Associations of Urine Biomarkers During Ambulatory Acute Kidney Injury With Subsequent Recovery in Kidney Function: Findings From the SPRINT Study.

Abstract

RATIONALE & OBJECTIVE Serum creatinine elevations in the ambulatory setting frequently occur during antihypertensive treatment and complicate clinical management, but few tools are available to distinguish whether kidney function will recover in this setting. This study evaluated if urine biomarkers of glomerular and tubular health are associated with subsequent recovery of eGFR after acute kidney injury (AKI) occurred in the ambulatory setting during blood pressure treatment. STUDY DESIGN Longitudinal analysis of clinical trial participants. SETTING & PARTICIPANTS 652 participants in the Systolic Blood Pressure Intervention Trial (SPRINT) who developed AKI in the ambulatory setting, defined as a rise in serum creatinine of ≥0.3 mg/dL from baseline detected at the 1-year or 2-year study visits. EXPOSURE Eight urine biomarkers measured at baseline and at the study visit when ambulatory AKI was detected. OUTCOME <50% recovery in eGFR ("non-recovery") at 12-months. ANALYTICAL APPROACH Multivariable logistic regression models, stratified by randomization arm, to evaluate biomarker associations with the odds of non-recovery in eGFR. RESULTS Mean age was 70 ±10 years; eGFR at baseline was 62 ± 25 mL/min/1.73 m2, and eGFR at the time of serum creatinine elevation was 42 ± 12 mL/min/1.73 m2. Among biomarkers measured at the time ambulatory AKI was detected, higher urine albumin (OR per 1-SD higher: 1.72; 95% CI: 1.10, 2.70) and lower epidermal growth factor (OR 0.46; 95% CI: 0.26, 0.79) were associated with non-recovery in the standard BP treatment arm; higher urine α-1 microglobulin (OR 1.45; 1.09, 1.92), lower epidermal growth factor (OR 0.62; 95% CI: 0.46, 0.83) and lower kidney injury molecule-1 (OR 0.75; 95% CI: 0.59, 0.96) were associated with non-recovery of eGFR in the intensive BP treatment arm. LIMITATIONS Persons with diabetes and proteinuria >1 g/d were excluded. CONCLUSIONS Among adults enrolled in a BP treatment trial who developed ambulatory AKI, urine biomarkers reflecting glomerular injury and tubular dysfunction may help to distinguish whether kidney function will subsequently recover. PLAIN-LANGUAGE SUMMARY Elevations in serum creatinine can occur when treating hypertension and complicate clinical management, but there are few tools available to distinguish whether an individual's kidney function will subsequently recover. In this study, we investigated the association of kidney biomarkers measured in the urine with subsequent kidney function among individuals in the outpatient setting who develop a rise in serum creatinine. We found that biomarkers reflecting worse glomerular injury and tubular dysfunction are associated with the risk of an individual's kidney function not recovering. These results suggest that a broader assessment of kidney health when serum creatinine increases in the outpatient setting may help distinguish subsequent trajectories in kidney function.