• Johann Morelle, Céline Marechal, Zanzhe Yu, Huguette Debaix, Tanguy Corre, Mark Lambie, Marion Verduijn, Friedo Dekker, Philippe Bovy, Pieter Evenepoel, Bert Bammens, Rafael Selgas, Maria A Bajo, Annemieke M Coester, Amadou Sow, Nicolas Hautem, Dirk G Struijk, Raymond T Krediet, Jean-Luc Balligand, Eric Goffin, Ralph Crott, Pierre Ripoche, Simon Davies, and Olivier Devuyst.
• From the Division of Nephrology, Cliniques Universitaires Saint-Luc (J.M., E.G., O.D.), and Institut de Recherche Expérimentale et Clinique (J.M., C.M., H.D., A.S., N.H., J.-L.B., E.G., O.D.) and Institut de Recherche Santé et Société, Faculty of Public Health (R.C.), UCLouvain, Brussels, the Division of Nephrology, Clinique Saint-Joseph, Liege (P.B.), and the Department of Microbiology, Immunology, and Transplantation, Nephrology and Renal Transplantation Research Group, KU Leuven (P.E., B.B.), and the Department of Nephrology, Dialysis, and Renal Transplantation, University Hospitals Leuven (P.E., B.B.), Leuven - all in Belgium; the Department of Nephrology, Shanghai Jiao Tong University School of Medicine and Renji Hospital, Shanghai, China (Z.Y.); the Faculty of Medicine and Health Sciences, Keele University, Keele, United Kingdom (Z.Y., M.L., S.D.); the Institute of Physiology, University of Zurich, Zurich (H.D., O.D.), and the Center for Primary Care and Public Health (Unisanté), University of Lausanne, Lausanne (T.C.) - both in Switzerland; the Department of Clinical Epidemiology, Leiden University Medical Center, Leiden (M.V., F.D.), the Division of Nephrology, Department of Medicine, Amsterdam University Medical Center, University of Amsterdam, Amsterdam (A.M.C., D.G.S., R.T.K.), and the Department of Surgery, University Medical Center Groningen, Groningen (A.M.C.) - all in the Netherlands; the Division of Nephrology, Hospital Universitario La Paz, and Instituto de Investigación Sanitaria La Paz, Red de Investigación Renal, Universidad Autonoma, Madrid (R.S., M.A.B.); and Institut National de la Transfusion Sanguine, Paris (P.R.).
• N. Engl. J. Med. 2021 Oct 21; 385 (17): 1570-1580.

BackgroundVariability in ultrafiltration influences prescriptions and outcomes in patients with kidney failure who are treated with peritoneal dialysis. Variants in AQP1, the gene that encodes the archetypal water channel aquaporin-1, may contribute to that variability.MethodsWe gathered clinical and genetic data from 1851 patients treated with peritoneal dialysis in seven cohorts to determine whether AQP1 variants were associated with peritoneal ultrafiltration and with a risk of the composite of death or technique failure (i.e., transfer to hemodialysis). We performed studies in cells, mouse models, and samples obtained from humans to characterize an AQP1 variant and investigate mitigation strategies.ResultsThe common AQP1 promoter variant rs2075574 was associated with peritoneal ultrafiltration. Carriers of the TT genotype at rs2075574 (10 to 16% of patients) had a lower mean (±SD) net ultrafiltration level than carriers of the CC genotype (35 to 47% of patients), both in the discovery phase (506±237 ml vs. 626±283 ml, P = 0.007) and in the validation phase (368±603 ml vs. 563±641 ml, P = 0.003). After a mean follow-up of 944 days, 139 of 898 patients (15%) had died and 280 (31%) had been transferred to hemodialysis. TT carriers had a higher risk of the composite of death or technique failure than CC carriers (adjusted hazard ratio, 1.70; 95% confidence interval [CI], 1.24 to 2.33; P = 0.001), as well as a higher risk of death from any cause (24% vs. 15%, P = 0.03). In mechanistic studies, the rs2075574 risk variant was associated with decreases in AQP1 promoter activity, aquaporin-1 expression, and glucose-driven osmotic water transport. The use of a colloid osmotic agent mitigated the effects of the risk variant.ConclusionsA common variant in AQP1 was associated with decreased ultrafiltration and an increased risk of death or technique failure among patients treated with peritoneal dialysis. (Funded by the Swiss National Science Foundation and others.).Copyright © 2021 Massachusetts Medical Society.

36 keywords...

hide…