title: Copeptin Associates with Cause-Specific Mortality in Patients with Impaired Renal Function: Results from the LURIC and the 4D Study.
abstract: In chronic kidney disease (CKD) arginine vasopressin (AVP) cannot efficiently act via renal V2-receptors. AVP is upregulated leading to augmented activation of V1a- and V1b-receptors, which might contribute to the increase in cardiovascular and infectious complications in CKD. Here, we evaluate copeptin, a surrogate of AVP, and its association with cause specific mortality among patients within the whole spectrum of renal function.
  
  
  
  Copeptin was measured in baseline samples from the LURIC (n = 3131 patients with coronary angiograms) and the 4D-Study (n = 1241 type 2 diabetic hemodialysis patients). Patients were stratified into 4 groups: estimated glomerular filtration rate (eGFR) ≥90 mL/min/1.73 m2, 60-89 mL/min/1.73 m2, <60 mL/min/1.73 m2, and hemodialysis. The association of copeptin with mortality was assessed by Cox proportional hazards regression during 9.9 years of median follow-up in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study and 4 years of median follow-up in the German Diabetes Dialysis Study (4D-Study).
  
  
  
  Median copeptin increased with decreasing eGFR: 5.6 [interquartile range (IQR), 3.1-8.1] pmol/L (eGFR ≥90 mL/min/1.73 m2), 6.7 (2.9-10.5) pmol/L (eGFR 60-89 mL/min/1.73 m2), 15.3 (6.7-23.9) pmol/L (eGFR <60 mL/min/1.73 m2), and 80.8 (51.2-122) pmol/L (hemodialysis), respectively. Per SD increase in copeptin, the risk of coronary, infectious, and all-cause mortality increased by 25, 30, and 15% [hazard ratios (HR), 1.25; 95% CI, 1.13-1.39; HR, 1.30; 95% CI, 0.98-1.71; and HR, 1.15; 95% CI, 1.05-1.25], respectively, in patients with eGFR 60-89 mL/min/1.73 m2. Except for coronary death, results were similar among patients with more advanced renal disease. No significant association was found in patients with normal renal function.
  
  
  
  Copeptin concentrations were independently associated with coronary, infectious, and all-cause mortality in patients with renal impairment. In patients with normal renal function no significant association was found.
authors.affiliation: Department of Medicine 1, Division of Nephrology, and krane_v@ukw.de.|Comprehensive Heart Failure Centre, University Hospital of Würzburg, Würzburg, Germany.
authors.forename: Vera
authors.initials: V
authors.lastname: Krane
authors.affiliation: Instituto de Saúde Coletiva, Federal University of Bahia, Salvador, Brazil.|BGStats Consulting, Vienna, Austria.
authors.forename: Bernd
authors.initials: B
authors.lastname: Genser
authors.affiliation: Medical Clinic V (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology), Medical Faculty Mannheim, University of Heidelberg, Germany.
authors.forename: Marcus E
authors.initials: ME
authors.lastname: Kleber
authors.affiliation: Department of Medicine 1, Division of Nephrology, and.|Comprehensive Heart Failure Centre, University Hospital of Würzburg, Würzburg, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Drechsler
authors.affiliation: Medical Clinic V (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology), Medical Faculty Mannheim, University of Heidelberg, Germany.|Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.|Synlab Academy, Synlab Services GmbH, Mannheim, Germany.
authors.forename: Winfried
authors.initials: W
authors.lastname: März
authors.affiliation: Medical Clinic V (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology), Medical Faculty Mannheim, University of Heidelberg, Germany.
authors.forename: Graciela
authors.initials: G
authors.lastname: Delgado
authors.affiliation: Comprehensive Heart Failure Centre, University Hospital of Würzburg, Würzburg, Germany.|Department of Internal Medicine 1, Division of Endocrinology, University of Würzburg, Würzburg, Germany.
authors.forename: Bruno
authors.initials: B
authors.lastname: Allolio
authors.affiliation: Department of Medicine 1, Division of Nephrology, and.|Comprehensive Heart Failure Centre, University Hospital of Würzburg, Würzburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Wanner
authors.affiliation: Leipzig University Medical Center, IFB Adiposity Diseases, Leipzig, Germany.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Fenske
mesh_terms: D005260:Female; D005500:Follow-Up Studies; D005858:Germany; D006020:Glycopeptides / Q000097:blood*; D006801:Humans; D007668:Kidney / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D051437:Renal Insufficiency / Q000097:blood* / Q000503:physiopathology; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000401:mortality / Q000503:physiopathology*; D012307:Risk Factors
chemical_list: D006020:Glycopeptides; C048197:copeptins