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Abstract: FR-PO193

Kidney Tubular Damage and Risk of Cardiovascular Disease and Mortality Among SPRINT Participants with CKD

Session Information

Category: CKD (Non-Dialysis)

  • 1901 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention

Authors

  • Jotwani, Vasantha, Kidney Health Research Collaborative & SFVAMC, San Francisco, California, United States
  • Lee, Alexandra K., Kidney Health Research Collaborative & SFVAMC, San Francisco, California, United States
  • Katz, Ronit, University of Washington, Seattle, Washington, United States
  • Garimella, Pranav S., UCSD, San Diego, California, United States
  • Malhotra, Rakesh, UCSD, San Diego, California, United States
  • Estrella, Michelle M., Kidney Health Research Collaborative & SFVAMC, San Francisco, California, United States
  • Ix, Joachim H., UCSD, San Diego, California, United States
  • Shlipak, Michael, Kidney Health Research Collaborative & SFVAMC, San Francisco, California, United States
Background

Novel urine biomarkers have enabled earlier detection of kidney tubular damage, but their prognostic value for adverse cardiovascular outcomes is uncertain. We hypothesized that urinary biomarkers of tubular injury would be associated with higher risks for cardiovascular events and mortality in persons with chronic kidney disease (CKD).

Methods

We measured urine concentrations of interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), monocyte chemoattractant protein-1 (MCP-1), and chitinase-3-like protein-1 (YKL-40) among 2,377 participants of the Systolic Blood Pressure Intervention Trial who had an eGFR<60 ml/min/1.73 m2. We used Cox proportional hazards models to evaluate biomarker associations with CVD events and all-cause mortality.

Results

At baseline, the mean age was 72±9 years and eGFR was 48±11 ml/min/1.73m2. Over a median of 3.8 years, 305 CVD events (3.6% per year) and 233 all-cause deaths (2.6% per year) occurred. After multivariable adjustment, including baseline eGFR and albuminuria, higher urine IL-18 and YKL-40 concentrations were independently associated with higher mortality risk (Table). The biomarkers did not have statistically significant associations with CVD events. Associations were similar when stratified by randomization arm.

Conclusion

Among hypertensive, nondiabetic patients with CKD, urine IL-18 and YKL-40 were independently associated with higher mortality risk but not with CVD events. The remaining markers were not associated with CVD or mortality risk.

Associations of urine biomarkers with CVD events and mortality among SPRINT participants with CKD at baseline (N = 2,377)
BiomarkerCVD events
Hazard Ratio (95% CI)
All-cause mortality
Hazard Ratio (95% CI)
IL-181.06 (0.96, 1.18)1.14 (1.01, 1.29)
KIM-10.93 (0.86, 1.02)0.96 (0.86, 1.06)
NGAL1.03 (0.96, 1.11)1.03 (0.95, 1.12)
MCP-11.04 (0.94, 1.15)1.03 (0.91, 1.17)
YKL-401.04 (0.99, 1.10)1.08 (1.02, 1.14)

Hazard ratios per doubling in biomarker. Models adjust for age, sex, race, intervention arm, baseline eGFR, urine albumin, urine creatinine, smoking status, history of CVD or heart failure, number of antihypertensive medications, statin use, systolic and diastolic blood pressures, body mass index, and lipid profiles.

Funding

  • NIDDK Support