Department of Surgical Pathology, Tokyo Women's Medical University, 8-1, Kawada-Cho, Shinjuku-Ku, Tokyo, 162-8666, Japan.
Department of Anatomy, Showa University School of Medicine, Tokyo, Japan.
Virchows Arch. 2023 Dec;483(6):809-819. doi: 10.1007/s00428-023-03703-6. Epub 2023 Nov 18.
Primary focal segmental glomerulosclerosis (FSGS) is thought to be caused by circulating factors leading to podocytopathy, whereas segmental sclerotic lesions (FSGS lesions) have several causes. We studied the clinicopathological differences of FSGS-lesions in 258 cases of FSGS in renal allografts, depending on the following accompanying pathophysiology: recurrence of primary FSGS, calcineurin inhibitor (CNI)-induced arteriolopathy, antibody-mediated rejection (ABMR), and other conditions. All cases were categorized with the Columbia classification. Recurrent FSGS developed the earliest after transplantation and showed the highest percentage of the collapsing (COL) variant in which collapse of the glomerular capillaries with epithelial hypertrophy was apparent. FSGS accompanying CNI-induced arteriolopathy predominantly developed the not otherwise specified (NOS) variant, showing severe ultrastructural endothelial injury. On the contrary, approximately 7% of the cases showed the COL variant, presenting glomerular endothelial damage such as double contours of glomerular basement membrane and endothelial cell swelling as well as epithelial cell proliferation. FSGS with ABMR had the highest creatinine levels and cellular variant percentage, with marked inflammation and ultrastructural endothelial injury. Approximately two-thirds of the cases without ABMR, CNI-induced arteriopathy, or recurrent FSGS had other coexisting conditions such as glomerulonephritis, T cell-mediated rejection, and reflux nephropathy with progressive tubulointerstitial fibrosis. Most of these cases were of the NOS variant. The clinicopathologic features of post-transplant FSGS differed depending on the associated conditions, and endothelial injury was apparent especially in cases of CNI-induced arteriolopathy and ABMR. Precise observation of FSGS lesions may facilitate the diagnosis and clinical management of FSGS during renal transplantation.
原发性局灶节段性肾小球硬化症（FSGS）被认为是由循环因子引起的，导致足细胞病变，而节段性硬化病变（FSGS 病变）有多种原因。我们研究了 258 例肾移植中 FSGS 病变的临床病理差异，取决于以下伴随的病理生理学：原发性 FSGS 的复发、钙调神经磷酸酶抑制剂（CNI）诱导的小动脉病、抗体介导的排斥反应（ABMR）和其他情况。所有病例均采用哥伦比亚分类进行分类。复发性 FSGS 在移植后最早发生，具有最高比例的塌陷（COL）变体，其中明显可见肾小球毛细血管塌陷伴上皮细胞肥大。伴有 CNI 诱导的小动脉病的 FSGS 主要发展为非特指（NOS）变体，表现出严重的超微结构内皮损伤。相反，大约 7%的病例表现出 COL 变体，表现出肾小球内皮损伤，如肾小球基底膜双层轮廓和内皮细胞肿胀以及上皮细胞增殖。伴有 ABMR 的 FSGS 具有最高的肌酐水平和细胞变体百分比，表现出明显的炎症和超微结构内皮损伤。大约三分之二的无 ABMR、CNI 诱导的小动脉病或复发性 FSGS 的病例伴有其他共存条件，如肾小球肾炎、T 细胞介导的排斥反应和反流性肾病伴进行性肾小管间质纤维化。这些病例中的大多数为 NOS 变体。移植后 FSGS 的临床病理特征因相关条件而异，内皮损伤在 CNI 诱导的小动脉病和 ABMR 中尤为明显。对 FSGS 病变的精确观察可能有助于在肾移植期间诊断和管理 FSGS。
