Could Repeated Cardio-Renal Injury Trigger Late Cardiovascular Sequelae in Extreme Endurance Athletes?

Sports Medicine https://doi.org/10.1007/s40279-022-01734-8 REVIEW ARTICLE Could Repeated Cardio‑Renal Injury Trigger Late Cardiovascular Sequelae in Extreme Endurance Athletes? Johannes Burtscher1,2 · Paul‑Emmanuel Vanderriele1 · Matthieu Legrand3 · Hans‑Georg Predel4 · Josef Niebauer5 · James H. O’Keefe6 · Grégoire P. Millet2 · Martin Burtscher7 Accepted: 2 July 2022 © The Author(s) 2022 Abstract Regular exercise confers multifaceted and well-established health benefits. Yet, transient and asymptomatic increases in markers of cardio-renal injury are commonly observed in ultra-endurance athletes during and after competition. This has raised concerns that chronic recurring insults could cause long-term cardiac and/or renal damage. Indeed, extreme endurance exercise (EEE) over decades has sometimes been linked with untoward cardiac effects, but a causal relation with acute injury markers has not yet been established. Here, we summarize the current knowledge on markers of cardiac and/or renal injury in EEE athletes, outline the possible interplay between cardiac and kidney damage, and explore the roles of various factors in the development of potential exercise-related cardiac damage, including underlying diseases, medication, sex, training, competition, regeneration, mitochondrial dysfunction, oxidative stress, and inflammation. In conclusion, despite the undisputed health benefits of regular exercise, we speculate, based on the intimate link between heart and kidney diseases, that in rare cases excessive endurance sport may induce adverse cardio-renal interactions that under specific, hitherto undefined conditions could result in persistent cardiac damage. We highlight future research priorities and provide decision support for athletes and clinical consultants who are seeking safe strategies for participation in EEE training and competition. Key Points * Martin Burtscher 1 Department of Biomedical Sciences, University of Lausanne, Lausanne, Switzerland 2 Institute of Sport Sciences, University of Lausanne, Lausanne, Switzerland 3 Department of Anesthesia and Perioperative Care, Division of Critical Care Medicine, University of California, San Francisco, CA, USA 4 Department of Preventive and Rehabilitative Sport Medicine and Exercise Physiology, Institute for Cardiology and Sports Medicine, German Sport University, Cologne, Germany 5 University Institute of Sports Medicine, Prevention and Rehabilitation, Paracelsus Medical University Salzburg, Salzburg, Austria 6 Saint Luke’s Mid America Heart Institute, University of Missouri-Kansas City, Kansas City, MO, USA 7 Medical Section, Department of Sport Science, University of Innsbruck, Fürstenweg 185, 6020 Innsbruck, Austria Clear evidence for long-term cardiac and/or renal damage resulting from chronic recurring insults from extreme endurance exercising is still missing. A better understanding of this association is important to enable endurance athletes to reap all the health benefits from exercising without risk of cardiac/renal adversities. 1 Introduction Case GF is a 58-year-old male with intermittent atrial fibrillation (AF), medically treated mild hypertension, and stage 3 chronic kidney disease (CKD), with a creatinine of 132.6 μmol/L and an estimated glomerular filtration rate (eGFR) of 48 mL/min/1.73 m 2. For the past 20 years his creatinine has typically ranged from 115 to 132.6 μmol/L. Vol.:(0123456789) J. Burtscher et al. Currently, he has no signs or symptoms of renal or cardiac disease despite his stage 3 CKD. He has been an avid exerciser most of his adult life and began training for and competing in endurance exercise events at age 35 years, at which time his renal function was normal. Due to an orthopedic injury, he is currently doing only light exercise in the form of walking and recreational bicycling totaling not more than 3 h/week. Renal workup was largely unremarkable showing no vasculitis, glomerulonephritis, renal cysts, kidney stones, or renal artery stenosis, and the patient did not have a family history of kidney disease. In the past he had typically performed several marathons and half marathons each year, occasionally competed in ultramarathon events, and over the last decade he has completed seven full-distance Ironman® triathlons. On two occasions following extreme exercise efforts (a 50 km ultramarathon and an Ironman® triathlon) he developed rhabdomyolysis with acute kidney injury requiring hospitalization. Could repeated participation in extreme endurance competitions have led to cumulative kidney injury, and could this increase the risk of permanent cardiac disease for this patient? Cases like the one described above raise the question whether extreme endurance exercise (EEE) under certain conditions may increase risks for cardiovascular (CV) and/or renal damage. In light of the impressive general benefits of exercise, it is of utmost importance to identify these conditions and dispel concerns in the absence of relevant risk factors. Regular physical activity (PA), including exercise, which is defined as planned, structured, repeated, and goal-directed PA, is among the most important lifestyle factors for positively influencing cardiorespiratory fitness, healthy aging, and longevity [1, 2]. Public health guidelines recommend at least 150–300 min of PA at moderate aerobic intensity or 75–150 min at vigorous intensity per week [2]. However, much more PA may be necessary to achieve maximal health benefits. Indeed, a large prospective cohort study demonstrated that maximal longevity gains can be found at about 700 min of moderate or 350 min of vigorous activity per week [3]. The increased life expectancy of elite athletes and especially endurance athletes [4], as compared with the general population, indicates that elite sports—thus involving exercise at high intensity and volume and in combination with competition-related stressors—might also reduce allcause mortality. Despite the pronounced CV as well as general health benefits conferred by regular PA, an increasing number of reports raise concerns about detrimental health effects associated with long-term EEE, i.e., life-long marathon (26.2 miles) and/or ultramarathon (any running event > 26.2 miles or 42.2 km) running [5–7]. For example, post-mortem analyses in highly trained athletes revealed left ventricle (LV) hypertrophy and interstitial myocardial fibrosis [5]. These authors suspected that life-long, repetitive bouts of demanding PA resulted in fibrous replacement of the myocardium, likely generating the pathological substrate for the propagation of fatal arrhythmias [5]. Others suggested that the extraordinary hemodynamic challenge (disproportionate increase in afterload and wall stress) of the right heart chambers may result in myocardial fatigue or damage when intense exercise is sustained for prolonged periods [6]. Generally, the heart adapts physiologically and anatomically in response to chronic end (...truncated)