title: Tacrolimus therapeutic drug monitoring and pediatric renal transplant graft outcomes.
abstract: Predose monitoring of tacrolimus levels is standard practice in the care of pediatric renal transplant patients. This is despite a paucity of data investigating the ideal target range in children, and controversy as to whether tacrolimus levels correlate with renal transplant outcomes. We performed a retrospective cohort analysis of 48 renal transplant patients at a single Canadian pediatric transplant center following the initiation of a tacrolimus-mycophenolate-prednisone-based IS protocol. We analyzed the relationship of graft function, as defined by GFR up to five yr post-transplant, to the preceding mean tacrolimus level. There was no significant correlation between absolute GFR and mean tacrolimus levels (r = 0.206, p = 0.38). However, a higher mean tacrolimus level, particularly ≥10 ng/mL in the first three months after transplantation, was associated with a slower rate of decline in GFR with time (r = 0.608, p = 0.004) and with a less likelihood of developing CKD five yr after transplant. We suggest that the optimal target range for tacrolimus levels may be at the upper end of what is currently practiced and that further research to validate these findings would be useful.
authors.affiliation: Division of Nephrology, Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Larkins
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Matsell
mesh_terms: D002648:Child; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation; D016014:Linear Models; D008297:Male; D015999:Multivariate Analysis; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D011241:Prednisone / Q000627:therapeutic use; D012189:Retrospective Studies; D016559:Tacrolimus / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D011241:Prednisone; D016559:Tacrolimus
keywords: kidney transplantation; outcome; pediatric; tacrolimus; therapeutic drug monitoring