Tubule dysfunction and injury and future risk of sepsis-associated acute kidney injury

Novel biomarkers can quantify both kidney tubule function, including proximal tubule reabsorptive (urine α-1 microglobulin (uα1m)) and tubule protein synthesis capacities (urine uromodulin (uUMOD)), and tubular injury (urine neutrophil gelatinase-associated lipocalin (uNGAL)). In a blood pressure trial, we reported that lower reabsorptive and synthetic protein capacity at times of health predicted future risk of acute kidney injury (AKI), but most AKI was related to hemodynamic causes in this trial. Associations between tubular function and injury and future AKI related to other causes is unknown.

We performed a case-control study in REGARDS, a population-based cohort study, among participants who provided urine at the baseline visit. We matched each septic AKI case by age, sex, race, and time from baseline to hospital admission 1 : 1 to a participant with sepsis who did not develop AKI (controls). Using conditional logistic regression, we evaluated the associations of uα1m, uUMOD, urine ammonium, and uNGAL with septic AKI.

Mean age was 69 ± 8 years, 44% were female, and 39% were Black participants. Median baseline eGFR among cases and controls was 73 (55, 90) and 82 (65, 92) mL/min/1.73m², and median albuminuria was 19 (8, 87) vs. 9 (5, 22) mg/g, respectively. No independent associations were observed between the tubule function or injury markers and subsequent risk of septic AKI once models were adjusted for baseline albuminuria, estimated glomerular filtration rate, and other risk factors.

Among community participants, tubule function and injury markers at times of health were not independently associated with future risk of septic AKI.