UCSF

Background

Kidney damage and reduced kidney function are potent risk factors for heart failure, but existing studies are limited to assessing albuminuria or estimated glomerular filtration rate (eGFR). We evaluated the associations of levels of urinary biomarkers of kidney tubular injury (interleukin 18 [IL-18] and kidney injury molecule 1 [KIM-1]) with future risk of heart failure.

Study design

Retrospective cohort study.

Setting & participants

2,917 participants without heart failure in the Health, Aging, and Body Composition (Health ABC) cohort.

Predictors

Ratios of urine KIM-1, IL-18, and albumin to creatinine (KIM-1:Cr, IL-18:Cr, and ACR, respectively).

Outcomes

Incident heart failure over a median follow-up of 12 years.

Results

Median values of each marker at baseline were 812 (IQR, 497-1,235)pg/mg for KIM-1:Cr, 31 (IQR, 19-56)pg/mg for IL-18:Cr, and 8 (IQR, 5-19) mg/g for ACR. 596 persons developed heart failure during follow-up. The top quartile of KIM-1:Cr was associated with risk of incident heart failure after adjustment for baseline eGFR, heart failure risk factors, and ACR (HR, 1.32; 95% CI, 1.02-1.70) in adjusted multivariate proportional hazards models. The top quartile of IL-18:Cr also was associated with heart failure in a model adjusted for risk factors and eGFR (HR, 1.35; 95% CI, 1.05-1.73), but was attenuated by adjustment for ACR (HR, 1.15; 95% CI, 0.89-1.48). The top quartile of ACR had a stronger adjusted association with heart failure (HR, 1.96; 95% CI, 1.53-2.51).

Limitations

Generalizability to other populations is uncertain.

Conclusions

Higher urine KIM-1 concentrations were associated independently with incident heart failure risk, although the associations of higher ACR were of stronger magnitude.