International Journal of Nephrology and Renovascular Disease (Oct 2018)
Low aquaporin-2 excretion in the nephrotic syndrome: an escape from the vasopressin regulating effect
Abstract
Mikhail Brovko,1 Lidia Kozlovskaya,1 Andrey Pulin,1,2 Sergey Moiseev,1 Victoria Sholomova,1 Dmitry Shchekochikhin,1 Daria Gognieva,1 Ludmila Milovanova,1 Victor Fomin1 1Sechenov First Moscow State Medical University, Moscow, Russia; 2Laboratory for Cell Technologies and Developmental Pathology, Federal State Budgetary Scientific Institution “Institute of General Pathology and Pathophysiology,” Moscow, Russia Purpose: Experimental studies suggest that the nephrotic syndrome is associated with “vasopressin escape”, characterized by low aquaporin-2 (AQP2) expression in the collecting duct despite high vasopressin secretion. We investigated this phenomenon in patients with the nephrotic syndrome. Patients and methods: We recruited 47 patients with proteinuric kidney disease who were distributed into the following four groups: 1) nephrotic syndrome with kidney dysfunction (n=10); 2) nephrotic syndrome with normal kidney function (n=16); 3) partial remission of nephrotic syndrome (n=10); and 4) minimal proteinuria (n=11). Nine healthy volunteers comprised a control group. Serum copeptin level (as a marker of vasopressin secretion) and urinary AQP2 were measured using ELISA. Results: Nephrotic syndrome was associated with a significant increase in serum copeptin levels compared with those in the other groups (all P<0.05). In patients with nephrotic syndrome and a partial remission of nephrotic syndrome combined, there was more than a ten-fold decrease in the median urinary AQP2 excretion (0.03 ng/mL) compared with healthy volunteers (0.41 ng/mL; P<0.001) and more than a five-fold decrease compared with patients with minimal proteinuria (0.21 ng/mL; P<0.05). Unlike copeptin levels, the median urinary AQP2 excretion in patients with minimal proteinuria also decreased but less significantly than in those with nephrotic syndrome. There was a negative correlation between the urinary AQP2 excretion and daily proteinuria (R=−0.41; P=0.005). Conclusion: Our clinical study was the first to demonstrate low AQP2 excretion in nephrotic syndrome that may indicate an escape from the vasopressin regulating effect. Keywords: nephrotic syndrome, aquaporin-2, copeptin, vasopressin escape