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

Abstract

OBJECTIVEPlasma 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 METHODSWe 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.RESULTSDuring 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.CONCLUSIONSPlasma copeptin may help to identify subjects with diabetic chronic kidney disease who are at high risk for renal function decline.

Vasopressin and hydration play a major role in the development of glucose intolerance and hepatic steatosis in obese rats

“…Additionally, VP was shown to contribute to albuminuria and to diabetes-induced nephropathy in animal models [20,21]. Epidemiological studies in humans are consistent with these findings [21][22][23].…”

Antagonism of vasopressin V2 receptor improves albuminuria at the early stage of diabetic nephropathy in a mouse model of type 2 diabetes

“…Cross-sectional and prospective studies in the general population have shown associations between plasma copeptin and albuminuria or renal function decline (Meijer et al, 2010;Enhorning et al, 2013;Roussel et al, 2015). High circulating copeptin concentration was also associated with the development and progression of diabetic nephropathy in patients with type 2 diabetes (Boertien et al, 2013;Velho et al, 2013;Hu et al, 2015;Pikkemaat et al, 2015;Zhu et al, 2016), and with prevalence of ESRD in subjects with long-standing type 1 diabetes (Bjornstad et al, 2016;Velho et al, 2016). Experimental data suggests a causal role of vasopressin in renal dysfunction through activation of the V2-receptor (V2R).…”

Copeptin Is Associated with Kidney Length, Renal Function, and Prevalence of Simple Cysts in a Population-Based Study

“…However, longitudinal studies in humans have shown that plasma copeptin levels increase before eGFR decreases. 44,45,47,48 A decreased urinary concentrating capacity precedes the decrease of GFR in numerous kidney diseases. Increased copeptin levels might be a marker of this early phase of renal dysfunction.…”

“…This association has been observed in prospective studies involving patients with ADPKD as well as patients with a renal transplant and patients with diabetes. [43][44][45][46][47][48] Only two studies have used a populationbased sample to test the hypothesis that AVP might be involved in the development of albuminuria. In the Prevention of Renal and Vascular Endstage Disease (PREVEND) study, which includes 7593 nondiabetic participants with an urinary albumin concentration $10 mg/L, circulating copeptin was positively associated with albuminuria and negatively with renal function in a cross-sectional analysis.…”