Presented at:
World Transplant Congress 2006
Boston, MA, TX, July 22-27, 2004
Preliminary Analysis of the ITN Registry of Tolerant Kidney Transplant Recipients
Newell KA, Burlingham WJ, Marks WH, Gisler TD, Seyfert VL, Turka LA, Suthanthiran M, Kirk AD
Emory University; University of Wisconsin; NIH-NIDDK; Swedish Medical Center; ITN and Cornell University.
Introduction: To analyze features contributing to tolerance, clinical data and biologic specimens were collected from tolerant and non-tolerant kidney transplant recipients and donors.
Methods: 107 patients were enrolled in the following groups: tolerant (16), steroid monotherapy (9), triple therapy (36), CAN (11), graft loss (7), identical twins (2), and donors for these groups (26). Tolerant patients were defined as off immunosuppression (IS) for > 1 year with a creatinine (Cr) at or near baseline. Samples were obtained for cellular assays, mRNA profiling, phenotypic analysis of PBMC, and characterization of alloantibodies.
Results: Of the 16 tolerant patients identified, all were recipients of primary transplants, 9 were male, 12 received living donor kidneys, and all except 1 were Caucasian. Of the 11 patients for whom HLA data is available, the number of HLA mismatches was 0 (6), 0 or 1 (1), 1 (2), 3 (1) and 5 (1). Primary diseases causing ESRD were immunologic (10), structural (4), and infectious (2). The average age at transplant was 31+13 yrs. The incidence of ACR in this group was 7%. The interval between transplantation and cessation of IS was 13+10 yrs. The mean Cr at the time of enrollment in the study was 1.1+0.4 mg/dL. Reasons for discontinuation of IS included non-adherence (10), malignancies (2), medication side-effects (2), and other/unknown (2). Preliminary comparison of the expression of 20 selected genes in urinary sediments of a subset of the patients (13 tolerant, 26 triple therapy, and 8 with CAN) revealed significant differences in the expression of IL-10, and CXCR3 (p<0.05). Analysis of microarray, alloantibody, and phenotypic data from a cohort of patients is in progress and will be presented.
Conclusions: This is the largest cohort of tolerant patients assembled for study. Our preliminary finding that the genes expressed in the urinary sediments of tolerant patients differ from non-tolerant patients may be of clinical importance. The availability of these cohorts will provide materials for ongoing investigations into tolerance mechanisms in transplantation.