Keisuke Sugimoto1, Tomoki Miyazawa2, Takuji Enya2, Kouhei Miyazaki2, Mitsuru Okada2, Tsukasa Takemura2. 1. Department of Pediatrics, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-sayama, Osaka, 589-8511, Japan. ksugimo@med.kindai.ac.jp. 2. Department of Pediatrics, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-sayama, Osaka, 589-8511, Japan.
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.
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: M J Mihatsch; T Antonovych; S O Bohman; R Habib; U Helmchen; L H Noel; S Olsen; R K Sibley; E Kemény; G Feutren Journal: Clin Nephrol Date: 1994-01 Impact factor: 0.975
Authors: Jessica Camacho; Alberto Rábano; Paula Marazuela; Anna Bonaterra-Pastra; Garazi Serna; Teresa Moliné; Santiago Ramón Y Cajal; Elena Martínez-Sáez; Mar Hernández-Guillamon Journal: Brain Pathol Date: 2021-09-12 Impact factor: 6.508