Morrissey P E, Gohh R, Shaffer D, Crosson A, Madras P N, Sahyoun A I, Monaco A P
Department of Pathology, Deaconess Hospital and Harvard Medical School, Boston, Massachusetts 02215, USA.
Transplantation. 1997 Mar 27;63(6):845-8. doi: 10.1097/00007890-199703270-00009.
Refractory rejection and cyclosporine (CsA)-induced nephropathy remain important causes of renal allograft loss. Previous studies demonstrated that 70-85% of the episodes of refractory acute rejection (AR) occurring in renal allograft recipients on a CsA-based immunosuppressive regimen could be salvaged by conversion to tacrolimus. No data are available regarding the correlation between allograft histology at the time of conversion and the response to tacrolimus. We examined the response to tacrolimus conversion in relation to preconversion biopsies stratified by the Banff criteria.
Since May 1992, we have converted 22 patients from CsA to tacrolimus as part of a rescue protocol. We report on 18 patients in whom 6-month follow-up was available after conversion for biopsy-proven AR (n=13) or CsA toxicity (n=5). Sixteen patients were recipients of renal allografts, including three second transplants, and two were recipients of kidney-pancreas transplants. All patients with AR were treated with one or more courses of methylprednisolone and OKT3 before conversion. Renal allograft biopsies were interpreted by a transplant pathologist blinded to the clinical history, and graded according to the Banff criteria. Responses to tacrolimus were scored as improved (creatinine returned to within 150% of baseline), stabilized (creatinine rise arrested), or failed (returned to dialysis). RESULTS; Mean follow-up was 17.3+/-8 months. Fourteen of 18 patients (78%) showed improvement or stabilization in renal function as assessed by creatinine at 6 months or 1 year (when available). Of the 13 patients with histological AR, nine (69%) improved, including five of six with borderline AR, two of three with grade I AR, and two of four with grade II AR. Of the four other patients with AR, two stabilized and two failed. Three of five patients with severe clinical rejection requiring dialysis (range 2-16 weeks) recovered renal function after conversion. Of five patients with CsA toxicity, two (40%) improved. Seven of eight patients who were converted to tacrolimus less than 90 days after transplantation improved, compared with only 4 of 10 who were converted more than 90 days after transplantation. No grafts were lost in patients with a creatinine <3.0 mg/dl at the time of conversion versus two of seven grafts lost when the creatinine was 3.1-5.0 mg/dl and two of eight grafts lost when the creatinine was >5.0 mg/dl.
The majority of steroid and antilymphocyte antibody (OKT3 or ATGAM) unresponsive rejections in patients on CsA-based immunosuppression will improve or stabilize after conversion to tacrolimus. There was no correlation with allograft histology stratified by the Banff criteria and the response to tacrolimus. Although there was a trend toward a poorer response with more severe histological rejection, higher serum creatinine at the time of conversion, and longer time from transplantation to conversion, favorable responses were noted in all groups. This indicates that a trial of conversion is warranted, irrespective of the histological severity of injury.
难治性排斥反应和环孢素（CsA）诱导的肾病仍然是肾移植失败的重要原因。先前的研究表明，在接受基于CsA的免疫抑制方案的肾移植受者中，70 - 85%的难治性急性排斥反应（AR）发作可通过转换为他克莫司得到挽救。关于转换时移植肾组织学与对他克莫司反应之间的相关性尚无数据。我们根据Banff标准，研究了转换为他克莫司后的反应与转换前活检的关系。
自1992年5月以来，作为一项挽救方案的一部分，我们将22例患者从CsA转换为他克莫司。我们报告了18例患者，转换后有6个月的随访数据，其中经活检证实为AR的有13例，CsA毒性的有5例。16例患者为肾移植受者，包括3例二次移植患者，2例为肾胰联合移植受者。所有AR患者在转换前均接受了一个或多个疗程的甲泼尼龙和OKT3治疗。肾移植活检由对临床病史不知情的移植病理学家进行解读，并根据Banff标准分级。对他克莫司的反应分为改善（肌酐恢复到基线的150%以内）、稳定（肌酐上升停止）或失败（恢复透析）。结果：平均随访时间为17.3±8个月。18例患者中有14例（78%）在6个月或1年（如有数据）时，根据肌酐评估肾功能有改善或稳定。在13例组织学诊断为AR的患者中，9例（69%）有改善，包括6例边缘性AR中的5例、3例I级AR中的2例和4例II级AR中的2例。其他4例AR患者中，2例稳定，2例失败。5例需要透析的严重临床排斥反应患者（透析时间2 - 16周）中有3例在转换后恢复了肾功能。5例CsA毒性患者中，2例（40%）有改善。移植后不到90天转换为他克莫司的8例患者中有7例改善，而移植后超过90天转换的10例患者中只有4例改善。转换时肌酐<3.0 mg/dl的患者无移植肾丢失，而肌酐为3.1 - 5.0 mg/dl时7例中有2例移植肾丢失，肌酐>5.0 mg/dl时8例中有2例移植肾丢失。
在接受基于CsA的免疫抑制治疗的患者中，大多数对类固醇和抗淋巴细胞抗体（OKT3或ATGAM）无反应的排斥反应在转换为他克莫司后会改善或稳定。与根据Banff标准分层的移植肾组织学和对他克莫司的反应之间无相关性。尽管随着组织学排斥反应更严重、转换时血清肌酐更高以及从移植到转换的时间更长，反应有变差的趋势，但所有组均观察到了良好的反应。这表明无论损伤的组织学严重程度如何，进行转换试验都是有必要的。
