Expression of Osteopontin and Transforming Growth Factor-beta in Childhood Minimal Change Nephrotic Syndrome After Cyclosporine Treatment

Lim, Beom Jin; Kim, Pyung Kil; Hong, Soon Won; Jeong, Hyeon Joo

Abstract

PURPOSE: One of the most important adverse effects of long-term cyclosporine therapy is nephrotoxicity, the morphologic changes of which include interstitial fibrosis and arteriolar hyalinization. Recently, several authors have shown that osteopontin plays an important role in the development of interstitial fibrosis by acting as a macrophage chemoattractant and stimulating the production of TGF-beta in experimental cyclosporine nephrotoxicity. However, the relationship between osteopontin and TGF-beta in humans has not been clearly documented so far. We studied the expression of osteopontin and TGF-beta in children with minimal change nephrotic syndrome treated with cyclosporine to demonstrate whether there is a relationship between cyclosporine toxicity and osteopontin expression as previously shown in animal models.
MATERIALS AND METHODS
Nineteen children (15 males and 4 females) were the subject of this study. Renal biopsies had been performed before and after the cyclosporine therapy (mean duration: 15.9 months). In 5 patients, additional biopsies were performed after completing the cyclosporine treatment (mean: 26 months). The expressions of osteopontin and TGF-beta were evaluated by immunohistochemistry in the glomeruli and tubulointerstitium.
RESULTS
Osteopontin expression was significantly increased in the glomerular mesangium and tubules after cyclosporine treatment. But there was no statistically significant increase of TGF-beta in the interstitium. There was no significant increase in tubular osteopontin and interstitial TGF-beta expression in those cases developing interstitial fibrosis after cyclosporine treatment compared with cases those not developing interstitial fibrosis. No significant changes in osteopontin or TGF-beta expression were observed in subsequent 5 biopsy samples after discontinuation of cyclosporine compared with the first follow up biopsies.
CONCLUSION
These results suggest that osteopontin is a nonspecific marker of renal injury rather than a mediator of interstitial fibrosis in cyclosporine nephrotoxicity of human.