Erdosteine Versus N-acetyl Cysteine as a Potential Therapy for Hepatorenal Syndrome

Abstract
Background: Hepatorenal Syndrome (HRS) is a unique form of acute kidney injury seen in patients with acute liver failure or chronic liver disease in absence of any other iden-tifiable cause of renal failure. Hepatorenal syndrome is asso-ciated with significant morbidity and mortality.
Aim of Study: The aim of this study was to assess the safety and efficacy of Erdosteine versus N-acetyl cysteine with octreotide and albumin in the treatment of hepatorenal syndrome in cirrhotic patients.
Patients and Methods: The study enrolled 60 liver cirrhosis patients diagnosed to have hepatorenal syndrome who were randomized to receive Erdosteine 300mg or N-acety-lcysteine 600mg three times daily with octreotide (100μgsc three times a day) midodrine (12.5mg orally three times a day) and albumin (1g/kg body weight up to a maximum of 100g) or receive octreotide, midodrine and albumin as a control for two weeks. Renal function was assessed before and after treatment. Side effects and improvement of liver function were recorded.
Results: In NAC group; creatinine level was significantly lower after the second week of therapy than baseline level (p=0.006), also there was significantly higher GFR after the first and the second weeks of therapy than baseline level (p= 0.038, 0.001 respectively) and significant higher GFR after the second week than after the first week of therapy (p= 0.015). Meanwhile, no significant difference of creatinine or GFR was detected in Erdosteine group or when the three groups were compared.
In NAC group, Child-Pugh score significantly improved compared to control group after 2 weeks of therapy (p=0.004). In the first and second weeks of therapy, the grade of enceph-alopathy was significantly lower in Erdosteine group (p=0.032, 0.040) and in NAC group (p=0.009, 0.004) compared to control group.
The side effects were few with no significant difference between their occurrences in the three groups.
Conclusion: This study was a pilot study that investigated the effects of Erdosteine versus NAC on human patients with HRS. No significant difference of creatinine or GFR was detected when Erdosteine, NAC and control groups were compared. Improvement of Child-Pugh score in NAC group and hepatic encephalopathy in Erdosteine group were second-ary outcomes of our study.
As these drugs had a high safety profile, we recommend further studies using higher doses of the drugs for longer periods and enrollment of larger number of patients to optimize treatment of HRS.