Copeptin, a surrogate marker of vasopressin, is associated with microalbuminuria in a large population cohort

Abstract

Urinary albumin excretion is a powerful predictor of progressive cardiovascular and renal disease. In rats and humans, administration of a synthetic vasopressin analogue, 1-desamino-8-D-arginine-vasopressin, increases urinary albumin excretion; however, it is unknown if endogenous vasopressin levels influence albumin excretion. To determine this we measured copeptin, a marker of endogenous vasopressin levels, and its association with urinary albumin excretion in 7593 patients in the PREVEND study, a prospective population based, observational cohort. Urinary albumin excretion was measured in two consecutive 24-h urine samples by nephelometry while copeptin was measured by an immunoassay. Median copeptin concentrations were significantly higher in males than females and high levels were associated with significantly lower 24-h urine volumes of high osmolarity. With increasing quintiles of copeptin levels, the percentage of microalbuminuric subjects increased from 13 to 25 for males and from 8 to15 for females. This association was independent of age and other potential confounders; however, we found an interaction between age and copeptin in their association with urinary albumin excretion. Our study shows that plasma copeptin levels are associated with microalbuminuria, consistent with the hypothesis that vasopressin is involved in urinary albumin excretion. If future studies show that this association is causal, then drinking more water or pharmacological intervention to decrease plasma vasopressin may have beneficial effects on the kidney, especially in the elderly.

Sex differences in the association between plasma copeptin and incident type 2 diabetes: the Prevention of Renal and Vascular Endstage Disease (PREVEND) study

“…With regard to the differences in copeptin levels in men and women, the higher plasma copeptin level in men was consistently observed in our study and in previous studies [4,[29][30][31]. Sex is one of the major determinants of plasma levels of copeptin.…”

“…We and others have shown before that higher plasma copeptin levels are positively associated with the metabolic syndrome, insulin resistance, the inflammatory marker hs-CRP and higher UAE in cross-sectional studies [4,29,30]. Likewise, all these conditions are known to be predictors for the risk of type 2 diabetes [13].…”

“…The main reason for this may be that reliable measurements of AVP are difficult in large collections of samples. AVP in blood is mainly bound to platelets in circulation and is unstable in isolated plasma [3,4]. In addition, most AVP measurements have relatively limited sensitivity.…”

Copeptin, a Surrogate Marker of Vasopressin, Is Associated with Disease Severity in Autosomal Dominant Polycystic Kidney Disease

“…However, in these ADPKD patients we did not find significant associations between copeptin and 24-hour urinary volume, 24-hour urinary osmolarity, or fractional urea excretion. This is in contrast to what is described in healthy subjects (31) and renal transplant recipients (32) and suggests that ADPKD patients do not respond effectively to VP. In line with this assumption is the observation that ADPKD patients have an impaired urinary concentrating capacity that is already present when GFR is still normal (33).…”

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).…”