Faculty Bibliography

Antibody-mediated rejection (AMR) after desensitization for a positive crossmatch (+XM) live donor renal transplant can be severe and result in sudden onset oliguria and loss of the allograft. Attempts to rescue these kidneys using plasmapheresis (PP) and IVIg may be ineffective due to the magnitude of antibody burden that must be controlled to prevent renal thrombosis or cortical necrosis. We review our experience using splenectomy combined with PP/IVIg as rescue therapy for patients experiencing an acute deterioration in renal function and a rise in donor-specific antibody within the first posttransplant week after desensitization for a +XM. Five patients underwent immediate splenectomy followed by PP/IVIg and had return of allograft function within 48 h of the procedure. Emergent splenectomy followed by PP/IVIg may be an effective treatment for reversing severe AMR.

A session of the 14 International Histocompatibility Workshop brought together experts representing the major clinical protocols, clinical research, and basic research dealing with overcoming the barrier of alloantibody in transplantation and in understanding the mechanisms by which those antibodies exert their effect on a transplanted organ. This report is an integration of the presentations of those scientists.

Subclinical antibody-mediated rejection (AMR) has been described in renal allograft recipients with stable serum creatinine (SCr), however whether this leads to development of chronic allograft nephropathy (CAN) remains unknown. We retrospectively reviewed data from 83 patients who received HLA-incompatible renal allografts following desensitization to remove donor-specific antibodies (DSA). Ten patients had an allograft biopsy showing subclinical AMR [stable SCr, neutrophil margination in peritubular capillaries (PTC), diffuse PTC C4d, positive DSA] during the first year post-transplantation; 3 patients were treated with plasmapheresis and intravenous immunoglobulin. Three patients had a subsequent rise in SCr and an associated biopsy with AMR; 5 others showed diagnostic or possible subclinical AMR on a later protocol biopsy. One graft was lost, while remaining patients have normal or mildly elevated SCr 8-45 months post-transplantation. However, the mean increase in CAN score (cg + ci + ct + cv) from those biopsies showing subclinical AMR to follow-up biopsies 335 +/- 248 (SD) days later was significantly greater (3.5 +/- 2.5 versus 1.0 +/- 2.0, p = 0.01) than that in 24 recipients of HLA-incompatible grafts with no AMR over a similar interval (360 +/- 117 days), suggesting that subclinical AMR may contribute to development of CAN.

One of the greatest obstacles to the implementation of regional or national kidney paired donation programs (KPD) is the need for the donor to travel to their matched recipient's hospital. While transport of the kidney is an attractive alternative, there is concern that prolonged cold ischemia time (CIT) would diminish the benefits of live donor transplantation (LDTx). To examine the impact of increased CIT in LDTx, 1-year serum creatinine (SCr), delayed graft function (DGF), acute rejection (AR) and allograft survival (AS) were analyzed in 38 467 patients by 2 h CIT groups (0-2, 2-4, 4-6 and 6-8 h) using data from the United Network for Organ Sharing/Organ Procurement and Transplantation Network (UNOS/OPTN). Adjusted probabilities of DGF and AR were estimated in multivariate logistic regression models and AS was examined in multivariate Cox proportional hazards models. Although some increase in DGF was observed between the 0-2 h (4.7%) and 4-6 h (8.3%) groups, prolonged CIT did not result in inferior SCr, increased AR or compromised AS in any group with >2 h CIT compared with the 0-2 h group. Comparable long-term outcomes for these grafts suggests that transport of live donor organs may be a feasible alternative to donor travel in KPD regions where CIT can be limited to 8 h.