Colchicine and Perioperative Acute Kidney Injury: A Substudy of the COP-AF Randomized Clinical Trial

Perioperative inflammation may result in organ injury, including acute kidney injury (AKI). Colchicine, an anti-inflammatory drug, may help protect the organs from inflammation. This clinical trial substudy examined whether colchicine reduced the risk of perioperative AKI compared with placebo.

Prespecified substudy of a placebo-controlled randomized clinical trial.

Patients aged 55 years or older undergoing major noncardiac thoracic surgery enrolled in the Colchicine for the Prevention of Perioperative Atrial Fibrillation (COP-AF) trial from 45 centers in 11 countries (2018-2023). Patients were excluded for a history of atrial fibrillation, for taking antiarrhythmic medication, or for a preoperative estimated glomerular filtration rate (eGFR) < 30 mL/min per 1.73 m².

Participants were randomized 1:1 to 0.5 mg oral colchicine or placebo, given twice daily for a total of 10 days. Patients, health care providers, data collectors, and outcome adjudicators were masked to the treatment assignment.

Perioperative AKI, defined as an increase in serum creatinine concentration of either ≥0.3 mg/dL within 48 hours of surgery or ≥50% within 7 days of surgery. Alternative definitions of AKI were examined, as was effect modification by pre-existing chronic kidney disease (CKD).

Among 3,209 patients enrolled in the main trial, 2,947 were included in this substudy (mean age, 68 years; mean eGFR, 83 mL/min/1.73 m²) and were randomly allocated to receive colchicine (n = 1,476) or placebo (n = 1,471). Perioperative AKI occurred in 67 participants (4.7%) in the colchicine group and in 63 participants (4.4%) in the placebo group (risk ratio [RR], 1.07 [95% CI, 0.76-1.50], P = 0.72; risk difference [RD], 0.3% [95% CI, -1.2% to 1.8%]). The RD of AKI in patients with CKD treated with colchicine versus placebo was -0.9%, and it was 0.5% in those without CKD (interaction P = 0.62).

Limited statistical power to detect small clinically important effects on AKI treated with dialysis.

Among patients undergoing noncardiac thoracic surgery, the risk of perioperative AKI did not differ between patients allocated to receive colchicine versus placebo.

Grants from academic (Department of Medicine, Western University; Division of Cardiology, McMaster University), government (Canadian Institutes of Health Research; General Research Fund, Research Grants Council, Hong Kong Special Administrative Region, China), and not-for-profit (Accelerating Clinical Trials Consortium; Innovation Fund of the Alternative Funding Plan for the Academic Health Sciences Centres of Ontario; Population Health Research Institute; Hamilton Health Sciences; Hanela Foundation) sources.

Registered at ClinicalTrials.gov with study number NCT03310125.

Inflammation during and after surgery can lead to organ injury, including acute kidney injury (AKI). Colchicine, an anti-inflammatory drug, may help protect the organs from inflammation. This prespecified kidney substudy of the COP-AF trial (a placebo-controlled, randomized clinical trial of 3,209 patients aged 55 years and older having major noncardiac thoracic surgery), examined the effect of oral colchicine (0.5 mg tablet, taken twice daily starting within 4 hours before surgery for a total of 10 days) on the risk of perioperative AKI. The study found that the risk of perioperative AKI did not differ between patients assigned to receive colchicine versus placebo. The results were consistent for multiple definitions of AKI and in patients with pre-existing chronic kidney disease.