86 results on '"Riella, Leonardo V"'
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2. The Banff 2022 Kidney Meeting Work Plan: Data-driven refinement of the Banff Classification for renal allografts
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Roufosse, Candice, Naesens, Maarten, Haas, Mark, Lefaucheur, Carmen, Mannon, Roslyn B., Afrouzian, Marjan, Alachkar, Nada, Aubert, Olivier, Bagnasco, Serena M., Batal, Ibrahim, Bellamy, Chris O.C., Broecker, Verena, Budde, Klemens, Clahsen-Van Groningen, Marian, Coley, Shana M., Cornell, Lynn D., Dadhania, Darshana, Demetris, Anthony J., Einecke, Gunilla, Farris, Alton B., Fogo, Agnes B., Friedewald, John, Gibson, Ian W., Horsfield, Catherine, Huang, Edmund, Husain, Syed A., Jackson, Annette M., Kers, Jesper, Kikić, Željko, Klein, Amanda, Kozakowski, Nicolas, Liapis, Helen, Mangiola, Massima, Montgomery, Robert A., Nankinvell, Brian, Neil, Desley A.H., Nickerson, Peter, Rabant, Marion, Randhawa, Parmjeet, Riella, Leonardo V., Rosales, Ivy, Royal, Virginie, Sapir-Pichhadze, Ruth, Sarder, Pinaki, Sarwal, Minnie, Schinstock, Carrie, Stegall, Mark, Solez, Kim, van der Laak, Jeroen, Wiebe, Chris, Colvin, Robert B., Loupy, Alexandre, and Mengel, Michael
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The XVIth Banff Meeting for Allograft Pathology was held in Banff, Alberta, Canada, from September 19 to 23, 2022, as a joint meeting with the Canadian Society of Transplantation. In addition to a key focus on the impact of microvascular inflammation and biopsy-based transcript analysis on the Banff Classification, further sessions were devoted to other aspects of kidney transplant pathology, in particular T cell–mediated rejection, activity and chronicity indices, digital pathology, xenotransplantation, clinical trials, and surrogate endpoints. Although the output of these sessions has not led to any changes in the classification, the key role of Banff Working Groups in phrasing unanswered questions, and coordinating and disseminating results of investigations addressing these unanswered questions was emphasized. This paper summarizes the key Banff Meeting 2022 sessions not covered in the Banff Kidney Meeting 2022 Report paper and also provides an update on other Banff Working Group activities relevant to kidney allografts.
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- 2024
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3. The Banff 2022 Kidney Meeting Report: Reappraisal of microvascular inflammation and the role of biopsy-based transcript diagnostics
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Naesens, Maarten, Roufosse, Candice, Haas, Mark, Lefaucheur, Carmen, Mannon, Roslyn B., Adam, Benjamin A., Aubert, Olivier, Böhmig, Georg A., Callemeyn, Jasper, Clahsen-van Groningen, Marian, Cornell, Lynn D., Demetris, Anthony J., Drachenberg, Cinthia B., Einecke, Gunilla, Fogo, Agnes B., Gibson, Ian W., Halloran, Philip, Hidalgo, Luis G., Horsfield, Catherine, Huang, Edmund, Kikić, Željko, Kozakowski, Nicolas, Nankivell, Brian, Rabant, Marion, Randhawa, Parmjeet, Riella, Leonardo V., Sapir-Pichhadze, Ruth, Schinstock, Carrie, Solez, Kim, Tambur, Anat R., Thaunat, Olivier, Wiebe, Chris, Zielinski, Dina, Colvin, Robert, Loupy, Alexandre, and Mengel, Michael
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The XVI-th Banff Meeting for Allograft Pathology was held at Banff, Alberta, Canada, from 19th to 23rd September 2022, as a joint meeting with the Canadian Society of Transplantation. To mark the 30th anniversary of the first Banff Classification, premeeting discussions were held on the past, present, and future of the Banff Classification. This report is a summary of the meeting highlights that were most important in terms of their effect on the Classification, including discussions around microvascular inflammation and biopsy-based transcript analysis for diagnosis. In a postmeeting survey, agreement was reached on the delineation of the following phenotypes: (1) "Probable antibody-mediated rejection (AMR)," which represents donor-specific antibodies (DSA)-positive cases with some histologic features of AMR but below current thresholds for a definitive AMR diagnosis; and (2) "Microvascular inflammation, DSA-negative and C4d-negative," a phenotype of unclear cause requiring further study, which represents cases with microvascular inflammation not explained by DSA. Although biopsy-based transcript diagnostics are considered promising and remain an integral part of the Banff Classification (limited to diagnosis of AMR), further work needs to be done to agree on the exact classifiers, thresholds, and clinical context of use.
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- 2024
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4. Antibody Responses Against Emerging SARS-CoV-2 Omicron Lineages After the Fourth Dose of mRNA Vaccine in Kidney Transplant Recipients
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Al Jurdi, Ayman, Gassen, Rodrigo B., Borges, Thiago J., Lape, Isadora T., Morena, Leela, Hullekes, Frank, Efe, Orhan, Kotton, Camille N., and Riella, Leonardo V.
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- 2023
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5. Kidney organoids: a pioneering model for kidney diseases.
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Tekguc, MURAT, GAAL, RONALD C. VAN, UZEL, SEBASTIEN G.M., GUPTA, NAVIN, RIELLA, LEONARDO V., LEWIS, JENNIFER A., and MORIZANE, RYUJI
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The kidney is a vital organ that regulates the bodily fluid and electrolyte homeostasis via tailored urinary excretion. Kidney injuries that cause severe or progressive chronic kidney disease have driven the growing population of patients with end-stage kidney disease, leading to substantial patient morbidity and mortality. This irreversible kidney damage has also created a huge socioeconomical burden on the healthcare system, highlighting the need for novel translational research models for progressive kidney diseases. Conventional research methods such as in vitro 2D cell culture or animal models do not fully recapitulate complex human kidney diseases. By contrast, directed differentiation of human induced pluripotent stem cells enables in vitro generation of patient-specific 3D kidney organoids, which can be used to model acute or chronic forms of hereditary, developmental, and metabolic kidney diseases. Furthermore, when combined with biofabrication techniques, organoids can be used as building blocks to construct vascularized kidney tissues mimicking their in vivo counterpart. By applying gene editing technology, organoid building blocks may be modified to minimize the process of immune rejection in kidney transplant recipients. In the foreseeable future, the universal kidney organoids derived from HLA-edited/deleted induced pluripotent stem cell (iPSC) lines may enable the supply of bioengineered organotypic kidney structures that are immune-compatible for the majority of the world population. Here, we summarize recent advances in kidney organoid research coupled with novel technologies such as organoids-on-chip and biofabrication of 3D kidney tissues providing convenient platforms for high-throughput drug screening, disease modelling, and therapeutic applications. [ABSTRACT FROM AUTHOR]
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- 2022
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6. Recurrent complement-mediated Hemolytic uremic syndrome after kidney transplantation.
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Obata, Shota, Hullekes, Frank, Riella, Leonardo V., and Cravedi, Paolo
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Hereditary forms of hemolytic uremic syndrome (HUS), formerly known as atypical HUS, typically involve mutations in genes encoding for components of the alternative pathway of complement, therefore they are often referred to as complement-mediated HUS (cHUS). This condition has a high risk of recurrence in the transplanted kidney, leading to accelerated graft loss. The availability of anti-complement component C5 antibody eculizumab has enabled successful transplantation with a notably reduced recurrence rate and improved prognosis. Open questions are related to the potential for complement inhibitor discontinuation, ideal timing of treatment withdrawal, and patient selection based on genetic abnormalities. Our review delves into the pathophysiology, classification, genetic predispositions, and management strategies for cHUS in the native and transplant kidneys. • Patients with complement-mediated HUS (cHUS) have a high risk of recurrence in the transplanted kidney and accelerated graft loss. • The availability of anti-complement component C5 antibody eculizumab has significantly reduced the rate of recurrence and improved prognosis, allowing for successful transplantation. • Currently, it is still unclear whether complement inhibitor therapy can be safely discontinued, what the ideal timing of treatment withdrawal is, and whether genetic abnormalities can identify patients in whom withdrawal is safer. [ABSTRACT FROM AUTHOR]
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- 2024
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7. Immune checkpoint inhibitors in kidney transplantation
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Alzahrani, Nora, Al Jurdi, Ayman, and Riella, Leonardo V.
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- 2023
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8. Nephrotic-range proteinuria: a potential risk factor for failure of tixagevimab-cilgavimab prophylaxis
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Al Jurdi, Ayman, El Mouhayyar, Christopher, Efe, Orhan, Jeyabalan, Anushya, and Riella, Leonardo V.
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Background: Pre-exposure prophylaxis with tixagevimab-cilgavimab has been shown to reduce the incidence of SARS-CoV-2 infection in immunocompromised individuals. Individuals with nephrotic-range proteinuria can lose immunoglobulins such as tixagevimab-cilgavimab in the urine and, therefore, may derive less benefit from tixagevimab-cilgavimab. There are no published studies evaluating the association of nephrotic-range proteinuria with failure of tixagevimab-cilgavimab prophylaxis. Methods: We conducted a retrospective observational cohort study of all individuals at our center who received tixagevimab-cilgavimab while they had nephrotic-range proteinuria. Each individual in the nephrotic group was matched 1:3 with controls who were matched for B cell depletion therapy in addition to the total dose and date of first tixagevimab-cilgavimab administration. The primary outcome was the development of breakthrough SARS-CoV-2 infection after receiving tixagevimab-cilgavimab. Results: Sixteen patients received tixagevimab-cilgavimab between January 1st, 2022, and June 30th, 2022, at a time when they had nephrotic-range proteinuria. Proteinuria levels and serum creatinine levels were higher while serum albumin levels were lower in the nephrotic group compared to the control group. At a median follow-up of 251 days, 38% of individuals in the nephrotic group had developed breakthrough SARS-CoV-2 infections, compared to only 13% in the control group at a median follow-up of 238 days. Nephrotic-range proteinuria was associated with a higher incidence of breakthrough infection (log-rank P= 0.04). Conclusions: Nephrotic-range proteinuria may increase the risk of failure of tixagevimab-cilgavimab pre-exposure prophylaxis. Prospective studies to validate these findings and to evaluate the optimal dosing strategy of antibody-based prophylaxis in this group of patients are needed.
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- 2023
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9. Banff Human Organ Transplant Transcripts Correlate with Renal Allograft Pathology and Outcome: Importance of Capillaritis and Subpathologic Rejection
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Rosales, Ivy A., Mahowald, Grace K., Tomaszewski, Kristen, Hotta, Kiyohiko, Iwahara, Naoya, Otsuka, Takuya, Tsuji, Takahiro, Takada, Yusuke, Acheampong, Ellen, Araujo-Medina, Milagros, Bruce, Amy, Rios, Andrea, Cosimi, Anthony Benedict, Elias, Nahel, Kawai, Tatsuo, Gilligan, Hannah, Safa, Kassem, Riella, Leonardo V., Tolkoff-Rubin, Nina E., Williams, Winfred W., Smith, Rex Neal, and Colvin, Robert B.
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Microarray analysis of renal allograft biopsies has revealed important insights, including TCMR and AMR gene sets, but is limited to specially processed samples without pathology confirmation. We used the NanoString nCounter platform to perform mRNA analysis of archived formalin-fixed paraffin-embedded kidney allograft biopsies with the Banff Human Organ Transplant Panel. We correlated Banff pathology scores in the same tissue block with validated and custom gene sets and showed the importance of capillaritis. We identified subpathological transcripts that standard pathology would not have detected and transcripts, pathology, and clinical variables that predicted graft failure in TCMR and CAMR. These findings highlight the utility of archived samples in transplant pathology research and expand our understanding of the pathogenesis of rejection.
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- 2022
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10. Tixagevimab/cilgavimab pre-exposure prophylaxis is associated with lower breakthrough infection risk in vaccinated solid organ transplant recipients during the omicron wave
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Al Jurdi, Ayman, Morena, Leela, Cote, Mariesa, Bethea, Emily, Azzi, Jamil, and Riella, Leonardo V.
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The neutralizing monoclonal antibody combination of tixagevimab/cilgavimab has been shown to reduce the risk of SARS-CoV-2 infection in unvaccinated individuals during the Alpha (B.1.1.7) and Delta (B.1.617.2) waves. However, data on the efficacy and safety of tixagevimab/cilgavimab in vaccinated solid organ transplant recipients during the Omicron wave is limited. To address this, we conducted a retrospective cohort study comparing 222 solid organ transplant recipients (SOTRs) who received tixagevimab/cilgavimab for pre-exposure prophylaxis and 222 vaccine-matched solid organ transplant recipients who did not receive tixagevimab/cilgavimab. Breakthrough SARS-CoV-2 infections occurred in 11 (5%) of SOTRs who received tixagevimab/cilgavimab and in 32 (14%) of SOTRs in the control group (p< .001). In the tixagevimab/cilgavimab group, SOTRs who received the 150–150 mg dose had a higher incidence of breakthrough infections compared to those who received the 300–300 mg dose (p= .025). Adverse events were uncommon, occurring in 4% of our cohort and most were mild. There was no significant change in serum creatinine or liver chemistries in kidney and liver transplant recipients, respectively. In conclusion, we found that tixagevimab/cilgavimab use is safe and associated with a lower risk of breakthrough SARS-CoV-2 infection in vaccinated solid organ transplant recipients during the Omicron wave.
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- 2022
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11. Tixagevimab/cilgavimab pre‐exposure prophylaxis is associated with lower breakthrough infection risk in vaccinated solid organ transplant recipients during the omicron wave
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Al Jurdi, Ayman, Morena, Leela, Cote, Mariesa, Bethea, Emily, Azzi, Jamil, and Riella, Leonardo V.
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The neutralizing monoclonal antibody combination of tixagevimab/cilgavimab has been shown to reduce the risk of SARS‐CoV‐2 infection in unvaccinated individuals during the Alpha (B.1.1.7) and Delta (B.1.617.2) waves. However, data on the efficacy and safety of tixagevimab/cilgavimab in vaccinated solid organ transplant recipients during the Omicron wave is limited. To address this, we conducted a retrospective cohort study comparing 222 solid organ transplant recipients (SOTRs) who received tixagevimab/cilgavimab for pre‐exposure prophylaxis and 222 vaccine‐matched solid organ transplant recipients who did not receive tixagevimab/cilgavimab. Breakthrough SARS‐CoV‐2 infections occurred in 11 (5%) of SOTRs who received tixagevimab/cilgavimab and in 32 (14%) of SOTRs in the control group (p< .001). In the tixagevimab/cilgavimab group, SOTRs who received the 150–150 mg dose had a higher incidence of breakthrough infections compared to those who received the 300–300 mg dose (p= .025). Adverse events were uncommon, occurring in 4% of our cohort and most were mild. There was no significant change in serum creatinine or liver chemistries in kidney and liver transplant recipients, respectively. In conclusion, we found that tixagevimab/cilgavimab use is safe and associated with a lower risk of breakthrough SARS‐CoV‐2 infection in vaccinated solid organ transplant recipients during the Omicron wave. A retrospective matched cohort study shows that tixagevimab‐cilgavimab pre‐exposure prophylaxis in vaccinated solid organ transplant recipients is associated with a lower risk of breakthrough SARS‐CoV‐2 infection during the Omicron wave.
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- 2022
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12. Antibody-mediated rejection: prevention, monitoring and treatment dilemmas
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Rodriguez-Ramirez, Sonia, Al Jurdi, Ayman, Konvalinka, Ana, and Riella, Leonardo V.
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- 2022
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13. Recurrent C3 glomerulopathy after kidney transplantation.
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Obata, Shota, Vaz de Castro, Pedro A.S., Riella, Leonardo V., and Cravedi, Paolo
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The complement system is part of innate immunity and is pivotal in protecting the body against pathogens and maintaining host homeostasis. Activation of the complement system is triggered through multiple pathways, including antibody deposition, a mannan-binding lectin, or activated complement deposition. C3 glomerulopathy (C3G) is a rare glomerular disease driven by complement dysregulation with high post-transplantation recurrence rates. Its treatment is mainly based on immunosuppressive therapies, specifically mycophenolate mofetil and glucocorticoids. Recent years have seen significant progress in understanding complement biology and its role in C3G pathophysiology. New complement-tergeting treatments have been developed and initial trials have shown promising results. However, challenges persist in C3G, with recurrent post-transplantation cases leading to suboptimal outcomes. This review discusses the pathophysiology and management of C3G, with a focus on its recurrence after kidney transplantation. • C3 glomerulopathy (C3G) is a rare glomerular disease driven by complement dysregulation with high post-transplantation recurrence rates. • Treatment of native cases is primarily based onmycophenolate mofetil and glucocorticoids, but these immunosuppressice drugs are often ineffective in recurrent cases. • The growing availability of complement-targeting therapies is expected to improve the outcomes of affected individuals. [ABSTRACT FROM AUTHOR]
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- 2024
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14. Expert Opinion Special Feature: Patient Selection for Initial Clinical Trials of Pig Organ Transplantation
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Pierson, Richard N., Allan, James S., Cooper, David K.C., D’Alessandro, David A., Fishman, Jay A., Kawai, Tatsuo, Lewis, Gregory D., Madsen, Joren C., Markmann, James F., and Riella, Leonardo V.
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- 2022
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15. T cell depletion increases humoral response by favoring T follicular helper cells expansion
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Gassen, Rodrigo Benedetti, Borges, Thiago J., Pérez-Sáez, María José, Zhang, Hengcheng, Al Jurdi, Ayman, Llinàs-Mallol, Laura, Aoyama, Bruno, Lima, Maurício, Pascual, Julio, Sage, Peter T., Murakami, Naoka, and Riella, Leonardo V.
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Antibody-mediated rejection is a major cause of long-term graft loss in kidney transplant patients. T follicular helper (Tfh) cells are crucial for assisting B cell differentiation and are required for an efficient antibody response. Anti-thymocyte globulin (ATG) is a widely used lymphocyte-depleting induction therapy. However, less is known about how ATG affects Tfh cell development and donor-specific antibody (DSA) formation. We observed an increase in circulating Tfh cells at 6 months after kidney transplant in patients who received ATG. Using an NP-OVA immunization model, we found that ATG-treated mice had a higher percentage of Tfh cells, germinal center B cells, and higher titers of antigen-specific antibodies compared to controls. ATG-treated animals had lower levels of IL-2, a known Bcl-6 repressor, but higher levels of IL-21, pSTAT3 and Bcl-6, favoring Tfh differentiation. In a mouse kidney transplant model, ATG-treated recipients showed an increase in Tfh cells, DSA and C4d staining in the allograft. Although ATG was effective in depleting T cells, it favored the expansion of Tfh cells following depletion. Concomitant use of IL-2, tacrolimus, or rapamycin with ATG was essential to control Tfh cell expansion. In summary, ATG depletion favors Tfh expansion, enhancing antibody-mediated response.
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- 2022
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16. T cell depletion increases humoral response by favoring T follicular helper cells expansion
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Gassen, Rodrigo Benedetti, Borges, Thiago J., Pérez‐Sáez, María José, Zhang, Hengcheng, Al Jurdi, Ayman, Llinàs‐Mallol, Laura, Aoyama, Bruno, Lima, Maurício, Pascual, Julio, Sage, Peter T., Murakami, Naoka, and Riella, Leonardo V.
- Abstract
Antibody‐mediated rejection is a major cause of long‐term graft loss in kidney transplant patients. T follicular helper (Tfh) cells are crucial for assisting B cell differentiation and are required for an efficient antibody response. Anti‐thymocyte globulin (ATG) is a widely used lymphocyte‐depleting induction therapy. However, less is known about how ATG affects Tfh cell development and donor‐specific antibody (DSA) formation. We observed an increase in circulating Tfh cells at 6 months after kidney transplant in patients who received ATG. Using an NP‐OVA immunization model, we found that ATG‐treated mice had a higher percentage of Tfh cells, germinal center B cells, and higher titers of antigen‐specific antibodies compared to controls. ATG‐treated animals had lower levels of IL‐2, a known Bcl‐6 repressor, but higher levels of IL‐21, pSTAT3 and Bcl‐6, favoring Tfh differentiation. In a mouse kidney transplant model, ATG‐treated recipients showed an increase in Tfh cells, DSA and C4d staining in the allograft. Although ATG was effective in depleting T cells, it favored the expansion of Tfh cells following depletion. Concomitant use of IL‐2, tacrolimus, or rapamycin with ATG was essential to control Tfh cell expansion. In summary, ATG depletion favors Tfh expansion, enhancing antibody‐mediated response. In mouse models of immunization and kidney transplantation, ATG treatment alone creates a favorable microenvironment for the generation of T follicular helper cells, leading to higher titers of antigen‐specific antibodies through a mechanism involving low IL‐2 levels.
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- 2022
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17. Successful Treatment of Posttransplant Monoclonal Gammopathy-associated C3 Glomerulopathy With Plasma Cell Clone-directed Therapy
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Al Jurdi, Ayman, Cohen Bucay, Abraham, Riella, Leonardo V., Yee, Andrew J., Abdelmalek, Cherif, Klepeis, Veronica, Kimura, Shoko, and Safa, Kassem
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- 2024
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18. T-cell Exhaustion in Organ Transplantation
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Angeletti, Andrea, Cantarelli, Chiara, Riella, Leonardo V., Fribourg, Miguel, and Cravedi, Paolo
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Exhaustion of T cells occurs in response to long-term exposure to self and foreign antigens. It limits T cell capacity to proliferate and produce cytokines, leading to an impaired ability to clear chronic infections or eradicate tumors. T-cell exhaustion is associated with a specific transcriptional, epigenetic, and metabolic program and characteristic cell surface markers’ expression. Recent studies have begun to elucidate the role of T-cell exhaustion in transplant. Higher levels of exhausted T cells have been associated with better graft function in kidney transplant recipients. In contrast, reinvigorating exhausted T cells by immune checkpoint blockade therapies, while promoting tumor clearance, increases the risk of acute rejection. Lymphocyte depletion and high alloantigen load have been identified as major drivers of T-cell exhaustion. This could account, at least in part, for the reduced rates of acute rejection in organ transplant recipients induced with thymoglobulin and for the pro-tolerogenic effects of a large organ such as the liver. Among the drugs that are widely used for maintenance immunosuppression, calcineurin inhibitors have a contrasting inhibitory effect on exhaustion of T cells, while the influence of mTOR inhibitors is still unclear. Harnessing or encouraging the natural processes of exhaustion may provide a novel strategy to promote graft survival and transplantation tolerance.
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- 2022
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19. Discovery of Autoantibodies Targeting Nephrin in Minimal Change Disease Supports a Novel Autoimmune Etiology
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Watts, Andrew J.B., Keller, Keith H., Lerner, Gabriel, Rosales, Ivy, Collins, A. Bernard, Sekulic, Miroslav, Waikar, Sushrut S., Chandraker, Anil, Riella, Leonardo V., Alexander, Mariam P., Troost, Jonathan P., Chen, Junbo, Fermin, Damian, Yee, Jennifer L., Sampson, Matthew G., Beck, Laurence H., Henderson, Joel M., Greka, Anna, Rennke, Helmut G., and Weins, Astrid
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Although corticosteroids are an effective first-line therapy for minimal change disease, relapse, steroid dependence, and intolerance are common in this podocytopathy of unknown etiology. The efficacy of B cell?targeted therapies in some patients suggests an autoantibody-mediated etiology. This study describes the novel discovery in both adults and children with minimal change disease of autoantibodies targeting nephrin, a critical component of the podocyte slit diaphragm that ensures integrity of the glomerular filtration barrier. This observation aligns with the established proteinuric effect of antinephrin antibodies demonstrated in animal models. These findings identify an important autoimmune mechanism in a subset of patients with minimal change disease and provide a framework for the application and development of precision medicine strategies in this condition.
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- 2022
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20. Recurrent Glomerular Disease after Kidney Transplantation
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Uffing, Audrey, Hullekes, Frank, Riella, Leonardo V., and Hogan, Jonathan J.
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Recurrent glomerular disease after kidney transplant remains an important cause of allograft failure. Many of the different entities post-transplant still suffer from incomplete knowledge on pathophysiology, and therefore lack targeted and effective therapies. In this review, we focus on specific clinical dilemmas encountered by physicians in managing recurrent glomerular disease by highlighting new insights into the understanding and treatment of post-transplant focal segmental glomerulosclerosis, membranous nephropathy, atypical hemolytic uremic syndrome, C3 glomerulopathy, amyloid light-chain (AL) amyloidosis, and IgA nephropathy.
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- 2021
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21. Mineral Bone Disorders in Kidney Transplantation.
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Al Jurdi, Ayman, Da Silva Martins, Janaina, and Riella, Leonardo V.
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KIDNEY transplantation ,BONE fractures ,BONE remodeling ,BONE diseases ,CLINICAL trials ,MINERALS ,BONE density - Abstract
Bone disease after kidney transplantation is associated with an increased risk of fractures, morbidity, and mortality. Its pathophysiology is complex, involving multiple contributors including pretransplant bone disease, immunosuppressive medications, and changes in the parathyroid-bone-kidney axis. Risk scores, bone turnover markers, and noninvasive imaging modalities are only able to partially predict the fracture risk in kidney transplant recipients. The optimal management of bone disease after kidney transplantation has not yet been established, with only a limited number of randomized clinical trials evaluating the efficacy of treatment regimens in kidney transplant recipients. This review focuses on the pathophysiology, evaluation, prevention, and treatment of post-kidney transplant mineral and bone disease as guided by recent evidence. [ABSTRACT FROM AUTHOR]
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- 2021
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22. Opioids and Kidney Transplantation.
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Lafargue, Marie-Camille, Caliskan, Yasar, Lentine, Krista L., and Riella, Leonardo V.
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KIDNEY transplantation ,INFECTIOUS disease transmission ,LIVER transplantation ,PATIENT education ,OPIOIDS - Abstract
The United States has faced an unprecedented opioid crisis in recent years, which has led to an increase in opioid overdose-related deaths and, consequently, an increase in the number of potential deceased donors available for transplantation. This new pool of potential organ donors is composed of younger donors with higher infectious disease transmission risk. The use of organs from these donors requires appropriate patient education, informed consent, and post-transplant monitoring practices. Prescription opioid use is also an important component of the evaluation of transplant and living donor candidates because it may impact outcomes and eligibility for the procedures. In kidney transplant recipients, prescription opioid use predicts a higher risk of mortality, graft loss, and post-transplant complications. These effects seem to be proportional to the levels of opioid use, and to parallel patterns in other transplant populations such as liver, heart and lung recipients. Among living kidney donors, predonation prescription opioid use is associated with an increased risk of re-admission after nephrectomy. Overall, the opioid epidemic creates educational needs for patients awaiting deceased donor transplant, and also impacts the evaluation and care of transplant candidates. Among transplant candidates and recipients, the identification of patients with chronic opioid use should prompt multidisciplinary evaluation and management strategies to minimize risks. [ABSTRACT FROM AUTHOR]
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- 2021
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23. Anticoagulation Thromboprophylaxis Is More Effective than Antiplatelet Thromboprophylaxis for Individuals with High-Risk Membranous Nephropathy
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Al Jurdi, Ayman, El Mouhayyar, Christopher, Yatim, Karim, Efe, Orhan, Muhsin, Saif A., Riella, Leonardo V., Zonozi, Reza, Laliberte, Karen A., Niles, John, and Jeyabalan, Anushya
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- 2023
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24. Post-Transplant Recurrence of Glomerular Diseases: Analysis of the CureGN Database
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Efe, Orhan, Ribas, Guilherme Taborda, Larkina, Maria, Al Jurdi, Ayman, Hullekes, Frank E., Mariani, Laura H., and Riella, Leonardo V.
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- 2023
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25. Gene Expression Profiling in Kidney Transplants with Immune Checkpoint Inhibitor–Associated Adverse Events
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Adam, Benjamin A., Murakami, Naoka, Reid, Graeme, Du, Katie, Jasim, Ruqaya, Boils, Christie L., Bu, Lihong, Hill, Peter D., Murray, Allan G., Renaudin, Karine, Roufosse, Candice, Weins, Astrid, Wen, Kevin, Riella, Leonardo V., and Mengel, Michael
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- 2021
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26. The failing kidney allograft: A review and recommendations for the care and management of a complex group of patients
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Lubetzky, Michelle, Tantisattamo, Ekamol, Molnar, Miklos Z., Lentine, Krista L., Basu, Arpita, Parsons, Ronald F., Woodside, Kenneth J., Pavlakis, Martha, Blosser, Christopher D., Singh, Neeraj, Concepcion, Beatrice P., Adey, Deborah, Gupta, Gaurav, Faravardeh, Arman, Kraus, Edward, Ong, Song, Riella, Leonardo V., Friedewald, John, Wiseman, Alex, Aala, Amtul, Dadhania, Darshana M., and Alhamad, Tarek
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The return to dialysis after allograft failure is associated with increased morbidity and mortality. This transition is made more complex by the rising numbers of patients who seek repeat transplantation and therefore may have indications for remaining on low levels of immunosuppression, despite the potential increased morbidity. Management strategies vary across providers, driven by limited data on how to transition off immunosuppression as the allograft fails and a paucity of randomized controlled trials to support one approach over another. In this review, we summarize the current data available for management and care of the failing allograft. Additionally, we discuss a suggested plan for immunosuppression weaning based upon the availability of re-transplantation and residual allograft function. We propose a shared-care model in which there is improved coordination between transplant providers and general nephrologists so that immunosuppression management and preparation for renal replacement therapy and/or repeat transplantation can be conducted with the goal of improved outcomes and decreased morbidity in this vulnerable patient group.
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- 2021
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27. The failing kidney allograft: A review and recommendations for the care and management of a complex group of patients
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Lubetzky, Michelle, Tantisattamo, Ekamol, Molnar, Miklos Z., Lentine, Krista L., Basu, Arpita, Parsons, Ronald F., Woodside, Kenneth J., Pavlakis, Martha, Blosser, Christopher D., Singh, Neeraj, Concepcion, Beatrice P., Adey, Deborah, Gupta, Gaurav, Faravardeh, Arman, Kraus, Edward, Ong, Song, Riella, Leonardo V., Friedewald, John, Wiseman, Alex, Aala, Amtul, Dadhania, Darshana M., and Alhamad, Tarek
- Abstract
The return to dialysis after allograft failure is associated with increased morbidity and mortality. This transition is made more complex by the rising numbers of patients who seek repeat transplantation and therefore may have indications for remaining on low levels of immunosuppression, despite the potential increased morbidity. Management strategies vary across providers, driven by limited data on how to transition off immunosuppression as the allograft fails and a paucity of randomized controlled trials to support one approach over another. In this review, we summarize the current data available for management and care of the failing allograft. Additionally, we discuss a suggested plan for immunosuppression weaning based upon the availability of re‐transplantation and residual allograft function. We propose a shared‐care model in which there is improved coordination between transplant providers and general nephrologists so that immunosuppression management and preparation for renal replacement therapy and/or repeat transplantation can be conducted with the goal of improved outcomes and decreased morbidity in this vulnerable patient group. In the context of the failing allograft, the authors focus on preparation for return to dialysis and/or retransplantation, personalization of immunosuppression weaning, reduction of sensitization risk in anticipation of repeat transplantation, and optimization of shared care between transplant providers and general nephrologists.
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- 2021
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28. Recurrence of IgA Nephropathy after Kidney Transplantation in Adults
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Uffing, Audrey, Pérez-Saéz, Maria José, Jouve, Thomas, Bugnazet, Mathilde, Malvezzi, Paolo, Muhsin, Saif A., Lafargue, Marie-Camille, Reindl-Schwaighofer, Roman, Morlock, Alina, Oberbauer, Rainer, Buxeda, Anna, Burballa, Carla, Pascual, Julio, von Moos, Seraina, Seeger, Harald, La Manna, Gaetano, Comai, Giorgia, Bini, Claudia, Russo, Luis Sanchez, Farouk, Samira, Nissaisorakarn, Pitchaphon, Patel, Het, Agrawal, Nikhil, Mastroianni-Kirsztajn, Gianna, Mansur, Juliana, Tedesco-Silva, Hélio, Ventura, Carlucci Gualberto, Agena, Fabiana, David-Neto, Elias, Akalin, Enver, Alani, Omar, Mazzali, Marilda, Manfro, Roberto Ceratti, Bauer, Andrea Carla, Wang, Aileen X., Cheng, Xingxing S., Schold, Jesse D., Berger, Stefan P., Cravedi, Paolo, and Riella, Leonardo V.
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- 2021
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29. Posttransplant Lymphoproliferative Disorder Following Kidney Transplantation: A Review
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Sprangers, Ben, Riella, Leonardo V., and Dierickx, Daan
- Abstract
Posttransplant lymphoproliferative disorder (PTLD) is one of the most feared complications following kidney transplantation. Over a 10-year period, the risk of PTLD in kidney transplant recipients (KTRs) is 12-fold higher than in a matched nontransplanted population. Given the number of kidney transplants performed, KTRs who experience PTLD outnumber other organ transplant recipients who experience PTLD. Epstein-Barr virus infection is one of the most important risk factors for PTLD, even though 40% of PTLD cases in contemporary series are not Epstein-Barr virus–associated. The overall level of immunosuppression seems to be the most important driver of the increased occurrence of PTLD in solid organ transplant recipients. Reduction in immunosuppression is commonly accepted to prevent and treat PTLD. Although the cornerstone of PTLD treatment had been chemotherapy (typically cyclophosphamide-doxorubicin-vincristinr-prednisone), the availability of rituximab has changed the treatment landscape in the past 2 decades. The outcome of PTLD in KTRs has clearly improved as a result of the introduction of more uniform treatment protocols, improved supportive care, and increased awareness and use of positron emission tomography combined with computed tomography in staging and response monitoring. In this review, we will focus on the most recent data on epidemiology, presentation, risk factors, and management of PTLD in KTRs.
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- 2021
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30. A multi-center study on safety and efficacy of immune checkpoint inhibitors in cancer patients with kidney transplant
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Murakami, Naoka, Mulvaney, Patrick, Danesh, Melissa, Abudayyeh, Ala, Diab, Adi, Abdel-Wahab, Noha, Abdelrahim, Maen, Khairallah, Pascale, Shirazian, Shayan, Kukla, Aleksandra, Owoyemi, Itunu O., Alhamad, Tarek, Husami, Samir, Menon, Madhav, Santeusanio, Andrew, Blosser, Christopher D., Zuniga, Sandra Carias, Soler, Maria Jose, Moreso, Francesc, Mithani, Zain, Ortiz-Melo, David, Jaimes, Edgar A., Gutgarts, Victoria, Lum, Erik, Danovitch, Gabriel M., Cardarelli, Francesca, Drews, Reed E., Bassil, Claude, Swank, Jennifer L., Westphal, Scott, Mannon, Roslyn B., Shirai, Keisuke, Kitchlu, Abhijat, Ong, Song, Machado, Shana M., Mothi, Suraj S., Ott, Patrick A., Rahma, Osama, Hodi, F. Stephen, Sise, Meghan E., Gupta, Shruti, Leaf, David E., Devoe, Craig E., Wanchoo, Rimda, Nair, Vinay V., Schmults, Chrysalyne D., Hanna, Glenn J., Sprangers, Ben, Riella, Leonardo V., and Jhaveri, Kenar D.
- Abstract
Immune checkpoint inhibitors (ICIs) are widely used for various malignancies. However, their safety and efficacy in patients with a kidney transplant have not been defined. To delineate this, we conducted a multicenter retrospective study of 69 patients with a kidney transplant receiving ICIs between January 2010 and May 2020. For safety, we assessed the incidence, timing, and risk factors of acute graft rejection. For efficacy, objective response rate and overall survival were assessed in cutaneous squamous cell carcinoma and melanoma, the most common cancers in our cohort, and compared with stage-matched 23 patients with squamous cell carcinoma and 14 with melanoma with a kidney transplant not receiving ICIs. Following ICI treatment, 29 out of 69 (42%) patients developed acute rejection, 19 of whom lost their allograft, compared with an acute rejection rate of 5.4% in the non-ICI cohort. Median time from ICI initiation to rejection was 24 days. Factors associated with a lower risk of rejection were mTOR inhibitor use (odds ratio 0.26; 95% confidence interval, 0.09-0.72) and triple-agent immunosuppression (0.67, 0.48-0.92). The objective response ratio was 36.4% and 40% in the squamous cell carcinoma and melanoma subgroups, respectively. In the squamous cell carcinoma subgroup, overall survival was significantly longer in patients treated with ICIs (median overall survival 19.8 months vs. 10.6 months), whereas in the melanoma subgroup, overall survival did not differ between groups. Thus, ICIs were associated with a high risk of rejection in patients with kidney transplants but may lead to improved cancer outcomes. Prospective studies are needed to determine optimal immunosuppression strategies to improve patient outcomes.
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- 2021
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31. Nomenclature in nephrology: preserving ‘renal’ and ‘nephro' in the glossary of kidney health and disease
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Kalantar-Zadeh, Kamyar, McCullough, Peter A., Agarwal, Sanjay Kumar, Beddhu, Srinivasan, Boaz, Mona, Bruchfeld, Annette, Chauveau, Philippe, Chen, Jing, de Sequera, Patricia, Gedney, Nieltje, Golper, Thomas A., Gupta, Malini, Harris, Tess, Hartwell, Lori, Liakopoulos, Vassilios, Kopple, Joel D., Kovesdy, Csaba P., Macdougall, Iain C., Mann, Johannes F. E., Molony, Donald, Norris, Keith C., Perlmutter, Jeffrey, Rhee, Connie M., Riella, Leonardo V., Weisbord, Steven D., Zoccali, Carmine, and Goldsmith, David
- Abstract
A recently published nomenclature by a “Kidney Disease Improving Global Outcomes” (KDIGO) Consensus Conference suggested that the word “kidney” should be used in medical writings instead of “renal” or “nephro” when referring to kidney disease and kidney health. Whereas the decade-old move to use “kidney” more frequently should be supported when communicating with the public-at-large, such as the World Kidney Day, or in English speaking countries in communications with patients, care-partners, and non-medical persons, our point of view is that “renal” or “nephro" should not be removed from scientific and technical writings. Instead, the terms can coexist and be used in their relevant contexts. Cardiologists use “heart” and “cardio” as appropriate such as “heart failure” and “cardiac care units” and have not replaced “cardiovascular” with “heartvessel”, for instance. Likewise, in nephrology, we consider that “chronic kidney disease” and “continuous renal replacement therapy” should coexist. We suggest that in scientific writings and technical communications, the words “renal” and “nephro" and their derivatives are more appropriate and should be freely used without any pressure by medical journals to compel patients, care-partners, healthcare providers, researchers and other stakeholders to change their selected words and terminologies. We call to embrace the terms “kidney”, “renal” and “nephro” as they are used in different contexts and ask that scientific and medical journals not impose terminology restrictions for kidney disease and kidney health. The choice should be at the discretion of the authors, in the different contexts including in scientific journals.
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- 2021
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32. Recurrence of membranous nephropathy after kidney transplantation: a multicenter retrospective cohort study
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Hullekes, Frank, Uffing, Audrey, Verhoeff, Rucháma, Seeger, Harald, von Moos, Seraina, Mansur, Juliana, Mastroianni-Kirsztajn, Gianna, Silva, Helio Tedesco, Buxeda, Anna, Pérez-Sáez, María José, Arias-Cabrales, Carlos, Collins, A. Bernard, Swett, Christie, Morená, Leela, Loucaidou, Marina, Kousios, Andreas, Malvezzi, Paolo, Bugnazet, Mathilde, Russo, Luis Sanchez, Muhsin, Saif A., Agrawal, Nikhil, Nissaisorakarn, Pitchaphon, Patel, Het, Al Jurdi, Ayman, Akalin, Enver, Neto, Elias David, Agena, Fabiana, Ventura, Carlucci, Manfro, Roberto C., Bauer, Andrea Carla, Mazzali, Marilda, Vinicius de Sousa, Marcos, La Manna, Gaetano, Bini, Claudia, Comai, Giorgia, Reindl-Schwaighofer, Roman, Berger, Stefan, Cravedi, Paolo, and Riella, Leonardo V.
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Membranous nephropathy (MN) is a leading cause of kidney failure worldwide, and frequently recurs after transplant. Available data originated from small retrospective cohort studies or registry analyses. Therefore, uncertainties remain on risk factors for MN recurrence and response to therapy. Within the Post-Transplant Glomerular Disease (TANGO) Consortium, we conducted a retrospective multicenter cohort study examining the MN recurrence rate, risk factors, and response to treatment. This study screened 22,921 patients across three continents and included 194 patients who underwent a kidney transplant due to biopsy-proven MN. The cumulative incidence of MN recurrence was 31% at 10 years post-transplant. Patients with a faster progression towards end-stage kidney disease (ESKD) were at higher risk of developing recurrent MN (hazard ratio (HR) of 0.55 per decade (95%CI; 0.35-0.88). Moreover, elevated pre-transplant levels of anti-PLA2R antibodies were strongly associated with recurrence (HR 18.58; 95%CI; 5.37- 64.27). Patients receiving rituximab for MN recurrence had a higher likelihood of achieving remission than patients receiving RAAS inhibition alone. In sum, MN recurs in one-third of patients post-transplant and serum PLA2R antibodies shortly before transplant could aid in risk-stratifying patients for MN recurrence. Moreover, patients receiving rituximab had a higher rate of treatment response.
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- 2024
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33. Advancing mouse models for transplantation research
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Cravedi, Paolo, Riella, Leonardo V., Ford, Mandy L., Valujskikh, Anna, Menon, Madhav C., Kirk, Allan D., Alegre, Maria-Luisa, Alessandrini, Alessandro, Feng, Sandy, Kehn, Patricia, Najafian, Nader, Hancock, Wayne W., Heeger, Peter S., Maltzman, Jonathan S., Mannon, Roslyn B., Nadig, Satish N., Odim, Jonah, Turnquist, Heth, Shaw, Julia, West, Lori, Luo, Xunrong, Chong, Anita S., and Bromberg, Jonathan S.
- Abstract
Mouse models have been instrumental in understanding mechanisms of transplant rejection and tolerance, but cross-study reproducibility and translation of experimental findings into effective clinical therapies are issues of concern. The Mouse Models in Transplantation symposium gathered scientists and physician-scientists involved in basic and clinical research in transplantation to discuss the strengths and limitations of mouse transplant models and strategies to enhance their utility. Participants recognized that increased procedure standardization, including the use of prespecified, defined endpoints, and statistical power analyses, would benefit the field. They also discussed the generation of new models that incorporate environmental and genetic variables affecting clinical outcomes as potentially important. If implemented, these strategies are expected to improve the reproducibility of mouse studies and increase their translation to clinical trials and, ideally, new Food and Drug Administration–approved drugs.
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- 2024
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34. Accelerated chronic skin changes without allograft vasculopathy: A 10-year outcome report after face transplantation.
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Kollar, Branislav, Rizzo, Natalie M., Borges, Thiago J., Haug, Valentin, Abdulrazzak, Obada, Kauke, Martin, Safi, Ali-Farid, Lian, Christine G., Marty, Francisco M., Rutherford, Anna E., Mitchell, Richard N., Murphy, George F., Tullius, Stefan G., Riella, Leonardo V., and Pomahac, Bohdan
- Abstract
Long-term outcomes after face transplantation are rarely reported in the scientific literature. Here we present outcome data of a partial face allograft recipient 10 years after transplantation. Medical records were reviewed for functional and psychosocial outcomes as well as complications. Histopathologic analyses of autopsy tissues and characterization of skin immune cells were performed. The patient retained long-term motor and sensory function, though with a noticeable drop in sensory function after year 5. Social reintegration of the patient was marked by reconnection with his family and participation in public social activities. Immunosuppressive therapy consisted of tacrolimus (target levels 6–8 ng/mL after the first year), mycophenolate, and prednisone, while steroids were completely weaned between years 1 and 7. One acute cellular rejection episode of grade II or higher occurred on average per year and led to chronic skin changes (papillary dermal sclerosis with superficial hyalinization, epidermal thinning with loss of rete ridges, perieccrine fibrosis), but the allograft vessels, muscles, adipose tissue, and bone were spared. Allograft skin was characterized by increased number of CD4+ TNF-α/IL17A producing T-cells as compared with native skin. Long-term kidney function was maintained at 60 mL/min estimated glomerular filtration rate. Unfortunately, the preexisting hepatitis C virus infection with liver cirrhosis was resistant to 3 treatments with new direct-acting antivirals and eventually hepatocellular carcinoma developed, causing the patient's death 10 years after transplantation. This report suggests that face transplants can maintain their function for at least 10 years. Chronic skin changes can occur independently of allograft vasculopathy. [ABSTRACT FROM AUTHOR]
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- 2020
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35. Preventing Coronavirus Disease 2019 in Kidney Transplant Recipients: Where Should We Begin?
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Riella, Leonardo V., Azzi, Jamil R., and Cravedi, Paolo
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Context:Chronic immunosuppression is associated with an increased risk of opportunistic infections. Although kidney transplant recipients with coronavirus disease 2019 (COVID-19) have higher mortality than the general population, data on their risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are unknown. Subject of Review:A recent single-center screening study from the UK (Transplantation. 2021 Jan 1;105(1):151–7) showed that 89 (10.4%) of 855 consecutive kidney transplant recipients tested positive for SARS-CoV-2 antibodies. Risk factors for infection included a nonwhite background, diabetes, and a history of allograft rejection. Risk factors for mortality in individuals who developed COVID-19 were older age and receiving steroids. Second Opinion:This study shows that the rate of SARS-CoV-2 infection in kidney transplant recipients is similar to the one observed in the general population in the same area (13%), indicating that transplant recipients are not at increased risk of COVID-19. However, the investigators raise the interesting point that since transplant individuals were advised to shelter earlier than the general population, they may be in fact more susceptible. This statement is hard to substantiate, but the identification of specific risk factors for infection and poor outcomes is crucial to tailor strategies to prevent spread of the infection. This is particularly important, considering that kidney transplant recipients may be at increased risk of prolonged viral spread and in-host viral mutations, making them not just a particularly fragile population for COVID-19 but also a potentially major source of further contagions.
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- 2021
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36. Mineral Bone Disorders in Kidney Transplantation
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Al Jurdi, Ayman, Da Silva Martins, Janaina, and Riella, Leonardo V.
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Summary:Bone disease after kidney transplantation is associated with an increased risk of fractures, morbidity, and mortality. Its pathophysiology is complex, involving multiple contributors including pretransplant bone disease, immunosuppressive medications, and changes in the parathyroid–bone–kidney axis. Risk scores, bone turnover markers, and noninvasive imaging modalities are only able to partially predict the fracture risk in kidney transplant recipients. The optimal management of bone disease after kidney transplantation has not yet been established, with only a limited number of randomized clinical trials evaluating the efficacy of treatment regimens in kidney transplant recipients. This review focuses on the pathophysiology, evaluation, prevention, and treatment of post–kidney transplant mineral and bone disease as guided by recent evidence.
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- 2021
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37. Evidence of potent humoral immune activity in COVID‐19‐infected kidney transplant recipients
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Hartzell, Susan, Bin, Sofia, Benedetti, Claudia, Haverly, Meredith, Gallon, Lorenzo, Zaza, Gianluigi, Riella, Leonardo V., Menon, Madhav C., Florman, Sander, Rahman, Adeeb H., Leech, John M., Heeger, Peter S., and Cravedi, Paolo
- Abstract
Whether kidney transplant recipients are capable of mounting an effective anti‐severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) adaptive immune response despite chronic immunosuppression is unknown and has important implications for therapy. Herein, we analyzed peripheral blood cell surface and intracellular cytokine phenotyping by flow cytometry along with serum antibody testing in 18 kidney transplant recipients with active coronavirus disease 2019 (COVID‐19) infection and 36 matched, transplanted controls without COVID‐19. We observed significantly fewer total lymphocytes and fewer circulating memory CD4+and CD8+T cells in the COVID‐19 subjects. We also showed fewer anergic and senescent CD8+T cells in COVID‐19 individuals, but no differences in exhausted CD8+T cells, nor in any of these CD4+T cell subsets between groups. We also observed greater frequencies of activated B cells in the COVID‐19 patients. Sixteen of 18 COVID‐19 subjects tested for anti‐SARS‐CoV‐2 serum antibodies showed positive immunoglobulin M or immunoglobulin G titers. Additional analyses showed no significant correlation among immune phenotypes and degrees of COVID‐19 disease severity. Our findings indicate that immunosuppressed kidney transplant recipients admitted to the hospital with acute COVID‐19 infection can mount SARS‐CoV‐2‐reactive adaptive immune responses. The findings raise the possibility that empiric reductions in immunosuppressive therapy for all kidney transplant recipients with active COVID‐19 may not be required. Hospitalized kidney transplant recipients with COVID‐19 infection can mount anti‐SARS‐CoV‐2–adaptive immune responses, despite ongoing immunosuppression, raising the possibility that empiric reduction of immunosuppression may not be required.
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- 2020
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38. COVID‐19 and kidney transplantation: Results from the TANGO International Transplant Consortium
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Cravedi, Paolo, Mothi, Suraj S., Azzi, Yorg, Haverly, Meredith, Farouk, Samira S., Pérez‐Sáez, María J., Redondo‐Pachón, Maria D., Murphy, Barbara, Florman, Sander, Cyrino, Laura G., Grafals, Monica, Venkataraman, Sandheep, Cheng, Xingxing S., Wang, Aileen X., Zaza, Gianluigi, Ranghino, Andrea, Furian, Lucrezia, Manrique, Joaquin, Maggiore, Umberto, Gandolfini, Ilaria, Agrawal, Nikhil, Patel, Het, Akalin, Enver, and Riella, Leonardo V.
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Kidney transplant recipients may be at a high risk of developing critical coronavirus disease 2019 (COVID‐19) illness due to chronic immunosuppression and comorbidities. We identified hospitalized adult kidney transplant recipients at 12 transplant centers in the United States, Italy, and Spain who tested positive for COVID‐19. Clinical presentation, laboratory values, immunosuppression, and treatment strategies were reviewed, and predictors of poor clinical outcomes were determined through multivariable analyses. Among 9845 kidney transplant recipients across centers, 144 were hospitalized due to COVID‐19 during the 9‐week study period. Of the 144 patients, 66% were male with a mean age of 60 (±12) years, and 40% were Hispanic and 25% were African American. Prevalent comorbidities included hypertension (95%), diabetes (52%), obesity (49%), and heart (28%) and lung (19%) disease. Therapeutic management included antimetabolite withdrawal (68%), calcineurin inhibitor withdrawal (23%), hydroxychloroquine (71%), antibiotics (74%), tocilizumab (13%), and antivirals (14%). During a median follow‐up period of 52 days (IQR: 16‐66 days), acute kidney injury occurred in 52% cases, with respiratory failure requiring intubation in 29%, and the mortality rate was 32%. The 46 patients who died were older, had lower lymphocyte counts and estimated glomerular filtration rate levels, and had higher serum lactate dehydrogenase, procalcitonin, and interleukin‐6 levels. In sum, hospitalized kidney transplant recipients with COVID‐19 have higher rates of acute kidney injury and mortality. In this multinational cohort of 144 kidney transplanted patients from 11 transplant centers in the US and Europe who were hospitalized for COVID‐19, acute kidney injury occurred in 52% and respiratory failure requiring intubation occurred in 29%, with an overall mortality of 32%.
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- 2020
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39. Noncirrhotic hyperammonemia after deceased donor kidney transplantation: A case report
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Li, George Z., Tio, Maria C., Pak, Linda M., Krier, Joel, Seifter, Julian L., Tullius, Stefan G., Riella, Leonardo V., Malek, Sayeed K., and Stergachis, Andrew B.
- Abstract
A 72-year-old woman with end-stage kidney disease due to recurrent urinary tract infections and obstructive uropathy of a solitary kidney presented to our hospital for renal transplantation. She underwent successful transplantation of a deceased donor allograft, but developed acute mental status deterioration on the fifth postoperative day. Her serum ammonia was found to be markedly elevated to 447 μmol/L in the setting of normal hepatic function. She was treated with emergent dialysis and empiric antibiotics targeting urea-splitting organisms, and ultimately made a full neurologic recovery with stable renal allograft function. Noncirrhotic hyperammonemia (NCH) is an exceedingly rare clinical entity but seems to have a predilection for patients who have undergone solid organ transplantation. This report emphasizes the importance of rapid diagnosis and initiation of treatment for NCH, which is associated with a high rate of mortality and irreversible neurological morbidity. We outline the successful workup and management approach for this patient.
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- 2019
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40. Noncirrhotic hyperammonemia after deceased donor kidney transplantation: A case report
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Li, George Z., Tio, Maria C., Pak, Linda M., Krier, Joel, Seifter, Julian L., Tullius, Stefan G., Riella, Leonardo V., Malek, Sayeed K., and Stergachis, Andrew B.
- Abstract
A 72‐year‐old woman with end‐stage kidney disease due to recurrent urinary tract infections and obstructive uropathy of a solitary kidney presented to our hospital for renal transplantation. She underwent successful transplantation of a deceased donor allograft, but developed acute mental status deterioration on the fifth postoperative day. Her serum ammonia was found to be markedly elevated to 447 μmol/L in the setting of normal hepatic function. She was treated with emergent dialysis and empiric antibiotics targeting urea‐splitting organisms, and ultimately made a full neurologic recovery with stable renal allograft function. Noncirrhotic hyperammonemia (NCH) is an exceedingly rare clinical entity but seems to have a predilection for patients who have undergone solid organ transplantation. This report emphasizes the importance of rapid diagnosis and initiation of treatment for NCH, which is associated with a high rate of mortality and irreversible neurological morbidity. We outline the successful workup and management approach for this patient. The authors describe the successful work‐up and management of a patient who developed noncirrhotic hyperammonemia after deceased donor kidney transplantation, an exceedingly rare clinical entity with high rates of mortality and irreversible neurologic morbidity.
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- 2019
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41. Utility of Anti-PLA2R and Anti-THSD7A Antibodies in Predicting Membranous Nephropathy Recurrence: A Multi-Center Retrospective Cohort Study
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Hullekes, Frank E., Verhoeff, Rucháma, Cravedi, Paolo, and Riella, Leonardo V.
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- 2023
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42. Validation of Diagnostic, Prognostic, and Predictive Performances of a Novel Urinary Exosomal mRNA Clinical Test
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El Fekih, Rania, Haynes, Brian C., Merhej, Tamara, Halawi, Ahmad, Younis, Nour K., Chandraker, Anil K., Riella, Leonardo V., Skog, Johan, and Azzi, Jamil R.
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- 2023
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43. Safety and Efficacy of Mycophenolate Reduction After Kidney Transplantation
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Yatim, Karim, Jurdi, Ayman Al, Ribas, Guilherme Taborda, Morena, Leela, and Riella, Leonardo V.
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- 2023
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44. Inhibitory innate receptors and their potential role in transplantation.
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Lima, Karina, Ribas, Guilherme T., Riella, Leonardo V., and Borges, Thiago J.
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The regulatory arm of the immune system plays a crucial role in maintaining immune tolerance and preventing excessive immune responses. Immune regulation comprises various regulatory cells and molecules that work together to suppress or regulate immune responses. The programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) are examples of inhibitory receptors that counteract activating signals and fine-tune immune responses. While most of the discoveries of immune regulation have been related to T cells and the adaptive immune system, the innate arm of the immune system also has a range of inhibitory receptors that can counteract activating signals and suppress the effector immune responses. Targeting these innate inhibitory receptors may provide a complementary therapeutic approach in several immune-related conditions, including transplantation. In this review, we will explore the potential role of innate inhibitory receptors in controlling alloimmunity during solid organ transplantation. • Like the adaptive immune system, innate immunity has inhibitory receptors • Innate inhibitory receptors counteract effector immune responses • Innate inhibitory receptors have a potential role in controlling alloimmunity • Targeting these receptors may provide a complementary therapy in transplantation [ABSTRACT FROM AUTHOR]
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- 2023
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45. Response to letter entitled: Tixagevimab/cilgavimab pre-exposure prophylaxis and breakthrough infection risk in vaccinated solid organ transplant recipients: Concern for immortal time bias effect
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Al Jurdi, Ayman, Morena, Leela, and Riella, Leonardo V.
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- 2023
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46. Notch-1 Inhibition Promotes Immune Regulation in Transplantation Via Regulatory T Cell–Dependent Mechanisms
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Magee, Ciara N., Murakami, Naoka, Borges, Thiago J., Shimizu, Tetsunosuke, Safa, Kassem, Ohori, Shunsuke, Cai, Songjie, Uffing, Audrey, Azzi, Jamil, Elyaman, Wassim, Charbonnier, Louis-Marie, Liu, Kaifeng, Toprak, Demet, Visner, Gary, Chatila, Talal A., Siebel, Christian W., Najafian, Nader, and Riella, Leonardo V.
- Abstract
Supplemental Digital Content is available in the text.
- Published
- 2019
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47. Outstanding questions in transplantation: B cells, alloantibodies, and humoral rejection
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Chong, Anita S., Rothstein, David M., Safa, Kassem, and Riella, Leonardo V.
- Abstract
Over the past three decades, improved immunosuppression has significantly reduced T cell–mediated acute rejection rates, but long‐term graft survival rates have seen only marginal improvement. The cause of late graft loss has been under intense investigation, and chronic antibody‐mediated rejection (AMR) has been identified as one of the leading causes, thus providing a strong rationale for basic science investigation into donor‐specific B cells and antibodies in transplantation and ways to mitigate their pathogenicity. In 2018, the American Society of Transplantation launched a community‐wide online discussion of Outstanding Questions in Transplantation, and the topic of B cell biology and donor‐specific antibody prevention emerged as a major area of interest to the community, leading to a highly engaged dialogue, with comments from basic and translational scientists as well as physicians (http://community.myast.org/communities/community-home/digestviewer). We have summarized this discussion from a bedside to bench perspective and have organized this review into outstanding questions within the paradigm that AMRis a leading cause of graft loss in the clinic, and points of view that challenge aspects of this paradigm. We also highlight opportunities for basic and translational scientists to contribute to the resolution of these questions, mapping important future directions for the transplant research field. The authors summarize the continuum of discussion regarding B cell biology, donor‐specific antibody formation, and antibody‐mediated rejection, focusing on the degree to which these processes contribute to graft loss, and discuss points of view that challenge aspects of this paradigm. See the introduction to this minireview on page 2149.
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- 2019
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48. Outstanding questions in transplantation: B cells, alloantibodies, and humoral rejection
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Chong, Anita S., Rothstein, David M., Safa, Kassem, and Riella, Leonardo V.
- Abstract
Over the past three decades, improved immunosuppression has significantly reduced T cell–mediated acute rejection rates, but long-term graft survival rates have seen only marginal improvement. The cause of late graft loss has been under intense investigation, and chronic antibody-mediated rejection (AMR) has been identified as one of the leading causes, thus providing a strong rationale for basic science investigation into donor-specific B cells and antibodies in transplantation and ways to mitigate their pathogenicity. In 2018, the American Society of Transplantation launched a community-wide online discussion of Outstanding Questions in Transplantation, and the topic of B cell biology and donor-specific antibody prevention emerged as a major area of interest to the community, leading to a highly engaged dialogue, with comments from basic and translational scientists as well as physicians (http://community.myast.org/communities/community-home/digestviewer). We have summarized this discussion from a bedside to bench perspective and have organized this review into outstanding questions within the paradigm that AMR is a leading cause of graft loss in the clinic, and points of view that challenge aspects of this paradigm. We also highlight opportunities for basic and translational scientists to contribute to the resolution of these questions, mapping important future directions for the transplant research field.
- Published
- 2019
- Full Text
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49. The Evolving Clinical Presentation of Acute Rejection in Facial Transplantation
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Haug, Valentin, Kollar, Branislav, Obed, Doha, Kiwanuka, Harriet, Turk, Marvee, Wo, Luccie, Tasigiorgos, Sotirios, Kueckelhaus, Maximillian, Riella, Leonardo V., and Pomahac, Bohdan
- Abstract
IMPORTANCE: Acute rejection is one of the most frequent complications in facial transplantation, with potentially severe consequences for the recipient if overlooked. Clinical signs, such as erythema or edema, are helpful to diagnose acute rejection in the early follow-up stage; however, it is not well known whether these clinical signs remain reliable markers of acute rejection beyond the second posttransplant year. OBJECTIVE: To determine the diagnostic value of clinical signs of acute rejection after facial transplantation over time. DESIGN, SETTING, AND PARTICIPANTS: A retrospective, single-center cohort study was conducted of patients who underwent facial transplantation at Brigham and Women’s Hospital between April 2009 and October 2014, with up to an 8-year follow-up. Medical records were reviewed until September 30, 2017. The medical records from 104 encounters with 7 patients who underwent partial or full facial transplantation were analyzed for symptoms of rejection, immunosuppressive therapy, and histopathologic findings. MAIN OUTCOMES AND MEASURES: The occurrence of 5 clinical signs of acute rejection were evaluated: erythema, edema, exanthema, suture line erythema, and mucosal lesions. Odds ratios (ORs) were calculated to determine the statistically significant association of these signs with the histopathologic diagnosis of rejection. In addition, tacrolimus blood levels, as a surrogate marker of immunosuppressive therapy, were evaluated. RESULTS: Of the 7 patients included in the study, 5 were men. The mean follow-up was 66 months (range, 35-101). Of 104 clinical encounters, 46 encounters (44.2%) represented rejection episodes and 58 encounters (55.8%) represented no-rejection episodes. Beyond 2 years posttransplantation, only erythema (OR, 6.53; 95% CI, 1.84-20.11; P = .004) and exanthema (OR, ∞; 95% CI, 2.2-∞; P = .004) were demonstrated to be reliable clinical signs of acute rejection in facial transplantation. There was also a statistically significant association of subtherapeutic tacrolimus levels with late rejection episodes (OR, 3.79; 95% CI, 1.25-12.88; P = .03). In addition, the occurrence of subclinical rejection was more frequent during later follow-up times (7 [24.1%] late rejections vs 1 [5.9%] early rejection). Five of 8 subclinical rejections (62.5%) were associated with subtherapeutic tacrolimus levels. CONCLUSIONS AND RELEVANCE: Clinical signs of acute rejection in facial transplantation appear to be of limited diagnostic value, particularly after the second postoperative year. Until alternative biomarkers for rejection are identified, protocol skin biopsies will remain necessary for guiding assessments of allograft rejection. LEVEL OF EVIDENCE: 3.
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- 2019
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50. Chronic rejection of human face allografts
- Author
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Krezdorn, Nicco, Lian, Christine G., Wells, Michael, Wo, Luccie, Tasigiorgos, Sotirios, Xu, Shuyun, Borges, Thiago J., Frierson, Rayven M., Stanek, Ewelina, Riella, Leonardo V., Pomahac, Bohdan, and Murphy, George F.
- Abstract
Face vascularized composite allografts (FVCAs) have helped patients with severe facial disfigurement, with acute rejection now largely controlled through iatrogenic immunosuppression. However, little is known regarding the incidence and mechanism(s) of more long-term pathologic alterations in FVCAs that may affect function and graft durability. Protocol surveillance biopsy specimens for up to an 8-year interval in 7 patients who received FVCAs at our institution revealed histopathologic evidence of chronic rejection. Clinical manifestations included features of premature aging, mottled leukoderma accentuating suture lines, telangiectasia, and dryness of nasal mucosa. Pathologic changes consisted of epidermal thinning accompanied by discrete foci of lymphocyte-mediated cytotoxicity, hyperkeratosis, follicular plugging, vascular ectasia, and sclerosis beneath the epidermal layer associated with collagen type I deposition. Genomic interrogation and immunohistochemistry of sclerotic zones revealed upregulation of the AP-1 pathway components, JunB and c-Fos, previously implicated in overproduction of type I dermal collagen in the setting of systemic sclerosis. We conclude that some patients develop chronic rejection in FVCAs with striking similarities to alterations seen in certain autoimmune cutaneous disorders (lupus erythematosus and scleroderma/chronic sclerodermoid graft-versus-host disease). Identification of relevant pathways and genes, such as JunB and c-Fos, may provide new targets for preventative therapies for chronic immune-mediated changes in vascularized composite allografts.
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- 2019
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