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1. Discrepant subtyping of blood type A2 living kidney donors: Missed opportunities in kidney transplantation

Author

Garg, Neetika, Warnke, Leza, Redfield, Robert R, Miller, Karen M, Cooper, Matthew, Roll, Garrett R, Chipman, Valerie, Thomas, Alvin, Leeser, David, Waterman, Amy D, and Mandelbrot, Didier A

Subjects
Kidney Disease, Transplantation, Organ Transplantation, Clinical Research, Renal and urogenital, Blood Grouping and Crossmatching, Humans, Kidney, Kidney Transplantation, Living Donors, Tissue and Organ Procurement, A2 subtyping, disparities, genotyping, living donor transplantation, Clinical Sciences, Surgery
Abstract

BackgroundDespite the institution of a new Kidney Allocation System in 2014, A2/A2B to B transplantation has not increased as expected. The current Organ Procurement and Transplantation Network policy requires subtyping on two separate occasions, and in the setting of discrepant results, defaulting to the A1 subtype. However, there is significant inherent variability in the serologic assays used for blood group subtyping and genotyping is rarely done.MethodsThe National Kidney Registry, a kidney paired donation (KPD) program, performs serological typing on all A/AB donors, and in cases of non-A1/non-A1B donors, confirmatory genotyping is performed.ResultsBetween 2/18/2018 and 9/15/2020, 13.0% (145) of 1,111 type A donors registered with the NKR were ultimately subtyped as A2 via genotyping. Notably, 49.6% (72) of these were subtyped as A1 at their donor center, and in accordance with OPTN policy, ineligible for allocation as A2.ConclusionInaccurate A2 subtyping represents a significant lost opportunity in transplantation, especially in KPD where A2 donors can not only facilitate living donor transplantation for O and highly sensitized candidates, but can also facilitate additional living donor transplants. This study highlights the need for improved accuracy of subtyping technique, and the need for policy changes encouraging optimal utilization of A2 donor kidneys.

Published
2021

2. Voucher-Based Kidney Donation and Redemption for Future Transplant

Author

Veale, Jeffrey L, Nassiri, Nima, Capron, Alexander M, Danovitch, Gabriel M, Gritsch, H Albin, Cooper, Matthew, Redfield, Robert R, Kennealey, Peter T, and Kapur, Sandip

Subjects
Clinical Research, Organ Transplantation, Kidney Disease, Transplantation, Renal and urogenital, Altruism, Directed Tissue Donation, Family, Female, Humans, Kidney Transplantation, Living Donors, Male, Registries, United States, Waiting Lists
Abstract

ImportancePolicy makers, transplant professionals, and patient organizations agree that there is a need to increase the number of kidney transplants by facilitating living donation. Vouchers for future transplant provide a means of overcoming the chronological incompatibility that occurs when the ideal time for living donation differs from the time at which the intended recipient actually needs a transplant. However, uncertainty remains regarding the actual change in the number of living kidney donors associated with voucher programs and the capability of voucher redemptions to produce timely transplants.ObjectiveTo examine the consequences of voucher-based kidney donation and the capability of voucher redemptions to provide timely kidney allografts.Design, setting, and participantsThis multicenter cohort study of 79 transplant centers across the US used data from the National Kidney Registry from January 1, 2014, to January 31, 2021, to identify all family vouchers and patterns in downstream kidney-paired donations. The analysis included living kidney donors and recipients participating in the National Kidney Registry family voucher program.ExposuresA voucher was provided to the intended recipient at the time of donation. Vouchers had no cash value and could not be sold, bartered, or transferred to another person. When a voucher was redeemed, a living donation chain was used to return a kidney to the voucher holder.Main outcomes and measuresDeidentified demographic and clinical data from each kidney donation were evaluated, including the downstream patterns in kidney-paired donation. Voucher redemptions were separately evaluated and analyzed.ResultsBetween 2014 and 2021, 250 family voucher-based donations were facilitated. Each donation precipitated a transplant chain with a mean (SD) length of 2.3 (1.6) downstream kidney transplants, facilitating 573 total transplants. Of those, 111 transplants (19.4%) were performed in highly sensitized recipients. Among 250 voucher donors, the median age was 46 years (range, 19-78 years), and 157 donors (62.8%) were female, 241 (96.4%) were White, and 104 (41.6%) had blood type O. Over a 7-year period, the waiting time for those in the National Kidney Registry exchange pool decreased by more than 3 months. Six vouchers were redeemed, and 3 of those redemptions were among individuals with blood type O. The time from voucher redemption to kidney transplant ranged from 36 to 155 days.Conclusions and relevanceIn this study, the family voucher program appeared to mitigate a major disincentive to living kidney donation, namely the reluctance to donate a kidney in the present that could be redeemed in the future if needed. The program facilitated kidney donations that may not otherwise have occurred. All 6 of the redeemed vouchers produced timely kidney transplants, indicating the capability of the voucher program.

Published
2021

3. Safety, pharmacokinetics, and pharmacodynamic activity of obinutuzumab, a type 2 anti-CD20 monoclonal antibody for the desensitization of candidates for renal transplant

Author

Redfield, Robert R, Jordan, Stanley C, Busque, Stephan, Vincenti, Flavio, Woodle, E Steve, Desai, Niraj, Reed, Elaine F, Tremblay, Simon, Zachary, Andrea A, Vo, Ashley A, Formica, Richard, Schindler, Thomas, Tran, Ha, Looney, Caroline, Jamois, Candice, Green, Cherie, Morimoto, Alyssa, Rajwanshi, Richa, Schroeder, Aaron, Cascino, Matthew D, Brunetta, Paul, and Borie, Dominic

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Kidney Disease, Patient Safety, Clinical Research, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, 6.2 Cellular and gene therapies, Renal and urogenital, Adolescent, Adult, Aged, Antibodies, Monoclonal, Humanized, Antigens, CD20, Antineoplastic Agents, Immunological, Cohort Studies, Desensitization, Immunologic, Female, Follow-Up Studies, Graft Survival, HLA Antigens, Humans, Kidney Failure, Chronic, Kidney Transplantation, Male, Maximum Tolerated Dose, Middle Aged, Patient Selection, Prognosis, Risk Factors, Tissue Distribution, Young Adult, alloantibody, B cell biology, clinical research, practice, clinical trial, immunosuppressant - fusion proteins and monoclonal antibodies, B cell specific, immunosuppression, immune modulation, kidney transplantation, nephrology, pharmacology, clinical research/practice, immunosuppressant - fusion proteins and monoclonal antibodies: B cell specific, immunosuppression/immune modulation, kidney transplantation/nephrology, Medical and Health Sciences, Surgery, Clinical sciences
Abstract

The limited effectiveness of rituximab plus intravenous immunoglobulin (IVIG) in desensitization may be due to incomplete B cell depletion. Obinutuzumab is a type 2 anti-CD20 antibody that induces increased B cell depletion relative to rituximab and may therefore be more effective for desensitization. This open-label phase 1b study assessed the safety, pharmacokinetics, and pharmacodynamics of obinutuzumab in highly sensitized patients with end-stage renal disease. Patients received 1 (day 1, n = 5) or 2 (days 1 and 15; n = 20) infusions of 1000-mg obinutuzumab followed by 2 doses of IVIG on days 22 and 43. Eleven patients received additional obinutuzumab doses at the time of transplant and/or at week 24. The median follow-up duration was 9.4 months. Obinutuzumab was well tolerated, and most adverse events were grade 1-2 in severity. There were 11 serious adverse events (SAEs) in 9 patients (36%); 10 of these SAEs were infections and 4 occurred after kidney transplant. Obinutuzumab plus IVIG resulted in profound peripheral B cell depletion and appeared to reduce B cells in retroperitoneal lymph nodes. Reductions in anti-HLA antibodies, number of unacceptable antigens, and the calculated panel reactive antibody score as centrally assessed using single-antigen bead assay were limited and not clinically meaningful for most patients (NCT02586051).

Published
2019

5. First World Consensus Conference on pancreas transplantation: Part II – recommendations

Author

Boggi, Ugo, Vistoli, Fabio, Andres, Axel, Arbogast, Helmut P., Badet, Lionel, Baronti, Walter, Bartlett, Stephen T., Benedetti, Enrico, Branchereau, Julien, Burke, George W., 3rd, Buron, Fanny, Caldara, Rossana, Cardillo, Massimo, Casanova, Daniel, Cipriani, Federica, Cooper, Matthew, Cupisti, Adamasco, Davide, Josè, Drachenberg, Cinthia, de Koning, Eelco J.P., Ettorre, Giuseppe Maria, Fernandez Cruz, Laureano, Fridell, Jonathan A., Friend, Peter J., Furian, Lucrezia, Gaber, Osama A., Gruessner, Angelika C., Gruessner, Rainer W.G., Gunton, Jenny E., Han, Duck-Jong, Iacopi, Sara, Kauffmann, Emanuele Federico, Kaufman, Dixon, Kenmochi, Takashi, Khambalia, Hussein A., Lai, Quirino, Langer, Robert M., Maffi, Paola, Marselli, Lorella, Menichetti, Francesco, Miccoli, Mario, Mittal, Shruti, Morelon, Emmanuel, Napoli, Niccolò, Neri, Flavia, Oberholzer, Jose, Odorico, Jon S., Öllinger, Robert, Oniscu, Gabriel, Orlando, Giuseppe, Ortenzi, Monica, Perosa, Marcelo, Perrone, Vittorio Grazio, Pleass, Henry, Redfield, Robert R., Ricci, Claudio, Rigotti, Paolo, Paul Robertson, R., Ross, Lainie F., Rossi, Massimo, Saudek, Frantisek, Scalea, Joseph R., Schenker, Peter, Secchi, Antonio, Socci, Carlo, Sousa Silva, Donzilia, Squifflet, Jean Paul, Stock, Peter G., Stratta, Robert J., Terrenzio, Chiara, Uva, Pablo, Watson, Christopher J.E., White, Steven A., Marchetti, Piero, Kandaswamy, Raja, and Berney, Thierry

Published
2021
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8. Kidney transplantation of highly sensitized recipients under the new kidney allocation system: A reflection from five different transplant centers across the United States

Author

Parsons, Ronald F, Locke, Jayme E, Redfield, Robert R, Roll, Garrett R, and Levine, Matthew H

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Organ Transplantation, Transplantation, Kidney Disease, Renal and urogenital, Blood Grouping and Crossmatching, Cost-Benefit Analysis, Government Regulation, HLA Antigens, Histocompatibility Testing, Humans, Immunization, Isoantibodies, Kidney Transplantation, Tissue Donors, Tissue and Organ Procurement, Transplant Recipients, Treatment Outcome, United States, Waiting Lists, Crossmatch, Allocation, Kidney transplantation, HLA, Sensitization, Immunology
Abstract

Deceased donor kidney allocation was reorganized in the United States to address several problems, including the highly sensitized patients disadvantaged with large, diverse repertoires of antibodies. Here, five transplant surgeons review their center's experience with the new allocation changes: highlighting areas of accomplishment, opportunities for improvement and, in some cases, stark differences in practice. Across these five centers the highly sensitized patients (CPRA ⩾98%) range from 5.5 to 9.2% of the 12,364 candidates on their collective waitlist. All centers reported greater rates of kidney transplantations in highly sensitized patients (12.4-27%). Three of the programs (Emory, UCSF, UW) relied upon the virtual crossmatch prior to organ acceptance in a majority of cases (70-86%)-the mere presence of antibody on HLA antibody screen was sufficient to exclude the donor in most cases at Emory and UCSF. Penn and UAB relied upon the physical flow crossmatch in almost all cases prior to proceeding with transplantation. Current or historical donor-specific antibody was occasionally crossed in certain cases at UW and UAB necessitating IVIG/plasmapheresis and/or B cell depletion perioperatively. Some authors raised concerns for cost efficiency given the increased need for organ/specimen transportation, and extensive use of hospital resources and ancillary services. In general, we found that the new allocation system has successfully achieved one of its primary goals-increased kidney transplantation in the disadvantaged, highly sensitized patients; the long-term outcomes in all patients and the cost ramifications of these changes will require continued reassessment and clarification.

Published
2017

13. Targeting host nucleotide biosynthesis with resveratrol inhibits emtricitabine-resistant HIV-1

Author

Heredia, Alonso, Davis, Charles, Amin, Mohammed N, Le, Nhut M, Wainberg, Mark A, Oliveira, Maureen, Deeks, Steven G, Wang, Lai-Xi, and Redfield, Robert R

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Infectious Diseases, HIV/AIDS, Genetics, Complementary and Integrative Health, Sexually Transmitted Infections, Infection, Anti-HIV Agents, Cells, Cultured, Deoxycytidine, Drug Resistance, Viral, Emtricitabine, Enzyme-Linked Immunosorbent Assay, HIV Core Protein p24, HIV Reverse Transcriptase, HIV-1, Humans, Lymphocytes, Mutation, Missense, Real-Time Polymerase Chain Reaction, Resveratrol, Stilbenes, Virus Replication, antiretroviral therapy, cytosine analogs, drug resistance, emtricitabine, M184V mutation, nucleoside analog reverse transcriptase inhibitors, resource-limited setting, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Virology, Biomedical and clinical sciences, Health sciences
Abstract

ObjectiveThe M184V mutation in the HIV-1 reverse transcriptase gene is frequent (>50%) in patients, both in resource-rich and resource-limited countries, conferring high-level resistance (>100-fold) to the cytosine analog reverse transcriptase inhibitors lamivudine and emtricitabine. The reverse transcriptase enzyme of M184V HIV-1 mutants has reduced processivity, resulting in reduced viral replication, particularly at low deoxynucleotide (dNTP) levels. We hypothesized that lowering intracellular dNTPs with resveratrol, a dietary supplement, could interfere with replication of M184V HIV-1 mutants.Design and methodsEvaluation of the activity of resveratrol on infection of primary peripheral blood lymphocytes by wild-type and M184V mutant HIV-1. We assayed both molecular clones and primary isolates of HIV-1, containing M184V alone and in combination with other reverse transcriptase mutations. Viral infection was quantified by p24 ELISA and by quantitative real-time PCR analysis. Cell viability was measured by colorimetric 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assays.ResultsIn virus-infectivity assays, resveratrol did not inhibit replication of wild-type NL4-3 (resveratrol EC50 > 10 μmol/l), but it inhibited NL4-3 184V mutant (resveratrol EC50 = 5.8 μmol/l). These results were confirmed by real-time PCR analysis of early and late products of reverse transcription. Resveratrol inhibited molecular clones and primary isolates carrying M184V, alone or in combination with other reverse transcriptase mutations (resveratrol EC50 values ranging from 2.5 to 7.7 μmol/l).ConclusionsResveratrol inhibits HIV-1 strains carrying the M184V mutation in reverse transcriptase. We propose resveratrol as a potential adjuvant in HIV-1 therapy, particularly in resource-limited settings, to help control emtricitabine-resistant M184V HIV-1 mutants.

Published
2014

20. Implementation of HIV Palliative Care: Interprofessional Education to Improve Patient Outcomes in Resource-Constrained Settings, 2004–2012

Author

Delva, Guesley, Edozien, Anthony, Hachaambwa, Lotte, Maro, Peter, Nwandu, Anthea, Nwizu, Chidi, Obiefune, Michael, Oni, Babatunji, Patel, Devang, Sheneberger, Robert, Baribwira, Cyprien, Kiromera, Athanase, Tepper, Vicki, Oyebola, Folaju Olusegun, Kaiza-Kangalawe, Angela, Anthony Loy, George, Enejoh, Victor, Nwene, Ejike, Stanis-Ezeobi, Winifred, Shimabale, Mope, Gashongore, Ignace, Etienne-Mesubi, Martine, Alexander, Carla S., Pappas, Gregory, Amoroso, Anthony, Lee, Mei Ching, Brown-Henley, Yvonne, Memiah, Peter, O'Neill, Joseph F., Dix, Olivia, and Redfield, Robert R.

Published
2015
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32. Antiviral Activity of Single-Dose PRO 140, a CCR5 Monoclonal Antibody, in HIV-Infected Adults

Author

Jacobson, Jeffrey M., Saag, Michael S., Thompson, Melanie A., Fischl, Margaret A., Liporace, Ralph, Reichman, Richard C., Redfield, Robert R., Fichtenbaum, Carl J., Zingman, Barry S., Patel, Mahesh C., Murga, Jose D., Pemrick, Suzanne M., D'Ambrosio, Paul, Michael, Marti, Kroger, Hans, Ly, Hieu, Rotshteyn, Yakov, Buice, Robert, Morris, Stephen A., Stavola, Joseph J., Maddon, Paul J., Kremer, Alton B., and Olson, William C.

Published
2008
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39. Efficacy Testing of Recombinant Human Immunodeficiency Virus (HIV) gp160 as a Therapeutic Vaccine in Early-Stage HIV-1-Infected Volunteers

Author

rgp160 Phase II Vaccine Investigators, Birx, Deborah L., Loomis-Price, Lawrence D., Aronson, Naomi, Brundage, John, Davis, Charles, Deyton, Lawrence, Garner, Robin, Gordin, Fred, Henry, David, Holloway, William, Kerkering, Thomas, Luskin-Hawk, Roberta, McNeil, John, Michael, Nelson, Pierce, Phillip Foster, Poretz, Donald, Ratto-Kim, Silvia, Renzullo, Phil, Ruiz, Nancy, Sitz, Karl, Smith, Gale, Tacket, Carol, Thompson, Melanie, Tramont, Edmond, Yangco, Bienvenido, Yarrish, Robert, and Redfield, Robert R.

Published
2000

46. Early detection of SARS‐CoV‐2 and other infections in solid organ transplant recipients and household members using wearable devices

Author

Keating, Brendan J., primary, Mukhtar, Eyas H., additional, Elftmann, Eric D., additional, Eweje, Feyisope R., additional, Gao, Hui, additional, Ibrahim, Lina I., additional, Kathawate, Ranganath G., additional, Lee, Alexander C., additional, Li, Eric H., additional, Moore, Krista A., additional, Nair, Nikhil, additional, Chaluvadi, Venkata, additional, Reason, Janaiya, additional, Zanoni, Francesca, additional, Honkala, Alexander T., additional, Al‐Ali, Amein K., additional, Abdullah Alrubaish, Fatima, additional, Ahmad Al‐Mozaini, Maha, additional, Al‐Muhanna, Fahad A., additional, Al‐Romaih, Khaldoun, additional, Goldfarb, Samuel B., additional, Kellogg, Ryan, additional, Kiryluk, Krzysztof, additional, Kizilbash, Sarah J., additional, Kohut, Taisa J., additional, Kumar, Juhi, additional, O'Connor, Matthew J., additional, Rand, Elizabeth B., additional, Redfield, Robert R., additional, Rolnik, Benjamin, additional, Rossano, Joseph, additional, Sanchez, Pablo G., additional, Alavi, Arash, additional, Bahmani, Amir, additional, Bogu, Gireesh K., additional, Brooks, Andrew W., additional, Metwally, Ahmed A, additional, Mishra, Tejas, additional, Marks, Stephen D., additional, Montgomery, Robert A., additional, Fishman, Jay A., additional, Amaral, Sandra, additional, Jacobson, Pamala A., additional, Wang, Meng, additional, and Snyder, Michael P., additional

Published
2021
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47. Induction and Donor Specific Antibodies in Low Immunologic Risk Kidney Transplant Recipients

Author

Bath, Natalie M., primary, Djamali, Arjang, additional, Parajuli, Sandesh, additional, Mandelbrot, Didier, additional, Leverson, Glen, additional, Hidalgo, Luis, additional, Ellis, Thomas, additional, Descourouez, Jillian L., additional, Jorgenson, Margaret R., additional, Hager, Dave, additional, Kaufman, Dixon B., additional, and Redfield, Robert R., additional

Published
2020
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48. Incidence of pancreatitis in HIV-1-infected individuals enrolled in 20 adult AIDS clinical trials group studies: Lessons learned

Author

Reisler, Ronald B., Murphy, Robert L., Redfield, Robert R., and Parker, Robert A.

Subjects
HIV patients -- Health aspects, Pancreatitis -- Drug therapy, Antiviral agents -- Dosage and administration, Health
Abstract

A report on the incidence of clinical and laboratory defined pancreatitis in HIV-1-infected individuals treated with antiretrovirals (ARVs) is presented. The principal findings are that the combination of nucleoside reverse transcriptase inhibitors (NRTIs) selected and the pancreatitis definition chosen seem to have an impact on the incidence of pancreatitis.

Published
2005

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