Systematic review: renal and other clinically relevant outcomes in hepatorenal syndrome trials.

BACKGROUND: Although reversal of pretransplant renal dysfunction in hepatorenal syndrome reduces post-transplant complications, the overall impact on morbidity and mortality requires clarification.

AIM: To review trials of pharmacologic interventions in hepatorenal syndrome, with specific assessment of trial quality and study endpoints, including patient survival and renal outcome measures.

METHODS: Literature search and selection was carried out by a single reviewer. Data extraction and quality analysis were carried out by two independent reviewers.

RESULTS: Of 848 identified articles, 36 were eligible for inclusion. Twenty-one were full-text. Only 19% were randomized-controlled trials. About 50% of studies included only Type 1 hepatorenal syndrome patients. Serum creatinine, urine output and urine sodium were the most common renal outcome measures. Only 42% defined a primary renal endpoint. About 88% of articles reported mortality rates.

CONCLUSIONS: Existing literature of pharmacologic agents for use in hepatorenal syndrome is limited by poor study design, including non-randomization, heterogeneous study populations, lack of power, and limited use of clinically relevant outcomes. There is insufficient information in most trials to judge the impact of pharmacologic therapy on mortality or rates of transplantation. The validity of renal outcome measures as surrogate markers of more clinically relevant endpoints has not been established.