Association of serum uromodulin with ESKD and kidney function decline in the elderly: the cardiovascular health study
D Steubl, P Buzkova, PS Garimella, JH Ix… - American Journal of …, 2019 - Elsevier
American Journal of Kidney Diseases, 2019•Elsevier
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 & …
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 & …
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 ± 64 ng/mL and eGFR was 63 ± 19 mL/min/1.73 m2. 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.
Elsevier