Reduction in acute kidney injury stage predicts survival in patients with type-1 hepatorenal syndrome

Author:

Wong Florence1,Boyer Thomas D2,Sanyal Arun J3,Pappas Stephen C4,Escalante Shannon5,Jamil Khurram6

Affiliation:

1. Department of Medicine, Division of Gastroenterology, University of Toronto, Toronto, ON, Canada

2. Department of Medicine, University of Arizona, Tucson, AZ, USA

3. Gastroenterology, Virginia Commonwealth University, Richmond, VA, USA

4. Scientific Affairs, Orphan Therapeutics, Lebanon, NJ, USA

5. Biometrics, Mallinckrodt Pharmaceuticals, Bedminister, NJ, USA

6. Scientific Affairs, Mallinckrodt Pharmaceuticals, Bedminster, NJ, USA

Abstract

Abstract Background Hepatorenal syndrome type 1 (HRS-1), a form of acute kidney injury (AKI) in cirrhosis, has a median survival of days to weeks if untreated. The impact of reduction in AKI stage on overall survival in cirrhosis, independent of HRS reversal, is unclear. Methods The Randomized, placEbo-controlled, double-blind study to confirm the reVERSal of HRS-1 with terlipressin study assessed terlipressin versus placebo, both with albumin, as treatment for HRS-1 for ≤14 days. Renal dysfunction severity was categorized by AKI stage at enrollment. Baseline patient characteristics were evaluated as predictors of AKI improvement using a multivariate model; the association between AKI stage reduction and 90-day survival was assessed using linear regression. Results A total of 184 patients (terlipressin: n = 91; placebo: n = 93) with similar numbers in AKI Stages 1–3 (terlipressin/placebo, Stage 1: n = 25/26; Stage 2: n = 35/33; Stage 3: n = 31/34) were included. Predictors of AKI improvement were absence of alcoholic hepatitis, baseline serum creatinine and male gender. Overall survival was not significantly different across AKI stages (range 53–65%). In patients with no AKI worsening, 90-day survival was consistently better when AKI improved independent of HRS reversal, regardless of the initial AKI stage, with patients with Stage 1 at initial diagnosis achieving the greatest clinical benefit. A significant association was observed between AKI reduction and overall 90-day survival (P = 0.0022). Conclusions A reduction in AKI stage, independent of HRS reversal, was sufficient to improve overall survival in patients with HRS-1. The goal for HRS-1 treatment should be less stringent than absolute HRS reversal.

Funder

Mallinckrodt Pharmaceuticals

Publisher

Oxford University Press (OUP)

Subject

Transplantation,Nephrology

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