• Cheng-Wei Liu, Joshua Anih, Victoria Lebedeva, Ata Gungor, Carol Wang, Lily Park, and Pavel S Roshanov.
• Division of Nephrology, Department of Medicine, Western University, London, Ontario, Canada.
• J Clin Anesth. 2024 Jun 1; 94: 111417111417.

Study ObjectiveTo assess how kidney disease is handled in randomized trials evaluating the safety and efficacy of perioperative tranexamic acid, and to evaluate its effects across levels of kidney function.DesignSystematic review and meta-analysis of randomized controlled trials.SettingWe screened studies from a previous comprehensive systematic review, and updated its search of PubMed, Embase, and Cochrane CENTRAL to July 31, 2023.PatientsPatients undergoing non-obstetric surgery.InterventionsIntravenous tranexamic acid compared to placebo or usual care without tranexamic acid.MeasurementWe summarized the handling of kidney disease in eligibility criteria, dose adjustments for kidney function, and effects of tranexamic acid on thrombotic events, seizures, and bleeding by subgroups of kidney function.Main ResultsWe evaluated 300 trials with 53,085 participants; 45,958 participants (86.6%) were enrolled in 228 trials (76.0%) that explicitly excluded patients with kidney disease. Definitions of kidney diseased used for exclusion varied widely. Most were non-specific and some corresponded to mild disease. Only 5 trials adjusted dosing for kidney function. Meta-analysis of two large trials found tranexamic acid unlikely to substantially increase or decrease the occurrence of thrombotic events in patients with eGFR <60 mL/min/1.73m2 (RR, 0.95; 95% CI: 0.83 to 1.07) or ≥ 60 mL/min/1.73m2 (RR, 1.00; 95% CI, 0.91 to 1.11; P for subgroup difference = 0.47), but both trials excluded patients with severe kidney disease. No analysis could be performed regarding seizure risk. One large trial in noncardiac surgery reported similar reduction in bleeding across subgroups of kidney function but excluded patients with creatinine clearance <30 mL/min.ConclusionsThe large evidence base supporting perioperative tranexamic acid suffers from broad and unjustified exclusion of patients with kidney disease. Typical perioperative dosing of tranexamic acid is likely safe and effective in patients with creatinine clearance >30 mL/min, but effects in more severe kidney disease are unknown.Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

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