Marathon running and cell-cycle arrest biomarkers of acute kidney injury.

OBJECTIVES: Endurance exercise is known to cause a rise in serum creatinine. It is not known to what extent this rise reflects renal stress and a potential acute kidney injury (AKI). Increases in Insulin Like Growth Factor Binding Protein 7 (IGFBP7) and Tissue Inhibitor of Metalloprotinases-2 (TIMP-2), urinary biomarkers of cell cycle arrest and renal stress, are associated with the development of AKI in clinical populations. DESIGN: Repeated measures study. METHODS: Runners were recruited at the 2019 Brighton Marathon (UK) and provided urine and blood samples at baseline, immediately post-race and 24 h post-race. Serum creatinine, urinary creatinine and urinary IGFBP7 and TIMP-2 were analysed from the samples. RESULTS: Seventy nine participants (23 females, 56 males), aged 43 ±â€¯10 yrs. (mean ±â€¯SD), finish time 243 ±â€¯40mins were included for analysis. Serum creatinine increased over the race by 40 ±â€¯26% (p < 0.001), TIMP-2 increased by 555 ±â€¯697% (p < 0.001) and IGFBP7 increased by 1094 ±â€¯1491% (p < 0.001) over the race. A subset of twenty-two participants supplied samples 24 h post-race, reporting values similar to baseline for all variables. CONCLUSIONS: This study is the first to report large rises in IGFBP7 and TIMP-2 following marathon running. This suggests that rises in creatinine are not fully explained by changes in production and clearance and marathon running induces a state of kidney stress and potential injury.

Relative changes in brain and kidney biomarkers with Exertional Heat Illness during a cool weather marathon.

BACKGROUND: Medical personnel may find it challenging to distinguish severe Exertional Heat Illness (EHI), with attendant risks of organ-injury and longer-term sequalae, from lesser forms of incapacity associated with strenuous physical exertion. Early evidence for injury at point-of-incapacity could aid the development and application of targeted interventions to improve outcomes. We aimed to investigate whether biomarker surrogates for end-organ damage sampled at point-of-care (POC) could discriminate EHI versus successful marathon performance. METHODS: Eight runners diagnosed as EHI cases upon reception to medical treatment facilities and 30 successful finishers of the same cool weather marathon (ambient temperature 8 rising to 12 ºC) were recruited. Emerging clinical markers associated with injury affecting the brain (neuron specific enolase, NSE; S100 calcium-binding protein B, S100ß) and renal system (cystatin C, cysC; kidney-injury molecule-1, KIM-1; neutrophil gelatinase-associated lipocalin, NGAL), plus copeptin as a surrogate for fluid-regulatory stress, were sampled in blood upon marathon collapse/completion, as well as beforehand at rest (successful finishers only). RESULTS: Versus successful finishers, EHI showed significantly higher NSE (10.33 [6.37, 20.00] vs. 3.17 [2.71, 3.92] ug.L-1, P<0.0001), cysC (1.48 [1.10, 1.67] vs. 1.10 [0.95, 1.21] mg.L-1, P = 0.0092) and copeptin (339.4 [77.0, 943] vs. 18.7 [7.1, 67.9] pmol.L-1, P = 0.0050). Discrimination of EHI by ROC (Area-Under-the-Curve) showed performance that was outstanding for NSE (0.97, P<0.0001) and excellent for copeptin (AUC = 0.83, P = 0.0066). CONCLUSIONS: As novel biomarker candidates for EHI outcomes in cool-weather endurance exercise, early elevations in NSE and copeptin provided sufficient discrimination to suggest utility at point-of-incapacity. Further investigation is warranted in patients exposed to greater thermal insult, followed up over a more extended period.

Association between collapse and serum creatinine and electrolyte concentrations in marathon runners: a 9-year retrospective study.

OBJECTIVE: Abnormal biochemical measurements have previously been described in runners following marathons. The incidence of plasma sodium levels outside the normal range has been reported as 31%, and the incidence of raised creatinine at 30%. This study describes the changes seen in electrolytes and creatinine in collapsed (2010-2019 events) and noncollapsed (during the 2019 event) runners during a UK marathon. METHODS: Point-of-care sodium, potassium, urea and creatinine estimates were obtained from any collapsed runner treated by the medical team during the Brighton Marathons, as part of their clinical care, and laboratory measurements from control subjects. RESULTS: Results from 224 collapsed runners were available. Serum creatinine was greater than the normal range in 68.9%. About 6% of sodium results were below, and 3% above the normal range, with the lowest 132 mmol/l. Seventeen percent of potassium readings were above the normal range; the maximum result was 8.4 mmol/l, but 97% were below 6.0 mmol/l. In the control group, mean creatinine was significantly raised in both the collapse and control groups, with 55.4% meeting the criteria for acute kidney injury, but had resolved to baseline after 24 h. Sodium concentration but not the potassium was significantly raised after the race compared with baseline, but only 15% were outside the normal range. CONCLUSION: In this study, incidence of a raised creatinine was higher than previously reported. However, the significance of such a rise remains unclear with a similar rise seen in collapsed and noncollapsed runners, and resolution noted within 24 h. Abnormal sodium concentrations were observed infrequently, and severely abnormal results were not seen, potentially reflecting current advice to drink enough fluid to quench thirst.

High-sensitivity troponin T in marathon runners, marathon runners with heart disease and collapsed marathon runners.

Endurance exercise is an established cause of cardiac troponin (cTn) elevation, of further interest is whether this rise represents clinical significance. This study compared cTnT rise in three cohorts of marathon runners using a high-sensitivity assay; control runners, those with known heart disease and runners who collapsed at the finish line. Control runners (n = 126) and runners with heart disease (n = 12) were prospectively recruited with cTnT levels measured pre-race and at race completion. Collapsed runners (n = 15) were retrospectively recruited. A mixed model ANCOVA was used to compare the three groups. Pre-race median cTnT for the control group and heart disease groups was 3.9 ng/L (IQR 3.1 ng/L) and 4.1 ng/L (IQR 3.4 ng/L). Post-race values for the three groups were control 45.6 ng/L (IQR 42.5 ng/L), heart disease 41.2 ng/L (IQR 36.1 ng/L), and collapsed 41.9 ng/L (IQR 57.8 ng/L). Post-race cTnT and cTnT change were significantly correlated with pre-race cTnT within the control group (r = 0.38 and 0.30, P < 0.01). There was no difference in post-race cTnT (adjusted for pre-race cTnT) between the three groups. None of the runners reported symptoms suggestive of acute myocardial infarction on follow-up. These results demonstrate that marathon running is associated with an asymptomatic cTnT rise for all runners, and this rise is significantly correlated to baseline cTnT levels, in addition, marathon runners with pre-existing cardiac pathology or who collapse at the finish line do not exhibit an increased cTnT rise compared to healthy runners.