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

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.

Fig. 1

Potential triggers for “myocardial injury” in endurance athletes [22, 23, 25]. While a substantial amount of released cardiac troponin (cTn) from myofilaments indicates cardiac damage (A), the early releasable cTn can occur in absence of persistent cardiac damage (B). Metabolic stress associated with intensive endurance exercise may facilitate cardiomyocyte membrane permeability by increased metabolic energy demand, reactive oxygen species (ROS) production, perturbed calcium homeostasis, and increased filling pressures (C). The resulting cTn release is usually modest and of short duration

Fig. 2

Potential triggers of kidney injury in extreme endurance athletes. NSAIDs nonsteroidal anti-inflammatory drugs

Fig. 3

Summary of renal and cardiac injury markers as a consequence of extreme endurance exercise (EEE; see text and [12]). eGFR estimated glomerular filtration rate, NGAL neutrophil gelatinase-associated lipocalin, KIM-1 kidney injury molecule 1, TNF-α tumor necrosis factor α, IL-1 and -6 interleukins 1 and 6, ST2 suppression of tumorigenicity 2, NT-proBNP N-terminal pro-brain natriuretic peptide, H-FABP heart-type fatty acid binding protein

Fig. 4

Putative mechanisms of cardiac damage following renal dysfunction. RAAS renin–angiotensin–aldosterone system, DRP1 dynamin-related protein 1

Fig. 5

Modulators of potential adverse cardiac and renal effects of extreme endurance exercise (EEE) and potential accumulation of damage. While the mechanistic links require a better understanding, medical consultation may reduce the risk of long-term damage by especially taking into account the highlighted risk factors (blue ellipses). RAAS renin–angiotensin–aldosterone system, NS nervous system