Renal tubular toxicity of HMG-CoA reductase inhibitors

A patient developed direct renal tubular toxicity on high-dose HMG-CoA reductase inhibitor (statin) therapy. Considerable renal damage was present by the time the injury became apparent. Urine abnormalities regressed after stopping the drug and reappeared after about 2 weeks following re-challenge. Although tubular damage may be slight and relatively difficult to detect, it is possible that cumulative injury in susceptible individuals over a period of years may result in significant renal damage. HMG-CoA reductase inhibitors (statins) reduce morbidity and mortality from coronary heart disease, prevent strokes and possibly reduce renal disease as the result of cholesterol lowering, improved endothelial function, reduced inflammation and reduced oxidative stress [1]. Significant side effects associated with statins are infrequent. Myalgia and arthralgia are common (1–7%) but frank rhabdomyolysis is rare and is generally associated with concurrent fibrate use [2]. Liver enzyme abnormalities may occur but are generally mild and transient. Minor alimentary tract disturbance and neuropathy are infrequent [3]. Mechanisms of toxicity are poorly understood and potentially include interruption of a wide variety of metabolic functions including membrane glycoprotein composition and fluidity, chloride channel activation and impaired mitochondrial function by reduced ubiquinone synthesis that may render lipoproteins more susceptible to oxidation injury [4]. Renal damage associated with the use of statins is generally due to associated rhabdomyolysis causing acute tubular necrosis. To the best of our knowledge, direct renal tubular damage by statins has not been described. The case we describe appears to have developed dose-related tubular toxicity.