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Abstract: FR-PO197

Markers of Kidney Tubule Function and Risk of Cardiovascular Disease Events and Mortality in the SPRINT Trial

Session Information

Category: CKD (Non-Dialysis)

  • 1902 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

  • Garimella, Pranav S., University of California San Diego, San Diego, Colorado, United States
  • Lee, Alexandra K., Kidney Health Research Collaborative, UCSF & VA, San Francisco, California, United States
  • Ambrosius, Walter T., Wake Forest School of Medicine, Winston-Salem, North Carolina, United States
  • Bhatt, Udayan Y., The Ohio State University, Dublin, Ohio, United States
  • Cheung, Alfred K., University of Utah, Salt Lake City, Utah, United States
  • Chonchol, Michel, University of Colorado , Aurora, Colorado, United States
  • Craven, Timothy, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States
  • Hawfield, Amret T., Wake Forest School of Medicine, Winston-Salem, North Carolina, United States
  • Jotwani, Vasantha, Kidney Health Research Collaborative, UCSF & VA, San Francisco, California, United States
  • Killeen, Anthony Alexander, University of Minnesota, Minneapolis, Minnesota, United States
  • Punzi, Henry A., Punzi Medical Center, Carrollton, Texas, United States
  • Sarnak, Mark J., Tufts Medical Center, Boston, Massachusetts, United States
  • Shlipak, Michael, San Francisco VA Medical Center, San Francisco, California, United States
  • Ix, Joachim H., UCSD, San Diego, California, United States
Background

Biomarkers of tubule injury, inflammation and fibrosis have emerged as prognosticators of kidney and cardiovascular disease (CVD) outcomes. However, markers of tubular function have not been adequately evaluated as risk factors for CVD.

Methods

Using a sample of 2,377 persons with CKD at the baseline SPRINT visit, we evaluated the association of three urinary markers of tubular function; alpha-1 microglobulin (α1m), beta-2 microglobulin (β2m) and uromodulin with CVD events, heart failure and all-cause mortality using Cox regression over 3.7 years of follow up. Markers were log-transformed given skewed distributions.

Results

Mean age was 73 years, 40% were woman, 26% black, and mean glomerular filtration rate (GFR) was 46±11 ml/min/1.73m2. In multivariable analyses, each two-fold higher α1m was associated with a 33%, 31%, 61% and 85% greater risk of composite CVD, mortality, CVD death and acute coronary syndromes (ACS), respectively [table]. There was no association of β2m with any of the outcomes. Each two-fold higher uromodulin was associated with a 22%, 30% and 31% lower adjusted risk of composite CVD, HF and CVD death, respectively. These associations were not modified by baseline CVD or intervention arm.

Conclusion

Among non-diabetic persons with CKD, biomarkers of tubular function are associated with incident CVD and mortality independent of GFR and albuminuria.

Association of tubular function biomarkers with clinical outcomes among SPRINT participants with CKD

Funding

  • NIDDK Support