Evaluation of Acute Kidney Injury (AKI) Biomarkers FABP1, NGAL, Cystatin C and IL-18 in an Indian Cohort of Hospitalized Acute-on-chronic Liver Failure (ACLF) Patients

Abstract

Background/Aims

Acute-on-chronic liver failure (ACLF) is a complication of cirrhosis associated with systemic inflammation and organ dysfunction. In ACLF, the development of acute kidney injury (AKI) is associated with poor outcomes. FABP1, NGAL, Cys C and IL-18 have been shown to correlate with ACLF severity and mortality. Hence, our study aimed to evaluate the association of these biomarkers with organ dysfunctions, particularly AKI, in an Indian ACLF patient cohort.

Methods

151 study participants including ACLF (n = 91; with AKI n = 63, no-AKI n = 28), non-liver AKI (n = 30) and healthy controls (n = 30) were recruited. Serum ELISA was performed for biomarker estimation. Data interpolation and graphical representation were performed using GraphPad Prism and statistical analyses performed using STATA 14.0.

Results

FABP1 and Cys C levels were higher in ACLF-AKI patients compared to ACLF no-AKI (P-value ≤ 0.0005). Serum Cys C levels were significantly increased in non-liver AKI compared to ACLF-AKI (P-value ≤ 0.001). AUROC analysis showed better performance of Cys C (AUC 0.79; 95% CI (0.68–0.89)) compared to serum creatinine (AUC 0.71; 95% CI (0.61–0.82)) in discriminating AKI and no-AKI. Correlation analysis revealed positive correlations of FABP1 with creatinine and urea, Cys C with creatinine, urea and OF-Kidney, NGAL, and IL-18 with general markers of organ dysfunction. Plasma MTs) measured in a subset of ACLF patients were elevated in progression-to-AKI.

Conclusion

Our study showed that in an Indian population of ACLF patients with a high short-term mortality, serum Cys C and FABP1 were elevated in ACLF-AKI, however did not have predictive potential for ACLF-AKI. Cys C levels were significantly higher in non-liver AKI patients vs. ACLF-AKI and correlated with markers of kidney dysfunction whereas NGAL and IL-18 represented higher inflammation and total organ dysfunction. Hence, we conclude that these biomarkers were elevated in ACLF-AKI but did not have predictive potential for AKI in ACLF.