Copeptin independently predicts DM and abdominal obesity but not the cluster of MetS. Apart from predicting DM and abdominal obesity, elevated copeptin signals increased risk of microalbuminuria. Interestingly, the association between copeptin and later microalbuminuria was independent of both prevalent and incident DM and hypertension. Our findings suggest a relationship between a dysregulated vasopressin system and cardiometabolic risk, which could have implications for risk assessment and novel preventive treatments.

After several decades during which little attention was paid to vasopressin and/or urine concentration in clinical practice, interest in vasopressin has renewed with the availability of new, potent, orally active vasopressin-receptor antagonists--the vaptans--and with the results of epidemiological studies evaluating copeptin (a surrogate marker of vasopressin) in large population-based cohorts. Several experimental studies in rats and mice had previously shown that vasopressin, acting via vasopressin V2 antidiuretic receptors, contributes to the progression of chronic kidney disease; in particular, to autosomal dominant polycystic kidney disease. New epidemiological studies now suggest a role for vasopressin in the pathogenesis of diabetes mellitus and metabolic disorders via activation of hepatic V1a and/or pancreatic islet V1b receptors. The first part of this Review describes the adverse effects of vasopressin, as revealed by clinical and experimental studies in kidney diseases, hypertension, diabetes and the metabolic syndrome. The second part provides insights into vasopressin physiology and pathophysiology that may be relevant to the understanding of these adverse effects and that are linked to the excretion of concentrated nitrogen wastes and associated hyperfiltration. Collectively, the studies reviewed here suggest that more attention should be given to the vasopressin-thirst-urine concentration axis in clinical investigations and in patient care. Whether selective blockade of the different vasopressin receptors may provide therapeutic benefits beyond their present indication in hyponatraemia requires new clinical trials.

This study tests the possible influence of the urinary concentrating process and/or of vasopressin (AVP) on the progression of early chronic renal failure (CRF). Male Sprague-Dawley rats were submitted to 5/6 nephrectomy and were offered water ad libitum throughout the study. In addition, half of the rats (high water intake, HWI) received their food mixed with a water-rich agar gel. The other rats (normal water intake, NWI) ate the same amount of food plus agar in the usual dry powder form. This resulted in doubling the daily water ingestion in HWI. Renal function was studied for 10 wk and kidney morphology assessed thereafter. Increased water intake in HWI reduced solute-free water reabsorption and urine osmolality about threefold to 12 +/- 1 ml/day and 390 +/- 9 mosmol/kgH2O, respectively (week 5 as example). Hematocrit, plasma sodium, and plasma creatinine concentration were unchanged. The progressive increases in urinary protein excretion and in systolic blood pressure observed in this model of CRF were significantly slowed in HWI compared with NWI (at week 5, 8.6 +/- 1.8 vs. 23.1 +/- 6.2 mg protein/day and 142 +/- 8 vs. 167 +/- 10 mmHg, respectively). Remnant kidney weight per unit body weight was 21% lower in HWI than in NWI (P less than 0.02). Incidence of glomerulosclerosis was also reduced and was correlated with kidney weight (P less than 0.01). AVP plasma level (PAVP) and plasma renin activity (PRA) were measured in additional rats. PAVP was about twofold higher (P less than 0.05) and PRA twofold lower (P less than 0.001) in rats with 5/6 nephrectomy than in control rats with two kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)