Ibuprofen versus placebo effect on acute kidney injury in ultramarathons: a randomised controlled trial

Abstract

BackgroundDespite concerns that non-steroidal anti-inflammatory drugs (NSAIDs) contribute to acute kidney injury (AKI), up to 75% of ultramarathon runners ingest these during competition. The effect of NSAID on AKI incidence in ultramarathon runners is unclear.MethodsMultisite randomised double-blind placebo-controlled trial in the Gobi, Atacama, Ecuador and Sri Lankan deserts to determine whether ibuprofen (400 mg every 4 hours) would be non-inferior to placebo during a 50-mile (80 km) foot race. The primary outcome was incidence of AKI defined as severity categories of ‘risk’ of injury of 1.5× baseline creatinine (Cr) or ‘injury’ as 2× Cr, combined to calculate total incidence at the finish line. Non-inferiority margin for difference in AKI rates was defined as 15%.ResultsEighty-nine participants (47% ibuprofen and 53% placebo) were enrolled with similar demographics between groups. The overall incidence of AKI was 44%. Intent-to-treat analysis found 22 (52%) ibuprofen versus 16 (34%) placebo users developed AKI (18% difference, 95% CI –4% to 41%; OR 2.1, 95% CI 0.9 to 5.1) with a number needed to harm of 5.5. Greater severity of AKI was seen with ibuprofen compared with placebo (risk=38% vs 26%; 95% CI –9% to 34%; injury=14% vs 9%; 95% CI –10% to 21%). Slower finishers were less likely to encounter AKI (OR 0.67, 95% CI 0.47 to 0.98) and greater weight loss (−1.3%) increased AKI (OR 1.24, 95% CI 1.00 to 1.63).ConclusionThere were increased rates of AKI in those who took ibuprofen, and although not statistically inferior to placebo by a small margin, there was a number needed to harm of 5.5 people to cause 1 case of AKI. Consideration should therefore be taken before ingesting NSAID during endurance running as it could exacerbate renal injury.Trial registration numberNCT02272725.

Ultramarathon and Renal Function: Does Exercise-Induced Acute Kidney Injury Really Exist in Common Conditions?

“…It has been reported that up to 75% of ultra-endurance athletes use NSAIDs during the race (Wharam et al, 2006). Our present results, excluding subjects with the use of NSAIDs demonstrated a high decreased prevalence of AKI compared to studies whose included them (McCullough et al, 2011;Hewing et al, 2015;Mansour et al, 2017), highlighting the deleterious effects on renal function of the use of NSAIDs during an ultramarathon race, able to exacerbate renal injury (Lipman et al, 2017).…”

“…Further risk factors for acute kidney injury in ultra-endurance runners have been demonstrated as the use of NSAIDs (Lipman et al, 2017) sometimes leading to dramatic clinical situation of acute renal failure needing hospitalization (Poussel et al, 2013). In a previous "Infernal-Trail" race (2014), we observed a prevalence of self-medication during the race at 18% and NSAIDs has been consumed in half of the cases (Didier et al, 2017).…”

“…Lipman et al (2016Lipman et al ( , 2017 have found a prevalence of an acute kidney injury in ultra-marathon running close to 50% of all runners. A peculiar context associating dehydration and/or use of non-steroidal anti-inflammatory drugs (NSAIDs) have been documented in order to promote acute kidney injury associated to ultra-marathons (Hodgson et al, 2017;Lipman et al, 2017;Knechtle and Nikolaidis, 2018). Therefore, whether ultra-marathon running by itself increases the risk of acute kidney injury need to be clarified.…”

“…Among them, acute kidney injury, involving altered renal function, has often been reported in sports with prolonged and strenuous exercise, such as marathon running and has also been documented in ultramarathons (Boulter et al, 2011;Knechtle and Nikolaidis, 2018). Lipman et al (2016Lipman et al ( , 2017 have found a prevalence of an acute kidney injury in ultra-marathon running close to 50% of all runners. A peculiar context associating dehydration and/or use of non-steroidal anti-inflammatory drugs (NSAIDs) have been documented in order to promote acute kidney injury associated to ultra-marathons (Hodgson et al, 2017;Lipman et al, 2017;Knechtle and Nikolaidis, 2018).…”

Low-Osmolality Carbohydrate–Electrolyte Solution Ingestion Avoid Fluid Loss and Oxidative Stress after Exhaustive Endurance Exercise

“…A study of prolonged exercise (marathon) also demonstrated a decline in eGFR and increased biomarkers for kidney injury, but these were not associated with acute exercise [29]. Nonsteroidal anti-inflammatory drugs taken by athletes for analgesic purposes may exacerbate kidney damage, especially related to severe dehydration [30]. Acute exercise could induce significant creatinine elevation and a decrease in eGFR compared with baseline levels in the present study, but these levels gradually recovered after exercise ( Figure 3A,B).…”