Rhabdomyolysis in athletes: causes and their link to exercise load and pharmacology

Rhabdomyolysis is the massive destruction of skeletal muscle with the release of its 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 exercise, heat, dehydration, drugs, and supplements. Our editors explain 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 workout, especially with eccentric work, causes microdamage to muscle fibers. This is exactly what is felt as delayed-onset muscle soreness 24–72 hours later. At this time creatine kinase — an enzyme released from damaged cells — rises in the blood. This is a normal part of adaptation.

Rhabdomyolysis is spoken of when the damage becomes so massive that the body cannot keep up with 'processing' the breakdown products. Clinically this manifests as pronounced pain, swelling, and muscle weakness, and sometimes dark urine due to myoglobin. In the lab there is a sharp rise in creatine kinase; in clinical practice a threshold of at least five times the upper limit of normal is often used, although in athletes it is difficult to distinguish a 'normal' from a pathological reaction by the number alone.

The difference between physiological damage and rhabdomyolysis is not only quantitative. The decisive factor is the symptoms and consequences: whether there is kidney injury, electrolyte disturbances, whether swelling is growing in enclosed fascial spaces. That is 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 switch to a new program.

How muscle destruction 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 forms: 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 renal vessels worsen 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 lower leg) can cause compartment syndrome, which requires surgical intervention.

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

Exercise as a trigger: who is most at risk

The classic scenario of exertional rhabdomyolysis is a large volume of work that is unusual for the person. A newcomer who comes to a first high-intensity group class; an experienced athlete returning after a break and immediately working 'as before'; an athlete performing hundreds of repetitions of a single exercise at a competition or in a 'challenge.'

Eccentric work is especially traumatic — the phase of muscle lengthening under load: descents, lowering weights, jumps, 'negative' repetitions. It is precisely this that gives the greatest rise 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 itself damages muscle, and dehydration worsens 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 their condition.

Drugs, supplements, and substances that increase the risk

Pharmacology can add risk from several sides: directly damaging muscle, raising body temperature, provoking electrolyte disturbances, or reducing the kidneys' ability to cope with myoglobin. Below are 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 a rise in creatine kinase to rare rhabdomyolysis. People taking statins as prescribed should discuss a training plan with their doctor, but not stop the therapy on their own.

Stimulants act in combination: they raise heat production, constrict vessels, increase muscle activity, and reduce the sense 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 can cause fatal hyperthermia with rhabdomyolysis. Our editors emphasize: DNP is life-threatening.

As for anabolic steroids, the data are mostly limited to case reports where rhabdomyolysis developed against a background of a combination of drugs, extreme training, and dehydration. Creatine in controlled studies has not shown a connection with rhabdomyolysis, although it can slightly raise the creatinine level 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 muscle, but reduce blood flow in the kidneys. Against a background of dehydration and myoglobinuria, this can worsen kidney injury.

Individual predisposition and hidden diseases

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

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

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 easily' but to undergo an in-depth examination by a neurologist or a neuromuscular disease specialist.

Editorial conclusions

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

Pharmacology can significantly increase the risk: statins directly affect muscle, stimulants and DNP cause overheating, diuretics and alcohol disrupt electrolyte balance, and NSAIDs impair kidney protection.

Repeated episodes or rhabdomyolysis after moderate exercise require a search for hidden metabolic causes.

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

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