Identification of novel HLA alleles discovered in 2022-2023.

In this paper, we describe 10 novel HLA alleles discovered, submitted and officially named in the calendar years 2022 through the end of 2023.

Improving Outcomes after Allograft Nephrectomy through Use of Preoperative Angiographic Kidney Embolization.

BACKGROUND: Allograft nephrectomy (AN) has been associated with considerable perioperative morbidity. We aimed to determine if preoperative angiographic kidney embolization (PAKE) to induce graft thrombosis before AN improves outcomes. STUDY DESIGN: We reviewed adult kidney transplant alone patients who underwent AN at a single center from 2002 to 2020 and compared perioperative outcomes for patients with and without PAKE. RESULTS: Eighty patients underwent AN, including 54 (67.5%) with PAKE before AN and 26 (32.5%) with AN alone. PAKE was associated with significantly reduced blood loss (PAKE: mean 266 ± 292 mL vs AN alone: 495 ± 689 mL; p = 0.04) and reduced transfusion requirements (PAKE: mean 0.5 ± 0.8 packed red blood cell units vs AN alone: 1.6 ± 2.6 units; p = 0.004) despite similar preoperative hemoglobin levels. Mean operating time (PAKE: 142 ± 43 minutes vs AN alone: 202 ± 111 minutes; p = 0.001) and length of hospital stay (PAKE: 4.3 ± 2.0 days vs AN alone: 9.3 ± 9.4 days; p = 0.0003) also favored PAKE, as did the surgical complication rate (PAKE: 6/54 [11%] vs AN alone: 9/26 [35%], p = 0.02). Long-term patient survival after AN was comparable in both groups. CONCLUSIONS: PAKE was associated with lower intraoperative blood loss, fewer transfusions, reduced operating time, shorter length of stay, and fewer surgical complications compared with AN alone at our center.

Identification of novel HLA alleles discovered in 2019-2021.

In this paper, we describe 15 novel HLA alleles discovered and officially named in the calendar years 2019 through the first half of 2021.

NGS and HLA: The long road ahead.

This manuscript is a continuation of this laboratory's journey to identifying novel HLA alleles while performing routine clinical HLA laboratory testing. Since our last paper, we have identified an additional 28 novel HLA alleles that are identified and described herein. One novel allele was found in two unrelated patients that were HLA typed for different reasons at two different times, suggesting that novel alleles may be much more frequent than previously expected. If the rate of identification is hindered by bioinformatics challenges, there is a great potential for our patients to suffer needlessly from incomplete information in either diagnostics or unrecognized incompatibilities with potential donors.

New HLA alleles discovered by next generation sequencing in routine histocompatibility lab work in a medium-volume laboratory.

The immunogenetics research and clinical communities are undergoing a revolution in the way that Human Leukocyte Antigens (HLA) alleles are typed, thanks to the introduction and increasing acceptance of next-generation sequencing into laboratory practice. With the ability to sequence all exons of each allele, instead of the previously routine typing of exons 2 and 3 of class I and exon 2 of class II, the sequencing of previously unsequenced areas of HLA alleles is causing a host of new alleles to be discovered through the course of routine laboratory testing. In the first 4 months of routine next generation sequencing, we have identified 10 novel alleles that have been discovered through laboratory testing for all facets of HLA typing, i.e. solid organ transplantation, hematopoietic stem cell transplantation, disease association typing and pharmacogenomics testing. The advent of NGS HLA typing in routine clinical practice, and the concomitant routine typing of exons outside the norm, opens the window for rapid discovery of new HLA alleles and a potential for overwhelming the current HLA nomenclature naming conventions.

Optimal use of older donors and recipients in kidney transplantation.

BACKGROUND: The aging donor and recipient population have led to new challenges in kidney transplantation. The purpose of this study was to review retrospectively our single center experience in deceased-donor kidney transplantation, with respect to donor and recipient age. METHODS: From October 1, 2001, through February 20, 2004, we performed 144 deceased-donor kidney transplantations, which included 37 procedures (26%) in recipients > or =60 years old and 107 procedures (74%) in recipients 19 to 59 years old. The deceased-donor pool included 57 expanded criteria donors (ECD) and 87 standard criteria donors (defined as not ECD). ECD kidneys were used by matching estimated renal functional mass to recipient size (body mass index, <25 kg/m(2)), which included the use of dual kidney transplantations (n = 9). ECD kidney recipients were further selected on the basis of age >40 years and low immunologic risk. Recipients received rabbit antithymocyte globulin or alemtuzumab induction in combination with tacrolimus, mycophenolate mofetil, and steroids. RESULTS: The mean age differed between recipient groups (65 vs 46 years; P < .001). In recipients > or =60 years old, 23 recipients (62%) received kidney transplants from ECDs compared with 34 kidney transplants from ECDs (32%; P < .001) in recipients who were <60 years old. Patient survival was 89% in recipients who were > or =60 years old, compared with 95% in recipients who were <60 years old (P = .11), with a mean follow-up time of 27 months. Kidney graft survival rates were 84% in both recipient groups. Initial and subsequent graft function, rejection, infection, reoperation, length of stay, readmission, and resource use were similar among groups. CONCLUSION: By the matching of nephron mass with recipient size and avoiding the use of ECD kidneys in recipients with a high immunologic risk, short-term outcomes that are comparable with standard criteria donor kidneys in younger patients can be achieved with either older donors or recipients, regardless of age.

Intermediate-term outcomes with expanded criteria deceased donors in kidney transplantation: a spectrum or specter of quality?

OBJECTIVE: To compare intermediate-term outcomes in adult recipients of expanded criteria (ECD) versus concurrent standard criteria (SCD) deceased donor kidney transplants at a single center using a standardized approach. SUMMARY BACKGROUND DATA: Expanded criteria donors (ECDs) are a source of kidneys that increase the donor organ pool, but the value of transplanting these kidneys has been questioned because of concerns regarding diminished survival and predicted poorer intermediate-term outcomes. METHODS: Over a 47-month period, we performed 244 deceased donor kidney transplants into adult recipients, including 143 from SCDs and 101 from ECDs. Management algorithms were implemented to preserve nephron function, and recipient selection for an ECD kidney transplant was based on low immunologic risk. All patients received depleting antibody induction in combination with tacrolimus and mycophenolate mofetil. A total of 188 patients (77%) had at least a 1-year follow-up. RESULTS: ECDs were older, had a higher BMI, had an increased incidence of cerebrovascular brain death and preexisting donor hypertension, and had a lower estimated creatinine clearance (CrCl, all P < 0.01) compared with SCDs. Cold ischemic times were similar between groups, but more ECD kidneys were preserved with pulsatile perfusion (P < 0.01). ECD kidney recipients were older, less sensitized, had a lower BMI, had fewer 0-antigen mismatches, and had a shorter waiting time (all P < 0.01) compared with SCD kidney recipients. Actual patient (93%) and kidney graft (83%) survival rates were similar between groups with a mean follow-up of 24 months. The rates of delayed graft function (DGF), acute rejection, readmissions, operative complications, major infections, and resource utilization were comparable between groups. Renal function followed longitudinally was consistently better in SCD patients (P < 0.05). Black recipients had higher rates of DGF, acute rejection, and graft loss (P < 0.05), but the effects were less pronounced in the ECD group. CONCLUSIONS: By appropriate donor and recipient profiling and the use of management algorithms to project and protect renal function, excellent intermediate-term outcomes can be achieved with ECD kidney transplants that are comparable to SCD kidney transplants.

Human leukocyte antigen sensitization after structural cortical allograft implantations.

UNLABELLED: The incidence and significance of a donor-specific human leukocyte antigen antibody response to massive fresh-frozen human bone allograft implantation is not established. This study was a prospective, multicenter study of a cohort of consecutive patients who self-randomized themselves into two groups based on their alloantibody response to allograft bone transplant. The study hypothesis was that donor-directed antibodies are an independent risk factor influencing incorporation of massive frozen bone allografts. Pretransplant and posttransplant human leukocyte antigen alloantibody analysis was performed and correlated to determine pre-existing and graft-induced antibodies. The surgical outcomes of the two groups of patients were compared to determine the relationship between alloantibody response and bone graft incorporation. Preliminary results revealed that donor-specific human leukocyte antigen sensitization occurred in 17 of 32 (53%) of previously nonsensitized patients. A survival analysis of time to healing based on human leukocyte antigen status showed no evidence of an association between human leukocyte antigen status and time to healing. Longer followup in additional patients will be required to determine if this sensitization is correlated with an alteration in the time to union or with the quality or type of bone graft incorporation. LEVEL OF EVIDENCE: Therapeutic study, Level II. See the Guidelines for Authors for a complete description of levels of evidence.

Kidney and pancreas transplantation at Wake Forest University Baptist Medical Center.

More than 1,100 transplants have been performed at WFUBMC, including 60 pediatric transplants and 40 pancreas transplants. The one-year living donor kidney graft survival rate exceeds 90% and the 2 year deceased donor kidney graft survival rate exceeds 80%. The current active waiting list includes more than 300 candidates. Despite more transplants being performed, we continue to under-serve our referral area, which has among the highest rates of hypertension, diabetes, and end stage renal disease in the country. The AOTP has experienced a period of rapid growth over the past 2 years based upon sharing of zero HLA antigen-mismatched kidneys, use of ECD kidneys, liberalization of donor and recipient selection criteria, and the continued development of the pancreas transplant and laparoscopic donor nephrectomy programs. The pancreas transplant program will continue to grow as the waiting list enlarges and matures, with a 200% increase in activity expected within the next few years. The LDKT program will expand as more emphasis is placed on our pretransplant practice, including the more liberal application of laparoscopic donor nephrectomy, which has now become a standard procedure at our WFUBMC is involved in a number of clinical research projects studying new immunosuppressive agents and regimens. In this chapter, we have presented our recent experience with KTX in the elderly, ECD kidneys, alternate day Thymoglobulin administration, valganciclovir prophylaxis, SRL conversion using daclizumab bridge therapy, and pancreas transplantation with portal-enteric drainage. We plan to initiate a number of new protocols in the immediate future, including desensitization of the highly sensitized patient, ABO incompatible transplantation, transplantation of the HIV-positive patient, steroid withdrawal and avoidance regimens, living kidney donation from the anonymous altruistic donor, paired kidney exchanges from living donors, and islet transplantation. WFUBMC remains the most active donor hospital in North Carolina, and a non-heart beating donor protocol has been successfully initiated at our facility. Although much has been accomplished, a number of challenges remain. We look forward to building on our accomplishments, confronting the challenges, and achieving a level of excellence that could only be attained by mutual commitment from a dedicated, multidisciplinary team.