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Original Article

Initiation Strategies for Renal-Replacement Therapy in the Intensive Care Unit

Stéphane Gaudry, M.D., David Hajage, M.D., Fréderique Schortgen, M.D., Laurent Martin-Lefevre, M.D., Bertrand Pons, M.D., Eric Boulet, M.D., Alexandre Boyer, M.D., Guillaume Chevrel, M.D., Nicolas Lerolle, M.D., Ph.D., Dorothée Carpentier, M.D., Nicolas de Prost, M.D., Ph.D., Alexandre Lautrette, M.D., Anne Bretagnol, M.D., Julien Mayaux, M.D., Saad Nseir, M.D., Ph.D., Bruno Megarbane, M.D., Ph.D., Marina Thirion, M.D., Jean-Marie Forel, M.D., Julien Maizel, M.D., Ph.D., Hodane Yonis, M.D., Philippe Markowicz, M.D., Guillaume Thiery, M.D., Florence Tubach, M.D., Ph.D., Jean-Damien Ricard, M.D., Ph.D., and Didier Dreyfuss, M.D., for the AKIKI Study Group*


N Engl J Med | May 15, 2016 |DOI: 10.1056/NEJMoa1603017

BACKGROUND
The timing of renal-replacement therapy in critically ill patients who have acute kidney injury but no potentially life-threatening complication directly related to renal failure is a subject of debate. 

METHODS
In this multicenter randomized trial, we assigned patients with severe acute kidney injury (Kidney Disease: Improving Global Outcomes [KDIGO] classification, stage 3 [stages range from 1 to 3, with higher stages indicating more severe kidney injury]) who required mechanical ventilation, catecholamine infusion, or both and did not have a potentially life-threatening complication directly related to renal failure to either an early or a delayed strategy of renal-replacement therapy. With the early strategy, renal-replacement therapy was started immediately after randomization. With the delayed strategy, renal-replacement therapy was initiated if at least one of the following criteria was met: severe hyperkalemia, metabolic acidosis, pulmonary edema, blood urea nitrogen level higher than 112 mg per deciliter, or oliguria for more than 72 hours after randomization. The primary outcome was overall survival at day 60. 

RESULTS
A total of 620 patients underwent randomization. The Kaplan–Meier estimates of mortality at day 60 did not differ significantly between the early and delayed strategies; 150 deaths occurred among 311 patients in the early-strategy group (48.5%; 95% confidence interval [CI], 42.6 to 53.8), and 153 deaths occurred among 308 patients in the delayed-strategy group (49.7%, 95% CI, 43.8 to 55.0; P=0.79). A total of 151 patients (49%) in the delayed-strategy group did not receive renal-replacement therapy. The rate of catheter-related bloodstream infections was higher in the early-strategy group than in the delayed-strategy group (10% vs. 5%, P=0.03). Diuresis, a marker of improved kidney function, occurred earlier in the delayed-strategy group (P<0.001).

CONCLUSIONS
In a trial involving critically ill patients with severe acute kidney injury, we found no significant difference with regard to mortality between an early and a delayed strategy for the initiation of renal-replacement therapy. A delayed strategy averted the need for renal-replacement therapy in an appreciable number of patients. (Funded by the French Ministry of Health; ClinicalTrials.gov number, NCT01932190.) 

 Originally Appeared in The New England Journal of Medicine on May 15, 2016.

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