Copeptin Associates with Cause-Specific Mortality in Patients with Impaired Renal Function: Results from the LURIC and the 4D Study

BACKGROUND 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. METHODS 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). RESULTS 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. CONCLUSIONS 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.