Renal Replacement Therapy Intensity for Acute Kidney Injury and Recovery to Dialysis Independence

A Systematic Review and Individual Patient Data Meta-analysis

Ying Wang; Martin Gallagher; Qiang Li; Serigne Lo; Alan Cass; Simon Finfer; John Myburgh; Catherine Bouman; Robert Faulhaber-Walter; John A Kellum; Paul M Palevsky; Claudio Ronco; Patrick Saudan; Ashita Tolwani; Rinaldo Bellomo


Nephrol Dial Transplant. 2018;33(6):1017-1024. 

In This Article

Abstract and Introduction


Background: There is no consensus whether higher intensity dose renal replacement therapy (RRT) compared with standard intensity RRT has survival benefit and achieves better renal recovery in acute kidney injury (AKI).

Methods:In an individual patient data meta-analysis, we merged individual patient data from randomized controlled trials (RCTs) comparing high with standard intensity RRT in intensive care unit patients with severe AKI. The primary outcome was all-cause mortality. The secondary outcome was renal recovery assessed as the proportion of patients who were RRT dependent at key trial endpoints and by time to the end of RRT dependence.

Results: Of the eight prospective RCTs assessing different RRT intensities, seven contributed individual patient data (n = 3682) to the analysis. Mortality was similar between the two groups at 28 days [769/1884 (40.8%) and 744/1798 (41.4%), respectively; P = 0.40] after randomization. However, more participants assigned to higher intensity therapy remained RRT dependent at the most common key study point of 28 days [e.g. 292/983 (29.7%) versus 235/943 (24.9%); relative risk 1.15 (95% confidence interval 1.00–1.33); P = 0.05]. Time to cessation of RRT through 28 days was longer in patients receiving higher intensity RRT (log-rank test P = 0.02) and when continuous renal replacement therapy was used as the initial modality of RRT (log-rank test P = 0.03).

Conclusions: In severe AKI patients, higher intensity RRT does not affect mortality but appears to delay renal recovery.


Severe acute kidney injury (AKI) often requires renal replacement therapy (RRT) and is associated with high health care costs[1] and a high mortality rate.[2] Moreover, its incidence is >10 times that of end-stage kidney disease (ESKD)[3] and is increasing.[4,5] Finally, AKI survivors carry greater long-term mortality risks,[6] require more institutional care[7,8] and are more likely to develop chronic and end-stage kidney disease.[9]

During almost two decades, after an early influential study suggesting a survival benefit from higher dose intensity,[10] AKI research has focused on the effect of increasing RRT dose intensity. This led to several single-center trials[11–16] with variable findings and spawned two large multicenter trials that failed to confirm such survival benefit. In their aggregate, these randomized studies represent a large, comprehensive, prospectively collected dataset that can be analysed using the technique of individual patient data meta-analysis (IPDMA).

IPDMA uses raw individual-level data from each study for analysis and synthesis.[17,18] By obtaining direct individual data, it allows standardization of analyses across studies while maintaining the benefits of random allocation to study interventions. Thus, in the presence of almost identical patient details and interventions, IPDMA delivers the equivalent of a very large trial.[18] In the AKI setting, it may deliver greater statistical power to elucidate previously undetected effects upon renal outcomes, such as time to independence from RRT.

Accordingly, the Investigation, Management, Prognosis, Recovery, Observation, Value and Evaluation of Acute Kidney Injury (IMPROVE-AKI) collaboration brought together investigators from previous studies of RRT dose intensity in AKI to perform an IPDMA of the effects of RRT dose intensity with a focus on mortality and RRT independence.