Higher baseline urinary uromodulin was associated with slower annual eGFR decline (estimate 0.34; 95% CI 0.08-0.60) in the standard BP arm, an effect diminished by intensive BP control.
RCT (n=2,428)
Are baseline urinary biomarkers of tubule function associated with eGFR decline in patients with hypertension and CKD, and does intensive blood pressure control modify this association?
Baseline urinary biomarkers of tubular function predict eGFR decline in hypertensive patients with CKD, but this predictive value is attenuated by intensive blood pressure control.
Effect estimate: Estimate 0.34 (95% CI 0.08-0.60)
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.
Jotwani et al. (Wed,) conducted a rct in Hypertension and chronic kidney disease (n=2,428). Urinary biomarkers (uromodulin, β2-microglobulin, α1-microglobulin) was evaluated on Annualized relative change in eGFR (Estimate 0.34, 95% CI 0.08-0.60). Higher baseline urinary uromodulin was associated with slower annual eGFR decline (estimate 0.34; 95% CI 0.08-0.60) in the standard BP arm, an effect diminished by intensive BP control.