The timing of renal replacement therapy (RRT) initiation does not appear to influence survival in critically ill patients with severe acute kidney injury (AKI) who have no life-threatening conditions, new research suggests.

A team led by Didier Dreyfuss, MD, of the University of Paris Louis Mourier Hospital in France, conducted a systematic review and meta-analysis using individual patient data from 9 randomized trials with a low risk of bias published in the most recent decade (2008 to 2019). Of 1879 patients with AKI stage 2 or 3 based on Kidney Disease Improving Global Outcomes (KDIGO) guidelines or a renal Sequential Organ Failure Assessment score of 3 or higher, 946 were assigned to the delayed RRT group and 933 to the early RRT group.

Similar proportions of the early and delayed RRT groups died within 28 days (44% vs 43%), 60 days (51% vs 51%), and 90 days (55% vs 56%), Dr Dreyfuss’ team reported online ahead of print in The Lancet. A subgroup analysis also found no significant differences in mortality between patients with and without pre-existing chronic kidney disease.

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“Early” and “delayed” RRT were variably defined in each study. Early RRT typically started within 2 to 8 hours. Delayed RRT was initiated for different reasons, with start times ranging from 25 to 57 hours. In the delayed RRT group, 42% of patients ultimately had renal function recovery and never received RRT. Delayed RRT did not result in fewer RRT-free days, however, possibly due to underpowering.

Adverse events were uncommon. The investigators found no significant differences in the risks for hyperkalemia, severe cardiac rhythm disorder, and severe bleeding events between groups.

Mortality does not differ significantly according to whether RRT is initiated early or delayed in patients with AKI, Dr Drefuss’ team concluded. “The deliberate delay of RRT initiation under close patient supervision, and the initiation only when a clinical indication emerges, appears to be an acceptable approach, with the potential for resource savings,” they stated.

In an accompanying editorial, Gertrude Nieuwenhuijs-Moeke, MD, PhD, and Jan Stephan Sanders, MD, PhD, of the University of Groningen in The Netherlands lauded the study because it involved data from almost all relevant randomized clinical trials from the past decade, including patients with various pathophysiologic mechanisms underlying AKI.

“Overall, this meta-analysis shows that early initiation of RRT is not associated with improved outcome, and seems to support a delayed initiation strategy in critically ill patients, on the basis that a delay might avoid the need for any RRT in these patients,” the editorialists stated.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

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Gaudry S, Hajage D, Benichou N, et al. Delayed versus early initiation of renal replacement therapy for severe acute kidney injury: a systematic review and individual patient data meta-analysis of randomised clinical trials [published online April 23, 2020]. Lancet. doi: 10.1016/S0140-6736(20)30531-6

Nieuwenhuijs-Moeke GJ, Sanders JSF. Timing of renal replacement therapy in acute kidney injury: case closed? [published online April 23, 2020]. Lancet. doi: 10.1016/S0140-6736(20)30805-9