NDT Advance Access published online on September 3, 2009
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfp416
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Published by Oxford University Press [on behalf of the US Military] 2009
Incidence, predictors and associated outcomes of rhabdomyolysis after kidney transplantation
1 Nephrology Service, Walter Reed Army Medical Center, Washington, DC 2 F. Edward Hebert School of Medicine, Uniformed Services University of Health Sciences, Bethesda, MD 3 Organ Transplant Service 4 Rheumatology Service, Walter Reed Army Medical Center, Washington, DC 5 Division of Nephrology, Center for Outcomes Research, St. Louis University School of Medicine, St. Louis, MO 6 National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
Correspondence and offprint requests to: Frank P. Hurst; E-mail: frank.hurst{at}us.army.mil
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Abstract |
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Background. There are several case reports of rhabdomyolysis (RM) in renal transplant recipients, but the actual incidence of this complication is not known. Most of the reported cases have been attributed to drug–drug interactions with calcineurin inhibitors, with the majority of interactions reported between cyclosporine and 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins). Pharmacokinetic studies have demonstrated that cyclosporine increases statin drug levels, presumably via competitive inhibition of cytochrome P450 3A4.
Methods. In a retrospective cohort of 20 366 adult Medicare primary renal transplant recipients in the USRDS database transplanted from 1 January 2003 to 31 July 2005 and followed through 31 December 2005, we assessed Medicare claims for RM and dyslipidaemia (HPL), which was used as a surrogate for statin use.
Results. The incidence rate of RM post-transplant for the study period was 1.4 (95% CI 1.1–1.8) per 1000 person-years. By Cox regression analysis, cyclosporine (versus tacrolimus) use [AHR 2.36 (95% CI 1.23–4.35); P = 0.006] and black race [AHR 2.33 (95% CI 1.30–4.17); P = 0.005] were associated with RM. By Cox non-proportional hazards regression, RM was associated with graft loss (including death) [AHR 2.84 (95% CI 1.70–4.72); P < 0.001].
Conclusions. RM is a rare complication after renal transplantation and is significantly associated with allograft loss (including death). RM is significantly more likely to occur with cyclosporine (versus tacrolimus)-based immunosuppression and possibly in persons of black race. Increased surveillance for RM is warranted in these at-risk patients.
Keywords: 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors; calcineurin inhibitors; renal transplantation; rhabdomyolysis; USRDS
Received for publication: 5.11.08
Accepted in revised form: 23. 7.09