Markers of Tubule Cell Dysfunction Predict AKI

Among patients with chronic kidney disease (CKD), baseline biomarkers of tubule cell function are independent predictors of the later development of acute kidney injury (AKI), reports a study in Kidney International.

The researchers analyzed data on 2351 participants from the randomized Systolic Blood Pressure Intervention Trial (SPRINT). All had CKD (mean estimated glomerular filtration rate [eGFR] 49 mL/min/1.73 m2) and hypertension at baseline, but not diabetes. Participants were assigned intensive or standard systolic blood pressure targets: less than 120 versus less than 140 mm Hg. Study outcomes showed lower rates of cardiovascular disease and death with intensive blood pressure-lowering therapy, but a higher risk of AKI.

The current study analyzed baseline data on urinary markers of renal tubule dysfunction (alpha-1-microglobulin [α1m], beta-2 microglobulin [β2m], and uromodulin [UMOD]) and markers of renal tubule injury (kidney injury molecule-1 [KIM-1], neutrophil gelatinase-associated lipocalin [NGAL], interleukin-18 [IL-18], monocyte chemoattractant protein-1 [MCP-1]) and chitinase-3-like protein [YKL-40]). The two types of markers were analyzed for association with the risk of AKI, with adjustment for other factors.

Over a mean follow-up of 3.8 years, AKI developed in 184 participants—a rate of 7.8%. Acute kidney injury was more frequent in men and in black patients, as well as those assigned to the intensive blood pressure–lowering therapy.

Two markers of kidney tubular dysfunction—UMOD and α1m—were associated with AKI, independent of eGFR and albuminuria. Hazard ratios were 0.68 per twofold increase in UMOD and 1.20 per twofold increase in α1m. At the highest versus lowest quartiles, baseline UMOD and α1m were more strongly associated with AKI risk (HR 2.04 and 1.57, respectively) compared to the 3-month change in serum creatinine (HR 1.27). In contrast, increases of tubule cell injury markers occurred mainly after the AKI event.

Identifying CKD patients at particularly high risk of AKI may help to inform monitoring and prevention strategies. This study identifies markers of tubule cell dysfunction—lower UMOD and higher α1M—as predictors of future AKI risk. The researchers conclude: “[T]ubular cell function markers may reflect a vulnerable kidney with diminished capacity to counter acute insults and thus identify CKD individuals at heightened risk of future AKI” [Bullen AL, et al. The SPRINT trial suggests that markers of tubule cell function in the urine associate with risk of subsequent acute kidney injury while injury markers elevate after the injury. Kidney Int 2019; DOI: https://doi.org/10.1016].

June 2019 (Vol. 11, Number 6)