Risk factors for cyclosporine-induced tubulointerstitial lesions in children with minimal change nephrotic syndrome

Abstract

Duration of the CsA treatment and the duration of heavy proteinuria during CsA treatment were independent significant risk factors for the development of CsA-induced tubulointerstitial lesions in children with MCNS who had been treated with long-term moderate-dose CsA.

Renal Biopsy Findings in Children Receiving Long-Term Treatment with Cyclosporine A Given as a Single Daily Dose

“…Tubular atrophy associated with striped interstitial fibrosis, a typical feature CsA nephrotoxicity (Inoue et al 1999;Iijima et al 2002;Nakahata et al 2005), was not found in any of the study subjects, except one patient with SRNS. The patient with FSGS (Patient 8) showed interstitial lesions, however, there were mild and graded as group II, and the overall picture suggested a tendency towards improvement as compared to the pretreatment renal biopsy findings (Table 2).…”

“…However, CsA nephrotoxicity remains a major problem (Habib and Niaudet 1994;Inoue et al 1999;Iijima et al 2002). In this conventional CsA treatment protocol for NS, Inoue et al (1999) reported that a young age at the start of CsA treatment and a higher frequency of relapses during CsA treatment might be risk factors for the development of chronic CsA nephrotoxicity.…”

“…In this conventional CsA treatment protocol for NS, Inoue et al (1999) reported that a young age at the start of CsA treatment and a higher frequency of relapses during CsA treatment might be risk factors for the development of chronic CsA nephrotoxicity. Iijima et al (2002) recently reported that the duration of CsA treatment and the duration of heavy proteinuria during CsA treatment were significant risk factors for the development of CsA nephrotoxicity. Thus, an optimal CsA treatment strategy for children with NS, with administration of the lowest possible dose of the drug, would be desirable in order to minimize the treatment toxicity, while maintaining the treatment efficacy (Chishti et al 2001;Nakahata et al 2005).…”

“…Since CsA nephrotoxicity remains a major problem in CsA treatment (Habib and Niaudet 1994;Inoue et al 1999;Iijima et al 2002), in this study, we investigated the safety, from the histological standpoint, of long-term CsA treatment with the drug administered daily as a single-dose while maintaining the peak (between 1 and 2 hrs post-dosing, C 1 -C 2 ) blood level at around 800 ng/ ml, in children with NS and some rheumatic diseases Nakahata et al 2005;Tanaka et al 2005).…”

“…All the 8 patients underwent posttreatment renal biopsy following a mean CsA treatment duration of 20 months (9-36 months), with CsA administered as a single daily dose, in order to investigate the safety of the treatment protocol from the histological standpoint. Tubular atrophy associated with striped interstitial fibrosis is considered to be the most reliable indicator of CsA nephrotoxicity (Habib and Niaudet 1994;Inoue et al 1999;Kano et al 1999;Iijima et al 2002). The severity of the lesion was classified as group I (within normal limits), group II (mild; percentage of the interstitium involved, 1-50%), or group III (moderate or severe; percentage of the interstitium involved, > 50%), according to the modified method described by Habib and Niaudet (1994).…”