Advantages of cyclosporin A using 2-h levels in pediatric kidney transplantation

Clinical trials in adult liver and heart recipients have shown that management of cyclosporine (CsA) dose with 2-h levels (C2) leads to lower rejection rates and serum creatinine levels compared with C0 monitoring. Therefore, we investigated whether C2 monitoring might also improve late graft survival after kidney transplantation in children. To date, no results in adult renal transplantation and in pediatric transplantation have been published. Forty-nine stable pediatric kidney recipients with a minimum time of 1 year after transplantation (mean=7±5 years) entered the study. None of the patients had experienced an acute rejection up to 6 months before entering the study. CsA dosing was based on C0 monitoring for the first 6 months and then based on C2 monitoring for the following 6 months. C0 and C2 levels were measured at 4-weekly intervals. Percentage decline in glomerular filtration rate (GFR) and mean coefficients of variation of CsA levels (C_var) were calculated and compared during the 6-months periods. At the beginning of the study, the mean calculated GFR was 53±15 ml/min per 1.73 m². During the 6 months of C0 monitoring, the mean GFR decreased to 49±12 m/min per 1.73 m² (P=0.001, paired t-test). Six months after switching to C2 monitoring, the mean GFR remained stable, at 49±15 ml/min per 1.73 m² (P=0.3 paired t-test). The largest increase in GFR (3.9±7.9%) was found in patients with a decrease of their CsA dose of more than 5% under C2 monitoring. C_var was significantly lower under C2 than under C0 monitoring (0.24±0.10 vs. 0.30±0.15, P=0.02, unpaired t-test). We conclude that the switch to C2 monitoring helped to identify patients with CsA overdosing as well as to reduce variation in CsA level, which resulted in a halt in GFR decline.