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Abstract: TH-PO046

Markers of Kidney Tubule Cell Function and Risk of AKI

Session Information

Category: Acute Kidney Injury

  • 101 AKI: Epidemiology, Risk Factors, and Prevention

Authors

  • Bullen, Alexander, UCSD, San Diego, California, United States
  • Anderson, Cheryl A., University of California San Diego, La Jolla, California, United States
  • Cheung, Alfred K., University of Utah, Salt Lake City, Utah, United States
  • Estrella, Michelle M., University of California, San Francisco and San Francisco VA Medical Center, San Francisco, California, United States
  • Garimella, Pranav S., University of California San Diego, La Jolla, California, United States
  • Jotwani, Vasantha, University of California, San Francisco and San Francisco VA Medical Center, San Francisco, California, United States
  • Lash, James P., University of Illinois at Chicago, Chicago, Illinois, United States
  • Neyra, Javier A., University of Kentucky Medical Center, Lexington, Kentucky, United States
  • Punzi, Henry A., Punzi Medical Center, Carrollton, Texas, United States
  • Katz, Ronit, University of Washington, Seattle, Washington, United States
  • Shlipak, Michael, San Francisco VA Medical Center, San Francisco, California, United States
  • Ix, Joachim H., UCSD, San Diego, California, United States
Background

Novel biomarkers can quantify kidney tubular functions including proximal tubule reabsorption (alpha 1 microglobulin [a1m], and beta 2 microglobulin [b2m]) and tubule protein synthesis (uromodulin [umod]). Associations of tubule function measures with acute kidney injury (AKI) risk are uncertain. We evaluated associations of markers of kidney tubular function with AKI risk in participants with chronic kidney disease (CKD) in the SPRINT Trial.

Methods

Among 2351 participants with CKD (eGFR<60 ml/min), urine a1m, b2m and umod were measured by multiplex immunoassay (MesoScale Diagnostics) at the randomization visit. Cox proportional hazard models evaluated log-transformed biomarker levels as risk factors for AKI during 3.8 years mean follow-up. Sequential models adjusted for demographics, randomization arm, and urine creatinine (Model 1); baseline eGFR, uACR, and AKI risk factors (Model 2); and the other tubule function biomarkers (Model 3).

Results

Lower urine umod and higher a1m levels were each associated with higher AKI risk (Table). The association with uromodulin was independent of baseline eGFR and uACR (Model 2). Adjustment for all 3 tubule function markers strengthened associations of a1m which was independently associated with AKI in the final model. Results were similar in analyses stratified by randomization arm.

Conclusion

Assessment of tubule function by measurement of urine umod and a1m provides information of AKI risk independent of eGFR and albuminuria in persons with hypertension and CKD but without diabetes. Future studies should evaluate if dynamic changes in these markers can predict AKI risk in those exposed to intensive blood pressure lowering.

 Hazard Ratio (95% CI)P Value
 Per Doubling of Marker 
# AKI events/# at Risk 184/2351 
- Uromodulin  
-- Model 10.72 (0.64, 0.81)<0.001
-- Model 20.78 (0.67, 0.90)0.001
-- Model 30.71 (0.59, 0.85)<0.001
- Alpha-1 microglobulin
(α1m)
  
-- Model 11.22 (1.11, 1.34)<0.001
-- Model 21.08 (0.98, 1.19)0.13
-- Model 31.17 (1.04, 1.32)0.01

Funding

  • NIDDK Support