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Kidney Week

Abstract: SA-PO0077

Urine Complement Activation Factor Ba Is Associated with Major Adverse Kidney Events

Session Information

Category: Acute Kidney Injury

  • 102 AKI: Clinical, Outcomes, and Trials

Authors

  • Stenson, Erin K., University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
  • You, Zhiying, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
  • Semler, Matthew W, Vanderbilt University, Nashville, Tennessee, United States
  • Siew, Edward D., Vanderbilt University, Nashville, Tennessee, United States
  • Thurman, Joshua M., University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
  • Kendrick, Jessica B., University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
Background

Critically ill adults with acute kidney injury (AKI) have high morbidity and mortality and lack treatment options. The alternative pathway of complement has been implicated in AKI pathogenesis and complement targeted therapeutics exist. We aimed to determine the association between urine Ba, an activation fragment of the alternative pathway, and major adverse kidney events at 30 days (MAKE30).

Methods

A post-hoc analysis leveraged a prior clinical trial that enrolled critically ill adults. Urine was obtained on day 2, processed, frozen at -80°C, and urine Ba was quantified by ELISA. Primary outcome was MAKE30 and defined as composite outcome of death, new receipt of RRT, or persistent renal dysfunction (serum creatinine ≥200% of baseline) at 30 days. Univariate and multivariate logistic regression were used to determine differences and adjusted for APACHE-2 score (an illness severity estimate). Log value of urine Ba to base 2 was used in analysis. AUC-ROC curves were used to determine the ability to use urine Ba to predict MAKE30.

Results

250 patients were included of which 32 (13%) had MAKE30. Urine Ba was significantly higher in patients with MAKE30 outcomes (median 1138 ng/mL; IQR 386, 4288) compared to no MAKE 30 (median 113 ng/mL; IQR 38, 651); p <0.0001, Figure. On regression analyses, urine Ba was significantly associated with MAKE30 both in univariate analysis and after adjusting for APACHE score (Table1). Urine Ba had significant predictive capabilities for future development of MAKE30 outcomes with an AUC-ROC of 0.74 Figure.

Conclusion

Urine Ba is significantly increased in patients with MAKE30. Urine Ba may be helpful for prognostic or predictive enrichment of future clinical trials of complement inhibition to treat or prevent AKI in critically ill adults.

Univariate and multivariate analysis evaluating association between urine Ba and MAKE30.
ModelOdds Ratio (95% CI)p-value
Urine Ba Unadjusted1.41 (1.21, 1.64)0.008
Urine Ba Adjusted for APACHE-2 Score1.31 (1.11, 1.54)0.0011

Funding

  • NIDDK Support

Digital Object Identifier (DOI)