Background: Kidney tubular atrophy on biopsy is a strong predictor of chronic kidney disease (CKD) progression, but tubular health is poorly quantified by traditional measures including estimated glomerular filtration rate (eGFR) and albuminuria. We hypothesized that urinary biomarkers of impaired tubule function would be associated with faster eGFR declines in persons with CKD. Methods: We measured baseline urine concentrations of uromodulin, β2-microglobulin (β2m), and α1-microglobulin (α1m) among 2,428 participants of the Systolic Blood Pressure Intervention Trial with an eGFR <60 mL/min/1.73 m2. We used linear mixed models to evaluate biomarker associations with annualized relative change in eGFR, stratified by randomization arm. Results: At baseline, the mean age was 73 ± 9 years and eGFR was 46 ± 11 mL/min/1.73 m2. In the standard blood pressure treatment arm, each 2-fold higher urinary uromodulin was associated with slower % annual eGFR decline (0.34 [95% CI: 0.08, 0.60]), whereas higher urinary β2m was associated with faster % annual eGFR decline (-0.10 [95% CI: -0.18, -0.02]) in multivariable-adjusted models including baseline eGFR and albuminuria. Associations were weaker and did not reach statistical significance in the intensive blood pressure treatment arm for either uromodulin (0.11 [-0.13, 0.35], p value for interaction by treatment arm = 0.045) or β2m (-0.01 [-0.08, 0.08], p value for interaction = 0.001). Urinary α1m was not independently associated with eGFR decline in the standard (0.01 [-0.22, 0.23]) or intensive (0.03 [-0.20, 0.25]) arm. Conclusions: Among trial participants with hypertension and CKD, baseline measures of tubular function were associated with subsequent declines in kidney function, although these associations were diminished by intensive blood pressure control.
Bibliographical noteFunding Information:
M.G.S. has worked as a consultant for the University of Washington and has equity in TAI Diagnostics and Cricket Health, Inc. J.H.I. holds an investigator initiated research grant from Baxter International Inc. B.I.F. is a consultant for AstraZeneca and Rena-lytix AI Pharmaceuticals. P.S.G. has received speaker fees from Ot-suka. The results presented in this paper have not been published previously in whole or part, except in abstract form.
© 2020 S. Karger AG, Basel. All rights reserved.
Copyright 2020 Elsevier B.V., All rights reserved.
- Chronic kidney disease
- Urinary biomarkers
PubMed: MeSH publication types
- Journal Article
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't