Introduction Endurance activity is considered a hallmark of human evolution, but there is limited understanding of what constrains this capacity. The renal demands of endurance exercise often elicit cellular damage, and renal functional capacity is shaped by fetal growth, but whether birth weight (BW) directly affects exercise-induced renal damage is unknown. Methods Here, we test the extent to which birth weight shapes change in serum creatinine, a marker of kidney function, among 44 ultramarathon athletes racing in hot or cold conditions. Results On their own, sex, age, distance run, hydration status, and muscle damage explained ~33% of the variance in absolute creatinine change (p=0.009). The addition of linear and quadratic mean-centered birth weight terms and ultramarathon race significantly improved the model fit (p0.01), explaining ~58% of the variance in absolute creatinine change across the races (p0.001). In this model, hydration status and both birth weight terms were the significant predictors of creatinine change (all p0.05), indicating that both low and high birth weights were associated with a higher chance of transient elevation in creatinine after prolonged exercise. Holding all other variables constant, birth weight influences the kidney’s response to endurance exercise in a U-shaped manner, with the lowest increases in creatinine predicted at birth weights of ~3.8 kg. Discussion Renal functional capacity, proxied by BW, may thus have been central in constraining the upper limits of endurance activity in human evolution, helping us to understand why not just inadequate, but too much, physical activity can impair health.
Murray et al. (Wed,) studied this question.