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

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• Picked for Internal Medicine (paper of the day, 10 October 2026): Higher urinary EGF linked to lower AKI risk during acute

Abstract

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 aged ≥45 years in the reasons for geographic and racial differences in stroke study hospitalized for acute HF. We compared 400 AKI cases with 419 frequency-matched non-AKI controls. EXPOSURES: Biomarkers of tubular function (alpha-1 microglobulin, uromodulin, epidermal growth factor levels) and injury (kidney injury molecule-1 levels). OUTCOMES: AKI, defined as a serum creatinine level rise ≥ 0.3 mg/dL during HF admission. ANALYTICAL APPROACH: Logistic regression adjusted for demographics, comorbidities, urine creatinine, time to HF, estimated glomerular filtration rate, and albuminuria. RESULTS: Median time was 5.6 years from baseline to HF. AKI cases exhibited higher levels of alpha-1 microglobulin and lower levels of uromodulin and EGF than non-AKI controls. Higher EGF level was strongly associated with lower AKI risk (OR for fourth vs first quartile: 0.27; 95% CI, 0.16-0.46), persisting after adjustment for estimated glomerular filtration rate and albuminuria (OR, 0.49; 95% CI, 0.27-0.91). Continuous EGF level analysis showed a similar trend but was not significant in fully adjusted models (odds ratio 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 levels, measured years before HF, are associated with a lower risk of AKI during HF hospitalization. Tubular health may be associated with resilience against HF-related kidney injury.

Abstract as published, via PubMed.