Dominik Steubl1, Markus P Schneider2,3, Heike Meiselbach4, Jennifer Nadal5, Matthias C Schmid5, Turgay Saritas6, Vera Krane7, Claudia Sommerer8, Seema Baid-Agrawal9, Jakob Voelkl9,10, Fruzsina Kotsis11, Anna Köttgen11, Kai-Uwe Eckardt4,9, Jürgen E Scherberich12. 1. Department of Nephrology, Hospital Rechts der Isar, Technical University of Munich, Munich, Germany. 2. Department of Nephrology and Hypertension, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany dominik.steubl@tum.de Markus.Schneider@uk-erlangen.de. 3. Department of Nephrology and Hypertension, Klinikum Nürnberg, Paracelsus Medical University, Nürnberg, Germany. 4. Department of Nephrology and Hypertension, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany. 5. Department of Medical Biometry, Informatics, and Epidemiology (IMBIE), Faculty of Medicine, University of Bonn, Bonn, Germany. 6. Division of Nephrology and Clinical Immunology, University Hospital RWTH Aachen, Aachen, Germany. 7. Division of Nephrology, Department of Medicine I, University Hospital Würzburg, Würzburg, Germany. 8. Nephrology Unit, University Hospital Heidelberg, Heidelberg, Germany. 9. Department of Nephrology and Medical Intensive Care, Charité - Universitätsmedizin, Berlin, Germany. 10. Institute for Physiology and Pathophysiology, Johannes Kepler University Linz, Linz, Austria. 11. Division of Genetic Epidemiology, Institute for Biometry and Statistics, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany. 12. Department of Nephrology and Clinical Immunology, Hospital Munich-Harlaching, Teaching Hospital of the Ludwig Maximilian University of Munich, Munich, Germany.
Abstract
BACKGROUND AND OBJECTIVES: Uromodulin is exclusively produced by tubular epithelial cells and released into urine and serum. Higher serum uromodulin has been associated with lower risk for kidney failure in Chinese patients with CKD and with lower risk for mortality in the elderly and in patients undergoing coronary angiography. We hypothesized that lower serum uromodulin is associated with mortality, cardiovascular events, and kidney failure in white patients with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We measured serum uromodulin in 5143 participants enrolled in the German CKD (GCKD) study. The associations of baseline serum uromodulin with all-cause mortality, major adverse cardiovascular events (MACE; a composite of cardiovascular mortality, nonfatal myocardial infarction or stroke, or incident peripheral vascular disease), and kidney failure (dialysis or transplantation) were evaluated using multivariable Cox proportional hazard regression analyses in a cohort study design, adjusting for demographics, eGFR, albuminuria, cardiovascular risk factors, and medication. RESULTS: The mean age of participants was 60±12 years, 60% were male. Mean serum uromodulin concentration was 98±60 ng/ml, eGFR was 49±18 ml/min per 1.73 m2, and 78% had eGFR <60 ml/min per 1.73 m2. Participants in lower serum uromodulin quartiles had lower eGFR and higher albuminuria, prevalence of diabetes, hypertension, coronary artery disease, and more frequent history of stroke at baseline. During a follow-up of 4 years, 335 participants died, 417 developed MACE, and 229 developed kidney failure. In multivariable analysis, the highest serum uromodulin quartile was associated with lower hazard for mortality (hazard ratio [HR], 0.57; 95% CI, 0.38 to 0.87), MACE (HR, 0.63; 95% CI, 0.45 to 0.90), and kidney failure (HR, 0.24; 95% CI, 0.10 to 0.55) compared with the lowest quartile. CONCLUSIONS: Higher serum uromodulin is independently associated with lower risk for mortality, cardiovascular events, and kidney failure in white patients with CKD. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Deutsches Register für Klinische Studien (DRKS; German national database of clinical studies), DRKS00003971.
BACKGROUND AND OBJECTIVES:Uromodulin is exclusively produced by tubular epithelial cells and released into urine and serum. Higher serum uromodulin has been associated with lower risk for kidney failure in Chinese patients with CKD and with lower risk for mortality in the elderly and in patients undergoing coronary angiography. We hypothesized that lower serum uromodulin is associated with mortality, cardiovascular events, and kidney failure in white patients with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We measured serum uromodulin in 5143 participants enrolled in the German CKD (GCKD) study. The associations of baseline serum uromodulin with all-cause mortality, major adverse cardiovascular events (MACE; a composite of cardiovascular mortality, nonfatal myocardial infarction or stroke, or incident peripheral vascular disease), and kidney failure (dialysis or transplantation) were evaluated using multivariable Cox proportional hazard regression analyses in a cohort study design, adjusting for demographics, eGFR, albuminuria, cardiovascular risk factors, and medication. RESULTS: The mean age of participants was 60±12 years, 60% were male. Mean serum uromodulin concentration was 98±60 ng/ml, eGFR was 49±18 ml/min per 1.73 m2, and 78% had eGFR <60 ml/min per 1.73 m2. Participants in lower serum uromodulin quartiles had lower eGFR and higher albuminuria, prevalence of diabetes, hypertension, coronary artery disease, and more frequent history of stroke at baseline. During a follow-up of 4 years, 335 participants died, 417 developed MACE, and 229 developed kidney failure. In multivariable analysis, the highest serum uromodulin quartile was associated with lower hazard for mortality (hazard ratio [HR], 0.57; 95% CI, 0.38 to 0.87), MACE (HR, 0.63; 95% CI, 0.45 to 0.90), and kidney failure (HR, 0.24; 95% CI, 0.10 to 0.55) compared with the lowest quartile. CONCLUSIONS: Higher serum uromodulin is independently associated with lower risk for mortality, cardiovascular events, and kidney failure in white patients with CKD. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Deutsches Register für Klinische Studien (DRKS; German national database of clinical studies), DRKS00003971.
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