title: Cyclosporine A induced histological changes of Cathepsin L and CD2AP expression in renal glomeruli and tubules.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pediatrics, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-sayama, Osaka, 589-8511, Japan. ksugimo@med.kindai.ac.jp.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Sugimoto
authors.affiliation: Department of Pediatrics, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-sayama, Osaka, 589-8511, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Miyazawa
authors.affiliation: Department of Pediatrics, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-sayama, Osaka, 589-8511, Japan.
authors.forename: Takuji
authors.initials: T
authors.lastname: Enya
authors.affiliation: Department of Pediatrics, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-sayama, Osaka, 589-8511, Japan.
authors.forename: Kouhei
authors.initials: K
authors.lastname: Miyazaki
authors.affiliation: Department of Pediatrics, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-sayama, Osaka, 589-8511, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Okada
authors.affiliation: Department of Pediatrics, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-sayama, Osaka, 589-8511, Japan.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Takemura
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis*; D000293:Adolescent; D000328:Adult; D056668:Cathepsin L / Q000032:analysis*; D002648:Child; D016572:Cyclosporine / Q000009:adverse effects*; D003598:Cytoskeletal Proteins / Q000032:analysis*; D005260:Female; D005921:Glomerulonephritis / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D007684:Kidney Tubules / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D009404:Nephrotic Syndrome / Q000175:diagnosis / Q000188:drug therapy*; D050199:Podocytes / Q000201:enzymology; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C114545:CD2-associated protein; D003598:Cytoskeletal Proteins; D007166:Immunosuppressive Agents; D016572:Cyclosporine; C534281:CTSL protein, human; D056668:Cathepsin L
keywords: CD2AP; Cathepsin L; Childhood; Cyclosporine A; Cyclosporine nephrotoxicity; Nephrotic syndrome