3; Nielsen, L1; Pedersen, M3; Nørregaard, R1; Petersen, JAK4;
Jespersen4, B1,2; Birn, H1,2
1 Clinical Institute, Aarhus University Hospital – Skejby, 2 Department of Renal Medicine, Aarhus
University Hospital – Skejby, 3 Comparative Medicine Lab, Aarhus University Hospital – Skejby, 4
Department of Anaesthesiology, Aarhus University Hospital – Nørrebrogade
Effects of chloride on GFR and renal plasma flow in healthy volunteers- a randomized,
controlled, crossover study.
Anna E. Oczachowska-Kulik, Jens Jørgen Jensen, June Anita Ejlersen, Erling Bjerregaard Pe
dersen, Jesper Nørgaard Bech
University Clinic in Nephrology and Hypertension, Holstebro Hospital and Aarhus University,
Denmark
Transplantation
Chairs: Henrik Birn and Helle Thiesson
Felodipine Reduces Decline in Glomerular Filtration Rate in Lung Transplanted Patients
Treated with Cyclosporine: a Randomized Placebo Controlled Trial
Hornum M1, Iversen M2, Oturai P3, Andersen MJ2, Zemtsovski M4, Bredahl P4 Bjarnason N. H2,
Christiansen K.B6, Carlsen J2, Møller CH5, Feldt-Rasmussen B1, Perch M2 1Department of Nephrology, 2Department of Cardiology, Section for Lung Transplantation, 3Department of Clinical Physiology and Nuclear Medicine, 4Department of Cardiothoracic
Anaesthesiology, 5Department of Cardiothoracic Surgery, Rigshospitalet, University of
Copenhagen, Copenhagen, Denmark, 6Department of Public Health, Section of Biostatistics,
University of Copenhagen, Copenhagen, Denmark.
Simultaneous pancreas and kidney transplantation in Denmark 2015-17
Paul Krohn1 and Mads Hornum2, Henrik Birn8, Vibeke Rømming Sørensen2, Christian R.
Mortensen5, Eske K. Aasvang5, Per Bagi3, Helle Bruunsgaard6, Pernille Koefoed-Nielsen9,
Elisabeth R. Mathiesen4 and Thomas Almdal4, Jan Carstens8, Pär I Johansson9, Bo Nyhuus10,
Søren Schwartz Sørensen2 and Bo Feldt-Rasmussen2, Jens Hillingsø1 and Allan Rasmussen1
Department of Surgery and Transplantation 1, Department of Nephrology2, Department of
Endocrinology3, Department of Urology4, Department of Anaestisiology5, Department of
Immunology6, Capital Regional Blood Bank9, Department of Radiology10, Rigshospitalet,
University of Copenhagen, Copenhagen, Department of Nephrology8, Odense University Hospital6,
Odense and Department of Nephrology8, Department of Clinical Immunology9, Aarhus University
Hospital
Saturday the 6th of May 13:00 - 14:15
Dialysis
Chair: Lisbet Brandi and Rikke Borg
Unplanned start on PD does not affect patient or PD catheter survival: a multicenter,
prospective Danish observational cohort study.
Johan V Povlsen1, Kjeld E Otte2, Pia V Larsen3, Jesper N Bech4, Gabor Graenh5, Jørgen E
Jensen6, Per Ivarsen1.
Dept. Renal Medicine C1, Aarhus University Hospital, Dept. Internal Medicine, Fredericia Hospital2,
Holstebro Hospital4, Soenderborg Hospital5, Dept. Public Health, University of Southern Denmark3,
and Dept. Nephrology Y6, Odense University Hospital, Denmark
Bacteriology of the buttonhole cannulation tract in haemodialysis patients - A prospective
study with follow-up
Line D. Christensen, MD,1 Mai-Britt Skadborg, MD,1 Agnete H. Mortensen, RN,1 Nanna Lagoni,
RN,2 Jens K. Møller, MD, DMSc,3 Lars Lemming, MD, PhD,4 Irene Høgsberg, MD,2 Steffen E.
Petersen, MD,5 and Niels H. Buus MD, DMSc6,7
1Department of Renal Medicine, Aarhus University Hospital, Aarhus, Denmark; 2Department of
Medicine, Lillebaelt Hospital, Fredericia, Denmark; 3Department of Clinical Microbiology, Lillebaelt
Hospital, Vejle, Denmark; 4Department of Clinical Microbiology, Aarhus University Hospital,
Aarhus, Denmark; 5Department of Urology, Aarhus University Hospital, Aarhus, Denmark; 6Institute
of Clinical Medicine, Aarhus University Hospital, Aarhus Denmark; 7Department of Nephrology,
Aalborg University Hospital, Aalborg, Denmark.
Incretin effect is reduced in end-stage renal disease
Morten B. Jørgensen1, Thomas Idorn1, Casper Rydahl2, Henrik P. Hansen2, Iain Bressendorff3,
Lisbet Brandi3, Gerrit van Hall4,5, Jens J. Holst5,6, Filip K. Knop6,7, Mads Hornum1, Bo Feldt-
Rasmussen1
1Dept of Nephrology, Rigshospitalet, Denmark; 2Dept of Nephrology, Herlev Hospital, Denmark; 3Dept of Cardiology, Nephrology and Endocrinology, North Zealand Hospital, Denmark; 4CMCF,
Clinical Biochemistry, Rigshospitalet, Denmark; 5Department of Biomedical Sciences, University of
Copenhagen, Copenhagen, Denmark; 6The NNF Center for Basic Metabolic Research, University
of Copenhagen, Denmark; 7Center for Diabetes Research, Gentofte Hospital, Denmark.
Gastrointestinal motility in diabetic, pre-diabetic and non-diabetic patients with end-stage
renal disease
Bo Broberg1, Jan Lysgård Madsen2, Stefan Fuglsang2, Jens Juul Holst3, Casper Rydahl1, Thomas
Idorn4, Bo Feldt-Rasmussen4 and Mads Hornum4
1. Department of Nephrology, Copenhagen University Hospital Herlev, Copenhagen, Denmark; 2.
Department of Clinical Physiology and Nuclear Medicine, Centre for Functional and Diagnostic
Imaging and Research, Copenhagen University Hospital Hvidovre, Copenhagen, Denmark; 3.
Department of Biomedical Sciences & NNF Center for Basic Metabolic Research, The Panum
Institute, University of Copenhagen, Copenhagen, Denmark; 4. Department of Nephrology,
Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark
Chronic Kidney Disease
Chair: Jens Iversen and Ditte Hansen
Proteinuria is predicting long term Renal and Patient Outcome in ANCA associated
Vasculitis.
Wladimir Szpirt, Elizabeth Krarup Martin Egfjord
Rigshospitalet, Dept of Nephrology, Herlev Hospitalet, Dept of Nephrology, Copenhagen,
Denmark.
Interventional study targeting oral infections in Danish patients with chronic kidney disease
Juhl C1, Brandt T2, Frøjk M3, El-Ali N3,4, Kragelund C1, Eidemak I3 and Jensen SB1,5. 1Oral Medicine, Department of Odontology, University of Copenhagen 2School of Oral Health Care,
University of Copenhagen 3Nephrology, Department of Nephrology, Rigshospitalet 4Department of
Medical, Holbæk Hospital 5Department of Dentistry and Oral Health, Aarhus University
Sclerostin is associated with vascular calcifications, but not cardiovascular events in late
stage CKD
Jørgensen, Hanne Skou (1), Winther, Simon(2), Bøttcher, Morten (3), Hauge, Ellen-Margrethe (4),
Rejnmark, Lars (5), Svensson, My (6), Ivarsen, Per (1)
1 Department of Renal Medicine, Aarhus University Hospital, 2 Department of Cardiology, Aarhus
University Hospital, 3 Department of Internal Medicine, Hospital Unit West, Herning, 4 Department
of Rheumatology, Aarhus University Hospital, 5 Department of Endocrinology and Internal
Medicine, Aarhus University Hospital, 6 Department of Nephrology, Division of Medicine, Akershus
University Hospital, Oslo, Norway
Preeclampsia and the risk of later renal disease
Kristensen JH, Basit S, Wohlfahrt J, Damholt MB, Boyd HA
Department of Epidemiology Research, Statens Seruminstitut; Nefrologisk Klinik, Rigshospitalet
Blood pressure control in The Copenhagen Chronic Kidney Disease Cohort
Ellen Linnea Freese, Morten Buus Jørgensen, Ida Maria Hjelm Sørensen, Susanne Bro, Bo Feldt-
Rasmussen, Anne-Lise Kamper for The Copenhagen CKD Cohort Study Group.
Department of Nephrology, Rigshospitalet, Copenhagen
ABSTRACTS
Experimental physiology and pathophysiology
Fibroblast growth factor 23 (FGF23) regulates PTH levels in normocalcemia through FGF
receptor signaling in vivo
Maria Mace1,2, Eva Gravesen2, Anders Nordholm1, Jacob Hofman-Bang2, Klaus Olgaard2 & Ewa
Lewin1
Departments of Nephrology, Herlev Hospital1 & Rigshospitalet2, University of Copenhagen,
Denmark
Background: The primary regulation of PTH secretion is mediated by calcium. FGF23 is an
endocrine fibroblast growth factor (FGF), secreted from osteocytes, which regulates renal
phosphate reabsorption and calcitriol synthesis and degradation. FGF23 requires klotho as a co-
receptor for binding to the FGF receptors (FGFR). Parathyroid cells express both Klotho and
FGFRs. The physiological function of FGF23 in the parathyroid gland is not fully clarified.
Methods: Wistar rats were randomized to FGFR inhibition by PD173074 (20-40mg) or vehicle.
Acute hypocalcemia was induced by a continuous intravenuous EGTA infusion (40mM, 3ml/h) in
normal rats and rats after prior FGFR inhibition. Increasing doses (0.1, 1, and 10 µg) of
recombinant FGF23 were given to normal rats and rats after prior FGFR inhibition. Plasma Ca++,
phosphate, FGF23 and PTH were measured.
Results: Acute inhibition of FGFR resulted in a decrease in p-FGF23 (364±22 to 154±18 pg/ml,
p<0.05) and a concomitant increase in p-PTH levels (134±34 to 685±285 pg/ml, p<0.01). The PTH
secretory response was challenged by acute severe hypocalcemia (p-Ca++ decreased from
1.37±0.01 to 0.98±0.03 mmol/l, p<0.01). Again at normocalcemia PTH increased in FGFR inhibited
rats (85±13 to 182±10 pg/ml), while the maximal PTH secretion at low p-Ca++ was not different in
FGFR inhibited rats compared to vehicle treated rats (347±61 vs. 316±22). Exogenous rFGF23 0.1
µg inhibited rapidly, at 20 min, PTH levels in normal rats (137±71 to 10±4 pg/ml, p<0.05). In FGFR
inhibited rats 0.1 µg rFGF23 did not suppress PTH levels (270±50 vs. 347±62). Higher doses of
rFGF23 resulted in very high levels of p-FGF23 (12,000 & 120,000 pg/ml), which however had no
effect on PTH levels when the FGFR was inhibited.
Conclusion: FGF23 regulates PTH tonus in vivo via the FGF receptor. The inhibitory effect of
FGF23 on PTH is present at normal range of plasma ionized calcium, but not at low calcium levels,
when increased PTH secretion is needed.
Reversibility of Uremic Vascular Calcification
Eva Gravesen1, Maria L. Mace1,2, Anders Nordholm1,2, Jacob Hofman-Bang1, Klaus Olgaard1 &
Ewa Lewin 1,2
University of Copenhagen, 1Nephrological Department P, Rigshospitalet and 2Nephrological
Department B, Herlev Hospital, Copenhagen, Denmark
Background: Hyperphosphatemia and vascular calcification (VC) are frequent complications of
chronic renal failure (CRF) and associated with increased cardiovascular morbidity and mortality.
VC is developed early in CRF and it is therefore essential to know whether VC can be reversed.
High plasma phosphate (P) might induce VC via the P-transporter Pit1 and we have previously
demonstrated induction of Wnt-signalling and doubling of Pit1 expression in VC of uremic rats.
BMP7 has been shown to protect against development of VC in uremia. Thus the potential
reversibility of established VC was examined in two experimental models; 1. by performing an
isogenic transplantation (ATx) of the calcified aorta from uremic rats to non-uremic littermates and
2. by studying whether BMP7 treatment would reduce the degree of VC in uremia.
Methods: CRF and VC was induced in adult DA-rats by 5/6 nephrectomy, high P diet and
alfacalcidol treatment. After 14 weeks, severe VC was present. In model 1, the abdominal aorta
was transplanted orthotopically from CRF animals to healthy littermates. Control group had normal
to normal ATx. The animals were sacrificed 4 weeks after ATx. In model 2, CRF rats were
allocated either to 250µg/kg of BMP7 ip once weekly or vehicle for 8 weeks.
Results: Calcium (Ca) content in aorta of normal rats was below detection limit. Ca in the aorta
from uremic rats was significantly elevated to 17.0±0.2µg/mg in the proximal abdominal aorta and
similarly increased in the transplanted uremic aorta 15.9±0.6, indicating that removal of the uremic
milieu did not reverse the VC. In the BMP7 study Ca content was also significantly increased in the
uremic vehicle treated rats both in the distal abdominal aorta 1.9±0.2 and in proximal thoracic aorta
71±11, but no effect of BMP7 on Ca content was observed in the distal abdominal aorta 2.2±0.2 or
in the proximal thoracic aorta 54±7, despite a significant reduction in plasma-P levels 2.06±0.14 to
1.56±0.07mmol/L.
Conclusion: Normalization of the uremic environment in the ATX animals did not reverse
established calcification in uremic aorta. Treatment with BMP7 had no effect on aorta Ca content.
Neither did lowering of plasma-P to normal levels. Our results indicate that uremic VC should be
prophylactically treated, as reversibility of established VC seems very difficult to obtain.
Unilateral renal fibrosis and expression of pro-fibrotic factors in the contralateral kidney
Anders Nordholm1, Maria Mace1,2, Eva Gravesen2, Jacob Hofman-Bang2, Klaus Olgaard2 & Ewa
Lewin1
Departments of Nephrology, Herlev Hospital1 & Rigshospitalet2, University of Copenhagen;
Denmark
Background: Emerging concepts propose that circulating pathogenetic factors released from the
injured kidney, directly cause vasculopathy, bone disease, and progressive tubulointerstitial
damage. In the present study the time course of changes in pro- and anti-fibrotic genes in the
contralateral kidney (CK) to experimental unilateral ureter obstruction (UUO) was followed and
compared with those of the remnant kidney from the unilaterally nephrectomized rats (UNX).
Methods: UUO rats (n=30) were studied at 0, 4, 6 hr (H), 1 and 10 days (D) after UUO in parallel
with UNX control rats (n=30) as well as normal rats (n=6). Kidney expression of FGF23, Klotho,
BMP7, TGF-β and Periostin genes were examined.
Results: UUO caused induction of the FGF23 gene already at 4 H: 25±3 with a further increase at
6 H: 324±89 (p<0.01). A progressive up-regulation of pro-fibrotic TGF-β (Baseline: 0.51±0.07, D1:
0.69±0.11, D10: 1.51±0.17, p<0.01) and induction of Periostin (0.09±0.10 to D1: 0.67±0.40,
p<0.05) were observed in obstructed kidney (OK), while the kidney protecting factor, Klotho
declined at day 1 (B: 1.91±0.30; D1: 0.91±0.18 (p<0.01), D10: 0.21±0.02 (p<0.01). Similarly, in the
OK, a down-regulation of anti-fibrotic BMP7 (B: 0.87±0.11, D1: 0.57±0.07, D10: 0.63±0.08, p<0.01)
was observed. However, expressions of FGF 23, TGF-β, Periostin, Klotho and BMP7 were similar
in CK, UNX and normal kidneys at all time points and no induction of FGF23 or Periostin was
observed in the CK. Reduction of kidney mass by 50 % might affect the skeleton, as p- FGF23
increased in both UUO and UNX rats, however to similar level (Sham: 336±17, UUO : 660±62,
UNX: 751±96, D1).
Conclusion: Induction of unilateral renal fibrosis develops very rapidly in the UUO model, but does
not induce changes in expressions of pro-fibrotic factors, Periostin, TGF-β, FGF 23, or anti-fibrotic
BMP7 and Klotho in the CK, indicating that the CK is protected against circulating fibrotic factors.
The effect of CPT1A inhibition in renal ischemia/reperfusion organ injury – studies in a rat
model of bilateral renal artery occlusion leading to acute kidney injury
Mads Vammen Damgaard1,2, Rikke Nørregaard1, Søren Nielsen3 and Jørgen Frøkiær2 1Department of Clinical Medicine, Health, Aarhus University, Aarhus Denmark. 2Department of
Nuclear Medicine, Aarhus University Hospital, Aarhus Denmark. 3Department of Health Science
and Technology, Aalborg University, Aalborg, Denmark.
Background: Acute kidney injury (AKI) is a major clinical challenge with a high mortality rate and
a lack of effective therapeutic treatment of the most common course, i.e. ischemia/reperfusion-
injury (I/R-I).
Under hypoxic conditions during IR-I the fatty acid oxidation is not complete and results in the
production of fatty acid intermediates, which in turn can be converted into different prostaglandins
which can activate and attract the innate and cellular immune system.
Cellular homeostasis is disrupted due to energy depletion, leading to cell death.
This resulting in a marked inflammatory cascade, which causes further tissue damage[1],[2]. Thus,
inhibition of inflammatory responses after I/R injury is crucial to protect the kidneys from secondary
damage and thus facilitate recovery of the kidney tissue.
Fatty acid β-oxidation is the major metabolic pathway for generating ATP in the kidneys[3], which
is governed by carnitine palmitoyl transferase 1 (CPT1)[4].
Etomoxir is a synthetic compound that irreversible inhibit CPT1, thus resulting in less lipid
metabolism which have a higher O2 consumption ratio then ATP generation from glycolysis.
We hypothesized that CPT1A blockade could decrease the inflammatory response, reduce energy
consumption by lipid metabolism and alleviate renal I/R-I.
Methods Male adult Wistar rats were randomized into 4 groups with 7 animals per group. Each
group were subjected to either sham operation or renal I/R-I by bilateral renal artery clamping for
40 min. This was followed by administration of vehicle, low or high dose Etomoxir (1 or 5 mg/kg
BW/day). Blood and urine samples were collected every 24 hr. Termination at day 4.
Results Etomoxir treatment significantly lowered serum creatinine, BUN, osmolality and urine
protein levels elevated by I/R-I and reduced the expression of renal injury markers, KIM-1 and
NGAL (Fig. 1).
Etomoxir normalized the I/R-I induced increase in fractional excretion of sodium.
In both the renal cortex and inner medulla, AQP2 showed a tendency towards downregulation
following Etomoxir treatment, whereas AQP1-3 showed a tendency towards increased expression.
Conclusion: Etomoxir, known to inhibit CPT1 activity, improved renal dysfunction and attenuated
tissue injury after renal I/R injury. Decreasing the lipid metabolism for energy production and
attenuating the inflammatory response may provide a novel modality for treating renal I/R-I.
Grants: The study was supported by Danish Council for Independent Research (DFF)
Unilateral nephrectomy enhances perfusion in the renal medulla following ischemia-
reperfusion injury
Lassen, C.K. 1,2, Nielsen, P.M.2, 4, Qi, H.2, 4, Damgaard, M. 2, Laustsen, C. 4, Pedersen, M. 5, Birn,
H. 1, 3, Nørregaard, R. 2, Jespersen, B. 1, 2
1: Department of Renal Medicine, Aarhus University Hospital, Skejby; 2: Department of Clinical
Medicine, Aarhus University; 3: Department of Biomedicine, Aarhus University; 4: MR Research
Centre, Aarhus University; 5: Comparative Medicines Lab, Aarhus University
Background: Ischemia-reperfusion injury (IRI) is the leading cause of acute kidney injury. In
experimental studies, unilateral nephrectomy (UNx) protects against IRI in the remaining kidney.
The mechanisms underlying this protection remain to be elucidated. To uncover possible regional
changes in renal perfusion, oxygenation and sodium reabsorption, functional MRI techniques, i.a.
slice-selective T1-weighted-, blood oxygen level-dependent- and 23Na-MRI, were carried out.
Microarray analysis was conducted to identify renoprotective molecular pathways.
Methods: Wistar rats were randomized to either UNx or sham UNx immediately prior to 37
minutes of unilateral renal artery clamping or sham operation (n = 8 in each of the 4 groups). MRI
was performed prior to termination of the rats 24 hours after reperfusion. Blood and renal tissue
were harvested. RNA was isolated for microarray analysis.
Results: Perfusion was significanly improved in the renal medulla of both normal (p = 0.009) and
postischemic kidneys (p = 0.02) following UNx. Cortical hypoxia (p = 0.004) and lowering of the
sodium signal intensity in the renal medulla (p < 0.0001), suggesting lower sodium reabsoprtion,
were evident in both ischemic groups. This was associated with down-regulation of genes
encoding tubular sodium transporters (NKCC2 and eNaC). Strikingly, unilateral nephrectomy
decreased the expression of several known pro-fibrotic genes (α-SMA, collagen-Ia, and TGF-β)
following IRI. This may be related to the observed down-regulation of pro-inflammatory response
genes, including genes responsible for macrophage infiltration and activation (VCAM, MCP-1, and
Fig. 1. qPCR semi quantitative expression of A: Kidney injury molecule-1 (KIM-1) and, B: Neutrophil gelatinase-associated lipocalin
(NGAL).
Etomoxir treatment attenuated active renal tubular pathology shown as a significant decrease in, A: KIM-1 and, B: NGAL.
Termination 4 days after IR-I. ETO1 = 1 mg/kg BW/day. ETO5=5mg/kg BW/day. ARF, ETO1 + ETO5 Normalized to housekeeping
gen 18S. Sham normalized to 1. Values are means SE. *P<0,05. *** P<0,001.
MPEG-1). In addition, down-regulation of PDGFR-α and -β and up-regulation of BMP-3, the latter
known for TGF-β-antagonizing effects in bone remodelling, may play an important role.
Conclusion: Unilateral nephrectomy may exert renoprotective effects against IRI through
increased perfusion in the renal medulla and alleviation of the acute inflammatory response
Preservation of glycocalyx in experimental kidney transplantation
Kunisch, J1,2; Moeslund, N1,3; Nielsen, L1; Pedersen, M3; Nørregaard, R1; Petersen, JAK4;
Jespersen4, B1,2; Birn, H1,2
1 Clinical Institute, Aarhus University Hospital – Skejby, 2 Department of Renal Medicine, Aarhus
University Hospital – Skejby, 3 Comparative Medicine Lab, Aarhus University Hospital – Skejby, 4
Department of Anaesthesiology, Aarhus University Hospital – Nørrebrogade
Background: The endothelial glycocalyx is a dynamic network of glycoproteins and proteoglycans
that plays a central role in vascular permeability, adhesion of leukocyte and coagulation. The
glycocalyx can be disrupted by various conditions such as ischemia-reperfusion injury and fluid
overload. In particular, reperfusion of the kidney graft has been associated with endothelial
damage within the microcirculation. The present study evaluates the effect of variations in
perioperative fluid load on early kidney function and the preservation of the glycocalyx, during
kidney transplantation in pigs using kidneys from brain dead donors.
Methods: Recipient pigs were randomized to either high volume fluid therapy (HVF) or
individualized goal directed fluid therapy (IGDT) in addition to either continuous low dose nor-
epinephrine (NE)-infusion or no NE.
A model simulating the normal clinical conditions of a brain death donation was used.
Tissue samples including cortex and medulla were taken from the recipient kidney 10 hours post
reperfusion.
Kidney graft function was evaluated using measured GFR (mGFR). The preservation of glycocalyx
in kidney tissue was evaluated 10 hours after reperfusion by semiquantitation of the
immunofluorescent staining for alfa-linked N-acetylgalactosamine.
Results: Results showed no significant differences in mGFR between the four groups. Mean
fluorescence labelling for glycalyx in the glomeruli 10 hours after reperfusion revealed a
significantly greater mean level of fluorescence in the animals receiving IGDT without NE
compared to HVF with NE. A great between animal variation was also observed.
Conclusion: In conclusion, the study showed no difference in early kidney graft GFR as a result of
the different principles of fluid administration and pressor therapy. A structural difference on the
glycocalyx was observed between the IGDT without NE and HVF with NE. This may suggest that a
reduced fluid volume may result in better preservation of the glycocalyx.
Effects of chloride on GFR and renal plasma flow in healthy volunteers- a randomized,
controlled, crossover study.
Anna E. Oczachowska-Kulik, Jens Jørgen Jensen, June Anita Ejlersen, Erling Bjerregaard
Pedersen, Jesper Nørgaard Bech
University Clinic in Nephrology and Hypertension, Holstebro Hospital and Aarhus University,
Denmark
Backgrund: Chloride loading has been suggested as a risk factor for acute kidney injury (AKI).
Existing data suggest that chloride overload resulting from 0.9 % saline infusion may affect renal
hemodynamic parameters.
Objective: We compared the effects of intravenous infusion of 0.9 % saline (Cl 154 mmol/l) and
Plasma-Lyte (Cl 98 mmol/L) on GFR and renal plasma flow (RPF) in healthy humans using
99mTc-DTPA renography.
Methods: 15 healthy adult male subjects received a single 2-L intravenous infusion over 1 hour of
0.9% saline or Plasma-Lyte in a randomized manner.
Crossover studies were performed within 21 days. Renography was performed 75 min after
commencement of infusion. GFR and RPF was estimated using 99m-tc-DTPA renography using
the Patlak-Rutland method. Renography results were interpreted by 2 observers and average GFR
and RPF values from 2 observers were calculated.
Results: There was significant reduction in mean GFR after 0.9% saline comparing to mean GFR
after Plasma-lyte (113±3 vs. 119±3 ml/min, P=0,04). RPF also decreased, however not
significantly (977±70 vs. 1066±51 ml/min, P=0.19).
Conclusions: We have demonstrated that chloride loading with 0.9% saline infusion can lead to
GFR reduction and possibly reduction in RPF in humans. We suggest that changes in renal
hemodynamics may contribute to increased AKI risk associated with saline treatment.
Transplantation
Felodipine Reduces Decline in Glomerular Filtration Rate in Lung Transplanted Patients
Treated with Cyclosporine: a Randomized Placebo Controlled Trial
Hornum M1, Iversen M2, Oturai P3, Andersen MJ2, Zemtsovski M4, Bredahl P4 Bjarnason N. H2,
Christiansen K.B6, Carlsen J2, Møller CH5, Feldt-Rasmussen B1, Perch M2 1Department of Nephrology, 2Department of Cardiology, Section for Lung Transplantation, 3Department of Clinical Physiology and Nuclear Medicine, 4Department of Cardiothoracic
Anaesthesiology, 5Department of Cardiothoracic Surgery, Rigshospitalet, University of
Copenhagen, Copenhagen, Denmark, 6Department of Public Health, Section of Biostatistics,
University of Copenhagen, Copenhagen, Denmark.
Background. Calcium channel blockers may ameliorate the decline in renal function caused by
calcineurin inhibitors in lung transplant (LTX) recipients. We previously demonstrated a 47 ml/min
decline in glomerular filtration rate (GFR) 12 weeks after LTX and a 22% incidence of end-stage
renal disease after 10 years in LTX patients (pts). We hypothesized that treatment with the calcium
channel blocker, felodipine, given preoperatively and for 12 weeks would reduce this decline in
GFR.
Methods. In this double-blinded study 41 LTX recipients with normal kidney function were
randomized to receive placebo (20 pts) or felodipine (21 pts) started preoperatively and titrated to
10 mg or maximum tolerable dose. Only adult pts on the waiting list for pulmonary transplantation
were included. Primary endpoint was the change in renal function as measured by GFR using Cr-
51 labelled EDTA from LTX to 12 weeks hereafter.
Results. Treatment with felodipine resulted in a 35% lesser decrease in GFR compared to
placebo. In the treatment group we observed a mean decline in GFR of 31 ml/min/1.73m2 (-40 to -
22, 95% CI)) - from 96 ml/min/1.73m2 (range 88-108) to 64 ml/min/1.73m2 (range 51-83). In the
placebo group the mean decline was 48 ml/min/1.73m2 (95% CI: -57 to -39) - from 99
ml/min/1.73m2 (range 89-118) to 54 ml/min/1.73m2 (range 44 to 62), Fig 1. Thus, the difference in
the mean decline rate in GFR between groups at 12 weeks was 17 ml/min/1.73m2 (95% CI: 4-29
ml/min/1.73m2; P=0.01)). Hypotension occurred more frequently among felodipine-treated pt´s
compared with placebo (P<0.01). Blood pressure control assessed by systolic blood pressure at 3
weeks improved in pts treated with felodipine during the study period (P=0.048). Body weight did
not differ significantly in the two groups during the study.
Conclusions. Compared with placebo, felodipine ameliorated the initial decline in GFR caused by
calcineurin inhibitors after LTX.
Figure 1
0 1 2 3 4 5 6 7 8 9 1 0 1 1 1 2
0
2 0
4 0
6 0
8 0
1 0 0
1 2 0
G lo m e ru la r f i lt ra t io n ra te
T im e in w e e k s
GF
R (m
l/m
in
/1
.7
3m
2)
F e lo d ip in e
P la c e b o
Simultaneous pancreas and kidney transplantation in Denmark 2015-17
Paul Krohn1 and Mads Hornum2, Henrik Birn8, Vibeke Rømming Sørensen2, Christian R.
Mortensen5, Eske K. Aasvang5, Per Bagi3, Helle Bruunsgaard6, Pernille Koefoed-Nielsen9,
Elisabeth R. Mathiesen4 and Thomas Almdal4, Jan Carstens8, Pär I Johansson9, Bo Nyhuus10,
Søren Schwartz Sørensen2 and Bo Feldt-Rasmussen2, Jens Hillingsø1 and Allan Rasmussen1
Department of Surgery and Transplantation 1, Department of Nephrology2, Department of
Endocrinology3, Department of Urology4, Department of Anaestisiology5, Department of
Immunology6, Capital Regional Blood Bank9, Department of Radiology10, Rigshospitalet,
University of Copenhagen, Copenhagen, Department of Nephrology8, Odense University Hospital6,
Odense and Department of Nephrology8, Department of Clinical Immunology9, Aarhus University
Hospital
Background. In 2015 the Danish program for simultaneous pancreas and kidney transplantation
for type 1 diabetes patients was re-established. This followed a break in activities for 20 years. We
present the results for the first 10 recipients
Methods. All patients were allocated to the national waiting list after a multidisciplinary team
conference .Three to four weeks after transplantation they were referred to their local center. The
portal vein of the pancreas graft was sutured to the vena cava as a systemic drainage. A Y-
extension arterial graft was anastomosed to the right common iliac artery. Enteral drainage was
made by anastomosing donor duodenal loop to the recipient’s jejunum. The kidney graft was
transplanted according to our standard procedure. Insulin and glucose was infused postoperatively
until graft function as measured by C-peptide and blood glucose and titrated down until
gastrointestinal function. Ultrasound were performed twice daily for 7 days, to control organ-
perfusion and eventual fluid collections. Daily ward round by nephrologist and transplant surgeon.
Results. Mean age was 46±7 years (range 35-59 years). Nine patients were on haemodialysis and
1 was a pre-dialysis patient. Pancreas and renal function during the first 14 days are shown in
Table 1. All recipients were insulin-free at day 14. Four recipients were re-operated. The mean stay
was 2 days (range 1-6) in the intensive care unit, 13 days (range 9-20) in the surgical ward, and 6
days (range 0-15) in the nephrology ward. Two recipients had an episode of acute cellular
rejection. Time for last follow up for RH ptt was in median 323 days (range 77-553) and for AUH ptt
median 90 days (range 30-181). At this time all 10 recipients were alive and without need of insulin
and dialysis
Conclusions. The Danish simultaneous pancreas and kidney transplant program is now
successfully re-established. The first 10 recipients all have a well-functioning kidney and pancreas
graft.
Table 1
Pt id P-creatinine
(umol/L)
Day 0
P-creatinine
(umol/L)
Day 14
P-Glucose
(mmol/L)
Day 0
P-Glucose
(mmol/L)
Day 14
C-peptide
(IU/L)
Day 0
C-peptide
(IU/L)
Day 14
1 874 138 14,6 5,6 3 1590
2 474 118 9,2 5 5 1480
3 578 150 20,4 5,3 135 2560
4 344 200 12,4 4,3 41 2610
5 532 131 10,5 4,9 3 1640
6 441 111 8 5,2 5 2210
7 867 166 22,9 4,6 3 1730
8 988 173 22,2 5 143 1350
9 676 197 5,9 5,2 3 4280
10 512 116 19,7 4,5 9 1900
Dialysis
Unplanned start on PD does not affect patient or PD catheter survival: a multicenter,
prospective Danish observational cohort study.
Johan V Povlsen1, Kjeld E Otte2, Pia V Larsen3, Jesper N Bech4, Gabor Graenh5, Jørgen E
Jensen6, Per Ivarsen1.
Dept. Renal Medicine C1, Aarhus University Hospital, Dept. Internal Medicine, Fredericia Hospital2,
Holstebro Hospital4, Soenderborg Hospital5, Dept. Public Health, University of Southern Denmark3,
and Dept. Nephrology Y6, Odense University Hospital, Denmark.
Background: Unplanned start on dialysis remains a major problem for the dialysis community
worldwide. Hemodialysis (HD) based on a central venous catheter is still current practice to initiate
unplanned dialysis although it has consistently been associated with higher patient mortality and
morbidity. During the last decade, evolving experience with programmes for unplanned start on
peritoneal dialysis (PD) has been published, mainly small single center publications reporting
favourable short term clinical outcomes.
Methods: This is a prospective, non-interventional, observational Danish multicenter cohort study
based on 593 incident PD patients from 8 different dialysis clinics with a median follow up of 1236
days. Unplanned start on PD was defined as peritoneal rest between PD catheter implantation and
start on PD <14 days compared to planned start on PD with peritoneal rest ≥14 days.
Results: The patients in the unplanned group were significantly older than the patients in the
planned group, while there was no significant difference in sex or number of diabetics. After
adjustment, there was no significant difference in short term (3 months; HR 1.78; 95%-CI = 0.70-
4.50) or long term (total observation period with median follow up of 1236 days; HR 1.04; 0.81-
1.33) patient survival. Likewise, there was no significant difference in short (HR 1.27; 0.79 - 2.04)
or long term (HR 1.26; 0.97- 1.63) PD catheter survival, short (HR 1.41; 0.78 - 2.56) or long (HR
1.26; 0.93 - 1.70) term Peritonitis free survival and short (HR 0.77; 0.39 - 1.52) or long (HR 0.98;
0.63 - 1.50) term exit-site infection free survival.
Conclusion: In the present prospective cohort study, we could not demonstrate any significant
difference in patient and PD catheter survival or risk of infectious complications when comparing
outcomes of unplanned start PD patients with planned start PD patients. Accordingly, a revision of
current practise and guidelines should be considered in order to make unplanned start on PD right
after PD catheter implantation more available.
Bacteriology of the buttonhole cannulation tract in haemodialysis patients - A prospective
study with follow-up
Line D. Christensen, MD,1 Mai-Britt Skadborg, MD,1 Agnete H. Mortensen, RN,1 Nanna Lagoni,
RN,2 Jens K. Møller, MD, DMSc,3 Lars Lemming, MD, PhD,4 Irene Høgsberg, MD,2 Steffen E.
Petersen, MD,5 and Niels H. Buus MD, DMSc6,7 1Department of Renal Medicine, Aarhus University Hospital, Aarhus, Denmark; 2Department of
Medicine, Lillebaelt Hospital, Fredericia, Denmark; 3Department of Clinical Microbiology, Lillebaelt
Hospital, Vejle, Denmark; 4Department of Clinical Microbiology, Aarhus University Hospital,
Aarhus, Denmark; 5Department of Urology, Aarhus University Hospital, Aarhus, Denmark; 6Institute
of Clinical Medicine, Aarhus University Hospital, Aarhus Denmark; 7Department of Nephrology,
Aalborg University Hospital, Aalborg, Denmark.
Background: The buttonhole (BH) cannulation technique is popular but has been associated with
an increased rate of access-related infections. We describe the frequency and type of bacterial
colonization of the BH tract and related infectious complications.
Study design: Two-centre, prospective, observational, cohort study with nine months of follow-up.
Setting and participants: Eighty-four in-centre haemodialysis patients using the BH cannulation
technique.
Outcomes: Bacterial growth from the BH tract and the dialysis cannula tip after disinfection.
Measurements: Every four weeks over a period of three months, swaps were systematically
collected before dialysis, from 1) the skin surrounding the BH before disinfection, 2) the
cannulation tract after disinfection and scab removal and 3) the cannula tip after dialysis. Patients
with positive cultures from the BH tract or the cannula tip had the procedure repeated within one
week including blood cultures.
Results: Growth from the cannulation tract and/or cannula tip was found in 18%, 20% and 17% in
the three series, resulting in at least one positive culture from the BH tract in 30 patients (38%).
Positive cultures only from the cannula tip was obtained in 47% of positive BH’s. Sustained growth
was registered in 9 patients (11%) and a similar rate of silent bacteraemia was found. Most
common was staphylococci species (Aureus 25%, Epidermidis 41%). Besides slightly more
redness, BH’s with bacterial colonization did not show signs of inflammation. During follow-up
significantly more access-related infections were diagnosed in the BH positive group.
Limitations: No comparison to rope-ladder or area puncture cannulation technique. Blood cultures
were only obtained from BH positive patients.
Conclusion: Transient or sustained subclinical colonisation of the BH tract by staphylococci and
silent bacteraemia is common in haemodialysis patients, implying a substantial risk of access-
related infections. Our findings warrant a strict selection of patients for BH cannulation and possibly
a closer surveillance of BH bacteriology.
Incretin effect is reduced in end-stage renal disease
Morten B. Jørgensen1, Thomas Idorn1, Casper Rydahl2, Henrik P. Hansen2, Iain Bressendorff3,
Lisbet Brandi3, Gerrit van Hall4,5, Jens J. Holst5,6, Filip K. Knop6,7, Mads Hornum1, Bo Feldt-
Rasmussen1 1Dept of Nephrology, Rigshospitalet, Denmark; 2Dept of Nephrology, Herlev Hospital, Denmark; 3Dept of Cardiology, Nephrology and Endocrinology, North Zealand Hospital, Denmark; 4CMCF,
Clinical Biochemistry, Rigshospitalet, Denmark; 5Department of Biomedical Sciences, University of
Copenhagen, Copenhagen, Denmark; 6The NNF Center for Basic Metabolic Research, University
of Copenhagen, Denmark; 7Center for Diabetes Research, Gentofte Hospital, Denmark.
Background Incretin hormones play an important role in the pathogenesis of postprandial
hyperglycaemia including impaired glucose tolerance and diabetes. We hypothesised that uraemia
causes a (diabetes independent) reduced insulin secretion and glucagon suppression due to an
impaired effect of the two incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-
dependent insulinotropic polypeptide (GIP).
Methods Twelve chronic haemodialysis patients (ESRD) and 12 age, weight and height-matched
healthy controls (CTRL), all with normal glucose tolerance from oral glucose tolerance test
(OGTT), were included. Body composition was determined by a DXA-scan. On three separate
days, a 2 h euglycaemic clamp followed by a 2 h hyperglycaemic (3 mM above fasting level) clamp
were performed with concomitant randomised and double-blinded infusion of GLP-1 (1
pmol/kg/min), GIP (2 pmol/kg/min) or saline. A 30% lower infusion rate was used in the ESRD
group to obtain comparable plasma levels.
Results Patients and controls were well-matched and body composition did not differ. Fasting
plasma glucose and insulin were similar between groups while glucagon and intact GLP-1 and GIP
were significantly elevated in ESRD patients. The effect of GLP-1 to further increase insulin
concentrations relative to placebo levels tended to be lower during euglycaemia in ESRD (26 [-18
– 53]%, NS) and was significantly reduced during hyperglycaemia (50 [8 – 72]%, P=0.03).
Similarly, the effect of GIP relative to placebo levels tended to be lower during euglycaemia in
ESRD (23 [-5 – 43]%, NS) and was significantly reduced during hyperglycaemia (34 [13 – 50]%,
P=0.005). The effect of hyperglycaemia and GLP-1 to further suppress glucagon levels were also
reduced in ESRD.
Conclusions The effect of incretin hormones to increase insulin and suppress glucagon secretion
is reduced in end-stage renal disease. These impairments could contribute to the high prevalence
of postprandial hyperglycaemia in uraemia.
Gastrointestinal motility in diabetic, pre-diabetic and non-diabetic patients with end-stage
renal disease
Bo Broberg1, Jan Lysgård Madsen2, Stefan Fuglsang2, Jens Juul Holst3, Casper Rydahl1, Thomas
Idorn4, Bo Feldt-Rasmussen4 and Mads Hornum4
1. Department of Nephrology, Copenhagen University Hospital Herlev, Copenhagen, Denmark
2. Department of Clinical Physiology and Nuclear Medicine, Centre for Functional and Diagnostic
Imaging and Research, Copenhagen University Hospital Hvidovre, Copenhagen, Denmark
3. Department of Biomedical Sciences & NNF Center for Basic Metabolic Research, The Panum
Institute, University of Copenhagen, Copenhagen, Denmark
4. Department of Nephrology, Copenhagen University Hospital Rigshospitalet, Copenhagen,
Denmark
Background Patients with end-stage renal disease (ESRD) often suffer from nausea and reduced
appetite. Previous studies have indicated a delayed gastric emptying in patients with ESRD using
indirect methods. By scintigrafic technique we wanted to examine gastric emptying and oro-caecal
transit time after a mixed solid and liquid meal. We hypothesized that gastrointestinal transit time
was increased in ESRD patients with and without diabetes.
Methods We studied ESRD patients treated with chronic haemodialysis and either normal glucose
tolerance (n = 8), impaired glucose tolerance (n = 8), type 2 diabetes (n = 8), and healthy control
subjects (n = 8). All patients and controls were screened with an oral glucose tolerance test.
Gastrointestinal transit time was measured by repeated gamma camera imaging for 6 hours after
intake of a standardized mixed meal containing a 99mTc-labelled egg omelet and 111In-labelled
water.
Results All HD patients were age, gender and BMI matched with controls. ESRD patients with
diabetes were compared with ESRD patients without diabetes and with healthy controls. We did
not find any significant difference in gastric mean emptying time, time to 10% or 50% gastric
emptying, time to 15% gastric retention or colonic appearance time between ESRD patients with
diabetes and without diabetes or healthy controls. A mixed model analysis of variance describing
gastric mean emptying time showed that gastric mean emptying time was increased in ESRD
patients with diabetes, impaired glucose tolerance, lower BMI or male gender. Age did not
influence transit time. Figure 1 illustrates mean gastric emptying time for egg omelet in the 4
groups.
Conclusion Gastric emptying measured with scintigraphic technique did not differ between ESRD
patients and healthy controls. However, ESRD patients with diabetes, impaired glucose tolerance,
lower BMI or male gender did appear to have slower gastric emptying than normal glucose tolerant
ESRD patients and healthy controls.
Figure 1.
Chronic Kidney Disease
Proteinuria is predicting long term Renal and Patient Outcome in ANCA Associated
Vasculitis
Wladimir Szpirt, Elizabeth Krarup Martin Egfjord, Rigshospitalet, Nephrology, Herlev Hospitalet
Nephrology, Copenhagen, Denmark.
INTRODUCTION AND AIMS: Reports of proteinuria as a best predictor of long term renal outcome
in lupus nephritis (Euro-Lupus & Maintain Nephritis Trial) raised the question whether proteinuria in
AAV patients 3 and 12 months after treatment induction can be used for similar evaluation.
METHODS: A retrospective cohort study of all AAV pts. referred to our centre at Rigshospitalet
between 2000 and 2010 was performed. Induction treatment was given as prednisolone 1mg/kg +
low dose of cyclophosphamide (100 mg/day in pts < 65 years and 50 mg/day in pts > 65 years).
PLEX was given according to histology on renal biopsy and ANCA titers in 106 pts. All pts received
PCP prophylaxis since 2005. Azathioprine or Mycophenolate Mofetil was given for maintenance of
remission after 4 months. 128 pts were admitted and 116 followed for a mean of 2849 (53 – 5613)
observations days . In 104 patients 24 hours urine collection and proteinuria values at 3 and 12
months were available. A cut off proteinuria of 1 g/day was used for survival evaluation.
RESULTS: In 104 patients 24 hours urine collection was examined and results compared for
proteinuria of more or less than 1 g/day. After 3 and 12 months a median proteinuria of 0,89 g/day
(0,1 -8,8) and 0,43 g/day (0-6,2) was found respectively. At 3 months 48 patients had proteinuria of
< 1 g/day and 66 at 12 months. We compared renal outcome and patient survival at a cut off of 1
g/day and found a better kidney survival at 3 months ( P<0.05) and both a better patient survival
(P<0.05) and patient survival with functioning kidneys (P<0.001) at 12 months in patients with
proteinuria < 1 g/day. Totally 9 pts. (7.4%) died initially within 12 months of active vasculitis and six
more pts. died within 7 years without signs of active vasculitis. (Total mortality of 12.4%). Eleven
(9%) developed end stage renal failure. 36 relapses occurred during the total follow up, 12 during
the first year after induction.
CONCLUSIONS: Thus in our cohort, which has been treated with a relatively low dose CYC-
regime combined with standard CS and PLEX, proteinuria with a cut off < 1 g/day at 3 and 12
months seemed to be a good predictor of long term renal outcome and patient survival.
Interventional study targeting oral infections in Danish patients with chronic kidney disease
Juhl C1, Brandt T2, Frøjk M3, El-Ali N3,4, Kragelund C1, Eidemak I3 and Jensen SB1,5. 1Oral Medicine, Department of Odontology, University of Copenhagen 2School of Oral Health Care,
University of Copenhagen 3Nephrology, Department of Nephrology, Rigshospitalet 4Department of
Medical, Holbæk Hospital 5Department of Dentistry and Oral Health, Aarhus University
Background: Oral diseases are highly prevalent in the general population and commonly
associated with inflammation and infection. In general, infection and inflammation are common in
patients with chronic kidney disease (CKD).
Methods: The aim of this prospective, randomized, single-blinded, controlled intervention study
was to investigate whether a 1½-month period of intensive focused effort for improved oral hygiene
combined with non-surgical treatment can reduce oral inflammation (gingivitis index, probing
pocket depth, and bleeding on probing) and local infection (bacterial plaque index and candida
infection). The intervention group (n=34) were given tooth scaling, individualized instruction in oral
hygiene and treatment of mucosal infection, salivary gland dysfunction and fluoride treatment
performed by a dental hygienist at three visits. The control group (n= 35) received no intervention.
At baseline and the 3-month follow-up, a clinical oral examination was conducted by the same
investigator blinded to the grouping. Routine standard blood and saliva samples were collected.
Results: There were significant differences between the intervention and control group at the
follow-up examination where the intervention group had lower levels of bacterial plaque index
(p<0.0001), gingivitis index (p<0.0001), probing pocket depth (p=0.0004) and bleeding on probing
(p<0.0001) compared to the control group. There were no significant differences in the prevalence
of oral candidiasis, saliva flow rate and xerostomia in the intervention group compared to the
control group at the follow-up examination. Plasma C-reactive protein (CRP) was not collected
simultaneously with the examinations but salivary CRP will be analyzed.
Conclusion: An individualized focused effort for improved oral hygiene combined with non-
surgical treatment (over 1½ month) can reduce oral inflammation both clinically and statistically
significant in CKD patients with the effect lasting over a 3-month period.
Sclerostin is associated with vascular calcifications, but not cardiovascular events in late
stage CKD
Jørgensen, Hanne Skou (1), Winther, Simon(2), Bøttcher, Morten (3), Hauge, Ellen-Margrethe (4),
Rejnmark, Lars (5), Svensson, My (6), Ivarsen, Per (1)
1 Department of Renal Medicine, Aarhus University Hospital, 2 Department of Cardiology, Aarhus
University Hospital, 3 Department of Internal Medicine, Hospital Unit West, Herning, 4 Department
of Rheumatology, Aarhus University Hospital, 5 Department of Endocrinology and Internal
Medicine, Aarhus University Hospital, 6 Department of Nephrology, Division of Medicine, Akershus
University Hospital, Oslo, Norway
Background Sclerostin, a bone derived protein, has been linked to the presence of cardiovascular
calcifications. This study investigated the associations between sclerostin and mineral and bone
disorder in chronic kidney disease (CKD).
Methods Cardiac computed tomography scans were performed in 157 kidney transplant
candidates. Calcification scores (CS) were calculated for coronary arteries (CA), ascending aorta
(AA), descending aorta (DA), aortic valve (AoV) and mitral valve (MiV). Bone mineral density
(BMD) was measured at lumbar spine and total hip. Blood samples were drawn in the fasting state
and Sclerostin was analysed by ELISA (R&D).
Results Median age was 54 (range 32-72) yrs and 68% were men. Patients on dialysis (n=59,
62%) had 21% higher levels of sclerostin compared to pre-dialysis patients (CI 9 to 32%, p=0.001).
Sclerostin was positively correlated with age (r=0.32, p<0.001), BMI (r=0.26, p=0.001) and Z-
scores of lumbar spine (r=0.21, p=0.01) and total hip (r=0.53, p>0.001).
Higher levels of sclerostin were seen in patients with vascular calcifications (Figure 1). Sclerostin
was a positive predictor of CACS independent of age and sex (β=0.005, p=0.02); but when further
adjusting for dialysis therapy the association lost significance (p=0.07). During a median follow-up
of 4.3 yrs (range 3.1-5.8), 32 patients died, 23 had a major cardiovascular event (MACE) and 19
had a fragility fracture. Sclerostin levels above/below median did not predict all-cause mortality (p =
0.98), MACE (p = 0.13) or fragility fracture (p = 0.65). Nor were sclerostin as a continuous variable
associated with increased risk of events using univariate Cox regression (p=0.70, 0.76 and 0.60,
respectively).
Conclusions Sclerostin levels are positively association with both vascular calcification and bone
mass in CKD; but this does not appear to translate into a predictive ability for future events related
to mineral and bone disorder.
Preeclampsia and the risk of later renal disease
Kristensen JH, Basit S, Wohlfahrt J, Damholt MB, Boyd HA
Department of Epidemiology Research, Statens Seruminstitut; Nefrologisk Klinik, Rigshospitalet
Background: Preeclampsia (PE), a pregnancy disorder often characterized by renal
complications, has previously been associated with later end-stage renal disease. We conducted a
nationwide register-based cohort study to explore associations between PE and later kidney
disease.
Methods: Using Danish health registers, we identified all women with pregnancies lasting ≥20
weeks in Denmark, 1978-2015. PE included preeclampsia, eclampsia or HELLP syndrome
registered from 30 days before delivery to 7 days postpartum and was classified as early preterm,
late preterm or term based on timing of delivery (<34 weeks, 34-36 weeks or ≥37 weeks). We
followed women for post-pregnancy kidney disease from 3 months after their first delivery. ‘Acute
kidney disease’ included acute kidney insufficiency and acute tubulo-interstitial nephritis. ‘Chronic
kidney disease’ included chronic kidney insufficiency, hypertensive kidney insufficiency, chronic
tubulo-interstitial nephritis and glomerular disease. Using Cox regression analysis, we estimated
hazard ratios (HR) for kidney disease by history of earliest-onset PE.
Results: The study cohort consisted of 1,072,330 women followed for 19,994,470 person-years
(average: 18.6 years/woman). During follow-up, 6,060 women developed acute kidney disease and
3,082 developed chronic kidney disease. Compared with women without PE delivering in the same
gestational age interval, women with a history of PE had only modestly increased rates of acute
kidney disease, but significantly higher rates of post-pregnancy chronic kidney disease: early
preterm PE, HR 3.93, 95% confidence interval [CI] 2.90-5.33; late preterm PE, HR 2.81, 95% CI
2.13-3.71; term PE, HR 2.27, 95% CI 2.02-2.55. Associations for glomerular disease were
especially striking (e.g. early preterm PE, HR 5.27, 95% CI 3.32-8.35).
Conclusion: Our study provides the first population-based evidence that PE, early PE in
particular, is associated with several types of kidney disease later in life.
Blood pressure control in The Copenhagen Chronic Kidney Disease Cohort
Ellen Linnea Freese, Morten Buus Jørgensen, Ida Maria Hjelm Sørensen, Susanne Bro, Bo Feldt-
Rasmussen, Anne-Lise Kamper for The Copenhagen CKD Cohort Study Group.
Department of Nephrology, Rigshospitalet, Copenhagen
Background: The Copenhagen CKD Cohort including 1000 patients with CKD stage 1-5 (non-
dialysis) is established to study cardiovascular morbidity in CKD. This study examines if
antihypertensive therapy comply with guideline recommended blood pressure (BP) treatment goal
<140/90 mmHg and use of renin-angiotensin-system (RAS) blockade. We hypothesised that this
was the case for >80% of patients.
Methods: The first 481 patients from the cohort were included. After minimum 5 minutes rest,
office BP was measured three times in upright sitting position and calculated as mean of the last
two BPs. Using a standardised questionnaire patients were interviewed about lifestyle. Data on
antihypertensive therapy was obtained from the electronic prescription system.
Results: Mean age 57.6 years, 38.7% females. Most common renal diagnoses were chronic
glomerulonephritis (30.8%) and diabetic nephropathy (12.5%). CKD stages 1-5 were 6.9%, 14.6%,
49.3%, 21.6% and 7.7%, respectively. 88.6% received antihypertensive therapy. Mean BP was
133/81 mmHg and 57.8% met BP treatment goal. Mean number of antihypertensive drugs was 2.4.
70.7% received RAS-blockade. Other common drugs included diuretics (68.3%), calcium channel
blockers (43.2%) and beta blockers (42.3%). 24.3% had 24-h BP measurements within previous 3
years.
BP above treatment goal was associated with older age, male sex, higher body mass index (BMI),
wider waist circumference and treatment with more antihypertensives (if treated).
Antihypertensive treatment was associated with older age, lower eGFR, more comorbidity, higher
BMI, wider waist circumference, less physical activity and more smoking pack-years.
Conclusion: Less than 60% of CKD patients had BP at treatment goal while RAS blocking agents
were predominantly used. There is a need for increased attention to BP control in patients with
CKD.