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 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.