Association of Kidney Tubule Dysfunction and Injury Biomarkers With Long-Term Risk of Acute Kidney Injury During Acute Congestive Heart Failure Hospitalizations

Rationale & Objective Acute kidney injury (AKI) frequently complicates acute heart failure (HF), yet predictors of HF-associated AKI remain poorly defined. We examined whether urinary biomarkers of tubular health, measured years before HF hospitalization predict subsequent AKI risk. Study Design Case-control study Setting & Participants Adults ≥45 years in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study hospitalized for acute heart failure (HF). We compared 400 acute kidney injury (AKI) cases with 419 frequency-matched non-AKI controls. Exposures Biomarkers of tubular function (alpha-1 microglobulin [A1M], uromodulin [UMOD], epidermal growth factor [EGF]) and injury (kidney injury molecule-1 [KIM-1]). Outcomes AKI, defined as a serum creatinine rise ≥0.3 mg/dL during HF admission. Analytical Approach Logistic regression adjusted for demographics, comorbidities, urine creatinine, time to HF, eGFR and albuminuria. Results Median time was 5.6 years from baseline to HF. AKI cases exhibited higher A1M and lower UMOD and EGF than non-AKI controls. Higher EGF was strongly associated with lower AKI risk (OR for 4th vs. 1st quartile: 0.27, 95% CI 0.16–0.46), persisting after adjustment for eGFR and albuminuria (OR 0.49, 95% CI 0.27–0.91). Continuous EGF analysis showed a similar trend but was not significant in fully adjusted models (OR per 2-fold increase: 0.89, 95% CI 0.77–1.04). No other biomarkers independently predicted AKI. Limitations Extended time from baseline to HF hospitalization. Conclusions Higher urinary EGF, measured years before HF, is associated with lower risk of AKI during HF hospitalization. Tubular health may be associated with resilience against HF-related kidney injury.