Serum uromodulin and decline of kidney function in older participants of the population-based KORA F4/FF4 study

Author:

Then Cornelia12ORCID,Then Holger L3,Lechner Andreas124,Thorand Barbara45,Meisinger Christa67,Heier Margit58,Peters Annette459,Koenig Wolfgang91011,Rathmann Wolfgang12,Scherberich Jürgen13,Seissler Jochen123

Affiliation:

1. Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Ludwig-Maximilians-Universität München, Munich, Germany

2. Clinical Cooperation Group Diabetes, Ludwig-Maximilians-Universität München and Helmholtz Zentrum München, Munich, Germany

3. Freie Waldorfschule Augsburg, Augsburg, Germany

4. German Center for Diabetes Research (DZD), München-Neuherberg, Germany

5. Institute of Epidemiology, Helmholtz Zentrum München–German Research Center for Environmental Health, Neuherberg, Germany

6. Independent Research Group Clinical Epidemiology, Helmholtz Zentrum München–German Research Center for Environmental Health, Neuherberg, Germany

7. Department of Epidemiology, Ludwig-Maximilians-Universität München, UNIKAT Augsburg, Munich, Germany

8. KORA Study Center, University Hospital Augsburg, Augsburg, Germany

9. DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany

10. Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm, Germany

11. Deutsches Herzzentrum München, Technische Universität München, Munich, Germany

12. German Diabetes Center, Leibniz Institute at Heinrich Heine University Düsseldorf, Institute of Biometrics and Epidemiology, Düsseldorf, Germany

13. Klinikum München-Harlaching, Teaching Hospital of the Ludwig-Maximilians-Universität, Munich, Germany

Abstract

Abstract Background Uromodulin, a tissue-specific tubular glycoprotein, has recently emerged as a promising biomarker for kidney function and tubular integrity. However, the association of serum uromodulin (sUmod) with renal function decline is still unknown in an older general population. Methods We analysed the association of sUmod with the estimated glomerular filtration rate (eGFR) and albuminuria in 1075 participants of the population-based Cooperative Health Research in the Region of Augsburg (KORA) F4 study, ages 62–81 years, at baseline and prospectively after a mean follow-up time of 6.5 years (n = 605) using logistic and linear regression models as well as receiver operating characteristics (ROC) analyses. Results Cross-sectionally, sUmod was positively associated with eGFR (β = 0.31 ± 0.02 per higher standard deviation sUmod; P < 0.001) and inversely associated with the urinary albumin:creatinine ratio (β = −0.19 ± 0.04; P < 0.001) after adjustment for sex, age, body mass index, arterial hypertension, prediabetes and diabetes. After multivariable adjustment including baseline eGFR, sUmod was not associated with incident chronic kidney disease (CKD), defined as a decrease in eGFR <60 mL/min/1.73 m2 after 6.5 years of follow-up {odds ratio [OR] 1.02 [95% confidence interval (CI) 0.77–1.36] per higher SD sUmod} but was inversely associated with advanced CKD, defined as incident eGFR <45 mL/min/1.73 m2 [OR 0.64 (95% CI 0.42–0.98)]. The ROC showed no added predictive value of sUmod for kidney function decline in the fully adjusted model. Conclusions Higher sUmod was inversely associated with progression to advanced kidney disease but does not provide additional predictive value for the development of CKD in elderly participants of the population-based KORA study.

Funder

Helmholtz Zentrum München – German Research Center for Environmental Health

German Federal Ministry of Education and Research

State of Bavaria

Virtual Diabetes Institute

Clinical Cooperation Group Diabetes

Ludwig-Maximilians-University München

Helmholtz Zentrum München

German Diabetes Center

Deutsche Diabetes Gesellschaft

German Research Foundation

Publisher

Oxford University Press (OUP)

Subject

Transplantation,Nephrology

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