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 whether urine biomarkers of glomerular and tubular health are associated with subsequent recovery of estimated glomerular filtration rate (eGFR) after acute kidney injury (AKI) has occurred in the ambulatory setting during blood pressure (BP) treatment.

Study design: Longitudinal analysis of clinical trial participants.

Setting & participants: 652 participants in SPRINT (the Systolic Blood Pressure Intervention Trial) in whom AKI developed in the ambulatory setting, defined as an increase in serum creatinine of≥0.3mg/dL from baseline detected at the 1-year or 2-year study visit.

Exposure: Eight urine biomarkers indexed to urine creatinine (Cr) measured at baseline and at the study visit when ambulatory AKI was detected.

Outcome: <50% recovery in eGFR ("nonrecovery") at 12 months.

Analytical approach: Multivariable logistic regression models, stratified by randomization arm, to evaluate biomarker associations with the odds of nonrecovery of eGFR.

Results: Mean age was 70±10 years; eGFRs were 62±25mL/min/1.73m² at baseline and 42±12mL/min/1.73m² at the time of ambulatory AKI. Among biomarkers measured at the time ambulatory AKI was detected, higher urine albumin-Cr ratio (OR per 1-standard deviation higher, 1.72; 95% CI, 1.10-2.70) and lower epidermal growth factor/Cr (OR, 0.46; 95% CI, 0.26-0.79) were associated with nonrecovery of eGFR in the standard BP treatment arm; higher urine α-1 microglobulin-Cr ratio (OR, 1.45; 1.09-1.92), lower epidermal growth factor Cr ratio (OR, 0.62; 95% CI, 0.46-0.83), and lower kidney injury molecule-1-Cr ratio (OR, 0.75; 95% CI, 0.59-0.96) were associated with nonrecovery of eGFR in the intensive BP treatment arm.

Limitations: Persons with diabetes and proteinuria>1g/d were excluded.

Conclusions: Among adults enrolled in a BP treatment trial who experienced ambulatory AKI, urine biomarkers reflecting glomerular injury and tubular dysfunction may help to distinguish whether kidney function will subsequently recover.

Plain-language summary: Increases in serum creatinine concentration 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 in whom an increase in serum creatinine occurs. 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.

Keywords: Kidney tubules; SPRINT; acute kidney injury; biomarker; blood pressure; hypertension; prerenal azotemia; renal failure.