Abstract
Introduction
Statins are widely prescribed due to their proven benefit in reducing cardiovascular event risk. Statin use comes with the potential for myopathy. Rhabdomyolysis is a rare (0.1%) but serious adverse effect, most often occurring within the first year of therapy. Acute kidney injury (AKI) is the most severe complication of rhabdomyolysis and significantly increases mortality. Management includes statin discontinuation, aggressive fluid resuscitation, urine alkalization, and occasionally dialysis.
We present a case of severe statin-induced rhabdomyolysis causing AKI, in which fluid resuscitation was limited by a complex cardiac history.
Case Info
A 73-year-old woman with a history of cardiogenic shock following acute myocardial infarction and resulting ischemic cardiomyopathy and systolic heart failure, presented with two weeks of myalgias, progressive weakness, and fatigue, along with two days of dark urine. She had recently lifted heavy furniture at home. Her medications included rosuvastatin 40 mg and ezetimibe 10 mg. Exam revealed hypotension (BP 90/60 mmHg) and new bilateral lower extremity weakness (3/5). Initial labs showed creatinine 6.8 mg/dL (baseline 1.1) and anion gap metabolic acidosis. Muscle enzymes were markedly elevated: CPK 74,916 U/L, myoglobin >30,000 ng/mL, aldolase 196.9 U/L, AST 938 U/L, and ALT 531 U/L. Urinalysis revealed blood without RBCs, consistent with myoglobinuria. Autoimmune workup was negative, including anti–3-hydroxy-3-methylglutaryl–coenzyme A reductase (anti-HMGCR) and myositis-specific antibodies.
She was diagnosed with statin-induced rhabdomyolysis complicated by AKI, with recent physical exertion possibly contributing. Management included discontinuation of rosuvastatin, cautious intravenous hydration (starting at 125 mL/h, tapered based on urine output and volume status), a bicarbonate infusion later transitioned to oral therapy, and midodrine to support renal perfusion. Urine output improved to ~3 L/24h by day three, while creatinine peaked at 8.0 mg/dL on day four and declined to 4.1 mg/dL at discharge.
Disc Clinical
Statin-induced rhabdomyolysis is characterized by rapid skeletal muscle breakdown with release of intracellular components, including CPK (often >40-fold above normal), aldolase, myoglobin, and electrolytes.
Statins inhibit HMGCR, decreasing cholesterol synthesis while also reducing production of coenzyme Q, a component of the mitochondrial electron transport chain. The resulting coenzyme Q depletion impairs ATP generation, leading to myocyte injury. AKI results from volume depletion and myoglobin-induced tubular obstruction and cytotoxicity. Statin users engaging in strenuous exercise may face a higher risk of rhabdomyolysis, though definitive evidence is lacking.
The “classic” triad of muscle pain, weakness, and dark-colored urine is not always present, and diagnosis often requires a high index of suspicion.
Fluid resuscitation, given early and in high volumes with targeted urine output, is the cornerstone of management. Our patient’s complex cardiac history limited fluid administration. Bicarbonate was added to initial fluids based on evidence that urine alkalization can mitigate myoglobin-induced tubular injury. Although dialysis is often required to manage volume overload and severe metabolic disturbances, it was ultimately not needed in this case.
Conclusion
Early recognition and management of rhabdomyolysis are essential to prevent AKI and improve outcomes. Evidence-based guidelines for fluid management or adjunctive therapies have not yet been established. Our case contributes to clinical experience in managing this condition, particularly in complex and high-risk scenarios.