Predictive factors for ciclosporin-associated nephrotoxicity in children with minimal change nephrotic syndrome

Aims: To identify the predictive factors for ciclosporin A (CyA)-associated nephrotoxicity (CAN) in children with minimal change nephrotic syndrome (MCNS). Methods: The clinical and laboratory findings of 58 children (median age 3.2 years, range 1.1-13.1 years, male:female 48:10) with MCNS who were treated with CyA from 1992 to 2002 were analysed retrospectively. Forty-eight (83%) of them were steroid dependent and 10 (17%) were steroid resistant. The starting dose of CyA was 5 mg/kg per day, and the desired drug level was kept at 100-200 ng/ml. Serial renal biopsies were performed before and after CyA therapy. Results: Twenty-two patients (38%) had CAN (group I) and 36 (62%) did not (group II). There were no differences in the age at onset, sex, initial response to steroids, duration of CyA therapy and relapse rates. However, the median CyA trough levels were significantly higher in group I than in group II (218.0±15.2 vs 171.8±6.7 ng/ml, p=0.01). Changes in creatinine clearance were more decreased in group I than in group II (-39.4±8.2 vs 2.7±4.3 ml/min per 1.73 m ², p<0.0001). Multiple logistic regression analysis also revealed the median CyA trough level was an independent risk factor for the development of CAN (OR 1.025, 95% CI 1.007 to 1.044, p=0.007). Conclusions: The median CyA trough level was an independent and significant risk factor for the development of CAN in children with MCNS receiving moderate-dose CyA.