title: Comparison of standard and accelerated initiation of renal replacement therapy in acute kidney injury.
abstract: In patients with severe acute kidney injury (AKI) but no urgent indication for renal replacement therapy (RRT), the optimal time to initiate RRT remains controversial. While starting RRT preemptively may have benefits, this may expose patients to unnecessary RRT. To study this, we conducted a 12-center open-label pilot trial of critically ill adults with volume replete severe AKI. Patients were randomized to accelerated (12 h or less from eligibility) or standard RRT initiation. Outcomes were adherence to protocol-defined time windows for RRT initiation (primary), proportion of eligible patients enrolled, follow-up to 90 days, and safety in 101 fully eligible patients (57 with sepsis) with a mean age of 63 years. Median serum creatinine and urine output at enrollment were 268 micromoles/l and 356 ml per 24 h, respectively. In the accelerated arm, all patients commenced RRT and 45/48 did so within 12 h from eligibility (median 7.4 h). In the standard arm, 33 patients started RRT at a median of 31.6 h from eligibility, of which 19 did not receive RRT (6 died and 13 recovered kidney function). Clinical outcomes were available for all patients at 90 days following enrollment, with mortality 38% in the accelerated and 37% in the standard arm. Two surviving patients, both randomized to standard RRT initiation, were still RRT dependent at day 90. No safety signal was evident in either arm. Our findings can inform the design of a large-scale effectiveness randomized control trial.
authors.affiliation: Division of Nephrology, St Michael's Hospital and University of Toronto, Toronto, Ontario, Canada.|Li Ka Shing Knowledge Institute of St Michael's Hospital, Toronto, Ontario, Canada.
authors.forename: Ron
authors.initials: R
authors.lastname: Wald
authors.affiliation: Department of Critical Care Medicine, Sunnybrook Health Sciences Centre and Interdepartmental Division of Critical Care, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Neill K J
authors.initials: NK
authors.lastname: Adhikari
authors.affiliation: Li Ka Shing Knowledge Institute of St Michael's Hospital, Toronto, Ontario, Canada.|Department of Critical Care Medicine, St Michael's Hospital, Toronto, Ontario, Canada.
authors.forename: Orla M
authors.initials: OM
authors.lastname: Smith
authors.affiliation: Division of Nephrology, London Health Sciences Centre and Western University, London, Ontario, Canada.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Weir
authors.affiliation: Applied Health Research Centre, St Michael's Hospital, Toronto, Ontario, Canada.
authors.forename: Karen
authors.initials: K
authors.lastname: Pope
authors.affiliation: Applied Health Research Centre, St Michael's Hospital, Toronto, Ontario, Canada.
authors.forename: Ashley
authors.initials: A
authors.lastname: Cohen
authors.affiliation: Applied Health Research Centre, St Michael's Hospital, Toronto, Ontario, Canada.|Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Kevin
authors.initials: K
authors.lastname: Thorpe
authors.affiliation: Division of Critical Care Medicine, The Ottawa Hospital and the University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Lauralyn
authors.initials: L
authors.lastname: McIntyre
authors.affiliation: Division of Critical Care Medicine, Centre Hospitalier Universite de Sherbrooke, Sherbrooke, Quebec, Canada.
authors.forename: Francois
authors.initials: F
authors.lastname: Lamontagne
authors.affiliation: Division of Critical Care Medicine, St Joseph's Healthcare, Hamilton, Ontario, Canada.
authors.forename: Mark
authors.initials: M
authors.lastname: Soth
authors.affiliation: Division of Critical Care, University Health Network, Toronto, Ontario, Canada.
authors.forename: Margaret
authors.initials: M
authors.lastname: Herridge
authors.affiliation: Division of Critical Care, Mt Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Stephen
authors.initials: S
authors.lastname: Lapinsky
authors.affiliation: Division of Nephrology, The Ottawa Hospital and the University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Edward
authors.initials: E
authors.lastname: Clark
authors.affiliation: Division of Nephrology, London Health Sciences Centre and Western University, London, Ontario, Canada.
authors.forename: Amit X
authors.initials: AX
authors.lastname: Garg
authors.affiliation: Division of Nephrology, The Ottawa Hospital and the University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Swapnil
authors.initials: S
authors.lastname: Hiremath
authors.affiliation: Li Ka Shing Knowledge Institute of St Michael's Hospital, Toronto, Ontario, Canada.|Applied Health Research Centre, St Michael's Hospital, Toronto, Ontario, Canada.|Critical Care Department, St Michael's Hospital, Toronto, Ontario, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Klein
authors.affiliation: Li Ka Shing Knowledge Institute of St Michael's Hospital, Toronto, Ontario, Canada.|Department of Anesthesiology, St Michael's Hospital, Toronto, Ontario, Canada.
authors.forename: C David
authors.initials: CD
authors.lastname: Mazer
authors.affiliation: Division of Nephrology, University Health Network, Toronto, Ontario, Canada.
authors.forename: Robert M A
authors.initials: RM
authors.lastname: Richardson
authors.affiliation: Division of Critical Care Medicine, St Joseph's Healthcare, Hamilton, Ontario, Canada.
authors.forename: M Elizabeth
authors.initials: ME
authors.lastname: Wilcox
authors.affiliation: Li Ka Shing Knowledge Institute of St Michael's Hospital, Toronto, Ontario, Canada.|Critical Care Department, St Michael's Hospital, Toronto, Ontario, Canada.
authors.forename: Jan O
authors.initials: JO
authors.lastname: Friedrich
authors.affiliation: Li Ka Shing Knowledge Institute of St Michael's Hospital, Toronto, Ontario, Canada.|Critical Care Department, St Michael's Hospital, Toronto, Ontario, Canada.
authors.forename: Karen E A
authors.initials: KE
authors.lastname: Burns
authors.affiliation: Division of Critical Care Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Sean M
authors.initials: SM
authors.lastname: Bagshaw
mesh_terms: D058186:Acute Kidney Injury / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology / Q000628:therapy*; D000368:Aged; D002170:Canada; D016638:Critical Illness; D005240:Feasibility Studies; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D007668:Kidney / Q000503:physiopathology*; D007902:Length of Stay; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D017582:Renal Replacement Therapy / Q000009:adverse effects / Q000401:mortality; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors; D061665:Time-to-Treatment; D016896:Treatment Outcome; D057832:Watchful Waiting