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Abstract: FR-PO196

Urine Markers of Kidney Tubule Cell Injury and Kidney Function Decline: Results from SPRINT Trial

Session Information

Category: CKD (Non-Dialysis)

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

Authors

  • Malhotra, Rakesh, UCSD, San Diego, California, United States
  • Katz, Ronit, University of Washington, Seattle, Washington, United States
  • Jotwani, Vasantha, UCSF, San Francisco, California, United States
  • Shlipak, Michael, San Francisco VA Medical Center, San Francisco, California, United States
  • Ix, Joachim H., UCSD, San Diego, California, United States
Background

Tubulo-interstitial fibrosis and atrophy are important risk markers for chronic kidney disease (CKD) progression on kidney biopsy, but are not evaluated in clinical testing. We examined the association between urinary kidney tubule injury biomarkers with subsequent loss of kidney function in persons with non-diabetic CKD who participated in The Systolic Blood Pressure Intervention Trial (SPRINT).

Methods

Among 2428 SPRINT participants with CKD (eGFR <60 ml/min/1.73m2) at baseline, we measured urine concentrations of markers of injury (interleukin-18 [uIL-18], kidney injury molecule-1[uKIM-1], and neutrophil gelatinase-associated lipocalin [uNGAL]), inflammation (monocyte chemoattractant protein-1 [uMCP-1]) and repair (human cartilage glycoprotein-40 [uYKL-40]). We used linear mixed models to evaluate the associations of each biomarker with annualized change in eGFR; and used proportional hazards regression to evaluate the renal composite outcome of 50% eGFR decline, transplant or end-stage renal disease.

Results

At baseline, the mean age was 73±9 years and mean eGFR was 46±11 ml/min/1.73m2; 60% were men and 66% were white. During 3.8 years mean follow-up, there were 87 composite renal events. In adjusted continuous models, higher uIL-18, uNGAL and uYKL-40 concentrations were associated with faster eGFR decline (Table). Associations with the renal composite endpoint appeared non-linear, with heightened risk in the highest quartile. The high quartiles of uKIM-1 (hazard ratio 2.84 [95% CI 1.31 to 6.17), uYKL-40 (1.95 [1.08 to 3.51]) and uMCP-1 (2.43 [1.13 to 5.23]) were each associated with risk of the renal composite outcome relative to the lowest quartiles. Associations were similar in the two randomization arms.

Conclusion

Urine markers of tubule cell injury provide information about risk of subsequent loss of kidney function independent of eGFR and albuminuria. Future studies are required to determine if dynamic changes in urine tubule injury markers provide information on subsequent risk of CKD progression.

Funding

  • NIDDK Support