Lou H X, Vathsala A
Department of Pharmacy, Singapore General Hospital, Singapore.
Transplant Proc. 2004 Sep;36(7):2090-1. doi: 10.1016/j.transproceed.2004.08.104.
In a randomized control trial of mycophenolate mofetil (MMF) versus azathioprine (AZA) with cyclosporine and steroids, we demonstrated that MMF reduced acute rejection (AR) among renal allograft recipients (RTX) who were of low to moderate risk. However, 10% had AR when converted from MMF to AZA at 6 months, postrenal transplantation (RT). Two clinical markers, abnormal serum creatinine (SCr) and proteinuria at 6 months, post-RT, were associated with AR postconversion. The present study examined the safety of such conversion in selected high-risk RTX at 1 year of MMF therapy.
Thirteen high-risk RTX receiving MMF for either high panel reactive antibody (n = 9) or following AR (n = 4), with normal SCr and no proteinuria at 1 year, were selected for conversion. The incidence of AR, adverse events, and renal parameters (SCr, creatinine clearance, proteinuria) at 6 months postconversion was evaluated. Eight high-risk RTX who did not meet these selection criteria were retrospectively reviewed and used as controls.
Renal parameters (SCr 123 +/- 26 vs 129 +/- 27 mumol/L; pre- vs postconversion) were not significantly different; no episodes of AR or proteinuria were documented. Azathioprine was discontinued in two patients due to leukopenia. In the control group, one patient had graft loss from chronic rejection, whereas one developed posttransplant lymphoproliferative disease necessitating MMF withdrawal.
These results suggest that selective conversion from MMF to AZA after 1 year is safe, even in high-risk RTX. Normal SCr and absence of proteinuria are good screening parameters to identify patients at low risk for AR following such conversion.
在一项霉酚酸酯（MMF）与硫唑嘌呤（AZA）联合环孢素和类固醇的随机对照试验中，我们证明MMF可降低低至中度风险的肾移植受者（RTX）的急性排斥反应（AR）。然而，肾移植（RT）后6个月从MMF转换为AZA时，10%的患者发生了AR。两个临床指标，即RT后6个月时血清肌酐（SCr）异常和蛋白尿，与转换后的AR相关。本研究探讨了在MMF治疗1年时，对选定的高风险RTX进行这种转换的安全性。
选择13例接受MMF治疗的高风险RTX，其中9例因高群体反应性抗体，4例因发生AR，在1年时SCr正常且无蛋白尿，进行转换。评估转换后6个月时的AR发生率、不良事件和肾脏参数（SCr、肌酐清除率、蛋白尿）。回顾性分析8例不符合这些选择标准的高风险RTX作为对照。
肾脏参数（转换前SCr为123±26 vs转换后为129±27μmol/L）无显著差异；未记录到AR或蛋白尿事件。2例患者因白细胞减少而停用硫唑嘌呤。在对照组中，1例患者因慢性排斥反应导致移植肾丢失，而1例发生移植后淋巴细胞增生性疾病，需要停用MMF。
这些结果表明，即使在高风险RTX中，MMF治疗1年后选择性转换为AZA也是安全的。SCr正常且无蛋白尿是识别此类转换后AR低风险患者的良好筛查参数。
