However, difficult-to-match donor-recipient mixtures, including broadly sensitized individuals, continue to pose challenging
However, difficult-to-match donor-recipient mixtures, including broadly sensitized individuals, continue to pose challenging. Combining desensitization and KPD for individuals who have strong antibody reactivity to a proposed but willing donor, while also keeping them within the deceased donor waiting list, increases the pool of potential donors. compatible living and deceased donor kidney transplants. We conclude that early enrollment in combined kidney donor exchange and tailored desensitization protocols are key strategies to improve care and rates of kidney transplantation in highly sensitized individuals. Keywords: desensitization, kidney exchanges, kidney transplantation, HLA antibodies, donor-specific antibodies Intro Kidney transplantation is the treatment of choice for individuals with end-stage renal disease (ESRD) (1). Sensitization is definitely a major barrier to successful kidney transplantation. Sensitized individuals comprise approximately 30% of the deceased donor waiting list and have the longest waiting times because of difficulty in finding a compatible donor (2). Despite priority status in the organ allocation algorithm, fewer than 15% of highly sensitized Cloxacillin sodium individuals are transplanted per year (3). Based on Organ Procurement and Transplantation Network (OPTN) data as of the end of 2010, although individuals with cumulative determined panel reactive antibody (cPRA) 80C95% have benefited with increased transplantation rates, those individuals with cPRA > 95% remain hard to transplant especially those fully sensitized with cPRA 100%. Current options for highly sensitized individuals with an immunologically incompatible live donor include desensitization, kidney combined donation (KPD), or a combination (4). For the past decade, desensitization offers been successful in select individuals. Current providers for desensitization include intravenous immunoglobulin (IVIG), rituximab, plasmapheresis, as well as newer providers such as bortezomib and eculizumab (5C7). Recent studies show a survival benefit that more than doubled by eight years for individuals undergoing desensitization and transplantation compared with remaining on dialysis (8). Regrettably, many individuals do not respond to desensitization, especially highly sensitized individuals with broad and strong human being leukocyte antigen (HLA) antibody reactivity. Furthermore, long-term results in positive crossmatch kidney transplant recipients may be inferior compared to immunologically compatible transplants (9). KPD is definitely a creative option that matches a more immunologically compatible donor having a recipient through hamartin a registry. However, difficult-to-match Cloxacillin sodium donor-recipient mixtures, including broadly sensitized individuals, continue to present a challenge. Combining desensitization and KPD for individuals who have strong antibody reactivity to a proposed but prepared donor, while also keeping them within the deceased donor waiting Cloxacillin sodium list, increases the pool of potential donors. We Cloxacillin sodium hypothesized that this combined approach would enable our highly sensitized individuals to be transplanted. Additional centers, including Johns Hopkins, have combined KPD and desensitization to increase transplant rates (10C12). Both desensitization and KPD programs are expensive and require significant resources. Therefore, we wanted to determine how best to use these strategies in highly sensitized individuals. We statement our experience of five highly sensitized individuals, all with cumulative cPRA 100%, who underwent desensitization in combination with KPD and successfully received kidney transplants. By cautiously analyzing donor and recipient HLA typing and antibodies, our objective is definitely to create a strategy on how to enroll donor-recipient pairs in KPD and prescribe desensitization therapy to enable successful transplantation in the very highly sensitized individuals. Case Histories The recipient demographic info, HLA typing, histocompatibility data, and medical results are depicted (Furniture 1C4). Desensitization therapy consisted of regular monthly high-dose intravenous immunoglobulin (IVIG) (2 gm/kg), rituximab (375 mg/m2) after four doses of IVIG, and plasmapheresis followed by bortezomib at 1.3 mg/m2 in one patient who did not respond to IVIG and rituximab. Immunosuppression was anti-thymocyte globulin induction, IVIG (2 gm/kg) at the time of transplant followed by another dose three weeks post-transplant, and mycophenolate mofetil (MMF), tacrolimus, and prednisone for maintenance immunosuppression. The individuals and their incompatible donors were entered into the National Kidney Registry (NKR). Table 1 Patient demographics DSA against Cw6. His protocol 3-month kidney biopsy showed borderline acute cellular rejection (C4d bad) treated with prednisone. He remains with superb graft function 22 weeks post-transplant (Table 4). Open in a separate window Number 1 Effect of intravenous immunoglobulin (IVIG) and bortezomib within the donor specific antibodies (DSA) in both the original meant donor (reddish) and the KPD donor (green) in Cloxacillin sodium case 3. Case 4 The patient is definitely a 33-year-old female with ESRD secondary to cortical necrosis after meningococcal sepsis (Table 1). She received a pediatric en bloc deceased donor kidney transplant in 1999. She experienced acute cellular rejection in 2001 and vesiculoureteral reflux requiring ureter reimplantation. She underwent transplant nephrectomy 2002 at which time she returned to dialysis. In 2009 2009 her mother (54 years-old, blood type O) arrived forward like a potential donor. Their FXM was positive: T-cell 399 MCS and B-cell 361 MCS. She started regular monthly IVIG infusions.