Novel predictors of response to therapy with terlipressin and albumin in Hepatorenal Syndrome-Acute Kidney Injury

Abstract

Background and Aim: Prognostication of response to pharmacological treatment of Hepatorenal Syndrome-Acute Kidney Injury (HRS-AKI), is crucial to identify patients with a low likelihood of treatment response, and fast track them for liver transplantation. We assessed the response rates to terlipressin-albumin therapy in HRS-AKI and determined early predictors of treatment response and survival. Methods: 84 patients diagnosed to have HRS-AKI (as per new ICA definition) and treated with terlipressin-albumin were included. Demographic, clinical, and laboratory variables obtained at baseline and changes during treatment were analyzed as predictors of HRS reversal by logistic regression analysis. Cox-regression models were used for assessing the association of variables with overall survival. Results: A complete response to therapy was seen in 54.8%, partial response in 14.3%, and no response in 31% of patients. The factors associated with complete response were the presence of systemic inflammatory response syndrome (SIRS), baseline serum creatinine, a rise in mean arterial pressure by day 3, and a reduction in the renal resistive index (Delta-RRI) by day 3 of treatment. Variables with independent predictive value of HRS reversal were the presence of SIRS at baseline (p=0.022;OR-15.749(CI:1.478-167.82)) and Delta-RRI >5% by day 3 (p=0.048;OR=6.67(CI:1.021-43.625)). Non-responders had higher mortality as compared to treatment responders at one month (27% vs 9%) and six months (74% vs 45%). Mean transplant-free survival at six months was significantly longer in complete responders (148 days vs 90 days,p<0.001). Response to treatment(HR-0.527;p=0.004) and MELD Na > 23(HR-1.071; p=0.018) were independent predictors of six-month mortality. Conclusions: SIRS and Delta-RRI are simple parameters to predict treatment response in HRS-AKI. Non-responders have higher mortality and should be identified early to expedite liver transplantation. In HRS-AKI, renal resistive index is a measure of the intrarenal vasoconstriction, and SIRS reflects the exaggerated systemic inflammation, both of which are reversed by terlipressin, leading to enhanced treatment response.