Ray El Boustany1,2, Irina Tasevska3, Esther Meijer4, Lyanne M Kieneker4, Sofia Enhörning3, Guillaume Lefèvre5, Kamel Mohammedi1,6, Michel Marre1,6,7, Frédéric Fumeron1,7, Beverley Balkau8,9, Nadine Bouby1,10, Lise Bankir1,11, Stephan Jl Bakker4, Ronan Roussel1,6,7, Olle Melander3, Ron T Gansevoort4, Gilberto Velho1. 1. Inserm Research Unit 1138, Centre de Recherche des Cordeliers, Paris, France. 2. Danone Nutricia Research, Palaiseau, France. 3. Departments of Internal Medicine and Clinical Sciences, Lund University, Malmö, Sweden. 4. Department of Internal Medicine, University Medical Center, Division of Nephrology, University of Groningen, Groningen, Netherlands. 5. Service de Biochimie et Hormonologie, Assistance Publique - Hôpitaux de Paris, Hôpitaux Universitaires Est Parisien-Tenon, Paris, France. 6. Department of Diabetology, Endocrinology and Nutrition, DHU Fire, Assistance Publique - Hôpitaux de Paris, Bichat Hospital, Paris, France. 7. UFR de Médecine, Université Paris Diderot, Sorbonne Paris Cité, Paris, France. 8. Inserm Research Unit 1018, Center for Research in Epidemiology and Population Health, Villejuif, France. 9. Université Paris Sud, Villejuif, France. 10. Université Paris Descartes, Sorbonne Paris Cité, Paris, France. 11. UPMC University Paris 6, Sorbonne Universités, Paris, France.
Abstract
BACKGROUND: The prevalence of chronic kidney disease (CKD) is increasing worldwide. The identification of factors contributing to its progression is important for designing preventive measures. Previous studies have suggested that chronically high vasopressin is deleterious to renal function. Here, we evaluated the association of plasma copeptin, a surrogate of vasopressin, with the incidence of CKD in the general population. METHODS: We studied 3 European cohorts: DESIR (n = 5,047; France), MDCS-CC (n = 3,643; Sweden), and PREVEND (n = 7,684; the Netherlands). Median follow-up was 8.5, 16.5, and 11.3 years, respectively. Pooled data were analyzed at an individual level for 4 endpoints during follow-up: incidence of stage 3 CKD (estimated glomerular filtration rate [eGFR] < 60 ml/min/1.73 m2); the KDIGO criterion "certain drop in eGFR"; rapid kidney function decline (eGFR slope steeper than -3 ml/min/1.73 m2/yr); and incidence of microalbuminuria. RESULTS: The upper tertile of plasma copeptin was significantly and independently associated with a 49% higher risk for stage 3 CKD (P < 0.0001); a 64% higher risk for kidney function decline, as defined by the KDIGO criterion (P < 0.0001); a 79% higher risk for rapid kidney function decline (P < 0.0001); and a 24% higher risk for microalbuminuria (P = 0.008). CONCLUSIONS: High copeptin levels are associated with the development and the progression of CKD in the general population. Intervention studies are needed to assess the potential beneficial effect on kidney health in the general population of reducing vasopressin secretion or action. FUNDING: INSERM and Danone Research Centre for Specialized Nutrition.
BACKGROUND: The prevalence of chronic kidney disease (CKD) is increasing worldwide. The identification of factors contributing to its progression is important for designing preventive measures. Previous studies have suggested that chronically high vasopressin is deleterious to renal function. Here, we evaluated the association of plasma copeptin, a surrogate of vasopressin, with the incidence of CKD in the general population. METHODS: We studied 3 European cohorts: DESIR (n = 5,047; France), MDCS-CC (n = 3,643; Sweden), and PREVEND (n = 7,684; the Netherlands). Median follow-up was 8.5, 16.5, and 11.3 years, respectively. Pooled data were analyzed at an individual level for 4 endpoints during follow-up: incidence of stage 3 CKD (estimated glomerular filtration rate [eGFR] < 60 ml/min/1.73 m2); the KDIGO criterion "certain drop in eGFR"; rapid kidney function decline (eGFR slope steeper than -3 ml/min/1.73 m2/yr); and incidence of microalbuminuria. RESULTS: The upper tertile of plasma copeptin was significantly and independently associated with a 49% higher risk for stage 3 CKD (P < 0.0001); a 64% higher risk for kidney function decline, as defined by the KDIGO criterion (P < 0.0001); a 79% higher risk for rapid kidney function decline (P < 0.0001); and a 24% higher risk for microalbuminuria (P = 0.008). CONCLUSIONS: High copeptin levels are associated with the development and the progression of CKD in the general population. Intervention studies are needed to assess the potential beneficial effect on kidney health in the general population of reducing vasopressin secretion or action. FUNDING: INSERM and Danone Research Centre for Specialized Nutrition.
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