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

Abstract

Cyclosporine (CsA) is effective for the treatment of children with steroid-dependent and -resistant nephrotic syndrome (NS), but it can result in chronic CsA nephrotoxicity including CsA-induced tubulointerstitial lesions. The factors responsible for the development of CsA-induced tubulointerstitial lesions are unknown. To identify the risk factors for the development of CsA-induced tubulointerstitial lesions in children with minimal change NS who had been treated with long-term moderate-dose CsA, we compared several clinical and laboratory factors of 37 patients with and without CsA-induced tubulointerstitial lesions by the Mann-Whitney U test, Fisher's exact test, and stepwise logistic-regression analysis. Thirteen patients had CsA-induced tubulointerstitial lesions and 24 patients had none. Among clinical and laboratory factors, the duration of CsA treatment (P = 0.003) and the duration of heavy proteinuria during CsA treatment (P = 0.024) were related to the development of CsA-induced tubulointerstitial lesions as determined by the univariate analyses. Indeed, CsA-induced tubulointerstitial lesions were found in 2 of 18 (11%) patients who had been treated with CsA for less than 24 months, but in 11 of 19 patients (58%) who had been treated for more than 24 months (P = 0.005). They were also found in 4 of 23 patients (17%) who had heavy proteinuria for less than 30 days during CsA treatment, but in 9 of 14 patients (64%) who had heavy proteinuria for more than 30 days (P = 0.006). Stepwise logistic-regression analysis revealed that the duration of CsA treatment for more than 24 months (chi2 = 6.203, P = 0.013) and the duration of heavy proteinuria during CsA treatment for more than 30 days (chi2 = 5.871, P = 0.015) were independent risk factors for the development of CsA-induced tubulointerstitial lesions. 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.