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AQP1 Promoter Variant, Water Transport, and Outcomes in Peritoneal Dialysis
Johann Morelle1, Céline Marechal1, Zanzhe Yu1
1From 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.).
A common aquaporin-1 (AQP1) gene variant impacts peritoneal dialysis ultrafiltration. This variant increases the risk of death or technique failure in patients with kidney failure.
Area of Science:
- Nephrology
- Genetics
- Physiology
Background:
- Ultrafiltration variability affects patient outcomes in peritoneal dialysis.
- Aquaporin-1 (AQP1) gene variants may influence this variability.
Purpose of the Study:
- To investigate the association between AQP1 variants and peritoneal ultrafiltration.
- To determine if AQP1 variants correlate with the risk of death or technique failure in peritoneal dialysis patients.
Main Methods:
- Clinical and genetic data from 1851 peritoneal dialysis patients were analyzed.
- Mechanistic studies in cells, mouse models, and human samples were conducted to characterize AQP1 variant effects.
- The association of the AQP1 promoter variant rs2075574 with ultrafiltration and patient outcomes was assessed.
Main Results:
- The AQP1 promoter variant rs2075574 was linked to reduced peritoneal ultrafiltration.
- Carriers of the TT genotype at rs2075574 exhibited lower net ultrafiltration compared to CC genotype carriers.
- TT genotype carriers faced a significantly higher risk of death or technique failure (adjusted HR, 1.70) and all-cause mortality.
Conclusions:
- A common AQP1 variant is associated with decreased ultrafiltration in peritoneal dialysis.
- This genetic variant increases the risk of adverse outcomes, including death or technique failure.
- Mitigation strategies, such as using colloid osmotic agents, may counteract the variant's effects.
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