Posttransplant Allosensitization in Low Immunological Risk Kidney and Kidney-Pancreas Graft Recipients

Abstract

Introduction. Posttransplantation allosensitization prevalence and effect on kidney grafts outcomes remain unsettled. Methods. Between 2007 and 2012, 408 patients received a primary kidney graft (with 68 patients also receiving a pancreas graft) after a negative cytotoxic crossmatch. All patients had a pretransplant negative anti-HLA screening and 0% panel reactive antibodies. We analyzed retrospectively the results of anti-HLA antibodies screening by Luminex assay, performed between 6 and 24 months after transplant, and searched for the risk factors for antibody positivity and its impact on kidney graft outcomes. Results. Anti-HLA antibodies prevalence at 6 months was 17.4%. Previous steroid-insensitive acute rejection was the only risk factor for both anti-HLA classes detected antibodies. Antithymocyte globulin induction was also a risk factor for anti-HLA-I antibodies. Antibody positivity status was associated with reduced graft function at 12 months and graft survival at 5 years (91.5% versus 96.4%, P = 0.03). In multivariable Cox analysis, delayed graft function (HR = 6.1, P < 0.01), HLA mismatches >3 (HR = 10.2, P = 0.03), and antibody positivity for anti-HLA class II (HR = 5.1, P = 0.04) or class I/II (HR = 13.8, P < 0.01) were independent predictors of graft loss. Conclusions. Allosensitization against HLA class II ± I after transplant was associated with adverse kidney graft outcomes. A screening protocol seems advisable within the first year in low immunological risk patients.

Perioperative Desensitization Improves Outcomes Among Crossmatch Positive Recipients of Deceased Donor Renal Transplants

“…1,2,8,9 This speculation is plagued by anecdotal reports, small sampling size, and considerable variation in the sensitivity of DSA detection. 1,2,8,9,14 –17 However, a common observation (also seen here) is that de novo DSAs are commonly directed against class II instead of class I. 9,14 –17 One longitudinal study observed that while DSAs appearing within the first postoperative year were equally directed against class I and class II, thereafter class II DSA dominated to 71% DSA+.…”

“…1,2,8,9,14-17 However, a common observation (also seen here) is that de novo DSAs are commonly directed against class II instead of class I. 9,[14][15][16][17] One longitudinal study observed that while DSAs appearing within the first postoperative year were equally directed against class I and class II, thereafter class II DSA dominated to 71% DSAþ. 9 The clinical relevance of this is actively debated.…”

“…Studies using multivariate analysis showed that class II DSA seemed more predictive than class I DSA of graft dysfunction or failure. 16,17 Conversely, other studies suggest DSA against either class is equally destructive. 15 Thus, we are unable to determine whether the prevalence of preexisting anti-class II among IVIG patients contributed to the ineffectual clearance of DSA and poorer graft survival.…”

Immunogenicity of Anti-HLA Antibodies in Pancreas and Islet Transplantation

“…The development of anti-HLA antibodies after transplantation (de novo anti-HLA antibodies) is also associated with reduced graft survival. In isolated pancreas or simultaneous kidney–pancreas transplantation and in islet transplantation, several reports have previously demonstrated that the development of anti-HLA antibodies after transplantation is a risk factor for graft function and graft survival (1,2,10,14). However, these studies usually include several centers with different immunosuppressive strategies and do not compare both procedures (pancreas vs. islet transplantation), with regard to the presence of anti-HLA antibodies, as an independent risk factor for graft function and graft survival.…”