Acute renal failure following kidney transplantation associated with myoglobinuria in patients treated with rapamycin

Background. Since using an immunosuppression regimen that includes rapamycin, we have occasionally encountered renal transplant patients who develop unexpected severe acute renal dysfunction. Biopsies obtained in these recipients demonstrate acute tubular necrosis (ATN) occasionally associated with tubular casts giving the classic appearance of myoglobin casts. Methods. We retrospectively reviewed all biopsies from consecutively transplanted kidneys engrafted between April 9, 2002 and June 29,2004 to determine the incidence of ATN,ATN with intratubular casts, and casts with the classic myoglobin appearance. The clinical setting, treatment, and outcomes of those patients with classic myoglobin-appearing casts are reviewed. Results. Histological ATN as the principal finding in at least one biopsy occurred in 10.5% (57/543) of patients. About half of these patients (30/57) had tubular casts present in at least one biopsy and in 14 of these the casts had a classic appearance of myoglobin casts. These myoglobin-appearing casts were only noted in patients receiving rapamycin. A review of 28 ATN biopsies from an earlier prerapamycin era did not demonstrate similar myoglobin-appearing casts. Immunostaining for myoglobin was positive in all 14 recipient biopsies. This was confirmed by western blot analyses in three of five patient biopsies tested. Three of three recipients tested had elevated serum creatine phosphokinase levels and detectable serum myoglobin. All 14 patients slowly resolved their acute renal dysfunction and no grafts were lost. Conclusion. We conclude that myoglobinuria with myoglobin cast formation can occur following rapamycin administration, and may be a causative factor in the development of unexpected severe acute renal dysfunction.