Non-steroidal Anti-inflammatory Affect on Kidneys in Endurance Distances

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.