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Abstract: SA-OR041

Relation of a Parsimonious Model of Factors Derived from 10 Biomarkers of Kidney Tubule Health with Decline in eGFR in the SPRINT Trial

Session Information

  • Biomarkers in CKD
    November 09, 2019 | Location: 152, Walter E. Washington Convention Center
    Abstract Time: 05:06 PM - 05:18 PM

Category: CKD (Non-Dialysis)

  • 2101 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention

Authors

  • Bullen, Alexander, UCSD, San Diego, California, United States
  • Katz, Ronit, University of Washington, Seattle, Washington, United States
  • Lee, Alexandra K., Kidney Health Research Collaborative, UCSF & VA, San Francisco, California, United States
  • Estrella, Michelle M., University of California, San Francisco and San Francisco VA Medical Center, 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

To move towards assimilation of the various information gained from multiple biomarkers, we have evaluated 10 urine biomarkers of kidney tubule health measured at baseline among SPRINT participants with chronic kidney disease (CKD). In prior analyses, we created summary scores of different dimensions of kidney tubule health using unsupervised exploratory factor analyses. Four factors were derived and found to be strongly associated with CVD events; associations that were stronger than individual markers. The goal of the current study was to evaluate if these 4 factors of tubule health are related with progression of CKD in SPRINT.

Methods

The factors comprised Factor 1: “tubule injury/repair” (urine NGAL, IL-18, & YKL-40); Factor 2: “tubule injury/fibrosis” (urine KIM-1 & MCP-1); Factor 3: “tubule reabsorption” (urine alpha-1 microglobulin & beta-2 microglobulin); and Factor 4: “tubular reserve” (urine umod & serum iPTH & iFGF-23). We selected SPRINT participants with eGFR <60 ml/min/1.73m2 at baseline and used linear mixed models to examine the association of the 4 factors of kidney tubule health with decline in kidney function.

Results

Among 2351 SPRINT participants two factors of tubule health, “tubule injury/fibrosis” and “tubular reserve” were associated with mean eGFR decline (percentage decrease per year), independent of baseline eGFR and albuminuria (Table). The magnitude of the association between these two factors and longitudinal eGFR changes was lower than the one seen with albuminuria (Table).

Conclusion

Assessment of tubule health by integrating tubule injury, fibrosis, and reserve factors provides information on CKD progression independent of baseline eGFR and albuminuria in persons with non-diabetic CKD.

Association of factors of tubule health and percentage of eGFR change per year
Factor of Tubule Health% eGFR change/year per SD increase of vector (95% CI)*
-Injury/Repair-0.01 (-0.19, 0.17)
-Injury/Fibrosis-0.17 (-0.35, -0.01)
-Reabsorption-0.03 (-0.21, 0.15)
-Reserve-0.59 (-0.77, -0.41)
ACR-1.65 (-1.82, -1.47)

*Adjusted for: age, sex, race, randomization arm, SBP, ACEi or ARB use, diuretic use, history of CVD or HF, current smoker, BMI, LDL, total cholesterol, baseline eGFR and albuminuria.

Funding

  • NIDDK Support