Rhabdomyolysis in Athletes: Causes and the Connection with Exertion and Pharmacology

Rhabdomyolysis is the massive destruction of skeletal muscles with the release of their contents into the blood. In sport it is often associated with extreme training, but in reality the risk is formed by a combination of factors: unaccustomed exertion, heat, dehydration, medications and supplements. Our editorial team explains what happens to the muscle, why the kidneys suffer and what role pharmacology plays.

What Rhabdomyolysis Is and How It Differs from Ordinary Muscle Soreness

Any intense training, especially with eccentric work, causes microdamage to muscle fibers. It is precisely this that is felt as delayed-onset muscle soreness (DOMS) 24–72 hours later. In the blood at this time creatine kinase rises — an enzyme that leaves the damaged cells. This is a normal part of adaptation.

Rhabdomyolysis is spoken of when the damage becomes so massive that the body does not manage to "process" the breakdown products. Clinically this manifests as pronounced pain, swelling and weakness of the muscles, and sometimes as dark urine due to myoglobin. In the laboratory — a sharp increase in creatine kinase; in clinical practice a threshold exceeding the upper limit of normal by at least fivefold is often used, although in athletes it is difficult to distinguish a "normal" from a pathological reaction by the figure alone.

The difference between physiological damage and rhabdomyolysis is not only quantitative. Decisive importance lies in the symptoms and consequences: whether there is kidney injury, electrolyte disturbances, whether swelling is increasing in the closed fascial spaces. That is precisely why the diagnosis is made by a doctor, not a calculator.

Exertional rhabdomyolysis is described in military recruits, marathon participants, functional-training athletes, cycling studios, and also in strength sports — especially after a long break or with an abrupt transition to a new program.

How the Destruction of Muscles Harms the Body

When the membrane of a muscle cell is damaged, an excess of sodium and calcium enters it. Calcium activates enzymes that destroy proteins and membranes, and the cell's energy reserves are depleted. A vicious circle is formed: the greater the damage, the less energy for its "repair."

From the dead cells, myoglobin, potassium, phosphates, uric acid and creatine kinase are released into the blood. Myoglobin in the acidic environment of the renal tubules forms casts and has a direct toxic effect, while dehydration and constriction of the kidney's blood vessels intensify the injury. The result can be acute kidney injury.

The release of potassium threatens hyperkalemia — a condition that can cause dangerous arrhythmias. Swelling of the muscles in tight compartments (for example, in the anterior compartment of the shin) is able to cause compartment syndrome, which requires surgical intervention.

It is important that the severity of the consequences is not always directly proportional to the level of creatine kinase. Many athletes have very high values without kidney injury, whereas in the presence of dehydration, heat or nephrotoxic drugs the risk of complications increases even with a more moderate elevation.

Exertion as a Trigger: Who Is at Greatest Risk

The classic scenario of exertional rhabdomyolysis is work of a large volume that is unaccustomed for the person. A beginner who comes to a first group session of high intensity; an experienced athlete who returns after a break and immediately works "as before"; an athlete who performs hundreds of repetitions of a single exercise at a competition or in a "challenge."

Especially traumatic is eccentric work — the phase of lengthening the muscle under load: descents, lowering the weight, jumps, "negative" repetitions. It is precisely this that produces the greatest increase in creatine kinase and the most pronounced soreness.

• a sharp increase in volume, especially of eccentric exercises;
• training to failure with a large number of repetitions;
• heat, high humidity, insufficient acclimatization;
• dehydration and training on an empty stomach during a strict diet;
• a recent viral illness;
• the pressure "not to stop" in a group or at a competition.

Heat deserves a separate mention. Heat stroke and rhabdomyolysis often go together: overheating in itself damages muscles, and dehydration worsens the blood supply to the kidneys. In military and sports protocols, control of the temperature regime is one of the main elements of prevention.

Finally, motivation matters. Athletes with a high pain threshold and strong motivation tend to ignore early signals — pain out of proportion to the load and unusual weakness — and continue training, worsening the condition.

Drugs, Supplements and Substances That Increase the Risk

Pharmacology can add risk from several sides: directly damaging muscles, raising body temperature, provoking electrolyte disturbances or reducing the kidneys' ability to cope with myoglobin. Below are the substances for which this connection is described in the clinical literature.

Statins are the best-known drug trigger. The consensus of the European Atherosclerosis Society (2015) describes a spectrum of statin-associated muscle symptoms: from pain without an increase in creatine kinase to rare rhabdomyolysis. People who take statins as prescribed should discuss a training plan with a doctor, but not give up therapy on their own.

Stimulants act in combination: they increase heat production, constrict blood vessels, enhance muscle activity and reduce the sensation of fatigue. That is why an athlete under their influence can "overwork" far beyond safe limits. DNP is a separate case: it is an industrial chemical that uncouples oxidative phosphorylation and is capable of causing fatal hyperthermia with rhabdomyolysis. Our editorial team emphasizes: DNP is life-threatening.

As for anabolic steroids, the data are mostly limited to descriptions of clinical cases, where rhabdomyolysis developed against the background of a combination of drugs, extreme training and dehydration. Creatine, in controlled studies, has not demonstrated a connection with rhabdomyolysis, although it may slightly raise the level of creatinine in tests, which should be taken into account during interpretation.

A separate risk is anti-inflammatory agents (NSAIDs), which athletes take "prophylactically" before long events. They do not destroy muscles, but they reduce blood flow in the kidneys. Against the background of dehydration and myoglobinuria this can worsen kidney injury.

Individual Predisposition and Hidden Diseases

The same volume of training in two people can produce completely different consequences. Part of this variability is genetic: in some people creatine kinase after exertion rises much more strongly than in most, without any complications.

At the same time, recurring episodes of rhabdomyolysis or episodes after moderate exertion may indicate a hidden metabolic myopathy — for example, a disorder of glycogen or fatty acid metabolism, a deficiency of carnitine palmitoyltransferase II, or a predisposition to malignant hyperthermia.

Carriage of the sickle cell trait is described as a risk factor for exertional collapse and rhabdomyolysis in athletes, especially during intense sprint tests in the heat. Hypothyroidism and recent viral infections also increase the risk.

Therefore, recurrent rhabdomyolysis is a reason not simply to "train more lightly," but to undergo an in-depth examination by a neurologist or a specialist in neuromuscular diseases.

Editorial Conclusions

Rhabdomyolysis in athletes most often arises at the intersection of several factors: an unaccustomed volume of exertion (especially eccentric), heat, dehydration and insufficient adaptation.

Pharmacology can significantly increase the risk: statins directly affect the muscles, stimulants and DNP cause overheating, diuretics and alcohol disrupt the electrolyte balance, and NSAIDs worsen the protection of the kidneys.

Recurring episodes or rhabdomyolysis after moderate exertion require a search for hidden metabolic causes.

We also recommend reading our materials about the prevention and diagnosis of rhabdomyolysis, about the creatine kinase test, and about a safe return to training after a break.

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