Shen S Y, Weir M R, Coughlin T R
Department of Medicine, University of Maryland Hospital, School of Medicine, Baltimore 21201.
Transplantation. 1989 Feb;47(2):223-9. doi: 10.1097/00007890-198902000-00005.
A prospective nonrandomized study was conducted to evaluate the results of two conversion protocols on two similar groups of renal graft recipients totaling 54 patients who were converted from CsA to AZA at 6-12 months posttransplant. With protocol I, 24 patients (3 haploidentical, 21 cadaveric recipients) were converted with a graft biopsy followed by a 14-day overlap of CsA and AZA before the CsA dose was tapered and discontinued in 6 days. Of the 24 patients, 8 were found to have occult rejection in biopsy and received methylprednisolone 500 mg boluses for three days before overlap started. Thirty patients (2 haploidentical, 28 cadaveric recipients) were converted with protocol II, which had CsA and AZA overlap and tapering schedules identical to those of protocol I without a preconversion biopsy. Follow-up extended as far as 3 years posttransplant. There was a substantial incidence of chronic rejection and graft loss after conversion in protocol II patients. We also found that there was a possible link between postconversion acute rejection and late graft loss from chronic rejection. The incidence of acute rejection after conversion was significantly lower among protocol I patients as compared with that of protocol II (4% vs. 37%, P less than 0.001). However, if 8 patients with occult rejection in the preconversion biopsy were added to the total number of postconversion rejection in protocol I, the incidence of postconversion rejection in this group (38%) would be similar to that of protocol II. Using the time of conversion as the onset of the risk, protocol I patients had better graft survival than protocol II (100% vs. 80%, P less than 0.005) at 3 years posttransplant. If conversion becomes necessary, we recommend a preconversion graft biopsy to identify and treat patients with occult rejection before the beginning of CsA and AZA overlap, especially for those patients whose creatinine is higher than 2 mg/dl without obvious cause before conversion.
进行了一项前瞻性非随机研究，以评估两种转换方案对两组相似的肾移植受者的效果，这两组共54例患者在移植后6至12个月从环孢素（CsA）转换为硫唑嘌呤（AZA）。按照方案I，24例患者（3例单倍体相同、21例尸体供肾受者）在移植肾活检后进行转换，然后在CsA剂量逐渐减少并在6天内停用之前，CsA和AZA重叠使用14天。在这24例患者中，8例在活检中发现隐匿性排斥反应，并在重叠开始前接受了三天的500毫克甲泼尼龙冲击治疗。30例患者（2例单倍体相同、28例尸体供肾受者）按照方案II进行转换，该方案中CsA和AZA的重叠及减量时间表与方案I相同，但没有转换前活检。随访延长至移植后3年。方案II患者转换后慢性排斥反应和移植肾丢失的发生率较高。我们还发现转换后急性排斥反应与慢性排斥反应导致的晚期移植肾丢失之间可能存在联系。与方案II相比，方案I患者转换后急性排斥反应的发生率显著更低（4%对37%，P<0.001）。然而，如果将转换前活检中有隐匿性排斥反应的8例患者加到方案I转换后排斥反应的总数中，该组转换后排斥反应的发生率（38%）将与方案II相似。以转换时间作为风险起始时间，移植后3年方案I患者的移植肾存活率优于方案II（100%对80%，P<0.005）。如果有必要进行转换，我们建议在CsA和AZA重叠开始前进行转换前移植肾活检，以识别和治疗隐匿性排斥反应患者，特别是那些在转换前肌酐高于2毫克/分升且无明显原因的患者。
