Anti-human leukocyte antigen immunization after early allograft nephrectomy.
ABSTRACT The occurrence of de novo anti-human leukocyte antigen (HLA) antibodies and donor-specific antibodies (DSAs) after early graft loss is not well known. The aims of this single-center study were to evaluate the incidence of de novo DSAs and non-DSA anti-HLA antibodies after allograft nephrectomy for early graft loss and to seek the predictive factors for the development of DSAs.
Thirty-two patients, who experienced an early graft loss (<3 months after transplantation) and required an allograft nephrectomy, and who were considered for retransplantation, were included in the study. Anti-HLA antibodies were assessed, using the Luminex assay, before transplantation, on day 15 and at months 1, 3, 6, and 9 after the nephrectomy, and then every 3 to 6 months until the last follow-up.
The median time between transplantation and allograft nephrectomy was 2.5 (0-81) days. The median follow-up was 335 (30-1441) days. At month 9, postallograft nephrectomy, the incidence of DSAs was 56.6% (17/30). Anti-HLA class I and class II DSAs were detected, respectively, in 33.3% (10/30) and 30% (9/30) of patients. The incidence of de novo non-DSA anti-HLA antibodies was 64% (19/30): of these, 83.3% reacted to the donors' epitopes. Induction therapy (type and dose) and the time between transplantation and allograft nephrectomy did not influence the incidence of DSAs. No independent predictive factor for the development of DSAs was identified.
Even after a short transplantation period, DSAs and non-DSA anti-HLA antibodies may develop in more than 50% of patients whose immunosuppression has been stopped after an allograft nephrectomy.
[Show abstract] [Hide abstract]
ABSTRACT: Aims: To identify the histopathological features of transplant nephrectomy (TN) specimens. Methods: We performed retrospective analysis of 73 nephrectomies to review the histopathology in detail and correlate the Banff grading characteristics of TN specimens with time post engraftment and clinical features. Retrospective data on donor-specific antibodies (DSA) were also collected. Results: The majority of patients who had TN in less than 3 months posttransplant (n = 20; median time to TN: 4 days) had hemorrhagic infarction; 7 patients (35%) had grade 3 acute rejection (AR). Patients who had TN later than 3 months posttransplant (n = 53; median time to TN: 67 months) had AR, grade 2B (21%) and 3 (43%), coexisting with advanced vascular injury in the form of interstitial hemorrhage, extensive interstitial fibrosis and tubular atrophy (IF/TA) as well as the presence of DSAs. Overall, the majority of patients without DSA pre-TN developed DSA post-TN. Conclusions: Our data revealed extensive inflammation and ongoing immunologic activity in a subset of patients with a failed graft. Careful and individualized approach based on clinical and laboratory data should guide the decision for transplant nephrectomy. © 2014 S. Karger AG, Basel.American Journal of Nephrology 12/2014; 40(5):491-498. DOI:10.1159/000369865 · 2.65 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: We have analyzed the relationship between donor mismatches at each HLA locus and development of HLA locus-specific antibodies in patients listed for repeat transplantation. HLA antibody screening was undertaken using single-antigen beads in 131 kidney transplant recipients returning to the transplant waiting list following first graft failure. The number of HLA mismatches and the calculated reaction frequency of antibody reactivity against 10,000 consecutive deceased organ donors were determined for each HLA locus. Two-thirds of patients awaiting repeat transplantation were sensitized (calculated reaction frequency over 15%) and half were highly sensitized (calculated reaction frequency of 85% and greater). Antibody levels peaked after re-listing for repeat transplantation, were independent of graft nephrectomy and were associated with length of time on the waiting list (odds ratio 8.4) and with maintenance on dual immunosuppression (odds ratio 0.2). Sensitization was independently associated with increasing number of donor HLA mismatches (odds ratio 1.4). All mismatched HLA loci contributed to the development of HLA locus-specific antibodies (HLA-A: odds ratio 3.2, HLA-B: odds ratio 3.4, HLA-C: odds ratio 2.5, HLA-DRB1: odds ratio 3.5, HLA-DRB3/4/5: odds ratio 3.9, and HLA-DQ: odds ratio 3.0 (all significant)). Thus, the risk of allosensitization following failure of a first renal transplant increases incrementally with the number of mismatches at all HLA loci assessed. Maintenance of re-listed patients on dual immunosuppression was associated with a reduced risk of sensitization.Kidney International advance online publication, 9 April 2014; doi:10.1038/ki.2014.106.Kidney International 04/2014; 86(5). DOI:10.1038/ki.2014.106 · 8.52 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: The number of patients reinitiating dialysis after a failed transplant increases over time and has more than doubled between the year 1988 and 2010 (an increase from 2463 to 5588). More importantly, patients returning to dialysis have been shown to have a greater than three-fold increase in the annual adjusted mortality rates compared with those with a functioning graft. Continuation of immunosuppression to preserve residual graft function has been implicated to be a contributing factor, seemingly due to immunosuppression-associated cardiovascular and infectious complications and malignancy risk, among others. Nonetheless, maintenance low-dose immunosuppression has been suggested to confer survival benefit in patients returning to peritoneal dialysis. Whether early vs late reinitiation of dialysis or whether transplantectomy has an impact on patient survival remains poorly defined. Consensus guidelines for the management of a failed allograft are lacking. In this article, we present a literature overview on the ideal timing of dialysis reinitiation after graft loss, the management of immunosuppression after graft failure, and the risks and benefits of transplantectomy. The authors' perspectives on the management of this special patient population are also discussed.05/2015; 4(2):148-59. DOI:10.5527/wjn.v4.i2.148