# Vasoconstrictor Therapy for Acute Kidney Injury Hepatorenal Syndrome: A Meta-Analysis of Randomized Studies

## TL;DR

This study compares vasoconstrictor treatments for acute kidney injury in cirrhosis patients, finding that terlipressin and nor-epinephrine are more effective than other combinations.

## Contribution

A meta-analysis comparing vasoconstrictor therapies for hepatorenal syndrome, identifying terlipressin and nor-epinephrine as superior for reversing kidney dysfunction.

## Key findings

- Terlipressin and nor-epinephrine are equally effective and better than midodrine and octreotide for reversing hepatorenal syndrome.
- No treatment improved liver transplant-free survival, and adverse effects were similar between terlipressin and nor-epinephrine.
- Lower baseline creatinine and MELD scores are associated with better treatment response.

## Abstract

Type 1 hepatorenal syndrome (HRS) is a rapid deterioration in kidney function in patients with cirrhosis. Data on efficacy of vasoconstrictors for type 1 HRS have shown mixed results.

Literature searched for randomized controlled trials comparing pharmacological therapy for HRS vs placebo or another drug for HRS. Primary outcome was HRS reversal (serum creatinine <1.5mg/dL on 2 readings), and secondary outcomes were liver transplant (LT) free survival and serious adverse events (SAE).

Sixteen studies on 1244 patients (mean age 50.3 yrs., 67.5% males, serum creatinine of 3.07 mg/dL, serum sodium 127.2 mEq/liter, and Model for End-stage Liver Disease (MELD) score of 30.9, and Child-Pugh score 11) with type 1 HRS treated with vasoconstrictors vs placebo or another drug were analyzed. All the patients received intravenous albumin infusion. (A) terlipressin vs placebo: Odds of HRS reversal were 3.3 folds with terlipressin without difference on LT-free patient survival. Terlipressin was associated with higher odds of SAE. (B) Nor-epinephrine (NE) vs terlipressin: No difference on HRS reversal, LT-free survival, and SAE. (C) Terlipressin or NE vs midodrine and octreotide: 91% lower odds of HRS reversal with midodrine and octreotide. There were no differences on SAE (10 of 64 vs 10 of 58, P = .812). Non-responders vs responders had higher mean MELD score (29 vs 27.8), P = .014 and serum creatinine (3.5 vs 3.1), P = .027.

Terlipressin and NE are similar and superior to midodrine octreotide combination for HRS reversal. No therapy improves LT-free patient survival. Response to treatment is better with lower baseline serum creatinine and MELD score. The risk of adverse effects is similar with terlipressin and NE. Studies are needed as basis to identify candidates with best response to treatment with excellent safety profile.