Sensitization trends after renal allograft failure: the role of DQ eplet mismatches in becoming highly sensitized.

Sensitization following renal allograft failure (AF) is highly variable. Some patients remain non-sensitized (NS), while others become highly sensitized (HS). We studied 66 NS patients who experienced AF after initial kidney transplantation. Post-failure, two main groups of NS panel reactive antibody (PRA) class I and II <10% and HS patients (PRA class I or II ≥80%) were identified. The impact of acute rejection (AR), immunosuppression withdrawal (ISW) at AF, allograft nephrectomy, graft intolerance syndrome (GIS), and both standard serologic and eplet-based mismatches (MM) in inducing HS status after failure was examined. Late PRA testing post-failure revealed 18 patients remained NS and 34 patients became HS. African American recipients, ISW at AF, DQB1 eplet MM, and presence of GIS were associated with becoming HS. Presence of total zero eplet MM, zero DQA1/B1 eplet MM, continuation of immunosuppression after failure, and a hyporesponsive immune status characterized by recurrent infections were features of NS patients. DQ eplet MM represents a significant risk for becoming HS after AF. Studies comparing ISW vs. continuation in re-transplant candidates with high baseline DQ eplet MM burden should be performed. This may provide insights if sensitization post-AF can be lessened.

Sensitization, pathologic, and imaging findings comparing symptomatic and quiescent failed renal allografts.

Late allograft failure (LAF) is a common cause of end stage renal disease. These patients face interrelated challenges regarding immunosuppression management, risk of graft intolerance syndrome (GIS), and sensitization. This retrospective study analyzes sensitization, pathology, imaging, and transfusion requirements in 33 LAFs presenting either with GIS (22) or grafts remaining quiescent (11). All patients underwent immunosuppression weaning to discontinuation at LAF. Profound increases in sensitization were noted for all groups and occurred in the GIS group prior to transplant nephrectomy (TxN). Patients with GIS experienced a major upswing in sensitization at, or before the time of their symptomatic presentation. For both GIS and quiescent grafts, sensitization appeared to be closely linked to immunosuppression withdrawal. Most transfusion naïve patients became highly sensitized. Fourteen patients in the GIS group underwent TxN which revealed grade II acute cellular rejection or worse, with grade 3 chronic active T-cell-mediated rejection. Blinded comparisons of computed tomography scan of GIS group revealed swollen allografts with fluid collections compared with the quiescent allografts (QAs), which were shrunken and atrophic. The renal volume on imaging and weight of explants nearly matched. Future studies should focus on interventions to avoid sensitization and GIS.

Human leukocyte antigen and adult living-donor liver transplantation outcomes: an analysis of the organ procurement and transplantation network database.

Human leukocyte antigen (HLA) compatibility has no clinically significant impact in cadaveric liver transplantation. Less is known regarding living-donor liver transplantation (LDLT). Our prior analysis of the Organ Procurement and Transplantation Network (OPTN) database suggested a higher graft failure rate in patients who underwent LDLT from donors with close HLA match. We further investigated the effect of HLA-A, -B, and -DR matching on 5-yr graft survival in adult LDLT by analyzing OPTN data regarding adult LDLT performed between 1998 and 2005. We evaluated associations between 5-yr graft survival and total, locus-specific, and haplotype match levels. Separate analyses were conducted for recipients with autoimmune (fulminant autoimmune hepatitis, cirrhosis secondary to autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis) or nonautoimmune liver disease. Multivariable Cox proportional hazard models were used to evaluate interactions and adjust for potential confounders. Among 631 patients with available donor/recipient HLA data, the degree of HLA match had no significant effect on 5-yr graft survival, even when analyzed separately in recipients with autoimmune vs. nonautoimmune liver disease. To be able to include all 1,838 adult LDLTs, we considered a first-degree related donor as substitute for a close HLA match. We found no difference in graft survival in related vs. unrelated pairs. In conclusion, our results show no detrimental impact of close HLA matching on graft survival in adult LDLT, including in recipients with underlying autoimmune liver disease.