• Alexander Zarbock, Mira Küllmar, Detlef Kindgen-Milles, Carola Wempe, Joachim Gerss, Timo Brandenburger, Thomas Dimski, Bartosz Tyczynski, Michael Jahn, Nils Mülling, Martin Mehrländer, Peter Rosenberger, Gernot Marx, Tim Philipp Simon, Ulrich Jaschinski, Philipp Deetjen, Christian Putensen, Jens-Christian Schewe, Stefan Kluge, Dominik Jarczak, Torsten Slowinski, Marc Bodenstein, Patrick Meybohm, Stefan Wirtz, Onnen Moerer, Andreas Kortgen, Philipp Simon, Sean M Bagshaw, John A Kellum, Melanie Meersch, and RICH Investigators and the Sepnet Trial Group.
• Department of Anesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany.
• JAMA. 2020 Oct 27; 324 (16): 1629-1639.

ImportanceAlthough current guidelines suggest the use of regional citrate anticoagulation (which involves the addition of a citrate solution to the blood before the filter of the extracorporeal dialysis circuit) as first-line treatment for continuous kidney replacement therapy in critically ill patients, the evidence for this recommendation is based on few clinical trials and meta-analyses.ObjectiveTo determine the effect of regional citrate anticoagulation, compared with systemic heparin anticoagulation, on filter life span and mortality.Design, Setting, And ParticipantsA parallel-group, randomized multicenter clinical trial in 26 centers across Germany was conducted between March 2016 and December 2018 (final date of follow-up, January 21, 2020). The trial was terminated early after 596 critically ill patients with severe acute kidney injury or clinical indications for initiation of kidney replacement therapy had been enrolled.InterventionsPatients were randomized to receive either regional citrate anticoagulation (n = 300), which consisted of a target ionized calcium level of 1.0 to 1.40 mg/dL, or systemic heparin anticoagulation (n = 296), which consisted of a target activated partial thromboplastin time of 45 to 60 seconds, for continuous kidney replacement therapy.Main Outcomes And MeasuresCoprimary outcomes were filter life span and 90-day mortality. Secondary end points included bleeding complications and new infections.ResultsAmong 638 patients randomized, 596 (93.4%) (mean age, 67.5 years; 183 [30.7%] women) completed the trial. In the regional citrate group vs systemic heparin group, median filter life span was 47 hours (interquartile range [IQR], 19-70 hours) vs 26 hours (IQR, 12-51 hours) (difference, 15 hours [95% CI, 11 to 20 hours]; P < .001). Ninety-day all-cause mortality occurred in 150 of 300 patients vs 156 of 296 patients (Kaplan-Meier estimator percentages, 51.2% vs 53.6%; unadjusted difference, -2.4% [95% CI, -10.5% to 5.8%]; unadjusted hazard ratio, 0.91 [95% CI, 0.72 to 1.13]; unadjusted P = .38; adjusted difference, -6.1% [95% CI, -12.6% to 0.4%]; primary adjusted hazard ratio, 0.79 [95% CI, 0.63 to 1.004]; primary adjusted P = .054). Of 38 prespecified secondary end points, 34 showed no significant difference. Compared with the systemic heparin group, the regional citrate group had significantly fewer bleeding complications (15/300 [5.1%] vs 49/296 [16.9%]; difference, -11.8% [95% CI, -16.8% to -6.8%]; P < .001) and significantly more new infections (204/300 [68.0%] vs 164/296 [55.4%]; difference, 12.6% [95% CI, 4.9% to 20.3%]; P = .002).Conclusions And RelevanceAmong critically ill patients with acute kidney injury receiving continuous kidney replacement therapy, anticoagulation with regional citrate, compared with systemic heparin anticoagulation, resulted in significantly longer filter life span. The trial was terminated early and was therefore underpowered to reach conclusions about the effect of anticoagulation strategy on mortality.Trial RegistrationClinicalTrials.gov Identifier: NCT02669589.

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