Agrawal P, Nada R, Ramachandran R, Rayat C S, Kumar A, Kohli H S
Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Indian J Nephrol. 2019 Mar-Apr;29(2):90-94. doi: 10.4103/ijn.IJN_422_17.
Focal segmental glomerulosclerosis (FSGS) is the most common cause of adult-onset nephrotic syndrome, but its pathophysiology is poorly understood. The question as to why only a subset of patients responds to treatment in unanswered. In the past few years, change of podocytic phenotype from stationary type in health to migratory type in disease has been described, of which loss of subpodocytic space is a surrogate marker. Diagnostic biopsies of adult-onset steroid-resistant calcineurin inhibitor-naïve primary FSGS cases, which were subsequently treated with tacrolimus were included in this retrospective study conducted from 2011 to 2013. The ultrastructure of all cases was studied in detail, especially in context to the presence or absence of subpodocytic space. In the present study, we have compared presence or absence of subpodocytic space in tacrolimus-responsive versus tacrolimus-resistant cases to identify potential electron microscopic features predictive of response to treatment, of which loss of subpodocytic space indicating migratory phenotype is the most important and consistent feature. The present series included 7 tacrolimus responsive cases (includes two cases with partial response) and seven tacrolimus-resistant cases. The tacrolimus-resistant patients were of older age, had a longer duration of illness, and a lower eGFR as compared to tacrolimus responsive cases. The subpodocytic space was preserved in patients on tacrolimus with complete remission and lost in patients with partial response and tacrolimus-resistant cases.
局灶节段性肾小球硬化（FSGS）是成人肾病综合征最常见的病因，但其病理生理学仍知之甚少。为何只有一部分患者对治疗有反应这一问题尚无答案。在过去几年中，已描述了足细胞表型从健康时的静止型转变为疾病时的迁移型，其中足细胞下间隙的丧失是一个替代标志物。本回顾性研究纳入了2011年至2013年期间诊断性活检的成人初发、对类固醇耐药且未使用过钙调神经磷酸酶抑制剂的原发性FSGS病例，这些病例随后接受了他克莫司治疗。对所有病例的超微结构进行了详细研究，尤其是关于足细胞下间隙的有无情况。在本研究中，我们比较了他克莫司反应性病例与他克莫司耐药性病例中足细胞下间隙的有无情况，以确定预测治疗反应的潜在电子显微镜特征，其中足细胞下间隙丧失表明迁移型表型是最重要且一致的特征。本系列包括7例他克莫司反应性病例（包括2例部分缓解病例）和7例他克莫司耐药性病例。与他克莫司反应性病例相比，他克莫司耐药性患者年龄更大、病程更长且估算肾小球滤过率（eGFR）更低。他克莫司治疗完全缓解的患者足细胞下间隙得以保留，而部分缓解患者和他克莫司耐药性病例的足细胞下间隙则丧失。
