New research reveals that the conditions we’re born with may influence how well our kidneys cope with the intense demands of endurance sports later in life.
Study: Birth weight shapes renal damage from prolonged endurance activity later in life. Image Credit: djile / Shutterstock.com
In a recent study published in Frontiers in Ecology and Evolution, researchers investigated how birth weight shapes changes in kidney function following prolonged physical activity in ultramarathon athletes competing in hot and cold environments.
How does exercise impact kidney health?
Regular physical activity strengthens the cardiovascular system, supports mental health, and reduces the risk of chronic disease. Despite these benefits, exercise stresses the kidneys' filtration, fluid, and electrolyte capabilities by reducing renal blood flow and glomerular filtration rate (GFR).
Prolonged exercise causes myoglobin to enter systemic circulation, which, if trapped within renal tubules, can further reduce oxygen supply and increase the risk of acute kidney injury (AKI). Dehydration exacerbates these effects by limiting renal perfusion, thereby facilitating the accumulation of nephrotoxic substances in the kidneys. Comparatively, overhydration leads to dilutional hyponatremia and renal stress, which similarly increases the risk of AKI, particularly among endurance athletes.
How early development predicts kidney resilience
It remains unclear how fetal development may impact the renal response to exercise later in life. Nevertheless, low birth weight, a feature of impaired intrauterine growth, can predict the likelihood of developing insulin resistance, type 2 diabetes, metabolic syndrome, and other forms of cardiovascular and renal disease.
According to the Developmental Origins of Health and Disease (DOHaD) hypothesis, certain tissues possess key cells that are largely established by birth, such as neurons in the brain and nephrons in the kidneys. Based on this observation, fetal growth impairment can affect the quantity and quality of these cells, contributing to adverse metabolic health outcomes later in life.
Nephrogenesis typically completes by 36 weeks of gestation, providing the fetus with the full complement of nephrons needed to sustain kidney function throughout life. Birth weight strongly correlates with nephron number, as fewer nephrons provide less surface area for blood filtration.
Among infants born with low birth weight, increased glomerular pressure responds to lower GFR, subsequently diminishing renal functional reserve (RFR). Reduced RFR interferes with how the kidneys respond to environmental stressors such as obesity, pregnancy, dietary patterns, or exercise.
Given the importance of endurance activity to human subsistence, survivorship, evolutionary fitness, and health, the limits of kidney function may also have profoundly shaped the evolution of endurance-based subsistence strategies in our species.
Ultramarathon athletes studied across hot and cold races
A total of 44 adult ultramarathon athletes, 15 female and 29 male, without a history of kidney disease or cancer, were included in the current study. All study participants completed pre-race questionnaires on their birth weight, demographics, training, and health, including their kidney function based on previous test results.
Anthropometric measurements such as height and body mass were recorded before the race, and body mass was re-measured after completing the race to infer hydration status as the percentage change in weight.
Serum creatinine and myoglobin levels were monitored to assess changes in renal stress (as a proxy marker of kidney function) and muscle injury, respectively, before and immediately after the ultramarathon. Samples were handled and frozen in similar standard laboratory conditions prior to biochemical determinations.
Statistical analyses were conducted using both parametric and non-parametric tests, which revealed significant differences between races and sexes. Hierarchical linear regression modeling was used to examine the independent effect of birth weight on creatinine levels over time.
Age, sex, race distance, hydration level, and muscle damage were considered as possible covariate factors in the final analysis. Birth weight variables were mean-centered, with both linear and quadratic terms included to test for possible non-linear effects.
Hydration and early growth strongly influenced kidney response
Athletes who performed endurance exercise experienced measurable kidney stress, as demonstrated by higher serum creatinine levels, in both the hot (Al Andalus Ultimate Trail, Spain) and cold (Rovaniemi150, Finnish Lapland) race environments. However, the magnitude of creatinine increase differed between these climates and race groups.
The average increase in creatinine levels was 0.5 mg/dL greater for athletes in the hot desert race than for those in colder regions, at 0.2 mg/dL. In addition to altered renal function, significantly greater body mass loss was observed among athletes competing in the hot race as compared to those in colder areas, suggesting that dehydration contributes to increased renal stress.
Athletes competing in the colder race exhibited significantly higher serum myoglobin levels despite lower creatinine elevations. Importantly, females tended to show a greater relative increase in creatinine levels than males, likely due in part to lower baseline levels, though not all differences were statistically significant.
Regression models controlling for age, gender, distance, hydration status, and musculoskeletal injury accounted for 33 % of the variance in creatinine responses. The consideration of birth weight, along with race type, in this analysis accounted for 58 % of the variation, indicating a significant independent influence of early growth on kidney responses.
Athletes with low birth weight (weighing less than 2.5 kg at birth) and those with high birth weight (4.5 kg or greater) exhibited a greater increase in serum creatinine levels after exercise, suggesting reduced renal functional reserve and lower resilience to physiological stress. Comparatively, individuals with a birth weight of 2.5-4.5 kg were less likely to experience large increases in creatinine levels, likely reflecting renal adaptability to prolonged physical activity. The lowest predicted creatinine changes were associated with a birth weight of 3.8 kg.
Hydration levels are a significant predictor of creatinine responses after strenuous exercise, independent of the effects of birth weight. Other factors, such as age, race, distance, and muscle damage, were less impactful on kidney function after birth weight and hydration were considered.
However, the authors note that creatinine changes reflect transient kidney stress and may indicate suspected acute kidney injury (AKI) based on standard criteria, rather than confirmed clinical AKI. The study also has several limitations, including reliance on self-reported birth weight, lack of data on gestational age and maternal health factors, and the highly self-selected nature of ultramarathon athletes, which may limit generalizability.
Download your PDF copy by clicking here.
Eccentric exercise builds muscle strength and size with less effort