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Abstract: SA-PO120

Association Between AKI and Biomarkers KIM-1, Urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL), and Cystatin C in Patients Undergoing Cardiac Surgery

Session Information

Category: Acute Kidney Injury

  • 102 AKI: Clinical, Outcomes, and Trials

Authors

  • Singh, Bhupinder, Renibus Therapeutics, Southlake, Texas, United States
  • Rodriguez, Jeannette, Renibus Therapeutics, Southlake, Texas, United States
  • Johnson, Ali C.m., Renibus Therapeutics, Southlake, Texas, United States
  • Zager, Richard A., Renibus Therapeutics, Southlake, Texas, United States
  • Ruiz, Stacey, Renibus Therapeutics, Southlake, Texas, United States
Background

Patients undergoing cardiac surgery are at risk of developing acute kidney injury (AKI), which negatively impacts short and long-term clinical outcomes. Biomarkers that provide earlier detection of AKI may allow for timely intervention. Urinary excretion of kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and cystatin C (CysC) is increased during experimental AKI. We investigated the association between these biomarkers and AKI in patients undergoing elective coronary artery bypass graft (CABG) and/or valve surgery on CPB.

Methods

Urine and plasma samples were collected from 121 adult patients who participated in a Phase 2 study designed to test the ability of an investigational drug (RBT-1) to induce an organ preconditioning response and prevent post-operative complications. AKI was defined as a ≥1.5X increase in serum creatinine (sCr) or oligoanuria through post-op Day 5 or need for dialysis. The study was neither powered nor enriched to test for potential RBT-1-induced AKI protection. Urine and plasma KIM-1, NGAL, and CysC were measured through post-op Day 3.

Results

Of the 121 patients, 22 (18.2%) developed AKI. Urinary levels of KIM-1 (uKIM-1) and CysC (uCysC) were higher in patients who did not develop AKI post-operatively (uKIM-1: 6.27 ng/mL vs 14.41 ng/mL [p=0.013]; uCysC: 2.92 ng/mL vs 6.45 ng/mL [p=0.011] for AKI vs No AKI). While uNGAL was higher in those who developed AKI (10.30 ng/mL vs 6.41 ng/mL), this result was not statistically significant (p=0.472). Correlation analyses indicated no relationship between max post-op sCr and uKIM-1 (r=0.0572), uCysC (r=0.2953), or uNGAL (r=0.3176). In contrast, plasma levels for these biomarkers were higher in patients who developed AKI post-op (KIM-1: 158 pg/mL vs 101 pg/mL; CysC: 2.39 mg/L vs. 1.61 mg/L; NGAL: 185 ng/mL vs. 126 ng/mL). Correlation analysis also showed a stronger relationship between max post-op sCr and plasma levels of CysC (r=0.7771, p<0.0001) and NGAL (r=0.7585, p<0.0001) at Day 3; no correlation was observed with KIM-1 (r=0.2941, p=0.001).

Conclusion

Urinary KIM-1, NGAL, and CysC did not correlate with AKI in this cohort of adults undergoing cardiac surgery. Plasma KIM-1, NGAL, CysC levels may hold greater promise and should be studied further.

Funding

  • Commercial Support – Renibus Therapeutics