대한신장학회

논문분류	추계학술대회 초록집
제목	사이를로스포린 신독성의 병리기전
저자	김용진
출판정보	1993; 1993(0):
키워드	N/A
초록	Lesions. 2) Acute renal failute with oligo-anuria, char- acterized by acute tubular necrosis is adopted because it is found more frequently with the administration of cyclosporine therapy than with conventional treatment. In cases of prolonged oligo-anuria of more than 2 to 3 weeks duration, slight diffuse interstitial fibrosis may develop. 3) Tubular toxicity include inclusion bodies in tubular epithelial cells (corresponding to giant mito- chondria), 'isometric tubular vacuolization, and mi- crocalcification. They may occur, however, in any com- bination may be found alone. 4) Vascular-interstitial toxicity (chronic toxicity) shows circular nodular pro- tein deposits and mucoid thickening of intima at small arterioles. Irregular foci or stripes of interstitial fibrosis with atrophic tubules are observed in the renal cortex. There is now a consensus that cyclosporine nephrotix- icity is the result of alterations in intrarenal hemodynamics. Various different experimental or clini- cal results may merely reflect varying responses of the kidney to primary vascular effect of cyclosporine, I. E. vascular constriction. Attempts to develop an animal model of acute and chronic cyclosporine toxicity have had liminted success. Two recent reports in which Spraque-Dawley rats were administered cyclosporine at 100 mg/kg/day sub- cutaneously for 10 days and 25mg/kg/day intraper- itoneally for 28 days resulted in renal lesions consistent with chronic cyclosporine nephrotixicity, I.e. vascular- intersitial toxicity. Acute toxicity. Rabbit model with 25 mg/kg/day intraperitoneally for 29 days is thought as more appropriate model to study nephrotoxiticity, since these structural entities are hallmarks of nephrotoxicity in man. Tubular toxicity models was not developed yet. Author measured renal procollagen alpha 1 ( I ), alpha 1 (III) and alpha 1 (IV) and beta-action m-RNA levels in cyclosporine-treated rodents before and after develop- ment of the histologic changes of chronic cyclosporine nephrotoxicity to evaluate them as a possible path- ogenetic link to the initiation of cyclosporine-induced renal scarring. Four week Cyclosporin-treated rats had focal cortical interstitial fibrosis and tubular atrophy. Cortical procollagen alpha 1 (I) Mrna levels were increased in Cyclosporin-treated group versus control rats at one week (p<0.02) and four weeks (p<0.02). One week medullary procollagen alpha 1 ( I ) and all other one week medullary, and one and four week cortical procollagen and B-actin Mrna levels were no different in cyclosporine group versus control rats. Morphologic abnormalities, and may represent an important step in the pathogenesis of cyclosporine- induced renal cortical fibrosis. We treated rats with thromboxane synthetase inhibitor and cyclosporine to reduce its toxicity for 28 days. TSI improves renal function in 28 day cyclosporine treated rats, but does not inhibit renal cortical procollagen Mrna increments or tubulointerstitial scarring. This suggests that cyclospor- ine associated fibrosis is, at least in part, mediated by non-hemodynamic or thromboxane independent mecha- nisms.
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