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J Korean Soc Pediatr Nephrol. 2000 Dec;4(2):127-135. Korean. Original Article.
Lee EJ , Lee ES , Hah JH , Kim YJ , Park YH .
Department of Pediatrics, Yeungnam University, College of Medicine, Taegu, Korea. yhpark@medical.yeungnam.ac.kr
Department of Phamacology, Yeungnam University, College of Medicine, Taegu, Korea.
Department of Pathology, Yeungnam University, College of Medicine, Taegu, Korea.
Abstract

PURPOSE: Cyclosporine(CsA) is a potent immunosuppressant but the use of CsA is associated with various side effects, especially nephrotoxicity. In the kidney, salt depletion activates the renin-angiotensin-aldosteron(RAS) system and accentuates chronic CsA nephropathy. We postulate that angiotensin converting enzyme inhibitors(ACEI) can prevent chronic CsA nephropathy, since ACEI may inhibit this cascades. This study was aimed to assess the effect of ACEI on chronic cyclosporin nephropathy in salt depleted rats. METHODS: 36 Fischer-344 rats were divided into 6 groups. Group I received normal salt diet(NSD). Group II received a low salt diet(LSD). Group III received CsA with a NSD. Group IV received CsA with a LSD. Group V received NSD+CsA with ACEI. Group VI received LSD+CsA with ACEI. Rats were sacrificed after six weeks, and the glomerular filtration rate(GFR), serum sodium, potassium and whole blood cyclosporine levels were measured. Renal tissues were sampled for the observation of histological changes. RESULTS: No differences in blood CsA level and serum sodium were found between groups during the course of this experiment. Serum potassium in group VI was significantly increased compared with group IV and V(P<0.05). In groups treated with CsA only and in those where CsA was combined with ACEI, GFR was found to be significantly more decreased in LSD than NSD, and GFR in group V was significantly decreased in comparison with group III (P<0.05). Renal histologic lesions associated with CsA, which consisted of cortical interstitial fibrosis, tubular atrophy and hyalinization of arterioles, were more severe in the LSD group. But, no differences were observed between the groups treated with CsA and ACEI, and the groups treated with only CsA. CONCLUSION: Salt depletion associated with the activation of the RAS system accentuated chronic CsA nephrotoxicity, but, ACEI could not reduce the functional and morphological changes of salt depleted kidneys, in which nephropathy can be exacerbated in spite of the blocking of the angiotensin II pathway. Further studies are required to elucidate whether ACEI ameliorated the effect of salt-depleted CsA nephrotoxicity upon the effective renal blood flow.

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