• Childhood Kidney Diseases
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• v.4 no.2
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• pp.127-135
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• 2000

Purpose: Cyclosporine(CsA) is a potent immunosuppressant but the use of CsA is associated with various side effects, especially nephrotoxicity. In tile kidney, salt depletion activates tile 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 goups. 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 me sampled for the observation of histological changes. Results: No differences in blood CsA level & 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 tile LSD group. But, no differences were observed between tile 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 Am ameliorated the effect of salt-depleted CsA nephrotoxicity upon the effective renal blood flow.

• Childhood Kidney Diseases
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• v.3 no.2
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• pp.130-144
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• 1999

Purpose : Long-term use of Cyclosporine(CsA) reduce renal blood flow by afferent arteriolar vasoconstriction and lead to chronic pathologic changes of CsA nephrotoxicity - 1) interstitial nephritis(IN); tubular atrophy (TA) and/or interstitial fibrosis(IF),2) arteriolopathy(AP). The Object of this study is to estimate the incidence of chronic pathologic CsA nephrotoxicity by duration of treatment and type of renal disease, relationship between histologic and clinical nephrotoxicity, and optimal duration of CsA therapy. Methods : 102 children with steroid resistant or dependent nephrotic syndrome confirmed by renal biopsy and treated with CsA from 1986 to 1997 were enrolled in this study(58 MCNS, 10 FSGS, 10 MGN, 15 $Henoch-Sch\"{o}nlein$ purpura nephritis with nephrotic syndrome (HSPN) and 9 IgA nephropathy with nephrotic syndrome(IgAN)). CsA was administered for 1yr, 1.5yr, 2yr in 24, 12, 22 MCNS patients and 2, 2, 6 FSGS patients respectively, 1yr, 2yr in MGN and 1yr in HSPN and IgAN. Sequential biopsies were done in all 102 patients after CsA treatment for evaluation of pathologic nephrotoxicity. Results : Complete remission rate was 92.2% (100% in MCNS and MGN, 80% in FSGS, 86.6% in HSPN and 55.5% in IgAN). Incidence of relapse during 6months after CsA treatment was significantly decreased compaed with relapsing spisodes during 6months before CsA treatment in MCNS(P<0.0001) and FSGS(P<0.0001). According to pathologic changes, 71 patients(69.6%) showed no pathological change, 24 patients(23.5%) showed IN and 7 patients(6.8%) showed AP. IN was 16.6%, 33.3%, 27.2% in 1, 1.5, 2 year of CsA treatment group in MCNS. AP was 0%, 16.6%, 9% in 1, 1.5, 2 year of CsA treatment group in MCNS. 14 out of 58 MCNS(24.1%) showed IN and 4 out of 58 MCNS(6.8%) showed AP. Incidence of pathologic change was significantly lower in CsA therapy of <1yr than >1yr(P=0.03). There were no significant difference of incidence of pathologic change in original renal disease, age and sex. Conclusion : Duration of CsA treatment was significant risk factor for nephrotoxicity and optimal duration seemed to be 1 year. Pathologic change due to nephrotoxicity did not correlate with deterioration of renal function and only detectable by renal biopsy.