Continued superior outcomes with modification and lengthened follow-up of a steroid-avoidance pilot with extended daclizumab induction in pediatric renal transplantation.
BACKGROUND
Corticosteroids have been invariant transplant immunosuppressives with numerous adverse effects. We previously reported 6-month results in 10 patients using extended daclizumab induction to safely eliminate steroid use in pediatric renal transplantation. This expanded pilot series discusses immunosuppression dosing modification to further minimize drug toxicity without sacrificing regimen efficacy.


METHODS
Fifty-seven pediatric renal transplant recipients were enrolled in the pilot steroid-free protocol. Extended daclizumab induction, tacrolimus, and mycophenolate mofetil (MMF) were intended maintenance drugs. Fourteen patients were equal to or younger than 5 years, and 43 patients were older than 5 years of age at transplantation. There were seven protocol breaks. Study patients underwent serial protocol transplant biopsies (n=246), and serum daclizumab and mycophenolic acid (MPA) trough levels were evaluated. In this efficacy study, controls were 50 historical-matched steroid-based children receiving tacrolimus with 100% 2-year graft survival and without delayed graft function.


RESULTS
Mean follow-up was 20 (range, 4.5-41) months with 98% overall graft and patient survival. At 1 year of analysis, steroid-free recipients showed significant improvements for clinical acute rejection (8%), graft function, hypertension, and growth, without increased infectious complications. Leukopenia, anemia, and allograft nephrotoxicity were addressed by solely decreasing MMF and tacrolimus dosing and/or by replacing MMF with sirolimus, without increasing acute rejection. Early daclizumab levels of more than 5 microg/mL were observed for the first time in children of all ages.


CONCLUSIONS
Pediatric renal transplantation is safe without steroids. Daclizumab first-dose doubling and extended use for 6 months replaces steroids effectively without evidence of overimmunosuppression and may be the pivotal cause for the reduced acute rejection seen in this trial. This pilot study provides preliminary data to test this protocol in a prospective, multicenter randomized study.
Sarwal
Minnie M
MM
Department of Pediatrics, Stanford University, Palo Alto, CA 94305, USA.
Vidhun
Jayakumar R
JR
Alexander
Steven R
SR
Satterwhite
Thomas
T
Millan
Maria
M
Salvatierra
Oscar
O
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001794:Blood Pressure; D002648:Child; D002675:Child, Preschool; D000077561:Daclizumab; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000453:epidemiology; D006400:Hematocrit; D006650:Histocompatibility Testing; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007223:Infant; D016030:Kidney Transplantation / Q000276:immunology / Q000502:physiology*; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010865:Pilot Projects; D011183:Postoperative Complications / Q000453:epidemiology; D013256:Steroids; D016559:Tacrolimus / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D013256:Steroids; D000077561:Daclizumab; D009173:Mycophenolic Acid; D016559:Tacrolimus