Abstract: TH-PO474

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

Session Information

Category: Chronic Kidney Disease (Non-Dialysis)

  • 303 CKD: Epidemiology, Outcomes - Cardiovascular

Authors

  • Jotwani, Vasantha, UCSF, San Francisco, California, United States
  • Katz, Ronit, University of Washington, Seattle, Washington, United States
  • Ix, Joachim H., UCSD, San Diego, California, United States
  • Gutierrez, Orlando M., UAB School of Medicine , Birmingham, Alabama, United States
  • Parikh, Chirag R., Yale University and VAMC, New Haven, Connecticut, United States
  • Sarnak, Mark J., Tufts Medical Center, Boston, Massachusetts, United States
  • Shlipak, Michael, San Francisco VA Medical Center, San Francisco, California, United States
Background

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 (α1m), pro-collagen type III N-terminal pro-peptide (PIIINP), and neutrophil gelatinase-associated lipocalin (NGAL), would be associated with higher risks for cardiovascular events and mortality among elders.

Methods

In this case-cohort study of participants enrolled in the Health, Aging, and Body Composition Study, we measured urine concentrations of α1m, PIIINP, and NGAL among randomly selected CVD cases (n=245), heart failure cases (n=220), and a subcohort (n=502). We used Cox proportional hazards models to evaluate biomarker associations with incident CVD, heart failure, and all-cause mortality.

Results

At baseline, the mean age was 74 years and eGFR was 73 ml/min/1.73m2. There were 248 deaths in the subcohort over a median follow-up of 12.4 years. After multivariable adjustment, urine α1m, PIIINP and NGAL were each associated with higher risks for CVD (Table). Urine α1m and NGAL were also associated with higher mortality risk. The biomarkers did not have statistically significant associations with heart failure.

Conclusion

Kidney tubular damage is an independent risk factor for CVD and death among elders. Future studies should investigate mechanisms by which renal tubular damage may adversely impact cardiovascular risk.

Associations of individual urine biomarkers with incident CVD, heart failure, and mortality
BiomarkerIncident CVD
HR (95% CI)
Heart failure
HR (95% CI)
All-cause mortality
HR (95% CI)
α1-microglobulin1.44 (1.11, 1.87)1.18 (0.94, 1.48)1.26 (1.07, 1.47)
PIIINP1.20 (1.00, 1.44)0.90 (0.77, 1.05)1.06 (0.94, 1.18)
NGAL1.12 (1.04, 1.20)0.96 (0.88, 1.04)1.07 (1.02, 1.12)

Hazard ratios per doubling in biomarker. Models adjust for demographics, cardiovascular risk factors, eGFR, urine albumin, and urine creatinine.

Funding

  • NIDDK Support