The efficacy of loop diuretics in acute renal failure: assessment using Bayesian evidence synthesis techniques

Abstract

Objective: To quantify the therapeutic efficacy of loop diuretics in acute renal failure using Bayesian evidence synthesis, because despite widespread use, the role of diuretics is controversial.

Data source: Randomized controlled trials or nonrandomized studies, 1966 to January 2007, identified from MEDLINE and EMBASE databases and manual bibliographic search.

Study selection: Studies with assessable predefined end points, exclusive of those pertaining to acute renal failure prophylaxis or chronic renal failure.

Data extraction: Data extraction was performed jointly by the first two authors; independent study assessment was via standard checklist, unblinded.

Data synthesis: The primary outcome was mortality; secondary outcomes were time to renal function normalization and total number of dialyses. Bayesian hierarchical random effects estimates of treatment effects were determined as risk ratio for mortality, incidence rate ratio for dialysis number, and mean difference for continuous measures. Bayesian outcome probabilities were calculated as probability (P) that risk ratio or incidence rate ratio of loop diuretics >1 and probability that mean difference >0. Five randomized controlled trials and eight nonrandomized studies were identified. Loop diuretics were not associated with decreased mortality in either randomized controlled trials or nonrandomized studies: overall risk ratio 1.10; 95% credible interval 0.85, 1.42; P(risk ratio >1) > 83.8%. The oliguric period was decreased by loop diuretics: overall mean difference -7.70 days; 95% credible interval -12.51, -2.08; P (mean difference >0) = 0.7%. Although the dialysis rate credible interval, loop diuretics vs. control, spanned unity (incidence rate ratio 0.71; 95% credible interval 0.47, 1.06), the probability that the incidence rate ratio exceeded unity indicated a substantial benefit: P (incidence rate ratio >1 = 4.1%. Uremic duration was not substantially different, loop diuretics vs. control: overall mean difference -1.54 days; 95% credible interval -5.62, 2.46; P [mean difference >0] = 17.8%).

Conclusions: Loop diuretics were not associated with improved survival benefit in acute renal failure, despite reduction in oliguric period and high probability of a significant reduction in dialysis numbers. Further studies to clarify this dichotomy appear mandated.