In 2014, a record number of individuals in the United States competed in a marathon; the increase in marathon participation to 550,600 has subsequently increased the need to more closely examine the relationship between marathon running and kidney injury. Because runners are generally seen as healthy athletes with trained physiology to tolerate high states of energy expenditure, the relationship between marathon running and kidney function has not been well studied.
Marathon runners can maximize their oxygen uptake nearly 50% more than healthy nonrunners of the same age; as oxygen uptake increases, cardiac output increases 3- to 5-fold above resting levels. However, according to Sherry G. Mansour, DO, and colleagues, the increased blood flow to skeletal muscles and skin is accompanied by a decrease of up to 25% in renal blood flow during strenuous activity compared with resting levels. Because in normal circumstances kidneys receive 20% of cardiac output, it is possible that this reduction in blood supply to the kidneys may lead to ischemic tubular damage.
Increases in core body temperature may also contribute to tubular damage in marathon runners, resulting in heat stress leading to kidney injury. Further, previous studies have demonstrated that kidney injury may occur during running even with adequate hydration.
The researchers conducted a prospective observational study designed to assess the kidney function of runners participating in the 2015 Hartford (Connecticut) Marathon. The study utilized conventional and renal biomarkers of injury and repair to highlight the association between rigorous activity and kidney function. Study results were reported in the American Journal of Kidney Diseases [2017;70(2):252-261].
The primary outcome of interest was acute kidney injury (AKI) defined by AKI Network (AKIN) criteria: stage 1 was defined as a 1.5- to 2-fold or 0.3 mg/dL increase in serum creatinine level within 48 hours of day 0 and stage 2 was defined as >2- to 3-fold increase in creatinine level. Microscopy score was defined by the number of granular casts and renal tubular epithelial cells.
Samples were collected 24 hours before the marathon (day 0), immediately following the marathon (day 1), and 24 hours after the marathon (day 2). Measurements of serum creatinine, creatinine kinase, and urine albumin were conducted, as was urine microscopy. The six biomarkers measured were: (1) interleukin 6 (IL-6); (2) IL-8; (3) IL-18; (4) kidney injury molecule 1 (KIM-1); (5) neutrophil gelatinase-associated lipocalin (NGAL); and (6) tumor necrosis factor a (TNF-a). Two repair markers were also examined: (1) human cartilage glycoprotein 39 (YKL-40) and (2) monocyte chemoattractant protein 1 (MCP-1).
Marathon participants were offered an online survey; 132 responded. Of those, 68 met inclusion criteria and 22 agreed to participate in the study. The cohort included nine men (41%) and 13 women (59%). Mean age was 44.2 years, mean body mass index was 22.4 kg/m2. Median running experience was 12 years and participants had completed a median of five marathons prior to the Hartford race. The cohort was healthy; two individuals had comorbid conditions (one had hypertension and one had type 2 diabetes). Average training for the marathon was 31.8 miles per week. Six participants had consumed nonsteroidal anti-inflammatory drugs within 2 weeks of the race, but not within 48 hours of race day; 11 participants were taking herbal supplements. All study participants completed the 26.2 miles; average finishing time was 4.02 hours.
In all runners, serum creatinine peaked on day 1. Median creatinine values on days 0, 1, and 2 were 0.81, 1.28, and 0.90 mg/dL, respectively. At least stage 1 AKI was seen in 82% of the runners; one runner developed AKI stage 2. Urine albumin also peaked on day 1. However, serum creatinine kinase level continued to increase 24 hours after the marathon. Day 2 values were significantly higher than days 0 and 1. Across all three time points, fractional excretion of sodium was <1%; there was a significant decrease from day 0 to days 1 and 2.
With the exception of YKL-40 and IL-8, there were no significant correlations between levels of creatine kinase and both conventional and novel biomarkers across the time points; YKL-40 positively correlated with creatine kinase level on day 1 (r=0.51; P<.02) and IL-8 negatively correlated with creatine kinase level on day 1 (r=–0.51; P<.003).
On day 0, urine microscopy yielded minimal findings; significant increases in scores among the runners were seen on days 1 and 2 (positive scores were seen in 9%, 65%, and 59% on days 0, 1, and 2, respectively). Sixteen runners (73%) were seen as having positive microscopy scores in day 1 or day 2.
Compared with days 0 and 2, there was significant elevation in levels of urine biomarkers. The highest-fold increases on day 1 compared with day 0 values were in IL-6, KIM-1, and IL-8. On day 1, levels of YKL-40 and MCP-1 peaked. MCP-I levels had a 7.5-fold increase on day 1 following completion of the marathon compared with day 0 levels.
The small sample size, making the findings subject to possible confounding, was cited as a limitation to the study by the researchers.
In summary, the researchers said, “in this study, we have shown that marathon runners develop an increase in creatinine level that is equivalent to AKI stages 1 and 2 based on AKIN criteria, with urine sediments that are diagnostic of acute tubular injury. This is accompanied by an increase in levels of injury and repair biomarkers, further indicating structural damage in the kidney. The results of our study are mainly hypothesis generating and should be further validated in larger cohorts.”
“Based on findings of urine microscopy, serum creatinine changes and novel biomarkers, marathon running causes acute kidney injury. However, this kidney injury is completely reversible within 48-72 hours after the race. However, it is unclear if repeated short-term injuries to the kidney due to marathon running may lead to long term fibrosis in participants with preexisting kidney disease or risk factors such as diabetes, hypertension, or NSAID use.Based on findings of urine microscopy, serum creatinine changes and novel biomarkers, marathon running causes acute kidney injury. However, this kidney injury is completely reversible within 48-72 hours after the race. However, it is unclear if repeated short-term injuries to the kidney due to marathon running may lead to long term fibrosis in participants with preexisting kidney disease or risk factors such as diabetes, hypertension, or NSAID use.”
~Chirag R. Parikh, MD, PhD, FACPProfessor of MedicineDirector, Program of Applied Translational ResearchYale University and Veterans Affairs Medical Center
- There are few data on the relationship between strenuous activity and kidney function; researchers conducted a prospective observational study of participants in the 2015 Hartford Marathon.
- Of the 22 marathon runners in the study, 82% developed an increase in creatinine level equivalent to acute kidney injury (AKI) stages 1 and 2, defined by AKI Network criteria.
- Levels of serum creatinine, urine albumin, and injury and repair biomarkers peaked on the day of the marathon, with significant elevation compared with the day prior to and the day following the marathon.