Artero M, Biava C, Amend W, Tomlanovich S, Vincenti F
Transplant Service, University of California, San Francisco 94143.
Am J Med. 1992 Apr;92(4):375-83. doi: 10.1016/0002-9343(92)90267-f.
Recurrent focal glomerulosclerosis (FGS) has been well documented since it was first reported in 1972. However, the course of the disease after transplantation and the optimal treatment regimen have not been well defined since the introduction of newer treatment modalities.
We reviewed all the charts of patients with biospy-proven FGS who received renal transplants at our institution from January 1980 through December 1990. Case histories consistent with diagnoses other than primary FGS (such as reflux nephropathy or intravenous drug use) were eliminated from the study. During this time period, 78 allografts were received by 71 patients with FGS. Independent variables that were analyzed included sex, race, time in months between the diagnosis of FGS and end-stage disease (dialysis or transplantation), age at time of transplantation, type of dialysis, source of allograft (cadaveric or living related), haplotype matching, donor-specific transfusions, age and sex of the donor, post-transplantation acute tubular necrosis, rejection episodes, immunosuppression regimen, use of plasmapheresis and angiotensin converting enzyme (ACE) inhibitors, and outcome.
FGS recurred in 25 allografts (32%) of 21 patients. Biopsy-proven diagnosis of recurrence was made a mean of 7.5 months (range: 0.5 to 44 months) after transplantation. Patients who had rapid progression to end-stage disease tended to experience more frequent recurrences. Of seven patients who received a second transplant, five patients lost the first graft to recurrent FGS, and four of those patients (80%) had a recurrence in the second allograft. Recurrent disease developed in 34% of patients concurrently treated with cyclosporine and in 28% of those treated with prednisone and azathioprine alone (NS). Patients with recurrent FGS who were treated with ACE inhibitors benefited from a significant reduction of proteinuria. Six patients underwent plasmapheresis after diagnosis of the recurrence. Three of five patients in whom the diagnosis was made early in the course of the disease and in whom plasmapheresis was initiated immediately had reversal of epithelial foot process effacement and remission of proteinuria. End-stage disease eventually developed in 14 allografts (56%) an average of 23.7 months (range: 1 to 65 months) after diagnosis of recurrent disease. The cause of failure was chronic rejection in four allografts and recurrent disease in the remaining 10 allografts.
FGS recurs in approximately 30% of allografts and causes graft loss in half of these. Patients who have lost a first allograft to recurrent FGS are at high risk for developing recurrent disease in a second allograft. Prolonged allograft survival is possible in patients with recurrent FGS and may best be obtained with a combination of treatment modalities including cyclosporine (perhaps in higher dosages than are routinely used in clinical renal transplantation), ACE inhibitors, and early use of plasmapheresis. The efficacy of these modalities supports the notion that recurrent FGS is caused by a circulating humoral mediator.
复发性局灶节段性肾小球硬化（FGS）自1972年首次报道以来已有充分记录。然而，自采用更新的治疗方式以来，移植后该病的病程及最佳治疗方案尚未明确界定。
我们回顾了1980年1月至1990年12月期间在我院接受肾移植且活检证实为FGS的所有患者病历。将与原发性FGS以外诊断相符的病史（如反流性肾病或静脉吸毒）排除在研究之外。在此期间，71例FGS患者接受了78次同种异体移植。分析研究的独立变量包括性别、种族、FGS诊断至终末期疾病（透析或移植）的时间（月）、移植时年龄、透析类型、同种异体移植物来源（尸体或活体亲属）、单倍型匹配、供者特异性输血、供者年龄和性别、移植后急性肾小管坏死、排斥反应、免疫抑制方案、血浆置换和血管紧张素转换酶（ACE）抑制剂的使用情况以及结局。
21例患者的25次同种异体移植（32%）出现FGS复发。活检证实复发的诊断平均在移植后7.5个月（范围：0.5至44个月）作出。快速进展至终末期疾病的患者复发往往更频繁。在接受第二次移植的7例患者中，5例患者的第一次移植物因复发性FGS而丢失，其中4例患者（80%）在第二次同种异体移植中复发。同时接受环孢素治疗的患者中34%出现复发性疾病，单独接受泼尼松和硫唑嘌呤治疗的患者中28%出现复发性疾病（无显著性差异）。接受ACE抑制剂治疗的复发性FGS患者蛋白尿显著减少。6例患者在复发诊断后接受了血浆置换。在疾病病程早期诊断且立即开始血浆置换的5例患者中，3例患者上皮足突消失逆转且蛋白尿缓解。14次同种异体移植（56%）最终发展为终末期疾病，平均在复发性疾病诊断后23.7个月（范围：1至65个月）。失败原因4次同种异体移植为慢性排斥反应，其余10次同种异体移植为复发性疾病。
FGS在约30%的同种异体移植中复发，其中半数导致移植物丢失。因复发性FGS而失去第一次同种异体移植的患者在第二次同种异体移植中发生复发性疾病的风险很高。复发性FGS患者有可能延长同种异体移植存活时间，或许通过包括环孢素（可能使用比临床肾移植常规用量更高的剂量）、ACE抑制剂和早期使用血浆置换在内的联合治疗方式可最佳地实现这一点。这些治疗方式的疗效支持复发性FGS由循环体液介质引起这一观点。
