Exertion-induced rhabdomyolysis in a patient on statin therapy

Sir,

We describe a patient on long-term statin treatment who developed acute renal failure (ARF) from rhabdomyolysis following severe unaccustomed exertion. Reviewing the available literature, we did not find reports of exertion-induced rhabdomyolysis and ARF requiring dialysis while on statins.

A 57-year-old male, with hypertension and hyperlipidaemia (on ramipril 2.5 mg, atorvastatin 10 mg daily for several years), went trekking and described it as ‘the most exhausting exercise in recent times’. Coming downhill, he noticed thigh pain and took two doses of a non-steroidal anti-inflammatory drug (NSAID). On day 3, his urine output decreased; examination showed blood presssure 160/100 mmHg and clinical evidence of fluid overload. Investigations showed: blood urea 141 mg/dl, creatinine 9.4 mg/dl, potassium 6.4 mEq/l, mildly deranged liver functions, no proteinuria, and no urinary casts or urine eosinophils. Serum creatine kinase (CK) was elevated: 3389 IU/l (normal 38–174 IU/l), as was lactate dehydrogenase 469 U/l (140–300 U/l) and serum myoglobin 617 µg/l (5–85 µg/l); urine myoglobin was negative. Haemodialysis was performed for hyperkalaemia and volume overload. Previous medications were stopped. Urine output improved by the fourth day of hospitalization and renal functions started improving in 1 week. At 6 weeks, urea was 32 mg/dl and creatinine 1.0 mg/dl.

In this patient, treatment with statins and the development of rhabdomyolysis following exertion raises the possibility of an association between the two, either direct or indirect. Our patient had several factors predisposing to ARF, i.e. volume depletion, use of an angiotensin-converting enzyme inhibitor (ACEI) and an NSAID, and severe exertion that could by itself cause rhabdomyolysis. It is probable that treatment with statins amplified the muscle damage caused by intense exertion. We can only speculate as to whether he would have developed rhabdomyolysis if he was not taking statins.

In studies looking at statins and exertion-induced muscle damage, patients receiving lovastatin had 62–77% higher CK levels after exercise compared with those on placebo, showing that statins increase exercise-induced muscle injury [1]. In another study, several patients on statins showed a post-exercise rise in serum CK, although there was no difference in average CK levels compared with placebo [2]. A personal report documented an exercise-induced CK rise with atorvastatin; the symptoms and CK levels normalized on stopping statins and reappeared after switching to pravastatin [3]. Theories of statin-induced rhabdomyolysis include effects on muscle cholesterol synthesis and isoprenoid levels [4]. Statins inhibit GTP activation. Exercise may unmask the effects of statins on skeletal muscle because GTP-dependent protein kinase pathways are important in muscle recovery following exercise [4].

Based on the association noted, it needs to be considered whether statins should be withheld prior to engaging in ‘more than an accustomed range’ of physical exertion. Most statins have a short half-life and withholding the drug for 2 days would be reasonably intelligent to avoid its contribution to muscle injury [5].

Conflict of interest statement. None declared.

Dilip Unnikrishnan and B. Satish

Department of Nephrology, Kerala Institute of Medical Sciences, Trivandrum, India Email: nairdilip{at}rediffmail.com

References

  1. Thompson PD, Zmuda JM, Domalik LJ, Zimet RJ, Staggers J, Guyton JR. Lovastatin increases exercise-induced skeletal muscle injury. Metabolism 1997; 46: 1206–1210[ISI][Medline]
  2. Thompson PD, Gadaleta PA, Yurgalevitch S, Cullinane E, Herbert PN. Effects of exercise and lovastatin on serum creatine kinase activity. Metabolism 1991; 40: 1333–1336[CrossRef][ISI][Medline]
  3. Torgovnick J, Arsura E. Statin-associated myopathy with normal creatine kinase levels. Ann Intern Med 2003; 138: 1007[Free Full Text]
  4. Thompson PD, Clarkson P, Karas RH. Statin-associated myopathy. J Am Med Assoc 2003; 289: 1681–1690[Abstract/Free Full Text]
  5. Ballantyne CM, Corsini A, Davidson MH et al. Risk for myopathy with statin therapy in high-risk patients. Arch Intern Med 2003; 163: 553–564[Abstract/Free Full Text]




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