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The feasibility and effectiveness of kidney paired donation (KPD) for the management of patients with incompatible donors were determined. Evidence suggests that recipients with incompatible live donors, even those with rare blood type combinations, can receive transplants through KPD with graft survival rates equivalent to directed, compatible liver donor transplants.

C4d deposition in peritubular capillaries is a specific marker for the presence of antidonor antibodies in renal transplant recipients and is usually associated with antibody-mediated rejection (AMR) in conventional allografts. In ABO-incompatible grafts, however, peritubular capillary C4d is often present on protocol biopsies lacking histologic features of AMR; the significance of C4d in this setting remains unclear. For addressing this, data from 33 patients who received ABO-incompatible renal allografts (after desensitization) were retrospectively reviewed. Protocol biopsies were performed at 1 and/or 3 and 6 mo after transplantation in each recipient and at 12 mo in 28 recipients. Twenty-one patients (group A) had strong, diffuse peritubular capillary C4d staining without histologic evidence of AMR or cellular rejection on their initial protocol biopsies. The remaining 12 patients (group B) had negative or weak, focal peritubular capillary C4d staining. Three grafts (two in group B) were lost but not as a result of AMR. Excluding these three patients, serum creatinine levels were similar in the two groups at 6 and 12 mo after transplantation and at last follow-up; however, recipients in group A developed significantly fewer overall chronic changes, as scored by the sum of Banff chronic indices, than group B during the first year after transplantation. These results suggest that diffuse peritubular capillary C4d deposition without rejection is associated with a lower risk for scarring in ABO-incompatible renal allografts; the generalizability of these results to conventional allografts remains unknown.

We present four cases of renal transplant recipients who were treated with bortezomib for four different indications, each of whom had circulating anti-HLA antibodies that were followed serially throughout their courses of bortezomib therapy. It is important to note that each patient was administered bortezomib in conjunction with other agents and therapies traditionally used for desensitization or the treatment of AMR. The results have been mixed. In some cases substantial decreases in HLA-antibody were temporally related to bortezomib therapy. In the one case of recalcitrant AMR there has been no reduction in DSA after 2 cycles of the drug. Bortezomib has been well tolerated. One patient developed reversible peripheral neuropathic pain while another experienced line sepsis, a urinary tract infection, and an invasive fungal skin infection. Again, this patient had also received protracted courses of plasmapheresis combined with T-cell and B-cell depleting agents. The use of these other drugs precludes the ability to rigorously evaluate the efficacy of bortezomib in isolation and points towards a need for large-scale, controlled trials to determine whether the drug's promising mechanism of action is applicable in the setting of solid organ transplantation.

Antibody-mediated barriers to renal transplantation, including donor specific anti-HLA and anti-blood group antibodies, have become an increasingly important issue over the last forty years as the organ shortage has continued to expand. The inevitable result of the unmet demand for compatible organs has been a continuous increase in recipient waiting times. Over the last decade, two treatment strategies have been developed to address this problem. These regimens rely on the immunomodulatory properties of intravenous immunoglobulin (IVIG) administered alone at relatively high doses, or at lower doses in combination with the non-selective depletion of antibodies from plasmapheresis. Both protocols have been successfully used for desensitization of patients with donor-specific anti-HLA antibody and have allowed for renal transplantation with excellent outcomes. The combined strategy of plasmapheresis/IVIG has also been successfully employed for renal transplantation in recipients of ABO blood group incompatible kidneys. This review will provide an overview of these therapies and their application to incompatible renal transplantation.

A stagnant supply of transplantable organs in the face of a relentless burgeoning of transplant waiting lists has created a crisis. Necessity continues to be the mother of invention and as the crisis has deepened it has served as a crucible for the development of new ways to think about perennial problems. Our program has taken a 2-pronged approach to increasing the organ supply for our patients. First, through innovations like the laparoscopic donor nephrectomy, ABO-incompatible and positive-crossmatch transplantation protocols, unconventional paired kidney exchanges, and the use of altruistic donors we have more than doubled our utilization of live donor organs. At the same time, we have developed algorithms and interrogative techniques to enhance the intelligent use of kidneys from expanded criteria donors for patients who do not have an available live donor. The laparoscopic nephrectomy has proven to be a safe and effective way of removing a significant barrier to live donation. Our results from 100 ABOi, (+)XM, and PKE transplants are similar to national statistics for compatible live donor transplants, suggesting that existing paradigms of compatibility can be safely expanded. These encouraging early outcomes and the savings they transmit to the health care system have allowed us to obtain insurance coverage for the InKTP programs, setting the stage for further expansion of these opportunities to broaden the options for patients with end-stage renal disease.