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Association of Serum Uromodulin With ESKD and Kidney Function Decline in the Elderly: The Cardiovascular Health Study.
Am J Kidney Dis. 2019 10; 74(4):501-509.AJ

Abstract

RATIONALE & OBJECTIVE

Uromodulin is released by tubular epithelial cells into the serum and lower levels are associated with more severe interstitial fibrosis and tubular atrophy. Low serum uromodulin (sUMOD) levels are associated with mortality and cardiovascular disease. However, little is known about the association of sUMOD levels with long-term kidney outcomes in older adults, a population with a high prevalence of interstitial fibrosis and tubular atrophy.

STUDY DESIGN

Case-cohort study and case-control study.

SETTING & PARTICIPANTS

Random subcohort (n=933) and additional cases of end-stage kidney disease (ESKD) and kidney function decline (≥30% decline in estimated glomerular filtration rate [eGFR]) during follow-up of the Cardiovascular Health Study (CHS).

PREDICTOR

sUMOD level.

OUTCOMES

ESKD (n=14) from the random subcohort and all additional ESKD cases from outside the random subcohort (n=39) during follow-up (10 years, case-cohort study); kidney function decline of≥30% eGFR at 9 years of follow-up in individuals with repeated eGFR assessments from the random subcohort (n=56) and additional cases (n=123). 224 participants from the random subcohort served as controls (case-control study).

ANALYTICAL APPROACH

Modified multivariable Cox regression for ESKD and multivariable logistic regression for kidney function decline. Both analyses adjusted for demographics, eGFR, urinary albumin-creatinine ratio, and other kidney disease progression risk factors.

RESULTS

Mean age of the random subcohort was 78 years, 40% were men, 15% were black. Mean sUMOD level was 127±64ng/mL and eGFR was 63±19mL/min/1.73m2. In multivariable analysis, each 1-SD higher sUMOD level was associated with 63% lower risk for ESKD (HR, 0.37; 95% CI, 0.14-0.95). In demographic-adjusted analyses of kidney function decline, each 1-SD higher sUMOD level was associated with 25% lower odds of kidney function decline (OR, 0.75; 95% CI, 0.60-0.95); after multivariable adjustment, the association was attenuated and no longer significant (OR, 0.88; 95% CI, 0.68-1.14).

LIMITATIONS

Possibility of survival bias in the kidney function decline analysis.

CONCLUSIONS

Higher sUMOD levels may identify elderly persons at reduced risk for ESKD.

Authors+Show Affiliations

Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston, MA; Division of Nephrology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.Department of Biostatistics, University of Washington, Seattle, WA.Division of Nephrology-Hypertension, University of California San Diego, San Diego, CA.Division of Nephrology-Hypertension, University of California San Diego, San Diego, CA.Department of Nephrology and Hypertension, Cincinnati Children's Hospital, University of Cincinnati, Cincinnati, OH.Department of Nephrology and Hypertension, Cincinnati Children's Hospital, University of Cincinnati, Cincinnati, OH.Benjamin Leon Center for Geriatric Research and Education, Herbert Wertheim College of Medicine, Florida International University, Miami, FL.Division of General Internal Medicine, University of California San Francisco, San Francisco, CA.Division of Nephrology, Kidney Research Institute, University of Washington, Seattle, WA.Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston, MA. Electronic address: msarnak@tuftsmedicalcenter.org.

Pub Type(s)

Journal Article
Observational Study
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

31128770

Citation

Steubl, Dominik, et al. "Association of Serum Uromodulin With ESKD and Kidney Function Decline in the Elderly: the Cardiovascular Health Study." American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation, vol. 74, no. 4, 2019, pp. 501-509.
Steubl D, Buzkova P, Garimella PS, et al. Association of Serum Uromodulin With ESKD and Kidney Function Decline in the Elderly: The Cardiovascular Health Study. Am J Kidney Dis. 2019;74(4):501-509.
Steubl, D., Buzkova, P., Garimella, P. S., Ix, J. H., Devarajan, P., Bennett, M. R., Chaves, P. H. M., Shlipak, M. G., Bansal, N., & Sarnak, M. J. (2019). Association of Serum Uromodulin With ESKD and Kidney Function Decline in the Elderly: The Cardiovascular Health Study. American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation, 74(4), 501-509. https://doi.org/10.1053/j.ajkd.2019.02.024
Steubl D, et al. Association of Serum Uromodulin With ESKD and Kidney Function Decline in the Elderly: the Cardiovascular Health Study. Am J Kidney Dis. 2019;74(4):501-509. PubMed PMID: 31128770.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association of Serum Uromodulin With ESKD and Kidney Function Decline in the Elderly: The Cardiovascular Health Study. AU - Steubl,Dominik, AU - Buzkova,Petra, AU - Garimella,Pranav S, AU - Ix,Joachim H, AU - Devarajan,Prasad, AU - Bennett,Michael R, AU - Chaves,Paolo H M, AU - Shlipak,Michael G, AU - Bansal,Nisha, AU - Sarnak,Mark J, Y1 - 2019/05/22/ PY - 2018/09/16/received PY - 2019/02/28/accepted PY - 2019/5/28/pubmed PY - 2020/4/1/medline PY - 2019/5/27/entrez KW - Tamm-Horsfall-protein KW - Uromodulin KW - cardiovascular disease (CVD) KW - chronic kidney disease (CKD) KW - end-stage renal disease (ESRD) KW - estimated glomerular filtration (eGFR) KW - kidney function decline KW - mortality KW - renal end point KW - sUMOD KW - tubular function SP - 501 EP - 509 JF - American journal of kidney diseases : the official journal of the National Kidney Foundation JO - Am J Kidney Dis VL - 74 IS - 4 N2 - RATIONALE & OBJECTIVE: Uromodulin is released by tubular epithelial cells into the serum and lower levels are associated with more severe interstitial fibrosis and tubular atrophy. Low serum uromodulin (sUMOD) levels are associated with mortality and cardiovascular disease. However, little is known about the association of sUMOD levels with long-term kidney outcomes in older adults, a population with a high prevalence of interstitial fibrosis and tubular atrophy. STUDY DESIGN: Case-cohort study and case-control study. SETTING & PARTICIPANTS: Random subcohort (n=933) and additional cases of end-stage kidney disease (ESKD) and kidney function decline (≥30% decline in estimated glomerular filtration rate [eGFR]) during follow-up of the Cardiovascular Health Study (CHS). PREDICTOR: sUMOD level. OUTCOMES: ESKD (n=14) from the random subcohort and all additional ESKD cases from outside the random subcohort (n=39) during follow-up (10 years, case-cohort study); kidney function decline of≥30% eGFR at 9 years of follow-up in individuals with repeated eGFR assessments from the random subcohort (n=56) and additional cases (n=123). 224 participants from the random subcohort served as controls (case-control study). ANALYTICAL APPROACH: Modified multivariable Cox regression for ESKD and multivariable logistic regression for kidney function decline. Both analyses adjusted for demographics, eGFR, urinary albumin-creatinine ratio, and other kidney disease progression risk factors. RESULTS: Mean age of the random subcohort was 78 years, 40% were men, 15% were black. Mean sUMOD level was 127±64ng/mL and eGFR was 63±19mL/min/1.73m2. In multivariable analysis, each 1-SD higher sUMOD level was associated with 63% lower risk for ESKD (HR, 0.37; 95% CI, 0.14-0.95). In demographic-adjusted analyses of kidney function decline, each 1-SD higher sUMOD level was associated with 25% lower odds of kidney function decline (OR, 0.75; 95% CI, 0.60-0.95); after multivariable adjustment, the association was attenuated and no longer significant (OR, 0.88; 95% CI, 0.68-1.14). LIMITATIONS: Possibility of survival bias in the kidney function decline analysis. CONCLUSIONS: Higher sUMOD levels may identify elderly persons at reduced risk for ESKD. SN - 1523-6838 UR - https://www.unboundmedicine.com/medline/citation/31128770/Association_of_Serum_Uromodulin_With_ESKD_and_Kidney_Function_Decline_in_the_Elderly:_The_Cardiovascular_Health_Study_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0272-6386(19)30664-X DB - PRIME DP - Unbound Medicine ER -