Safety and Efficacy of a Calcineurin-Inhibitor Avoidance Regimen in Pediatric Renal Transplantation
Jun-06
Journal Article
Authors:
Harmon, W.;
Meyers, K.;
Ingelfinger, J.;
McDonald, R.;
McIntosh, M.;
Ho, M.;
Spaneas, L.;
Palmer, J.;
Hawk, M.;
Geehan, C.;
Tinckam, K.;
Hancock, W.;
Sayegh, M.
Secondary:
J Am Soc Nephrol
Volume:
17
Pagination:
1735-1745
URL:
http://www.ncbi.nlm.nih.gov/pubmed/16687625
Keywords:
Adolescent; Calcineurin; Child; Female; Glomerular filtration rate; Graft Rejection; Graft Survival; Immunosuppressive Agents; kidney transplantation; Male; Pilot Projects; Time Factors; Treatment Outcome
Abstract:
<p>Thirty-four children were entered into a pilot trial of calcineurin inhibitor avoidance after living-donor kidney transplantation, the CN-01 study. Patients were treated with anti-CD25 mAb, prednisone, mycophenolate mofetil, and sirolimus. Twenty patients were maintained on the protocol for up to 3 yr of follow-up. One enrolled patient did not receive the transplant because of a donor problem, eight terminated because of one or more rejection episodes, four terminated because of adverse events, and one was lost to follow-up. Two grafts were lost, one as a result of chronic rejection and the other as a result of posttransplantation lymphoproliferative disorder. There were no deaths. The 6- and 12-mo acute rejection rates were 21.8 and 31.5%, respectively. GFR were stable throughout the course of the study, with a slight downward trend by 6 mo after transplantation followed by a slight upward trend to a mean of 70 ml/min thereafter. Early surveillance graft biopsies frequently showed focal interstitial mononuclear cellular infiltrates without overt vasculitis or tubulitis, but these infiltrates disappeared without treatment. Anti-HLA class I and II antibodies were detected in three patients before transplantation, and all three had acute rejections, including the two patients who lost their grafts. De novo anti-HLA Ab production occurred in only one patient after transplantation. There were two episodes of Epstein Barr virus-related posttransplantation lymphoproliferative disorder, one of which developed after the patient had been terminated from the study. It is concluded that calcineurin inhibitor-free immunosuppression can be safe and effective in pediatric living-donor renal transplantation. However, further modifications that are designed to lessen early rejection rates and decrease complications should be tested before this approach is used routinely.</p>