Kidney Week

Abstract: FR-OR021

Associations of Tubular Injury, Inflammation, and Repair Biomarkers with AKI in the SPRINT Trial

Session Information

• AKI: Epidemiology, Risk Factors, and Prevention
  October 26, 2018 | Location: 1B, San Diego Convention Center
  Abstract Time: 04:30 PM - 04:42 PM

Category: Acute Kidney Injury

• 101 AKI: Epidemiology, Risk Factors, and Prevention

Authors

• Estrella, Michelle M., Kidney Health Research Collaborative, UCSF & VA, San Francisco, California, United States

Michelle M. Estrella, MD

• Lee, Alexandra K., Kidney Health Research Collaborative, UCSF & VA, San Francisco, California, United States

Alexandra K. Lee,

• Bullen, Alexander, UCSD, San Diego, California, United States

Alexander Bullen,

• Jotwani, Vasantha, Kidney Health Research Collaborative, UCSF & VA, San Francisco, California, United States

Vasantha Jotwani,

• Malhotra, Rakesh, UCSD, San Diego, California, United States

Rakesh Malhotra,

• Parikh, Chirag R., Yale University and VAMC, New Haven, Connecticut, United States

Chirag R. Parikh,

• Ix, Joachim H., UCSD, San Diego, California, United States

Joachim H. Ix,

• Shlipak, Michael, Kidney Health Research Collaborative, UCSF & VA, San Francisco, California, United States

Michael Shlipak,

Background

Randomization to intensive BP treatment (SBP <120 mmHg) in SPRINT led to higher AKI risk compared to standard BP treatment (SBP <140 mmHg). Whether a greater burden of tubular disease predisposes to AKI has not been well evaluated.

Methods

Among SPRINT participants with CKD (eGFR <60 mL/min|1.73 m²), we measured baseline urine levels of tubular injury (NGAL, KIM1 and IL18), inflammation (IL18 and MCP1) and repair (YKL40) biomarkers using multiplex panels. Cox proportional hazards models were used to examine whether baseline biomarker levels (log₂-transformed and in quartiles) were independently associated with AKI, defined by hospital discharge AKI diagnosis listed within the top three reasons for hospitalization. We examined whether treatment arm assignment modified these associations by inclusion of interaction terms.

Results

Among 2412 CKD participants with urine biomarkers, the mean age was 73 and mean eGFR 45.9 mL/min/1.73m². A total of 190 AKI events occurred over a median 3.2 years of follow-up. YKL40, per 2-fold higher, was independently associated with higher risk of AKI (HR=1.09; 95% CI: 1.01-1.18). The highest versus lowest YKL40 quartile was significantly associated with risk of AKI in adjusted analyses (HR=1.82; 95% CI:1.17-2.83) (Figure). Treatment arm assignment did not influence this association. In contrast to YKL40, biomarkers of tubular injury and inflammation were not significantly associated with AKI risk in adjusted analyses.

Conclusion

Higher baseline urine YKL40 levels were associated with higher risk of AKI among SPRINT participants with CKD. These results suggest that CKD patients with greater activation of tubular repair mechanisms are more vulnerable to AKI.

Funding

• NIDDK Support