Urinary Biomarkers of Kidney Tubular Damage and Risk of Cardiovascular Disease and Mortality in Elders

Vasantha Jotwani, Ronit Katz, Joachim H. Ix, Orlando M. Gutiérrez, Michael Bennett, Chirag Parikh, Steven R. Cummings, Mark J. Sarnak, Michael G. Shlipak

Research output: Contribution to journalArticle

Abstract

Rationale & Objective: Novel urinary biomarkers have enabled earlier detection of kidney tubular damage, but their prognostic value for adverse cardiovascular outcomes is uncertain. We hypothesized that tubular damage, measured by urine α1-microglobulin (A1M), amino-terminal propeptide of type III procollagen (PIIINP), and neutrophil gelatinase-associated lipocalin (NGAL), would be associated with higher risks for cardiovascular events and mortality among elders. Study Design: Case-cohort study. Setting & Participants: This study included a randomly selected subcohort (n=502), cardiovascular disease (CVD) cases (n=245), and heart failure cases (n=220) from the Health, Aging, and Body Composition (Health ABC) Study. Predictors: Baseline urine A1M, PIIINP, and NGAL concentrations. Outcomes: Incident CVD, heart failure, and all-cause mortality. Analytical Approach: Cox proportional hazards models were used to evaluate biomarker associations with each outcome. Results: At baseline, mean age was 74 years and estimated glomerular filtration rate was 73 mL/min/1.73 m2. After adjustment for demographics, estimated glomerular filtration rate, albumin-creatinine ratio, and other cardiovascular risk factors, each doubling in biomarker concentration was associated with the following adjusted HRs for CVD: A1M, 1.51 (95% CI, 1.16-1.96); PIIINP, 1.21 (95% CI, 1.00-1.46); and NGAL, 1.12 (95% CI, 1.05-1.20). There were 248 deaths in the subcohort during a median follow-up of 12.4 years. Adjusted associations of each biomarker (HR per doubling) with all-cause mortality were: A1M, 1.29 (95% CI, 1.10-1.51); PIIINP, 1.05 (95%, 0.94-1.18); and NGAL, 1.07 (95% CI, 1.02-1.12). Biomarker concentrations did not have statistically significant associations with heart failure after multivariable adjustment. Limitations: Urine biomarkers were measured at a single time point; no validation cohort available. Conclusions: Kidney tubular damage is an independent risk factor for CVD and death among elders. Future studies should investigate mechanisms by which kidney tubular damage may adversely affect cardiovascular risk.

Keywords

  • amino-terminal propeptide of type III procollagen (PIIINP)
  • cardiovascular disease (CVD)
  • elderly
  • heart failure (HF)
  • mortality
  • neutrophil gelatinase-associated lipocalin (NGAL)
  • prognostication
  • tubular injury markers
  • Urine biomarker
  • α-microglobulin (A1M)

ASJC Scopus subject areas

  • Nephrology

Cite this

Urinary Biomarkers of Kidney Tubular Damage and Risk of Cardiovascular Disease and Mortality in Elders. / Jotwani, Vasantha; Katz, Ronit; Ix, Joachim H.; Gutiérrez, Orlando M.; Bennett, Michael; Parikh, Chirag; Cummings, Steven R.; Sarnak, Mark J.; Shlipak, Michael G.

In: American Journal of Kidney Diseases, 01.01.2018.

Research output: Contribution to journalArticle