title: The effect of long-term calcineurin inhibitor therapy on renal function in children after liver transplantation.
abstract: 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 Steroids were withdrawn at 3 months and cyclosporin/tacrolimus monotherapy was initiated 12 months post-OLT.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.
authors.affiliation: Liver Unit, Birmingham Children's Hospital, Birmingham, UK.
authors.forename: Nitika
authors.initials: N
authors.lastname: Arora-Gupta
authors.forename: Paul
authors.initials: P
authors.lastname: Davies
authors.forename: Patrick
authors.initials: P
authors.lastname: McKiernan
authors.forename: Deirdre A
authors.initials: DA
authors.lastname: Kelly
mesh_terms: D000293:Adolescent; D000367:Age Factors; D001379:Azathioprine / Q000627:therapeutic use; D065095:Calcineurin Inhibitors; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007223:Infant; D007668:Kidney / Q000187:drug effects*; D016031:Liver Transplantation; D008297:Male; D016555:Matched-Pair Analysis; D012189:Retrospective Studies; D018709:Statistics, Nonparametric; D015996:Survival Rate; D016559:Tacrolimus / Q000627:therapeutic use*
chemical_list: D065095:Calcineurin Inhibitors; D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D001379:Azathioprine; D016559:Tacrolimus