High-dose renal replacement therapy for acute kidney injury: Systematic review and meta-analysis.

OBJECTIVE: To determine the effect of renal replacement therapy dose on mortality and dialysis dependence in patients with acute kidney injury.

DATA SOURCES: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials to October 2009; PubMed "Related Articles;" bibliographies of included trials; and additional information from trial authors.

STUDY SELECTION: Randomized and quasi-randomized, controlled trials in adults with acute kidney injury prescribed highvs. standard-dose continuous renal replacement therapy (> or =30 mL/kg/hr vs. <30 mL/kg/hr), intermittent hemodialysis, or sustained low-efficiency dialysis (daily vs. alternate day, or by target biochemistry).

DATA EXTRACTION: Three authors independently selected studies and extracted data on outcomes and study quality. Meta-analyses used random-effects models.

DATA SYNTHESIS: Of 5416 citations, 12 trials (n = 3999) met inclusion criteria. Modalities included continuous renal replacement therapy (7 trials), intermittent hemodialysis (3 trials), sustained low-efficiency dialysis (1 trial), and all three (1 trial). Study quality was moderate-high. Meta-analyses found no effect of high-dose renal replacement therapy on mortality (risk ratio, 0.89; 95% confidence interval, 0.77-1.03; 12 trials; n = 3954) or dialysis dependence among survivors (risk ratio, 1.15; 95% confidence interval, 0.92-1.44; 8 trials with events; n = 1743). The effect on mortality was similar (all interaction p values were nonsignificant) in patients with sepsis (risk ratio, 1.02; 95% confidence interval, 0.85-1.23; 9 trials; n = 1786) vs. without sepsis (risk ratio, 0.89; 95% confidence interval, 0.75-1.05; 8 trials; n = 1955), treated exclusively with continuous renal replacement therapy (risk ratio, 0.87; 95% confidence interval, 0.71-1.06; 7 trials; n = 2462) vs. other modalities alone or in combination (risk ratio, 0.92; 95% confidence interval, 0.70 -1.21; 5 trials; n = 1492), and in trials with low (risk ratio, 0.96; 95% confidence interval, 0.85-1.09; 6 trials; n = 3475) vs. higher (risk ratio, 0.76; 95% confidence interval, 0.53-1.09; 6 trials; n = 479) risk of bias.

CONCLUSIONS: High-dose renal replacement therapy in acute kidney injury does not improve patient survival or recovery of renal function overall or in important patient subgroups, including those with sepsis.