Plasma Copeptin and Renal Outcomes in Patients With Type 2 Diabetes and Albuminuria

Abstract

OBJECTIVE Plasma copeptin, a surrogate for vasopressin, was associated with albuminuria in population-based studies. These associations are consistent with the effect of vasopressin on albuminuria observed in humans and rodents. The objective of this study was to determine whether plasma copeptin is an independent marker of risk of renal events in people with type 2 diabetes and albuminuria. RESEARCH DESIGN AND METHODS We studied 3,101 participants of the DIABHYCAR trial (6-year follow-up) with type 2 diabetes and albuminuria. A renal event was defined as doubling of serum creatinine or development of end-stage renal disease. RESULTS During follow-up, 86 renal events occurred in 76 subjects (2.45%). Incidences by tertiles of baseline plasma copeptin were 1.06% (T1), 1.45% (T2), and 4.84% (T3). They were 2.43% (T1), 5.11% (T2), and 11.81% (T3) for the subset of subjects with macroalbuminuria at baseline (n = 729). Hazard ratio for plasma copeptin tertiles as a risk for renal events was 4.79 (95% CI, 2.48–9.24; P < 0.0001; for T3 vs. T1). In a stepwise regression analysis, urinary albumin excretion and plasma copeptin remained positively associated and HDL cholesterol and estimated glomerular filtration rate were inversely associated with the incidence of renal events. These independent predictors explained ∼18% of the variance of the outcome. The yearly variations of estimated glomerular filtration rate by copeptin tertiles were −1.43 ± 0.51 (T1), −2.29 ± 0.49 (T2), and −3.52 ± 0.44 mL/min/1.73 m2 per year (T3) (P = 0.005) in subjects with macroalbuminuria. CONCLUSIONS Plasma copeptin may help to identify subjects with diabetic chronic kidney disease who are at high risk for renal function decline.