Sugimoto Keisuke, Miyazawa Tomoki, Enya Takuji, Miyazaki Kouhei, Okada Mitsuru, Takemura Tsukasa
Department of Pediatrics, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-sayama, Osaka, 589-8511, Japan.
Clin Exp Nephrol. 2017 Feb;21(1):83-91. doi: 10.1007/s10157-016-1257-9. Epub 2016 Mar 14.
Cyclosporine A (CsA) is used globally as an immunosuppressant for the treatment of immune-mediated nephrotic syndrome (NS). However, its long-term use causes nephrotoxicity characterized by tubulointerstitial injury and glomerulosclerosis. The present study aimed to investigate the associations between histomorphological findings and immunohistological expression of Cathepsin L (CatL) and CD2-associated protein (CD2AP) in patients with NS mediated with CsA.
A total of 18 patients with child-onset NS were divided into two groups after treatment with CsA for 2 years (group A; n = 10) and more than 4 years (group B; n = 8), respectively. Analyses of relationships between tubulointerstitial disorders and expression of CatL and CD2AP proteins were performed using immunohistochemistry of paired renal specimens.
Glomeruli with arteriole hyalinization were significantly increased in both groups depending on dosage periods, although degrees of tubule and interstitial injury did not differ between groups. CD2AP expression was significantly greater in podocytes (P = 0.046) and was significantly less in proximal tubule cells (P = 0.014) in patients of group B compared with those of group A. Moreover, CD2AP expression was significantly increased in lateral tubule cells in both groups (group A, P = 0.02; group B, P = 0.001), and CatL expression in glomeruli and tubule cells did not change with the duration of CsA treatment in either patient group.
CD2AP expression in renal tubules may histologically associate with tissue hypoxia and reflected recovery from CsA-mediated renal injury in patients, even with mild histological features of tubulointerstitial disorder.
环孢素A（CsA）在全球范围内用作免疫抑制剂，用于治疗免疫介导的肾病综合征（NS）。然而，其长期使用会导致以肾小管间质损伤和肾小球硬化为特征的肾毒性。本研究旨在探讨CsA介导的NS患者组织形态学结果与组织蛋白酶L（CatL）和CD2相关蛋白（CD2AP）免疫组织化学表达之间的关联。
将18例儿童期NS患者分别在接受CsA治疗2年（A组；n = 10）和4年以上（B组；n = 8）后分为两组。使用配对肾标本的免疫组织化学分析肾小管间质病变与CatL和CD2AP蛋白表达之间的关系。
两组中伴有小动脉玻璃样变的肾小球均随用药时间显著增加，尽管两组间肾小管和间质损伤程度无差异。与A组患者相比，B组患者足细胞中的CD2AP表达显著更高（P = 0.046），而近端肾小管细胞中的CD2AP表达显著更低（P = 0.014）。此外，两组外侧肾小管细胞中的CD2AP表达均显著增加（A组，P = 0.02；B组，P = 0.001），且任一患者组中肾小球和肾小管细胞中的CatL表达均不随CsA治疗时间而变化。
肾小管中的CD2AP表达在组织学上可能与组织缺氧相关，并反映了患者从CsA介导的肾损伤中恢复的情况，即使具有轻度的肾小管间质病变组织学特征。
