Ibuprofen versus placebo effect on acute kidney injury in ultramarathons: a randomised controlled trial
Up to 75% of ultramarathon runners take non-steroidal anti-inflammatory drugs during competition. In a multisite double-blind trial in desert ultramarathons (Gobi, Atacama, Ecuador, Sri Lanka), 89 runners took ibuprofen 400 mg every 4 hours or placebo during a 50-mile (80 km) stage.
Acute kidney injury (AKI) occurred in 44% overall: 52% on ibuprofen vs 34% on placebo, a number needed to harm of 5.5. The difference did not reach the trial's non-inferiority threshold, but the authors conclude that NSAID use during endurance running could exacerbate renal injury and should be considered carefully.
Participants
n=89 ultramarathon runners ("Eighty-nine participants"): 47% ibuprofen, 53% placebo, with similar demographics between groups.
Protocol
Intervention: ibuprofen 400 mg every 4 hours vs placebo, double-blind, during a 50-mile (80 km) foot race.
Primary outcome: incidence of AKI at the finish line: "risk" = 1.5× baseline creatinine, "injury" = 2× baseline creatinine, combined for total incidence.
Non-inferiority margin: 15% difference in AKI rates.
Key Results
Overall AKI incidence: 44%.
Intent-to-treat: AKI in 22 of the ibuprofen runners (52%) vs 16 on placebo (34%) — a difference of 18% (95% CI -4% to 41%); odds ratio 2.1 (95% CI 0.9 to 5.1); number needed to harm: 5.5.
AKI severity, ibuprofen vs placebo: "risk" category 38% vs 26% (95% CI -9% to 34%), "injury" category 14% vs 9% (95% CI -10% to 21%).
Slower finishers were less likely to develop AKI (OR 0.67, 95% CI 0.47 to 0.98).
Losing more body weight (-1.3%) raised the odds of AKI (odds ratio 1.24, 95% CI 1.00 to 1.63).
Authors: not statistically inferior to placebo "by a small margin".
Practical Application
In a randomised double-blind trial of 89 ultramarathon runners over a 50-mile (80 km) race, ibuprofen 400 mg every 4 hours was followed by acute kidney injury in 52% vs 34% on placebo — one extra case for every 5.5 runners who took it. To "can I take ibuprofen during my ultra?": the evidence here points against it; the kidney-injury rate rose, and the authors advise caution.
Honest reading of the statistics: the confidence interval for the difference (-4% to 41%) includes zero, so the trial could not prove harm, nor could it show ibuprofen was safe within its 15% margin.
Kidney stress is common in these races even without drugs: 44% overall had AKI, and more weight loss during the race went with more AKI.
Not from this paper; the base's own practice: vomiting, confusion, or very dark or absent urine during or after an ultra is a medical matter, not something to push through; how to drink in a road ultra is in SYNTH-65.
Limitations
n=89; the result missed the non-inferiority margin "by a small margin", and the confidence intervals are wide.
One dose (400 mg every 4 hours) in desert races; heat and multi-stage conditions may not transfer to temperate single-day events.
AKI defined by creatinine at the finish only; no follow-up of kidney function.
The associations with finishing speed and weight loss are observational within the trial.
Written from the abstract and record metadata only (full text not read).
How this entry was checked and changed
Why this level
registered RCT, n=89
Content correction 2026-09-27
2026-10-01: cross-reference repointed from a merged framework to the one that replaced it (SYNTH-01→31, 05→34, 09→70, 12/15→32, 19→26).