Bertelli Roberta, Ginevri Fabrizio, Caridi Gianluca, Dagnino Monica, Sandrini Silvio, Di Duca Marco, Emma Francesco, Sanna-Cherchi Simone, Scolari Francesco, Neri Tauro Maria, Murer Luisa, Massella Laura, Basile Giancarlo, Rizzoni Gianfranco, Perfumo Francesco, Ghiggeri Gian Marco
Laboratory on Pathophysiology of Uremia, G. Gaslini Children's Hospital,Genoa, Italy.
Am J Kidney Dis. 2003 Jun;41(6):1314-21. doi: 10.1016/s0272-6386(03)00364-0.
Posttransplant recurrence of focal segmental glomerulosclerosis (FSGS) occurs in a relevant proportion of FSGS patients and represents an important clinical emergency. It is taken as a proof of the existence of circulating permeability plasma factor(s) that are also putative effectors of original proteinuria in these patients. Familial forms of FSGS do not recur, but the discovery of numerous patients with sporadic FSGS and mutations of podocin (NPHS2, that is actually an inherited disease) who received a renal graft require a re-evaluation of the problem.
To evaluate the incidence of posttransplant recurrence of FSGS in patients with NPHS2, the authors screened for podocin mutations in 53 patients with the clinical and pathologic stigmata of FSGS who had renal failure and who had undergone renal transplantation.Results. Twelve children were found to carry a homozygous (n9) or a heterozygous (n4) mutation of podocin and were classified, according to current criteria, as patients with inherited FSGS. In 5 patients of this group (38%), proteinuria recurred after renal graft and in 2, renal biopsy results showed recurrence of FSGS. Prerecurrence serum of 3 patients of this cohort was tested for antipodocin antibodies with indirect immuno-Western utilizing human podocyte extracts and were found negative. The rate of FSGS recurrence was comparable in non-NPHS2-FSGS children (12 of 27) and adults (3 of 13). Also clinical outcome of recurrence and response to plasmapheresis and immunosuppressors were comparable, suggesting a common mechanism.
These data show a high rate of FSGS recurrence in patients with NPHS2 mutations that is comparable with idiopathic FSGS and describe the successful therapeutic approach. Recurrence of an apparently inherited disease should stimulate a critical review of the mechanisms of recurrence and of original proteinuria in these cases.
局灶节段性肾小球硬化（FSGS）移植后复发在相当一部分FSGS患者中出现，是一个重要的临床急症。这被视为循环通透性血浆因子存在的证据，这些因子也是这些患者原发性蛋白尿的假定效应物。FSGS的家族形式不会复发，但发现众多散发性FSGS且携带足突蛋白（NPHS2，实际上是一种遗传性疾病）突变的患者接受肾移植后，需要对该问题进行重新评估。
为评估NPHS2患者中FSGS移植后复发的发生率，作者对53例有FSGS临床和病理特征、已发生肾衰竭并接受肾移植的患者进行了足突蛋白突变筛查。结果。发现12名儿童携带足突蛋白的纯合（n = 9）或杂合（n = 4）突变，根据现行标准，被归类为遗传性FSGS患者。该组中有5例患者（38%）肾移植后蛋白尿复发，2例肾活检结果显示FSGS复发。利用人足细胞提取物通过间接免疫印迹法对该队列中3例患者复发前的血清检测抗足突蛋白抗体，结果为阴性。非NPHS2 - FSGS儿童（27例中的12例）和成人（13例中的3例）中FSGS复发率相当。复发的临床结局以及对血浆置换和免疫抑制剂的反应也相当，提示存在共同机制。
这些数据显示NPHS2突变患者中FSGS复发率较高，与特发性FSGS相当，并描述了成功的治疗方法。一种明显遗传性疾病的复发应促使对这些病例中复发机制和原发性蛋白尿机制进行批判性审视。
