Optimal dose of renal replacement therapy in acute kidney injury: a meta-analysis

Introduction

Acute kidney injury (AKI) requiring renal replacement therapy (RRT) increases mortality in the critically ill patient. Our objective was to systematically review randomized controlled trials (RCTs) examining the effect of the RRT dose on mortality.

Methods

In duplicate, we searched Medline, EMBASE and the Cochrane Central Register of Controlled Trials from inception to December 2008, using terms for all RRT modalities, AKI, and RCTs. Included RCTs compared different doses of RRT within a given modality (effluent rate in continuous RRT (CRRT), number of sessions per week in intermittent hemodialysis (IHD)) in patients with AKI, and reported mortality or dialysis dependence. We excluded RCTs that evaluated very high volume hemofiltration (continuous effluent rates >60 ml/kg/hour). Risk ratios (RRs) with 95% confidence intervals for mortality and dialysis dependence among survivors were calculated using random-effects models (RevMan 5). We investigated subgroup effects by modality (CRRT vs. IHD) and patient group (septic vs. nonseptic).

Results

Of 2,913 citations, seven RCTs (n = 2,255) met the inclusion criteria. Four RCTs used CRRT (35 to 48 vs. 20 ml/kg/hour); two RCTs used IHD (daily vs. alternate day); and the largest and only multicentre RCT (n = 1,124) integrated CRRT and IHD in high-dose and standard-dose arms. RCTs were generally of good quality. Meta-analysis did not demonstrate reduced mortality with high-dose RRT (RR = 0.86, 0.70 to 1.06). The effect was similar in patients (1) treated with CRRT (RR = 0.87, 0.71 to 1.06, five trials, n = 1,552) and IHD (RR = 0.95, 0.59 to 1.51, three trials, n = 703), and (2) with sepsis (RR = 1.08, 0.96 to 1.22, n = 896) and without sepsis (RR = 0.88, 0.65 to 1.20, n = 959) in the four trials with these data. High-dose RRT did not decrease dialysis dependence among all survivors (RR = 1.09, 0.83 to 1.43, five trials, n = 774) or in the subgroup treated only with CRRT (RR = 1.27, 0.62 to 2.59, three trials, n = 233). We estimate that if the ongoing multicentre RENAL RCT (planned n = 1,500, ClinicalTrials.gov NCT00221013) of high-dose versus standard-dose CRRT demonstrates the expected absolute mortality risk reduction (from 60% to 52%), the pooled mortality benefit would just reach statistical significance.

Conclusion

Current evidence does not demonstrate reduced mortality with high-dose RRT for AKI, even in the subgroup of patients with sepsis-associated AKI. Forthcoming results of the RENAL trial may contribute to more definitive results.