Vasopressin and urinary concentrating activity in diabetes mellitus

Abstract

In diabetes mellitus (DM), the high urine flow rate suggests that urinary concentrating capacity is impaired. However, several studies have shown that vasopressin is elevated in DM and the consequences of this elevation have not yet been characterized. This study reevaluated renal function and water handling in male Wistar rats with Streptozotocin-induced DM, and in control rats. During five weeks after induction of DM, urine was collected in metabolic cages and a blood sample was drawn during the third week. Control rats (CONT) were studied in parallel. On week 3, urine flow rate was tenfold higher in DM than in CONT rats and urinary osmolality was reduced by half along with a markedly higher osmolar excretion (DM/CONT = 5.87), due for a large part to glucose but also to urea (DM/CONT = 2.49). Glucose represented 52% of total osmoles (90.3 +/- 6.5 mmol/d out of 172 +/- 14 mosm/d). Free water reabsorption was markedly higher in DM rats compared to CONT (326 +/- 24 vs 81 +/- 5 ml/d). In other rats treated in the same way, urinary excretion of vasopressin was found to be markedly elevated (15.1 +/- 4.1 vs 1.44 +/- 0.23 ng/d). In DM rats, glucose concentration in urine was 17 fold higher than in plasma, and urea concentration 14 fold higher. Both urine flow rate and free water reabsorption were positively correlated with the sum of glucose and urea excretions (r = 0.967 and 0.653, respectively) thus demonstrating that the urinary concentrating activity of the kidney increased in proportion to the increased load of these two organic solutes. These results suggest that vasopressin elevation in DM contributes to increase urinary concentrating activity and thus to limit water requirements induced by the metabolic derangements of DM. The possible deleterious consequences of sustained high level of vasopressin in DM are discussed.