PATIENTS AND METHODSCase 1A 27-year-old man with end-stage renal disease secondary tocryptic etiology received his first renal allograft from his sister inMay 1998. Initially, he was treated with standard cyclosporine(CyA) and steroid dual immunosuppression. He had a rathersmooth recovery from the transplantation with rapid decrease ofhis serum creatinine levels. During serial follow-up of his CyApharmacokinetic studies, the average concentration of blood CyA(CsA-Cav) reached a maximum of 812 ng/mL on postoperative day9. His serum total bilirubin level (T-Bili) increased from 1.0 mg/dLpreoperatively to 1.7 mg/dL at that time. In order to avoid thehepatotoxicity and nephrotoxicity of CyA, the dose was reduced.Meanwhile, MMF was added to ensure sufficient immunosuppression.The patient was found to be icteric 1 week later and his T-Bili rose to3.7 mg/dL. Further investigation showed that his CyA-Cav decreasedto around 650 ng/mL. In order to further reduce the dose of CyA, thedose of MMF was increased to 1.5 g/d. But, unexpectedly, his T-Biliclimbed to 5.7 mg/dL in 1 day. MMF-induced hyperbilirubinemia wasstrongly suspected, and MMF was discontinued (Fig 1A).Case 2A 49-year-old man with end-stage renal disease secondary topolycystic kidney disease received his first kidney transplantationfrom a cadaveric donor in February 1999. He was initially treatedwith standard CyA/steroid dual immunosuppression. He developedposttransplant diabetes mellitus and had a Banff type IB biopsy-proven acute rejection episode on postoperative day 10. Therejection episode was successfully rescued by 4 days of rabbitantithymocyte immunoglobulin therapy. MMF (1.0 to 1.5 g/d) wasadded to rescue acute rejection. In addition, he continued toreceive CyA and steroids. Three days after he started to take MMF,his T-Bili increased to 2.7 mg/dL (Fig 1B).Abdominal sonography did not reveal any dilatation of intrahe-patic or common bile duct in either of them. Except for CyA, noother proicteric drugs were used in these two patients by retrospec-tive chart review. There were no significant changes of other liverfunction parameters, including serum alanine aminotransferase,aspartate aminotransferase, lactate dehydrogenase, alkaline phos-phatase, and hepatitis markers in both of them.RESULTS