Non-steroidal Anti-inflammatory Affect on Kidneys in Endurance Distances
Condition: Acute Kidney Injury; Exercise-associated Hyponatremia; Perceived Exertion
MeSH terms: Acute Kidney Injury; Hyponatremia
Intervention: Ibuprofen; Placebo
Intervention description: Ibuprofen; Tasteless and inert visually identical (to ibuprofen) pills
Intervention MeSH terms: Ibuprofen
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 91.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: ultramarathon; ibuprofen; acute kidney injury; exercise-associated hyponatremia; exertion

Summary:

      The specific aim of this study is to evaluate the safety of non-steroidal anti-inflammatory
      drugs (NSAIDs) and their impact on renal function and/or contribution to exercise-associated
      hyponatremia (EAH) during an ultramarathon foot race. There is currently much debate over
      whether NSAID ingestion during endurance events contributes to acute kidney injury. Endurance
      events often ignite a "perfect storm" of physiologic insults- heat stress, dehydration, and
      myopathy- which can all negatively impact kidney function. There is a concern that NSAIDs may
      further potentiate these negative effects as well as contribute to EAH through its
      anti-diuretic affect. To date, no powered, prospective study has ever examined the effects of
      NSAIDs on either of these two biochemical outcomes

      Ultramarathon endurance events, defined as any race longer than a marathon (26.2 miles), are
      increasing in popularity, with a 10% increase in annual participants, and more than 69,000
      finishers worldwide in 2013. Considerable literature has documented alterations in serum
      biochemical profiles of these endurance athletes, with consistent evidence of elevated serum
      creatinine (Cr) levels in healthy race finishers as well as those seeking medical care. While
      acute renal failure in ultramarathon runners is a rare occurrence, acute kidney injury is
      common, ranging from 34% in a single-stage ultramarathon to 55-80% in multi-stage
      ultramarathons. The evidence is equivocal regarding NSAID ingestion and AKI. One study showed
      that runners who ingested NSAIDs prior to marathons had greater post-race creatinine levels
      than matched controls as well as higher rates of hospitalization and acute renal failure.
      However, this contrasts with several other studies that showed a marked lack of difference in
      creatinine levels or development of acute kidney injury between NSAID users and non-users
      during ultramarathons. The only randomized trial to date on this subject found no difference
      in serum creatinine levels between the NSAID and placebo groups at ultramarathon race end,
      however conclusions were limited by a small unpowered sample size.

      Exercise associated hyponatremia (EAH), defined as a serum sodium concentration below
      135mEq/L, is recognized as a relatively common issue in endurance running events. The
      incidence of EAH varies depending upon the distance of the race, with reported values of
      3-28% for marathons, 23 - 38% for triathlons and 4-51% in single-stage ultramarathons. EAH is
      likely under-diagnosed as athletes are often asymptomatic. While EAH most often manifests as
      non-specific symptoms such as nausea, vomiting, dizziness, and fatigue, it can be a
      potentially fatal disease that can progress to encephalopathy, seizures, pulmonary edema, and
      death. There have been no large prospective studies examining the relationship between EAH
      and NSAID ingestion.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Any participant in a RacingThePlanet sanctioned event who understands the consent form
             in English.

        Exclusion Criteria:

          -  Allergic to any form of non-steroidal anti-inflammatory

          -  Taken a NSAID or steroid in prior 12 hours

          -  1 kidney

          -  Known to be pregnant or suspected to be pregnant