The effect of long-term calcineurin inhibitor therapy on renal function in children after liver transplantation

Calcineurin inhibitor drugs (CNI), cyclosporin and tacrolimus are potent immunosuppressants, which have improved survival after liver transplantation. We evaluated long-term renal function in children receiving calcineurin inhibitors after liver transplantation. A retrospective analysis of all children undergoing orthotopic liver transplantation (OLT) from 1989 to 1999 who survived 1-yr post-transplantation was performed. All received prednisolone and either cyclosporin and azathioprine or tacrolimus. Steroids were withdrawn at 3 months and cyclosporin/tacrolimus monotherapy was initiated 12 months post-OLT. Calculated glomerular filtration rate (cGFR) was calculated using the modified Counahan-Barratt formula and measured pretransplant, 3, 6 and 12 months post-transplant and annually thereafter. Data were analysed in a serial manner to evaluate the trend of cGFR over time selectively using the Wilcoxon signed rank test and paired t-tests as appropriate. A total of 113 patients (65 males:48 females) were followed up for more than 1 yr (maximum 5 yr). Median (range) age at transplantation was 26 months (3-177). There was a significant fall of 35% in cGFR at 3 months compared with the pretransplant value (p = 0.001). By 12 months following the reduction in immunosuppression dosage, renal function stabilized with a slight improvement in cGFR which reached 76% of the pretransplant value at 5 yr (p < 0.001). Children who were <1 yr of age at the time of OLT had better recovery of renal function than older children (p = 0.02). No association was seen with sex, the type of immunosuppression or the underlying diagnosis. Renal dysfunction is a known complication of CNI therapy. Despite an initial reduction in cGFR, which was associated with maximal immunosuppression, long-term low dose CNI therapy was not associated with continued deterioration of renal function, particularly in children who were transplanted as infants.