No myelosuppression when mizoribine is combined with allopurinol for the treatment of hyperuricemia in renal transplant patients

Background. In cadaveric renal transplant recipients, a commonly used triple immunosuppression regimen includes azathioprine, cyclosporin, and prednisolone. Azathioprine is a potential bone marrow suppressant. Allopurinol is a commonly used drug to treat hyperuricemia, which frequently occurs in kidney transplant recipients. Azathioprine is metabolized by xanthine oxidase, which is inhibited by allopurinol, leading to accumulation of its active metabolites, which are potential myelosuppressants. Moreover, in certain clinical situations, azathioprine is contraindicated. The immunosuppressive drug mizoribine has been used to prevent rejection of organ allografts in humans. Its effect is mediated through a different pathway in purine metabolism, and allopurinol does not interfere with its metabolism. Therefore, a combination of mizoribine with allopurinol does not cause myelosuppression. Methods. Thirteen cadaveric renal transplant recipients who had hyperuricemia were treated with allopurinol and mizoribine as an alternative to azathioprine, along with steroids and cyclosporin A. They were followed up for 12 months. Results. None of these patients developed bone marrow suppression and all had adequate control of hyperuricemia and had no deterioration in allograft function. Conclusions. Mizoribine can be safely combined with allopurinol in cadaveric renal transplant recipients who have hyperuricemia, without causing bone marrow suppression. Received: October 31, 2000 / Accepted: March 14, 2001