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1
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Eder M, Schrag TA, Havel EF, Kainz A, Omic H, Doberer K, Kozakowski N, Körmöczi GF, Schönbacher M, Fischer G, Strassl R, Breuer M, Weseslindtner L, Haupenthal F, Böhmig GA, Puchhammer-Stöckl E, Bond G, Görzer I, Eskandary F. Polyomavirus Nephropathy in ABO Blood Group-Incompatible Kidney Transplantation: Torque Teno Virus and Immunosuppressive Burden as an Approximation to the Problem. Kidney Int Rep 2024; 9:1730-1741. [PMID: 38899213 PMCID: PMC11184242 DOI: 10.1016/j.ekir.2024.04.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Accepted: 04/01/2024] [Indexed: 06/21/2024] Open
Abstract
Introduction Earlier reports suggest that patients after ABO-incompatible kidney transplantation (ABOi) are at enhanced risk of developing BK-virus (BKV, also known as BK polyomavirus [BKPyV]) nephropathy (BKPyVAN). It remains elusive whether this is a result of more intense immunosuppression or an ABOi-associated "intrinsic attribute." To address this question, we measured Torque Teno virus (TTV) loads as a quantitative proxy for immunosuppressive depth in ABOi recipients and compared them to human leukocyte antigen-incompatible (HLAi, i.e. pretransplant donor-specific antibody-positive) and standard-risk transplant recipients. Methods Our retrospective study screened 2256 consecutive kidney transplantations performed between 2007 and 2020 at the Medical University of Vienna. Out of 629 in-principle eligible transplantations, we were able to include 465 patients: 42 ABOi, 106 HLAi, and 317 control recipients. Longitudinal TTV- polymerase chain reaction (PCR) and BKV-PCR was carried out at predefined timepoints and ranged from pretransplant until month 24 posttransplantation. TTV loads and immunosuppression were evaluated in the context of BKV-associated complications. Results ABOi recipients had a higher TTV load compared to HLAi and controls both at month 3 (median 1.5 × 109 vs. 2.4 × 108 vs. 9.1 × 107; P = 0.010) and at month 6 (3.1 × 109 vs. 1.4 × 107 vs. 6.4 × 107; P = 0.014) posttransplantation. Tacrolimus exposure was significantly higher in ABOi patients compared to HLAi and control patients (ABOi vs. HLAi: P = 0.007; ABOi vs. controls: P < 0.0001). Biopsy-proven BKPyVAN was more frequent in ABOi recipients when compared to HLAi and control recipients (11.9% vs. 2.8% vs. 4.1%; P = 0.046). Conclusion Our data support the assumption that ABOi patients are indeed at higher risk to develop BKPyVAN. A higher TTV load and immunosuppressive burden suggest that intense immunosuppression, rather than an "intrinsic attribute" conferred by ABOi, may contribute to this finding.
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Affiliation(s)
- Michael Eder
- Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Tarek A. Schrag
- Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Ella F. Havel
- Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Alexander Kainz
- Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Haris Omic
- Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Konstantin Doberer
- Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | | | - Günther F. Körmöczi
- Department of Transfusion Medicine and Cell Therapy, Medical University of Vienna, Vienna, Austria
| | - Marlies Schönbacher
- Department of Transfusion Medicine and Cell Therapy, Medical University of Vienna, Vienna, Austria
| | - Gottfried Fischer
- Department of Transfusion Medicine and Cell Therapy, Medical University of Vienna, Vienna, Austria
| | - Robert Strassl
- Division of Clinical Virology, Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
| | - Monika Breuer
- Division of Clinical Virology, Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
| | | | - Frederik Haupenthal
- Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Georg A. Böhmig
- Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | | | - Gregor Bond
- Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria
| | - Irene Görzer
- Center for Virology, Medical University of Vienna, Vienna, Austria
| | - Farsad Eskandary
- Division of Nephrology and Dialysis, Department of Medicine III, Medical University of Vienna, Vienna, Austria
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Liefeldt L, Glander P, Friedersdorff F. [Outcome of ABO-incompatible living-donor kidney transplants : A plea for crossover living-donor kidney transplantation]. UROLOGIE (HEIDELBERG, GERMANY) 2024; 63:357-360. [PMID: 38507087 DOI: 10.1007/s00120-024-02316-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 02/26/2024] [Indexed: 03/22/2024]
Abstract
BACKGROUND The lack of postmortem donated organs is the background to varyingly high rates of living-donor kidney transplants worldwide. ABO blood group-incompatible living-donor kidney transplants have also been established for at least 20 years. The equivalence of the results of ABO-incompatible and ABO-compatible transplants has recently been questioned. OBJECTIVE In the sense of a critical reflection of our own kidney transplant program, we were interested in comparing ABO-incompatible with ABO-compatible living-donor kidney transplants. MATERIALS AND METHODS A retrospective analysis of the long-term outcomes of all living-donor kidney transplants performed at our center since the first ABO-incompatible transplants were performed in 2005 up to and including 2022 was performed. RESULTS Between 2005 and 2022, 1099 living kidney transplants were performed at the authors' center. Among them were 241 ABO-incompatible transplants. Transplant survival was significantly lower after ABO-incompatible donation than after ABO-compatible donation. This effect consisted of an increased mortality of the recipients, especially in the early phase, and a reduced longevity of the grafts. CONCLUSION Including ABO-incompatible pairs for living-donor kidney transplants in crossover programs can improve medical outcomes and reduce costs.
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Affiliation(s)
- L Liefeldt
- Medizinische Klinik mit Schwerpunkt Nephrologie und Internistische Intensivmedizin, Charité - Universitätsmedizin Berlin, Charité-Platz 1, 10117, Berlin, Deutschland.
| | - P Glander
- Medizinische Klinik mit Schwerpunkt Nephrologie und Internistische Intensivmedizin, Charité - Universitätsmedizin Berlin, Charité-Platz 1, 10117, Berlin, Deutschland
| | - F Friedersdorff
- Medizinische Klinik mit Schwerpunkt Nephrologie und Internistische Intensivmedizin, Charité - Universitätsmedizin Berlin, Charité-Platz 1, 10117, Berlin, Deutschland
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Matuschik L, Seifert G, Lammich K, Holzner P, Tanriver Y, Fichtner-Feigl S, Walz G, Schneider J, Jänigen B. Non-antigen-specific Immunoadsorption Is a Risk Factor for Severe Postoperative Infections in ABO-Incompatible Kidney Transplant Recipients. Transpl Int 2024; 37:12263. [PMID: 38550626 PMCID: PMC10974667 DOI: 10.3389/ti.2024.12263] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Accepted: 03/01/2024] [Indexed: 04/02/2024]
Abstract
ABO-incompatible (ABOi) living kidney transplantation (KTx) is an established procedure to address the demand for kidney transplants with outcomes comparable to ABO-compatible KTx. Desensitization involves the use of immunoadsorption (IA) to eliminate preformed antibodies against the allograft. This monocentric retrospective study compares single-use antigen-selective Glycosorb® ABO columns to reusable non-antigen-specific Immunosorba® immunoglobulin adsorption columns regarding postoperative infectious complications and outcome. It includes all 138 ABOi KTx performed at Freiburg Transplant Center from 2004-2020. We compare 81 patients desensitized using antigen-specific columns (sIA) to 57 patients who received IA using non-antigen-specific columns (nsIA). We describe distribution of infections, mortality and allograft survival in both groups and use Cox proportional hazards regression to test for the association of IA type with severe infections. Desensitization with nsIA tripled the risk of severe postoperative infections (adjusted HR 3.08, 95% CI: 1.3-8.1) compared to sIA. nsIA was associated with significantly more recurring (21.4% vs. 6.2%) and severe infections (28.6% vs. 8.6%), mostly in the form of urosepsis. A significantly higher proportion of patients with sIA suffered from allograft rejection (29.6% vs. 14.0%). However, allograft survival was comparable. nsIA is associated with a two-fold risk of developing a severe postoperative infection after ABOi KTx.
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Affiliation(s)
- Laura Matuschik
- Department of General and Visceral Surgery, Section of Transplant Surgery, Faculty of Medicine, Medical Center–University of Freiburg, Freiburg, Germany
| | - Gabriel Seifert
- Department of General and Visceral Surgery, Section of Transplant Surgery, Faculty of Medicine, Medical Center–University of Freiburg, Freiburg, Germany
| | - Katrin Lammich
- Department of General and Visceral Surgery, Section of Transplant Surgery, Faculty of Medicine, Medical Center–University of Freiburg, Freiburg, Germany
| | - Philipp Holzner
- Department of General and Visceral Surgery, Section of Transplant Surgery, Faculty of Medicine, Medical Center–University of Freiburg, Freiburg, Germany
| | - Yakup Tanriver
- Department of Medicine IV, Faculty of Medicine, Medical Center–University of Freiburg, Freiburg, Germany
| | - Stefan Fichtner-Feigl
- Department of General and Visceral Surgery, Section of Transplant Surgery, Faculty of Medicine, Medical Center–University of Freiburg, Freiburg, Germany
| | - Gerd Walz
- Department of Medicine IV, Faculty of Medicine, Medical Center–University of Freiburg, Freiburg, Germany
| | - Johanna Schneider
- Department of Medicine IV, Faculty of Medicine, Medical Center–University of Freiburg, Freiburg, Germany
| | - Bernd Jänigen
- Department of General and Visceral Surgery, Section of Transplant Surgery, Faculty of Medicine, Medical Center–University of Freiburg, Freiburg, Germany
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Deng Y, Frischnknecht L, Wehmeier C, de Rougemont O, Villard J, Ferrari-Lacraz S, Golshayan D, Gannagé M, Binet I, Wirthmueller U, Sidler D, Schachtner T, Schaub S, Nilsson J. Pre-transplant donor specific antibodies in ABO incompatible kidney transplantation - data from the Swiss transplant cohort study. Front Immunol 2024; 15:1355128. [PMID: 38361942 PMCID: PMC10867099 DOI: 10.3389/fimmu.2024.1355128] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Accepted: 01/16/2024] [Indexed: 02/17/2024] Open
Abstract
Background Living donor (LD) kidney transplantation in the setting of ABO blood group incompatibility (ABOi) has been previously reported to be associated with increased risk for antibody-mediated rejection (ABMR). It is however unclear if the presence of pre-transplant donor specific antibodies (DSA) works as an additive risk factor in the setting of ABOi and if DSA positive ABOi transplants have a significantly worse long-term outcome as compared with ABO compatible (ABOc) DSA positive transplants. Methods We investigated the effect of pre-transplant DSA in the ABOi and ABOc setting on the risk of antibody-mediated rejection (ABMR) and graft loss in a cohort of 952 LD kidney transplants. Results We found a higher incidence of ABMR in ABOi transplants as compared to ABOc transplants but this did not significantly affect graft survival or overall survival which was similar in both groups. The presence of pre-transplant DSA was associated with a significantly increased risk of ABMR and graft loss both in the ABOi and ABOc setting. We could not detect an additional risk of DSA in the ABOi setting and outcomes were comparable between DSA positive ABOi and ABOc recipients. Furthermore, a combination of DSA directed at both Class I and Class II, as well as DSA with a high mean fluorescence intensity (MFI) showed the strongest relation to ABMR development and graft loss. Conclusion The presence of pre-transplant DSA was associated with a significantly worse long-term outcome in both ABOi and ABOc LD kidney transplants and our results suggests that the risk associated with pre-transplant DSA is perhaps not augmented in the ABOi setting. Our study is the first to investigate the long-term effects of DSA in the ABOi setting and argues that pre-transplant DSA risk could potentially be evaluated similarly regardless of ABO compatibility status.
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Affiliation(s)
- Yun Deng
- Department of Immunology, University Hospital Zurich (USZ), Zurich, Switzerland
| | - Lukas Frischnknecht
- Department of Immunology, University Hospital Zurich (USZ), Zurich, Switzerland
| | - Caroline Wehmeier
- Clinic for Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland
| | - Olivier de Rougemont
- Department of Surgery and Transplantation, University Hospital Zurich, Zurich, Switzerland
| | - Jean Villard
- Transplantation Immunology Unit and National Reference Laboratory for Histocompatibility, Department of Diagnostic, Geneva University Hospitals, Geneva, Switzerland
| | - Sylvie Ferrari-Lacraz
- Transplantation Immunology Unit and National Reference Laboratory for Histocompatibility, Department of Diagnostic, Geneva University Hospitals, Geneva, Switzerland
| | - Déla Golshayan
- Transplantation Center, Lausanne University Hospital, Lausanne, Switzerland
| | - Monique Gannagé
- Service of Immunology and Allergy, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland
| | - Isabelle Binet
- Nephrology & Transplantation Medicine, Cantonal Hospital St. Gallen, St. Gallen, Switzerland
| | - Urs Wirthmueller
- Department of Laboratory Medicine, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland
| | - Daniel Sidler
- Department of Nephrology and Hypertension, Inselspital, Berne University Hospital and University of Berne, Berne, Switzerland
| | - Thomas Schachtner
- Division of Nephrology, University Hospital Zurich, Zurich, Switzerland
| | - Stefan Schaub
- Clinic for Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland
| | - Jakob Nilsson
- Department of Immunology, University Hospital Zurich (USZ), Zurich, Switzerland
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Pawar N, Tiwari V, Gupta A, Divyaveer S, Rather I, Chadha S, Bhargava V, Malik M, Gupta A, Bhalla AK, Rana D, Gupta P. ABO-Incompatible Renal Transplant: A Single-Center Experience from India. Indian J Nephrol 2024; 34:24-30. [PMID: 38645921 PMCID: PMC11003606 DOI: 10.4103/ijn.ijn_247_22] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Accepted: 01/31/2023] [Indexed: 04/23/2024] Open
Abstract
Introduction In view of ever-increasing end-stage renal disease (ESRD) population but inadequate availability of suitable donors, ABO-incompatible (ABOi) transplantation can be an important void filler. However, at present, ABOi transplantation is limited to a few centers in India and there is a lack of adequate experience and expertise to guide this program to other centers in the country. Methods Data of all the ABOi transplants performed from 2012 to 2021 in a tertiary care hospital was retrospectively analyzed. The anti-ABO antibody (IgG) titers (≤1:4) were considered safe before transplantation. Desensitization included rituximab, plasma exchange, or selective immunoadsorption column. Tacrolimus and mycophenolate mofetil were initiated at day -7. Induction agents included ATG, ATLG, basiliximab, or no induction. Postoperatively, anti-ABO titers were done daily for 2 weeks. Results A total of 202 patients underwent transplantation; of these, 195 patients whose data were for available for 12 months were included in the study. Mean duration of follow-up was 28.9 ± 21.7 months. UTI was the most common source of infection, occurring in almost half (46.1%) of the patients. Antibody-mediated rejection (ABMR; 15%) was common in the first year. Patient survival was 86.6% (169/195) at 1 year. Sepsis was the most common of death in more than two-thirds of the population, including coronavirus disease 2019 (COVID-19)-associated mortality in nine patients (4.6%). Death-censored graft survival was 89.3% (174/195). AMR was the leading cause of graft loss in almost half of the patients. Conclusion ABOi should be considered in ESRD patients for whom suitable ABO-compatible donor is not available. Higher rate of rejection and infection are still a major concern.
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Affiliation(s)
- Nikita Pawar
- Department of Nephrology, Sir Ganga Ram Hospital, New Delhi, Delhi, India
| | - Vaibhav Tiwari
- Department of Nephrology, Sir Ganga Ram Hospital, New Delhi, Delhi, India
| | - Anurag Gupta
- Department of Nephrology, Sir Ganga Ram Hospital, New Delhi, Delhi, India
| | - Smita Divyaveer
- Department of Nephrology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Imran Rather
- Department of Pharmacology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Shiv Chadha
- Department of Nephrology, Sir Ganga Ram Hospital, New Delhi, Delhi, India
| | - Vinant Bhargava
- Department of Nephrology, Sir Ganga Ram Hospital, New Delhi, Delhi, India
| | - Manish Malik
- Department of Nephrology, Sir Ganga Ram Hospital, New Delhi, Delhi, India
| | - Ashwani Gupta
- Department of Nephrology, Sir Ganga Ram Hospital, New Delhi, Delhi, India
| | - Anil Kumar Bhalla
- Department of Nephrology, Sir Ganga Ram Hospital, New Delhi, Delhi, India
| | - D.S. Rana
- Department of Nephrology, Sir Ganga Ram Hospital, New Delhi, Delhi, India
| | - Pallav Gupta
- Department of Pathology, Sir Ganga Ram Hospital, New Delhi, Delhi, India
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Ma Y, Man J, Gui H, Niu J, Yang L. Advancement in preoperative desensitization therapy for ABO incompatible kidney transplantation recipients. Transpl Immunol 2023; 80:101899. [PMID: 37433394 DOI: 10.1016/j.trim.2023.101899] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2023] [Revised: 07/04/2023] [Accepted: 07/07/2023] [Indexed: 07/13/2023]
Abstract
ABO incompatibility has long been considered an absolute contraindication for kidney transplantation. However, with the increasing number of patients with ESRD in recent years, ABO-incompatible kidney transplantation (ABOi-KT) has expanded the types of donors by crossing the blood group barrier through preoperative desensitization therapy. At present, the desensitization protocols consist of removal of preexisting ABO blood group antibody titers and prevention of ABO blood group antibody return. Studies have suggested similar patient and graft survival among ABOi-KT and ABOc-KT recipients. In this review, we will summarize the effective desensitization regimens of ABOi-KT, aiming to explore effective ways to improve the success rate and the long-term survival rate of ABOi-KT recipients.
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Affiliation(s)
- Yuhua Ma
- Department of Urology, The Second Hospital of Lanzhou University, Lanzhou, China; Gansu Province Clinical Research Center for Urology, Lanzhou, China; Second Clinical School, Lanzhou University, Lanzhou, China
| | - Jiangwei Man
- Department of Urology, The Second Hospital of Lanzhou University, Lanzhou, China; Gansu Province Clinical Research Center for Urology, Lanzhou, China; Second Clinical School, Lanzhou University, Lanzhou, China
| | - Huiming Gui
- Department of Urology, The Second Hospital of Lanzhou University, Lanzhou, China; Gansu Province Clinical Research Center for Urology, Lanzhou, China
| | - Jiping Niu
- Department of Urology, The Second Hospital of Lanzhou University, Lanzhou, China; Gansu Province Clinical Research Center for Urology, Lanzhou, China
| | - Li Yang
- Department of Urology, The Second Hospital of Lanzhou University, Lanzhou, China; Gansu Province Clinical Research Center for Urology, Lanzhou, China; Second Clinical School, Lanzhou University, Lanzhou, China.
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Bleasel JM, Wan SS, Chadban SJ, Ying T, Gracey DM, Aouad LJ, Chen QA, Utsiwegota M, Mawson J, Wyburn KR. ABO Incompatible Kidney Transplantation Without B-cell Depletion is Associated With Increased Early Acute Rejection: A Single-Center Australian Experience. Transpl Int 2023; 36:11567. [PMID: 37799670 PMCID: PMC10547868 DOI: 10.3389/ti.2023.11567] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Accepted: 09/12/2023] [Indexed: 10/07/2023]
Abstract
We performed a single-center retrospective cohort study of 66 consecutive ABO incompatible kidney transplants (ABOiKT) performed without B-cell depleting therapy. Outcomes were compared to an earlier era performed with rituximab (n = 18) and a contemporaneous cohort of ABO compatible live donor transplants (ABOcKT). Acute rejection within 3 months of transplant was significantly more common after rituximab-free ABOiKT compared to ABOiKT with rituximab (OR 8.8, p = 0.04) and ABOcKT (OR 2.9, p = 0.005) in adjusted analyses. Six recipients of rituximab-free ABOiKT experienced refractory antibody mediated rejection requiring splenectomy, and a further two incurred early graft loss with no such episodes amongst ABOiKT with rituximab or ABOcKT cohorts. Patient and graft survival were similar between groups over a median follow-up of 3.1 years. This observational evidence lends strong support to the continued inclusion of rituximab in desensitization protocols for ABOiKT.
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Affiliation(s)
- Jonathan M. Bleasel
- Department of Renal Medicine, Royal Prince Alfred Hospital, Sydney, NSW, Australia
| | - Susan S. Wan
- Department of Renal Medicine, Royal Prince Alfred Hospital, Sydney, NSW, Australia
- Kidney Node, Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia
| | - Steven J. Chadban
- Department of Renal Medicine, Royal Prince Alfred Hospital, Sydney, NSW, Australia
- Kidney Node, Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia
- Central Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia
| | - Tracey Ying
- Department of Renal Medicine, Royal Prince Alfred Hospital, Sydney, NSW, Australia
- Kidney Node, Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia
- Central Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia
| | - David M. Gracey
- Department of Renal Medicine, Royal Prince Alfred Hospital, Sydney, NSW, Australia
- Central Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia
| | - Leyla J. Aouad
- Department of Renal Medicine, Royal Prince Alfred Hospital, Sydney, NSW, Australia
- Kidney Node, Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia
- Central Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia
| | - Qian-Ao Chen
- Central Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia
| | - Mike Utsiwegota
- Department of Renal Medicine, Royal Prince Alfred Hospital, Sydney, NSW, Australia
| | - Jane Mawson
- Department of Renal Medicine, Royal Prince Alfred Hospital, Sydney, NSW, Australia
| | - Kate R. Wyburn
- Department of Renal Medicine, Royal Prince Alfred Hospital, Sydney, NSW, Australia
- Kidney Node, Charles Perkins Centre, University of Sydney, Sydney, NSW, Australia
- Central Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia
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Nakajima D, Yuasa I, Kayawake H, Tanaka S, Yamada Y, Yutaka Y, Hamaji M, Ohsumi A, Ikeda T, Suga T, Baba S, Hiramatsu H, Date H. The first successful case of ABO-incompatible living-donor lobar lung transplantation following desensitization therapy. Am J Transplant 2023; 23:1451-1454. [PMID: 37149042 DOI: 10.1016/j.ajt.2023.04.031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2023] [Revised: 04/12/2023] [Accepted: 04/28/2023] [Indexed: 05/08/2023]
Abstract
ABO-incompatible (ABO-I) living-donor lobar lung transplantation (LDLLT) was successfully performed in a 14-year-old girl who suffered from bronchiolitis obliterans due to graft-versus-host disease following hematopoietic stem cell transplantation. In the ABO-I LDLLT procedure, the blood type O patient received a right lower lobe donated from her blood type B father and a left lower lobe donated from her blood type O mother. Desensitization therapy, using rituximab, immunosuppressants, and plasmapheresis, was implemented for 3 weeks prior to transplantation to reduce the production of anti-B antibodies in the recipient and prevent acute antibody-mediated rejection after ABO-I LDLLT.
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Affiliation(s)
- Daisuke Nakajima
- Department of Thoracic Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
| | - Itsuki Yuasa
- Department of Thoracic Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Hidenao Kayawake
- Department of Thoracic Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Satona Tanaka
- Department of Thoracic Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Yoshito Yamada
- Department of Thoracic Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Yojiro Yutaka
- Department of Thoracic Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Masatsugu Hamaji
- Department of Thoracic Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Akihiro Ohsumi
- Department of Thoracic Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Tadashi Ikeda
- Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Takenori Suga
- Department of Pediatrics, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Shiro Baba
- Department of Pediatrics, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Hidefumi Hiramatsu
- Department of Pediatrics, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Hiroshi Date
- Department of Thoracic Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
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Jadaun SS, Agarwal S, Gupta S, Saigal S. Strategies for ABO Incompatible Liver Transplantation. J Clin Exp Hepatol 2023; 13:698-706. [PMID: 37440942 PMCID: PMC10333949 DOI: 10.1016/j.jceh.2022.12.008] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2022] [Accepted: 12/18/2022] [Indexed: 07/15/2023] Open
Abstract
Liver transplantation (LT) is a definitive treatment for the decompensated liver cirrhosis and fulminant liver failure. With limited availability of cadaveric liver allograft, ABO incompatible (ABOi) living donor liver transplantation (LDLT) plays an important part in further expansion of donor pool. Over the years, with the introduction of Rituximab and improving desensitisation protocol, outcomes of ABOi LDLT are on par with ABO compatible LT. However, ABOi LDLT protocol varies markedly from centre to centre. Intravenous Rituximab followed by plasmapheresis or immunoadsorption effectively reduce ABO isoagglutinins titre before transplant, thereby reducing the risk of antibody mediated rejection in the post-transplant period. Local infusion therapy and splenectomy are not used routinely at most of the centres in Rituximab era. Post-transplant immunosuppression usually consists of standard triple drug regime, and tacrolimus trough levels are targeted at higher level compared to ABO compatible LT. Introduction of newer therapies like Belatacept and Obinutuzumab hold promise to further improve outcomes and reduce the risk of antibody mediated rejection related complications. ABOi LT in emergency situations like acute liver failure and deceased donor LT is challenging due to limited time period for desensitisation protocol before transplant, and available evidence are still limited but encouraging.
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Affiliation(s)
- Shekhar S. Jadaun
- Department of Gastroenterology and Hepatology, Centre for Liver and Biliary Sciences, Max Super Speciality Hospital, Saket, New Delhi, India
| | - Shaleen Agarwal
- Liver Transplant and Gastrointestinal Surgery, Centre for Liver and Biliary Sciences, Max Super Speciality Hospital, Saket, New Delhi, India
| | - Subhash Gupta
- Liver Transplant and Gastrointestinal Surgery, Centre for Liver and Biliary Sciences, Max Super Speciality Hospital, Saket, New Delhi, India
| | - Sanjiv Saigal
- Department of Gastroenterology and Hepatology, Centre for Liver and Biliary Sciences, Max Super Speciality Hospital, Saket, New Delhi, India
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10
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Galili U. Antibody production and tolerance to the α-gal epitope as models for understanding and preventing the immune response to incompatible ABO carbohydrate antigens and for α-gal therapies. Front Mol Biosci 2023; 10:1209974. [PMID: 37449060 PMCID: PMC10338101 DOI: 10.3389/fmolb.2023.1209974] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2023] [Accepted: 06/09/2023] [Indexed: 07/18/2023] Open
Abstract
This review describes the significance of the α-gal epitope (Galα-3Galβ1-4GlcNAc-R) as the core of human blood-group A and B antigens (A and B antigens), determines in mouse models the principles underlying the immune response to these antigens, and suggests future strategies for the induction of immune tolerance to incompatible A and B antigens in human allografts. Carbohydrate antigens, such as ABO antigens and the α-gal epitope, differ from protein antigens in that they do not interact with T cells, but B cells interacting with them require T-cell help for their activation. The α-gal epitope is the core of both A and B antigens and is the ligand of the natural anti-Gal antibody, which is abundant in all humans. In A and O individuals, anti-Gal clones (called anti-Gal/B) comprise >85% of the so-called anti-B activity and bind to the B antigen in facets that do not include fucose-linked α1-2 to the core α-gal. As many as 1% of B cells are anti-Gal B cells. Activation of quiescent anti-Gal B cells upon exposure to α-gal epitopes on xenografts and some protozoa can increase the titer of anti-Gal by 100-fold. α1,3-Galactosyltransferase knockout (GT-KO) mice lack α-gal epitopes and can produce anti-Gal. These mice simulate human recipients of ABO-incompatible human allografts. Exposure for 2-4 weeks of naïve and memory mouse anti-Gal B cells to α-gal epitopes in the heterotopically grafted wild-type (WT) mouse heart results in the elimination of these cells and immune tolerance to this epitope. Shorter exposures of 7 days of anti-Gal B cells to α-gal epitopes in the WT heart result in the production of accommodating anti-Gal antibodies that bind to α-gal epitopes but do not lyse cells or reject the graft. Tolerance to α-gal epitopes due to the elimination of naïve and memory anti-Gal B cells can be further induced by 2 weeks in vivo exposure to WT lymphocytes or autologous lymphocytes engineered to present α-gal epitopes by transduction of the α1,3-galactosyltransferase gene. These mouse studies suggest that autologous human lymphocytes similarly engineered to present the A or B antigen may induce corresponding tolerance in recipients of ABO-incompatible allografts. The review further summarizes experimental works demonstrating the efficacy of α-gal therapies in amplifying anti-viral and anti-tumor immune-protection and regeneration of injured tissues.
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Affiliation(s)
- Uri Galili
- Department of Medicine, Rush University Medical College, Chicago, IL, United States
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11
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Okada M, Narumi S, Hasegawa Y, Futamura K, Hiramitsu T, Ichimori T, Goto N, Kobayashi T, Uchida K, Takeda A, Watarai Y. Optimal dose of rituximab in ABO-incompatible kidney transplantation in patients with low anti-A/B antibody titers: A single-center retrospective cohort study. Clin Transplant 2023; 37:e14915. [PMID: 36634703 DOI: 10.1111/ctr.14915] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 11/28/2022] [Accepted: 01/07/2023] [Indexed: 01/14/2023]
Abstract
BACKGROUND The clinical outcomes of ABO-incompatible (ABOi) kidney transplantation have improved with the introduction of desensitization therapy with rituximab. However, rituximab prevents not only antibody-mediated rejection (AMR) but also increases the risk of adverse events, such as infection. For ABOi kidney transplantation in patients with low anti-A/B antibody titers, we previously used a rituximab-free desensitization protocol and then initiated a single dose of 100 mg rituximab in 2016. We retrospectively compared the outcomes of ABOi kidney transplantation in patients with low anti-A/B antibody titers before and after the introduction of rituximab. METHODS ABOi kidney transplantations (n = 142) in patients with low anti-A/B antibody titers between 2007 and 2021 were included. Patients were divided into two groups (with and without rituximab) for desensitization. The primary outcomes were the incidence of acute AMR and infection. RESULTS Sixty-six patients were desensitized without rituximab (rituximab-free group), and 76 were pretreated with 100 mg rituximab (rituximab group) before transplantation. The incidence of acute AMR was significantly lower in the rituximab group than in the rituximab-free group (.0% [0/76] vs. 7.6% [5/66], respectively; p = .047). Post-transplantation anti-A/B antibody titers were also lower in the rituximab group than in the rituximab-free group. There was no significant difference in the incidence of adverse events, including infections, between the two groups. CONCLUSION In ABOi kidney transplantation patients with low anti-A/B antibody titers, the desensitization protocol with a single dose of 100 mg rituximab was effective in preventing acute AMR without increasing the risk of other adverse events.
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Affiliation(s)
- Manabu Okada
- Department of Transplant Surgery, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital, Nagoya, Japan.,Department of Transplant Nephrology, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital, Nagoya, Japan
| | - Shunji Narumi
- Department of Transplant Surgery, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital, Nagoya, Japan.,Department of Transplant Nephrology, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital, Nagoya, Japan
| | - Yuki Hasegawa
- Department of Transplant Surgery, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital, Nagoya, Japan.,Department of Transplant Nephrology, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital, Nagoya, Japan
| | - Kenta Futamura
- Department of Transplant Surgery, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital, Nagoya, Japan.,Department of Transplant Nephrology, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital, Nagoya, Japan
| | - Takahisa Hiramitsu
- Department of Transplant Surgery, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital, Nagoya, Japan.,Department of Transplant Nephrology, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital, Nagoya, Japan
| | - Toshihiro Ichimori
- Department of Transplant Surgery, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital, Nagoya, Japan.,Department of Transplant Nephrology, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital, Nagoya, Japan
| | - Norihiko Goto
- Department of Transplant Surgery, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital, Nagoya, Japan.,Department of Transplant Nephrology, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital, Nagoya, Japan
| | - Takaaki Kobayashi
- Department of Renal Transplant Surgery, Aichi Medical University School of Medicine, Nagakute, Japan
| | - Kazuharu Uchida
- Department of Renal Transplant Surgery, Masuko Memorial Hospital, Nagoya, Japan
| | - Asami Takeda
- Department of Nephrology, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital, Nagoya, Japan
| | - Yoshihiko Watarai
- Department of Transplant Surgery, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital, Nagoya, Japan.,Department of Transplant Nephrology, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital, Nagoya, Japan
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12
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Frutos MÁ, Crespo M, Valentín MDLO, Alonso-Melgar Á, Alonso J, Fernández C, García-Erauzkin G, González E, González-Rinne AM, Guirado L, Gutiérrez-Dalmau A, Huguet J, Moral JLLD, Musquera M, Paredes D, Redondo D, Revuelta I, Hofstadt CJVD, Alcaraz A, Alonso-Hernández Á, Alonso M, Bernabeu P, Bernal G, Breda A, Cabello M, Caro-Oleas JL, Cid J, Diekmann F, Espinosa L, Facundo C, García M, Gil-Vernet S, Lozano M, Mahillo B, Martínez MJ, Miranda B, Oppenheimer F, Palou E, Pérez-Saez MJ, Peri L, Rodríguez O, Santiago C, Tabernero G, Hernández D, Domínguez-Gil B, Pascual J. Recommendations for living donor kidney transplantation. Nefrologia 2022; 42 Suppl 2:5-132. [PMID: 36503720 DOI: 10.1016/j.nefroe.2022.07.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Accepted: 10/26/2021] [Indexed: 06/17/2023] Open
Abstract
This Guide for Living Donor Kidney Transplantation (LDKT) has been prepared with the sponsorship of the Spanish Society of Nephrology (SEN), the Spanish Transplant Society (SET), and the Spanish National Transplant Organization (ONT). It updates evidence to offer the best chronic renal failure treatment when a potential living donor is available. The core aim of this Guide is to supply clinicians who evaluate living donors and transplant recipients with the best decision-making tools, to optimise their outcomes. Moreover, the role of living donors in the current KT context should recover the level of importance it had until recently. To this end the new forms of incompatible HLA and/or ABO donation, as well as the paired donation which is possible in several hospitals with experience in LDKT, offer additional ways to treat renal patients with an incompatible donor. Good results in terms of patient and graft survival have expanded the range of circumstances under which living renal donors are accepted. Older donors are now accepted, as are others with factors that affect the decision, such as a borderline clinical history or alterations, which when evaluated may lead to an additional number of transplantations. This Guide does not forget that LDKT may lead to risk for the donor. Pre-donation evaluation has to centre on the problems which may arise over the short or long-term, and these have to be described to the potential donor so that they are able take them into account. Experience over recent years has led to progress in risk analysis, to protect donors' health. This aspect always has to be taken into account by LDKT programmes when evaluating potential donors. Finally, this Guide has been designed to aid decision-making, with recommendations and suggestions when uncertainties arise in pre-donation studies. Its overarching aim is to ensure that informed consent is based on high quality studies and information supplied to donors and recipients, offering the strongest possible guarantees.
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Affiliation(s)
| | - Marta Crespo
- Nephrology Department, Hospital del Mar, Barcelona, Spain
| | | | | | - Juana Alonso
- Nephrology Department, Hospital Regional Universitario de Málaga, Spain
| | | | | | - Esther González
- Nephrology Department, Hospital Universitario 12 Octubre, Spain
| | | | - Lluis Guirado
- Nephrology Department, Fundacio Puigvert, Barcelona, Spain
| | | | - Jorge Huguet
- RT Surgical Team, Fundació Puigvert, Barcelona, Spain
| | | | - Mireia Musquera
- Urology Department, Hospital Clinic Universitari, Barcelona, Spain
| | - David Paredes
- Donation and Transplantation Coordination Department, Hospital Clinic Universitari, Barcelona, Spain
| | | | - Ignacio Revuelta
- Nephrology and RT Department, Hospital Clinic Universitari, Barcelona, Spain
| | | | - Antonio Alcaraz
- Urology Department, Hospital Clinic Universitari, Barcelona, Spain
| | | | - Manuel Alonso
- Regional Transplantation Coordination, Seville, Spain
| | | | - Gabriel Bernal
- Nephrology Department, Hospital Universitario Virgen del Rocío, Seville, Spain
| | - Alberto Breda
- RT Surgical Team, Fundació Puigvert, Barcelona, Spain
| | - Mercedes Cabello
- Nephrology Department, Hospital Regional Universitario de Málaga, Spain
| | | | - Joan Cid
- Apheresis and Cell Therapy Unit, Haemotherapy and Haemostasis Department, Hospital Clinic Universitari, Barcelona, Spain
| | - Fritz Diekmann
- Nephrology and RT Department, Hospital Clinic Universitari, Barcelona, Spain
| | - Laura Espinosa
- Paediatric Nephrology Department, Hospital La Paz, Madrid, Spain
| | - Carme Facundo
- Nephrology Department, Fundacio Puigvert, Barcelona, Spain
| | | | | | - Miquel Lozano
- Apheresis and Cell Therapy Unit, Haemotherapy and Haemostasis Department, Hospital Clinic Universitari, Barcelona, Spain
| | | | | | | | | | - Eduard Palou
- Immunology Department, Hospital Clinic i Universitari, Barcelona, Spain
| | | | - Lluis Peri
- Urology Department, Hospital Clinic Universitari, Barcelona, Spain
| | | | | | | | - Domingo Hernández
- Nephrology Department, Hospital Regional Universitario de Málaga, Spain
| | | | - Julio Pascual
- Nephrology Department, Hospital del Mar, Barcelona, Spain.
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13
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Cozzi M, Donato P, Ugolini G, Nguefouet Momo RE, Nacchia F, Ballarini Z, Piccoli P, Cantini M, Caletti C, Andreola S, Gandini G, Gambaro G, Boschiero L. Outcomes in AB0 Incompatible Living Donor Kidney Transplantation: A Case – Control Study. Front Med (Lausanne) 2022; 9:932171. [PMID: 35935799 PMCID: PMC9353324 DOI: 10.3389/fmed.2022.932171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Accepted: 06/20/2022] [Indexed: 11/13/2022] Open
Abstract
BackgroundPatients waiting for a kidney transplant by far exceed available organs. AB0 incompatible living donor kidney transplantation (AB0i LDKT) represents an additional therapeutic strategy, but with higher risk for complications. We aimed at evaluating outcomes of AB0i LDKTs compared to compatible (AB0c) controls at our Institution.MethodsRetrospective matched case – control study (1:2) comparing AB0i vs. AB0c LDKTs from March 2012 to September 2021. Considered outcomes: graft function, acute rejection, sepsis, CMV infection, BK virus reactivation, death-censored graft survival, patient survival.ResultsSeventeen AB0i LDKTs matched to 34 AB0c controls. We found excellent graft function, comparable in the two groups, at all considered intervals, with an eGFR (ml/min/1.73 m2) of 67 vs. 66 at 1 year (p = 0.41), 63 vs. 64 at 3 years (p = 0.53). AB0i recipients had a statistically significant higher incidence of acute rejection, acute antibody-mediated rejection and sepsis within 30 days (p = 0.016; p = 0.02; p = 0.001), 1 year (p = 0.012; p = 0.02; p = 0.0004) and 3 years (p = 0.004; p = 0.006; p = 0.012) after surgery. There was no difference in CMV infection, BK virus reactivation, death-censored graft survival between the two groups. Patient survival was inferior in AB0i group at 1 and 3 years (88.2 vs. 100%; log-rank p = 0.03) due to early death for opportunistic infections. AB0i LDKTs spent longer time on dialysis (p = 0.04) and 82.3 vs. 38.3% controls had blood group 0 (p = 0.003).ConclusionsAB0i LDKT is an effective therapeutic strategy with graft function and survival comparable to AB0c LDKTs, despite higher rates of acute rejection and sepsis. It is an additional opportunity for patients with less chances of being transplanted, as blood group 0 individuals.
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Affiliation(s)
- Martina Cozzi
- Kidney Transplant Center, Department of Surgical Sciences, University and Hospital Trust of Verona, Verona, Italy
- Nephrology Postgraduate School, Department of Medicine, University of Verona, Verona, Italy
- *Correspondence: Martina Cozzi
| | - Paola Donato
- Kidney Transplant Center, Department of Surgical Sciences, University and Hospital Trust of Verona, Verona, Italy
| | - Gabriele Ugolini
- Kidney Transplant Center, Department of Surgical Sciences, University and Hospital Trust of Verona, Verona, Italy
| | | | - Francesco Nacchia
- Kidney Transplant Center, Department of Surgical Sciences, University and Hospital Trust of Verona, Verona, Italy
| | - Zeno Ballarini
- Kidney Transplant Center, Department of Surgical Sciences, University and Hospital Trust of Verona, Verona, Italy
| | - Pierluigi Piccoli
- Transfusion Medicine Unit, Department of Pathology and Diagnostic Services, University and Hospital Trust of Verona, Verona, Italy
| | - Maurizio Cantini
- Transfusion Medicine Unit, Department of Pathology and Diagnostic Services, University and Hospital Trust of Verona, Verona, Italy
| | - Chiara Caletti
- Renal Unit, Department of Medicine, University and Hospital Trust of Verona, Verona, Italy
| | - Stefano Andreola
- Nephrology Postgraduate School, Department of Medicine, University of Verona, Verona, Italy
- Renal Unit, Department of Medicine, University and Hospital Trust of Verona, Verona, Italy
| | - Giorgio Gandini
- Transfusion Medicine Unit, Department of Pathology and Diagnostic Services, University and Hospital Trust of Verona, Verona, Italy
| | - Giovanni Gambaro
- Nephrology Postgraduate School, Department of Medicine, University of Verona, Verona, Italy
- Renal Unit, Department of Medicine, University and Hospital Trust of Verona, Verona, Italy
| | - Luigino Boschiero
- Kidney Transplant Center, Department of Surgical Sciences, University and Hospital Trust of Verona, Verona, Italy
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14
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Recomendaciones para el trasplante renal de donante vivo. Nefrologia 2022. [DOI: 10.1016/j.nefro.2021.10.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
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15
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Eskandary F, Böhmig GA. ABO-Incompatibility: Time to Challenge the Paradigm of Equivalence in Live-Donor Kidney Transplantation? Transpl Int 2022; 35:10281. [PMID: 35210935 PMCID: PMC8862175 DOI: 10.3389/ti.2022.10281] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2021] [Accepted: 01/18/2022] [Indexed: 11/13/2022]
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16
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Jha PK, Bansal SB, Rana A, Nandwani A, Kher A, Sethi S, Jain M, Bansal D, Yadav DK, Gadde A, Mahapatra AK, Sodhi P, Ahlawat R, Kher V. ABO-Incompatible Kidney Transplantation in India: A Single-Center Experience of First Hundred Cases. Indian J Nephrol 2022; 32:42-46. [PMID: 35283580 PMCID: PMC8916160 DOI: 10.4103/ijn.ijn_465_20] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2020] [Revised: 10/24/2020] [Accepted: 11/30/2020] [Indexed: 11/04/2022] Open
Abstract
AIM ABO-incompatible (ABOi) kidney transplantation overcomes immunological barrier of blood group incompatibility. There have been very few published experiences of ABOi kidney transplantation from India. We present our single-center experience of the first hundred ABOi kidney transplants. MATERIAL AND METHODS This is a single-center retrospective study of consecutive first hundred ABOi kidney transplant with at least 6 months of follow-up. RESULTS During the study period (2011-2020), a total of 121 ABOi kidney transplants were performed. Of these, first hundred patients were analyzed. Median follow-up duration was 33 (10-101) months. Mean recipient and donor age were 41.5 ± 13 and 47.68 ± 11.25 years, respectively. Mean HLA mismatch was 4 ± 1.5. Median baseline anti-blood group antibody titer was 128 (2-1024). Most common recipient blood group was O. Patient and death censored graft survival was 93% and 94%, respectively, at median follow-up of 33 months. Biopsy-proven acute rejection (BPAR) rate was 17% with acute antibody-mediated rejection being 3%. Rate of infection was 37%, most common being urinary tract infection. CONCLUSION ABOi kidney transplant patients had acceptable patient and graft survival as well as BPAR rates. With current preconditioning protocol, infection rate was high.
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Affiliation(s)
- Pranaw Kumar Jha
- Department of Nephrology, Medanta – The Medicity, Sector 38, Gurugram, Haryana, India
| | - Shyam Bihari Bansal
- Department of Nephrology, Medanta – The Medicity, Sector 38, Gurugram, Haryana, India
| | - Abhyudaysingh Rana
- Department of Nephrology, Medanta – The Medicity, Sector 38, Gurugram, Haryana, India
| | - Ashish Nandwani
- Department of Nephrology, Medanta – The Medicity, Sector 38, Gurugram, Haryana, India
| | - Ajay Kher
- Department of Nephrology, Max Super Specialty Hospital, Vaishali, Ghaziabad, Uttar Pradesh, India
| | - Sidharth Sethi
- Department of Nephrology, Medanta – The Medicity, Sector 38, Gurugram, Haryana, India
| | - Manish Jain
- Department of Nephrology, Medanta – The Medicity, Sector 38, Gurugram, Haryana, India
| | - Dinesh Bansal
- Department of Nephrology, Medanta – The Medicity, Sector 38, Gurugram, Haryana, India
| | - Dinesh Kumar Yadav
- Department of Nephrology, Medanta – The Medicity, Sector 38, Gurugram, Haryana, India
| | - Ashwini Gadde
- Department of Nephrology, Medanta – The Medicity, Sector 38, Gurugram, Haryana, India
| | - Amit Kumar Mahapatra
- Department of Nephrology, Medanta – The Medicity, Sector 38, Gurugram, Haryana, India
| | - Puneet Sodhi
- Department of Nephrology, Medanta – The Medicity, Sector 38, Gurugram, Haryana, India
| | - Rajesh Ahlawat
- Department of Urology, Medanta Institute of Kidney and Urology, Gurugram, Haryana, India
| | - Vijay Kher
- Department of Nephrology, Medanta – The Medicity, Sector 38, Gurugram, Haryana, India
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17
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de Weerd AE, van den Brand JAJG, Bouwsma H, de Vries APJ, Dooper IPMM, Sanders JSF, Christiaans MHL, van Reekum FE, van Zuilen AD, Bemelman FJ, Nurmohamed AS, van Agteren M, Betjes MGH, de Jong MFC, Baas MC. ABO-incompatible kidney transplantation in perspective of deceased donor transplantation and induction strategies: a propensity-matched analysis. Transpl Int 2021; 34:2706-2719. [PMID: 34687095 PMCID: PMC9299000 DOI: 10.1111/tri.14145] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 10/13/2021] [Accepted: 10/20/2021] [Indexed: 01/10/2023]
Abstract
Kidney transplant candidates are blood group incompatible with roughly one out of three potential living donors. We compared outcomes after ABO‐incompatible (ABOi) kidney transplantation with matched ABO‐compatible (ABOc) living and deceased donor transplantation and analyzed different induction regimens. We performed a retrospective study with propensity matching and compared patient and death‐censored graft survival after ABOi versus ABOc living donor and deceased donor kidney transplantation in a nationwide registry from 2006 till 2019. 296 ABOi were compared with 1184 center and propensity‐matched ABOc living donor and 1184 deceased donor recipients (matching: recipient age, sex, blood group, and PRA). Patient survival was better compared with deceased donor [hazard ratio (HR) for death of HR 0.69 (0.49–0.96)] and non‐significantly different from ABOc living donor recipients [HR 1.28 (0.90–1.81)]. Rate of graft failure was higher compared with ABOc living donor transplantation [HR 2.63 (1.72–4.01)]. Rejection occurred in 47% of 140 rituximab versus 22% of 50 rituximab/basiliximab, and 4% of 92 alemtuzumab‐treated recipients (P < 0.001). ABOi kidney transplantation is superior to deceased donor transplantation. Rejection rate and graft failure are higher compared with matched ABOc living donor transplantation, underscoring the need for further studies into risk stratification and induction therapy [NTR7587, www.trialregister.nl].
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Affiliation(s)
- Annelies E de Weerd
- Department of Internal Medicine, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Jan A J G van den Brand
- Department of Nephrology, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Hanneke Bouwsma
- Department of Nephrology and Leiden Transplant Center, LUMC Leiden University Medical Center, Leiden, The Netherlands
| | - Aiko P J de Vries
- Department of Nephrology and Leiden Transplant Center, LUMC Leiden University Medical Center, Leiden, The Netherlands
| | - Ine Ph M M Dooper
- Department of Nephrology, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Jan-Stephan F Sanders
- Department of Nephrology, University Medical Center Groningen, Groningen, The Netherlands
| | | | - Franka E van Reekum
- Department of Nephrology, Utrecht University Medical Center, Utrecht, The Netherlands
| | - Arjan D van Zuilen
- Department of Nephrology, Utrecht University Medical Center, Utrecht, The Netherlands
| | - Frederike J Bemelman
- Department of Nephrology, Amsterdam University Medical Center, Amsterdam, The Netherlands
| | - Azam S Nurmohamed
- Department of Nephrology, Amsterdam University Medical Center, Amsterdam, The Netherlands
| | - Madelon van Agteren
- Department of Internal Medicine, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Michiel G H Betjes
- Department of Internal Medicine, Erasmus MC Transplant Institute, University Medical Center Rotterdam, Rotterdam, The Netherlands
| | - Margriet F C de Jong
- Department of Nephrology, University Medical Center Groningen, Groningen, The Netherlands
| | - Marije C Baas
- Department of Nephrology, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands
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18
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Liu J, Wang D. ABO(H) and Lewis blood group substances and disease treatment. Transfus Med 2021; 32:187-192. [PMID: 34569102 DOI: 10.1111/tme.12820] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Revised: 08/16/2021] [Accepted: 09/07/2021] [Indexed: 11/29/2022]
Abstract
Since the early 20th century, scientists have determined that blood group antigens can be inherited. With more and more studies have been devoted to finding the relationship between blood groups and diseases, the relationship of ABO(H) and Lewis blood groups and the development of human diseases have been summarised. In addition, many studies have shown that blood group substances, such as blood group antigen or related antibody, play an important role in disease prevention and treatment. This review focuses on the advances of ABO(H), Lewis blood group substances in the treatment of diseases, which has important significance for the development of novel therapeutic methods.
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Affiliation(s)
- Junting Liu
- Department of Transfusion Medicine, The First Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Deqing Wang
- Department of Transfusion Medicine, The First Medical Center of Chinese PLA General Hospital, Beijing, China
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19
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Nobakht E, Jagadeesan M, Paul R, Bromberg J, Dadgar S. Precision Medicine in Kidney Transplantation: Just Hype or a Realistic Hope? Transplant Direct 2021; 7:e650. [PMID: 33437865 PMCID: PMC7793397 DOI: 10.1097/txd.0000000000001102] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Revised: 10/27/2020] [Accepted: 10/29/2020] [Indexed: 12/17/2022] Open
Abstract
Desirable outcomes including rejection- and infection-free kidney transplantation are not guaranteed despite current strategies for immunosuppression and using prophylactic antimicrobial medications. Graft survival depends on factors beyond human leukocyte antigen matching such as the level of immunosuppression, infections, and management of other comorbidities. Risk stratification of transplant patients based on predisposing genetic modifiers and applying precision pharmacotherapy may help improving the transplant outcomes. Unlike certain fields such as oncology in which consistent attempts are being carried out to move away from the "error and trial approach," transplant medicine is lagging behind in implementing personalized immunosuppressive therapy. The need for maintaining a precarious balance between underimmunosuppression and overimmunosuppression coupled with adverse effects of medications calls for a gene-based guidance for precision pharmacotherapy in transplantation. Technologic advances in molecular genetics have led to increased accessibility of genetic tests at a reduced cost and have set the stage for widespread use of gene-based therapies in clinical care. Evidence-based guidelines available for precision pharmacotherapy have been proposed, including guidelines from Clinical Pharmacogenetics Implementation Consortium, the Pharmacogenomics Knowledge Base National Institute of General Medical Sciences of the National Institutes of Health, and the US Food and Drug Administration. In this review, we discuss the implications of pharmacogenetics and potential role for genetic variants-based risk stratification in kidney transplantation. A single score that provides overall genetic risk, a polygenic risk score, can be achieved by combining of allograft rejection/loss-associated variants carried by an individual and integrated into practice after clinical validation.
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Affiliation(s)
- Ehsan Nobakht
- Division of Renal Diseases and Hypertension, Department of Medicine, George Washington University School of Medicine, Washington, DC
| | - Muralidharan Jagadeesan
- Division of Renal Diseases and Hypertension, Department of Medicine, George Washington University School of Medicine, Washington, DC
| | - Rohan Paul
- Division of Renal Diseases and Hypertension, Department of Medicine, George Washington University School of Medicine, Washington, DC
| | - Jonathan Bromberg
- Department of Surgery, University of Maryland School of Medicine, Baltimore, MD
| | - Sherry Dadgar
- Division of Renal Diseases and Hypertension, Department of Medicine, George Washington University School of Medicine, Washington, DC
- Personalized Medicine Care Diagnostics Laboratory (PMCDx), Inc., Germantown, MD
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Mukherjee D, Hooda A, Jairam A, Nair RK, Sharma S. Use of immunoadsorption columns in ABO-incompatible renal transplantation: A prospective study at a tertiary care center in India. Med J Armed Forces India 2021; 77:15-21. [PMID: 33487860 PMCID: PMC7809516 DOI: 10.1016/j.mjafi.2019.08.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2019] [Accepted: 08/25/2019] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND We present our experience of ABO-incompatible renal transplant using immunoadsorption (IA) columns. We have compared efficacy of two commercially available columns. METHODS This single-center prospective study was conducted at Army Hospital Research and Referral, Delhi. All consecutive ABO-incompatible renal transplants from January 2014 to February 2018 were analyzed. Of 30 patients who underwent transplantations, 28 underwent antibody depletion with immunoadsorption columns. Of them, 14 cases were in the "Glycosorb group," while 14 in the "Adsopak group." RESULTS The donors in the Adsopak group were older than those in the Glycosorb group (p < 0.05). Both groups had spousal donors in majority. The cutoff for the antibody titer was 1:8. The median titer in the Adsopak group was 128 (range, 1:4 to 1:2048), while that in the Glycosorb group was 24 (range, 1:8 to 1:128). All patients in the Glycosorb group had baseline titers ≤1:128, while 13 patients in the Adsopak group had baseline titers ≤1:512. Nil titer was achievable with Glycosorb® (50%,7/14) but not with Adsopak® (P < 0.01). Around 4 sessions were required for the Glycosorb group, while around 8 sessions were required for the Adsopak group before transplantation (p < 0.001). The Glycosorb group was advantageous in terms of graft failure because no rejection was noticed in these patients in their follow-up period. Three patients in the Adsopak group developed rejection (two had mixed rejection, and one had antibody-mediated rejection). Four patients died of sepsis (three in the Glycosorb and one in the Adsopak group). Lower baseline serum creatinine level was achieved in the Glycosorb group. CONCLUSIONS Results of ABO-incompatible renal transplantation were satisfactory, and the use of immunoadsorption columns could effectively deplete antibody titers. Glycosorb columns were more efficient than Adsopak columns. Graft survival was better with Glycosorb. Posttransplant infections were a major cause of mortality.
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Affiliation(s)
- D. Mukherjee
- Senior Advisor (Med & Nephrology), Army Hospital (R&R), Delhi Cantt, India
| | - A.K. Hooda
- Director General (Org & Pers), O/o DGAFMS, Ministry of Defence, 'M' Block, New Delhi 110001, India
| | - A. Jairam
- Consultant (Med & Nephrology), Command Hospital (Eastern Command), Kolkata, India
| | - Ranjith K. Nair
- Senior Advisor (Med & Nephrology), Command Hospital (Eastern Command), Kolkata, India
| | - Sourabh Sharma
- Senior Resident (Med & Nephrology), Army Hospital (R&R), Delhi Cantt, India
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21
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Impact of rituximab on the T-cell flow cytometric crossmatch. Transpl Immunol 2020; 64:101360. [PMID: 33359130 DOI: 10.1016/j.trim.2020.101360] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2020] [Revised: 12/13/2020] [Accepted: 12/16/2020] [Indexed: 12/30/2022]
Abstract
Rituximab is frequently used in the setting of ABO-incompatible renal transplants, and highly sensitized patients. Its interference with B-cell flow cytometric crossmatch (B-FCXM) is well known. However, its effect on the T-cell flow cytometric crossmatch (T-FCXM) has not been described. We aimed to evaluate the effect of rituximab on the T-FCXM using non-pronase and pronase treated donor lymphocytes and compare results with the single antigen bead (SAB) assay. In this retrospective study, 28 patients on rituximab therapy were evaluated against 30 donors. Using non-pronase treated donor lymphocytes, all 30 FCXMs showed strong B-cell positivity {median (IQR) B-cell ratio: 184.65 (253.17)} which significantly reduced {1.0 (1.18); p < 0.00001} with pronase treatment. 'T-cell tailing' phenomenon was observed in 17/30 FCXMs in the non-pronase group as a 'tail of T-cells', indicating a rare sub-population. However, it disappeared in the pronase-treated group. SAB assay did not show donor-specific antibodies (DSA) in all 17 patients with 'T-cell tailing' phenomenon. Although, rituximab is described to impact only B-FCXM, we have consistently found 'T-cell tailing' in 57% of T-FCXMs, which clears with pronase treatment. The 'T-cell tailing' led to weak positive T-FCMX ratios due to increased MFI in the FL1 channel. However, the absence of DSA in all recipients reinforces the fact that this is a false positive finding and should not be misconstrued as a possible class I DSA. Structural homology of Fc receptors on activated T-cells to CD20 could be a possible explanation of the same and provide insight into a novel mechanism of action of rituximab.
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Sasaki H, Hotta K, Mitsuke A, Fukasawa Y, Tanabe T, Higuchi H, Takada Y, Harada H. Long-Term Outcome of ABO-Incompatible Kidney Transplantation in Patients Treated With Low-Dose Rituximab Regimen. Transplant Proc 2020; 53:989-994. [PMID: 33272650 DOI: 10.1016/j.transproceed.2020.10.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Revised: 09/07/2020] [Accepted: 10/01/2020] [Indexed: 11/15/2022]
Abstract
BACKGROUND Introduction of rituximab in the desensitization protocols for ABO-incompatible (ABOI) kidney transplantation (KTX) has afforded excellent results. However, the acceptability of minimal dosage of rituximab in these protocols remains to be defined. METHODS Sixty-three patients who underwent ABOI KTX were included in this study. The desensitization protocol consisted of plasmapheresis, tacrolimus, mycophenolate mofetil, methylprednisolone, intravenous immunoglobulin, basiliximab, and low-dose rituximab (100 mg/body). We evaluated the efficacy, safety, and long-term outcome of this protocol (group R, n = 39) and compared them with those of patients who underwent splenectomy (group S, n = 24). RESULTS Graft and patient survival at 10 years after KTX were comparable between the groups (94.4% [group R] vs 95.4% [group S] and 94.6% [group R] vs 95.8% [group S], respectively). The incidence of acute antibody-mediated rejection (AAMR) was similar in the 2 groups (10.2% vs 12.5%). There were no significant differences in the incidence of chronic active antibody-mediated rejection. Of the patients, 7 developed AAMR and 3 of these patients (1 in group R and 2 in group S) lost their grafts. There were no significant differences in the incidence of chronic active antibody-mediated rejection. The incidence of postoperative cytomegalovirus infection in group R was significantly lower than that in group S. Furthermore, the incidence of postoperative late-onset neutropenia was low in group R. CONCLUSIONS A low-dose rituximab regimen for ABOI KTX is acceptable for preventing AAMR with a low incidence of delayed adverse events.
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Affiliation(s)
- Hajime Sasaki
- Departments of Kidney Transplant Surgery, Sapporo City General Hospital, Sapporo, Japan
| | - Kiyohiko Hotta
- Department of Urology, Hokkaido University Hospital, Sapporo, Japan.
| | - Akihiko Mitsuke
- Departments of Kidney Transplant Surgery, Sapporo City General Hospital, Sapporo, Japan
| | - Yuichiro Fukasawa
- Department of Surgical Pathology, Sapporo City General Hospital, Sapporo, Japan
| | - Tatsu Tanabe
- Department of Urology, Hokkaido University Hospital, Sapporo, Japan
| | - Haruka Higuchi
- Departments of Kidney Transplant Surgery, Sapporo City General Hospital, Sapporo, Japan
| | - Yusuke Takada
- Department of Urology, Sapporo City General Hospital, Sapporo, Japan
| | - Hiroshi Harada
- Departments of Kidney Transplant Surgery, Sapporo City General Hospital, Sapporo, Japan
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Yoshinaga K, Araki M, Wada K, Maruyama Y, Mitsui Y, Sadahira T, Kubota R, Nishimura S, Kobayashi Y, Takeuchi H, Tanabe K, Kitagawa M, Morinaga H, Uchida HA, Kitamura S, Sugiyama H, Wada J, Watanabe M, Watanabe T, Nasu Y. Low-dose rituximab induction therapy is effective in immunological high-risk renal transplantation without increasing cytomegalovirus infection. Int J Urol 2020; 27:1136-1142. [PMID: 33012030 DOI: 10.1111/iju.14382] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Accepted: 08/17/2020] [Indexed: 11/30/2022]
Abstract
OBJECTIVES To analyze the effect and impact of low-dose rituximab induction therapy on cytomegalovirus infection in living-donor renal transplantation. METHODS A total of 92 recipients undergoing living-donor renal transplantation at Okayama University Hospital from May 2009 to August 2018 were evaluated retrospectively. Indications for preoperative rituximab (200 mg/body) were the following: (i) ABO major mismatch; (ii) ABO minor mismatch; (iii) donor-specific anti-human leukocyte antigen antibody-positive; and (iv) focal segmental glomerulosclerosis. We excluded four recipients who were followed <3 months, five who received >200 mg/body rituximab and seven who received prophylactic therapy for cytomegalovirus. RESULTS There were 59 patients in the rituximab group and 17 in the non-rituximab group. Groups differed significantly in age (median age 53 vs 37 years, respectively; P = 0.04), but not in sex (male 64% vs 65%, P = 1.00), focal segmental glomerulosclerosis (3% vs 0%, P = 1.00) or percentage of cytomegalovirus-seronegative recipients of renal allografts from cytomegalovirus-seropositive donors (12% vs 18%, P = 0.68). The estimated glomerular filtration rate did not differ significantly between groups until 24 months after transplantation. Cytomegalovirus clinical symptoms (10% vs 24%, P = 0.22), including fever ≥38°C (5% vs 12%, P = 0.31) and gastrointestinal symptoms (5% vs 12%, P = 0.31), and the 5-year survival rates of death-censored graft loss (90% vs 83%, P = 0.43) did not differ significantly between groups. CONCLUSIONS Low-dose rituximab induction therapy is effective in immunological high-risk recipients without increasing cytomegalovirus infection in the absence of valganciclovir prophylaxis.
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Affiliation(s)
- Kasumi Yoshinaga
- Departments of, Department of, Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan
| | - Motoo Araki
- Departments of, Department of, Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan
| | - Koichiro Wada
- Departments of, Department of, Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan
| | - Yuki Maruyama
- Departments of, Department of, Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan
| | - Yosuke Mitsui
- Departments of, Department of, Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan
| | - Takuya Sadahira
- Departments of, Department of, Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan
| | - Risa Kubota
- Departments of, Department of, Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan
| | - Shingo Nishimura
- Departments of, Department of, Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan
| | - Yasuyuki Kobayashi
- Departments of, Department of, Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan
| | - Hidemi Takeuchi
- Department of, Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan
| | - Katsuyuki Tanabe
- Department of, Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan
| | - Masashi Kitagawa
- Department of, Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan
| | - Hiroshi Morinaga
- Department of, Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan
| | - Haruhito Adam Uchida
- Department of, Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan
| | - Shinji Kitamura
- Department of, Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan
| | - Hitoshi Sugiyama
- Department of, Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan
| | - Jun Wada
- Department of, Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan
| | - Masami Watanabe
- Departments of, Department of, Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan
| | - Toyohiko Watanabe
- Departments of, Department of, Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan
| | - Yasutomo Nasu
- Departments of, Department of, Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Science, Okayama, Japan
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Langhorst C, Ganner A, Schneider J, Prager EP, Walz G, Pisarski P, Jänigen B, Zschiedrich S. Long-term Follow-up of ABO-Incompatible Kidney Transplantation in Freiburg, Germany: A Single-Center Outcome Report. Transplant Proc 2020; 53:848-855. [PMID: 33041078 DOI: 10.1016/j.transproceed.2020.09.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2020] [Revised: 08/11/2020] [Accepted: 09/06/2020] [Indexed: 11/15/2022]
Abstract
BACKGROUND ABO-incompatible kidney transplantation (ABOi-KT) is an established way to enlarge the donor pool around the world. Comparability of long-term success and complications to ABO-compatible kidney transplantation (ABOc-KT) are still under debate. METHODS We evaluated all patients with a living donor kidney transplantation performed between April 1, 2004, and March 31, 2019. RESULTS A total of 137 ABOi-KT and 346 ABOc-KT were analyzed. We excluded 4 ABOi-KT recipients and 178 ABOc-KT recipients with cyclosporine A-based immunosuppression or without basiliximab induction. Three patients of the ABOi-KT cohort and 6 patients of the ABOc-KT cohort were lost to follow-up and therefore excluded. The patient characteristics were comparable except for the higher age of transplant recipients in the ABOc-KT cohort and longer follow-up of the ABOi-KT cohort. The mean estimated 15-year recipient survival was 89% in the ABOi-KT cohort and 91% in the ABOc-KT cohort (P = .39). Mean estimated graft survival was 71% in the ABOi-KT cohort and 87% in the ABOc-KT cohort (P = .68). The estimated glomerular filtration rate (Modification of Diet in Renal Disease) measured in the last follow-up was 51 mL/min/1.73 m2 in the ABOi-KT cohort and 50 mL/min/1.73 m2 in the ABOc-KT cohort (P = .36). The incidence for antibody-mediated rejection, T cell-mediated rejections, and infectious complications requiring hospitalization was not different between the cohorts. In the ABOi-KT cohort, we found significantly more lymphoceles and consequent surgical revision procedures. CONCLUSIONS At our center, ABOi-KT has as good long-term results as ABOc-KT in terms of patient survival, graft survival, and complications, with the exception of increased lymphocele formation.
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Affiliation(s)
- Christina Langhorst
- Department of Nephrology and Primary Care, Medical Centre, University of Freiburg, Freiburg, Germany; Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Athina Ganner
- Department of Nephrology and Primary Care, Medical Centre, University of Freiburg, Freiburg, Germany; Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Johanna Schneider
- Department of Nephrology and Primary Care, Medical Centre, University of Freiburg, Freiburg, Germany; Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Eric Peter Prager
- Department of Nephrology and Primary Care, Medical Centre, University of Freiburg, Freiburg, Germany; Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Gerd Walz
- Department of Nephrology and Primary Care, Medical Centre, University of Freiburg, Freiburg, Germany; Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Przemyslaw Pisarski
- Faculty of Medicine, University of Freiburg, Freiburg, Germany; Department of General and Digestive Surgery, Medical Centre, University of Freiburg, Freiburg, Germany
| | - Bernd Jänigen
- Faculty of Medicine, University of Freiburg, Freiburg, Germany; Department of General and Digestive Surgery, Medical Centre, University of Freiburg, Freiburg, Germany
| | - Stefan Zschiedrich
- Faculty of Medicine, University of Freiburg, Freiburg, Germany; Renal Division, Department of Internal Medicine, Bürgerspital Solothurn, Solothurn, Switzerland.
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Donor specific anti HLA sensitization is associated with inferior short term outcome in ABO- incompatible renal transplantation. TRANSPLANTATION REPORTS 2020. [DOI: 10.1016/j.tpr.2020.100059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
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Cen M, Wang R, Kong W, Deng H, Lei W, Chen J. ABO-incompatible living kidney transplantation. Clin Transplant 2020; 34:e14050. [PMID: 32713064 DOI: 10.1111/ctr.14050] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2020] [Revised: 07/15/2020] [Accepted: 07/20/2020] [Indexed: 12/19/2022]
Abstract
ABO-incompatible living kidney transplantation is nowadays a routine procedure to expand living donor pool. The past decades have seen the evolution of desensitization protocol and immunosuppression regimen. Despite increased bleeding events, infectious complications, and rejection episodes reported in some studies, favorable graft and patient survival rate are now achieved, regardless of various protocols among transplant centers. Several issues such as the usage of rituximab and standardization of blood group antibody titration remain to be settled. The deposition of C4d is no longer the histopathologic hallmark of antibody-mediated rejection, which have inspired innovative strategies of peripheral molecular screening and the improvement of histological diagnosis of AMR (antibody-mediated rejection). The better understanding of the underlying mechanism might facilitate the distinction and therapeutic schemes of AMR.
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Affiliation(s)
- Menger Cen
- Kidney Disease Center, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Rending Wang
- Kidney Disease Center, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Weiwei Kong
- Kidney Disease Center, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Hao Deng
- Kidney Disease Center, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Wenhua Lei
- Kidney Disease Center, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Jianghua Chen
- Kidney Disease Center, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
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Effect of Rituximab Used as Induction in Patients with ABO Mismatch Kidney Transplant: A Systematic Review and Meta-analysis. Transplant Proc 2020; 52:3125-3128. [PMID: 32553506 DOI: 10.1016/j.transproceed.2020.02.166] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2020] [Revised: 02/08/2020] [Accepted: 02/15/2020] [Indexed: 11/20/2022]
Abstract
INTRODUCTION ABO-incompatible living kidney transplantation (ABOILKT) has steadily become more widespread. However, the optimal immunosuppressive regimen for ABOILKT remains uncertain. We aimed to determine the outcomes according to dose of rituximab induction. METHODS We conducted a systematic review and meta-analysis using random-effects modeling. We searched the following databases for all studies published through May 15, 2019: Cochrane Central Register, OVID MEDLINE, EMBASE, and PubMed. We reviewed all relevant reviews, registered trials, and relevant conference proceedings to compare clinical outcomes and survival according to dose of rituximab as induction in kidney transplantation. RESULTS Five trials with a total of 390 patients were included. Glomerular filtration rates, graft loss, antibody mediated rejection, T cell mediated rejection, fungal infection (Candida), and patient survival rates did not differ between the 200 mg single dose and 375 mg/m2 in rituximab groups. However, incidence rate of infection 0.470 (95% confidence interval [CI], 0.264 to 0.838) had a lower result than the 200 mg rituximab group. CONCLUSIONS The using of a 200 mg single dose of rituximab induction in ABOILKT has not only the same results for rejection, graft survival, and patient survival but also low incidence of infection after transplantation.
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Early Steroid Withdrawal Protocol With Basiliximab and Rituximab in ABO-Incompatible Kidney Transplant Recipients. Transplant Proc 2020; 52:1705-1708. [PMID: 32444132 DOI: 10.1016/j.transproceed.2020.01.139] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2019] [Accepted: 01/10/2020] [Indexed: 11/21/2022]
Abstract
OBJECTIVES Corticosteroids remain an important component of immunosuppressive regimens in high-risk kidney transplants. In this study, we investigated the efficacy of early steroid withdrawal with basiliximab and rituximab in ABO-blood type incompatible (ABO-i) recipients of kidney transplants. METHODS Between 2008 and 2019, 15 patients underwent ABO-i kidney transplantation. Seven of the 15 patients were treated with a steroid maintenance protocol and the remaining 8 with an early steroid withdrawal protocol. The immunosuppressive protocol consisted of tacrolimus, mycophenolate mofetil, and methylprednisolone (MP), with basiliximab administered as induction therapy. Rituximab was administered as a single 200-mg dose 1 to 4 weeks before kidney transplantation. Two to 4 sessions of either double-filtration plasmapheresis or regular plasmapheresis or both were performed to remove anti-AB antibodies before transplantation. During surgery, MP was administered at a dose of 500 mg; thereafter, the dosage was tapered rapidly, and the drug was discontinued on day 14 post transplant. RESULTS In the steroid maintenance group, 2 patients experienced acute antibody-mediated rejection (AMR). One patient with severe AMR had graft loss on postoperative day 4. Patient and graft survival rates in the steroid maintenance group were 100% and 86%, respectively. MP was successfully withdrawn in the steroid withdrawal group. In this group, there was no biopsy-proven rejection. Patient and graft survival rates were 100%, and when last measured, serum creatinine level ± SD was 1.6 ± 0.8 mg/dL. CONCLUSIONS Our protocol successfully enabled the early withdrawal of steroids in recipients of ABO-i grafts; however, further follow-up is necessary to confirm our results.
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Pandey P, Setya D, Sinha V, Bhatt A, Devra A, Chaudhary A, Ranjan S, Srivastava R, Kumar P, Singh MK. Therapeutic apheresis in
ABO
‐incompatible kidney and liver transplantation: A single‐center experience of 50 patients. Ther Apher Dial 2020; 25:103-117. [DOI: 10.1111/1744-9987.13495] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2019] [Revised: 02/07/2020] [Accepted: 03/31/2020] [Indexed: 12/23/2022]
Affiliation(s)
- Prashant Pandey
- Department of Transfusion Medicine, Histocompatibility and Molecular Biology Jaypee Hospital Noida India
| | - Divya Setya
- Department of Transfusion Medicine, Histocompatibility and Molecular Biology Jaypee Hospital Noida India
| | - Vijay Sinha
- Department of Transfusion Medicine, Histocompatibility and Molecular Biology Jaypee Hospital Noida India
| | - Anil Bhatt
- Department of Transfusion Medicine, Histocompatibility and Molecular Biology Jaypee Hospital Noida India
| | - Amit Devra
- Department of Transfusion Medicine, Histocompatibility and Molecular Biology Jaypee Hospital Noida India
| | - Abhideep Chaudhary
- Department of Transfusion Medicine, Histocompatibility and Molecular Biology Jaypee Hospital Noida India
| | - Shweta Ranjan
- Department of Transfusion Medicine, Histocompatibility and Molecular Biology Jaypee Hospital Noida India
| | - Roli Srivastava
- Department of Transfusion Medicine, Histocompatibility and Molecular Biology Jaypee Hospital Noida India
| | - Praveen Kumar
- Department of Transfusion Medicine, Histocompatibility and Molecular Biology Jaypee Hospital Noida India
| | - Mukesh Kumar Singh
- Department of Transfusion Medicine, Histocompatibility and Molecular Biology Jaypee Hospital Noida India
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Montagud-Marrahi E, Revuelta I, Cucchiari D, Piñeiro GJ, Ventura-Aguiar P, Lozano M, Cid J, Martorell J, Solé M, Quintana LF, Oppenheimer F, Diekmann F, Poch E, Campistol JM, Blasco M. Successful use of nonantigen-specific immunoadsorption with antihuman Ig-columns in kidney graft antibody-mediated rejection. J Clin Apher 2020; 35:188-199. [PMID: 32219886 DOI: 10.1002/jca.21779] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2019] [Revised: 03/10/2020] [Accepted: 03/11/2020] [Indexed: 11/11/2022]
Abstract
INTRODUCTION Nonantigen-specific immunoadsorption (IA) has proven to be effective in acute antibody-mediated rejection (aAMR). However, there is a lack of solid studies evaluating the safety and efficacy of IA with antihuman Ig-columns in aAMR. For chronic-active AMR (cAMR), no studies have evaluated the efficacy of nonantingen-specific IA with antihuman Ig-columns. The purpose of this study was to evaluate the role of nonantigen-specific IA with antihuman Ig-columns in the treatment of both aAMR and cAMR in kidney transplantation. MATERIAL AND METHODS In retrospective and observational study, kidney graft and recipient survival rates were assessed after treatment of aAMR and cAMR with nonantigen-specific IA with Ig-Flex columns (Therasorb) between January 2012 and May 2018. Protocols included nonantigen-specific IA, rituximab, intravenous immunoglobulin, and rescue plasma exchange, if necessary. RESULTS The study included 14 patients with AMR (acute in 9, chronic active in 5). For aAMR, mean follow-up was 13 ± 6 months, and patient and graft survival were, respectively, of 100% and 83%, with a mean increase in estimated glomerular filtration rate (eGFR) of 7.98 ± 12.96, 10.18 ± 16.71, and 11.43 ± 13.85 mL/min/1.72 m2 (P > .05) at 3, 12 months after treatment, and at the end of follow-up, respectively. For cAMR, mean follow-up was 14 ± 8 months, and patient and graft survival were, respectively, of 100% and 60%, with an average increase in eGFR of 4.30 ± 7.86, 5.64 ± 10.47, and 14.5 ± 7.86 mL/min/m2 (P > .05) at 3, 12 months after IA treatment, and at the end of the follow-up, respectively, although 40% did not respond and required chronic hemodialysis. CONCLUSION Nonantigen-specific IA with Ig-Flex columns was safe and effective for aAMR treatment in kidney transplantation. In cAMR, IA with Ig-Flex columns was associated with a satisfactory kidney graft survival, suggesting that IA could potentially offer some benefits supporting its indication in cAMR.
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Affiliation(s)
- Enrique Montagud-Marrahi
- Nephrology and Renal Transplantation Department, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain
| | - Ignacio Revuelta
- Nephrology and Renal Transplantation Department, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain
| | - David Cucchiari
- Nephrology and Renal Transplantation Department, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain
| | - Gaston J Piñeiro
- Nephrology and Renal Transplantation Department, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain
| | - Pedro Ventura-Aguiar
- Nephrology and Renal Transplantation Department, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain
| | - Miquel Lozano
- Apheresis Unit, Department of Hemotherapy and Hemostasis, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain
| | - Joan Cid
- Apheresis Unit, Department of Hemotherapy and Hemostasis, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain
| | - Jaume Martorell
- Immunology Department, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain
| | - Manel Solé
- Pathology Department, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain
| | - Luis F Quintana
- Nephrology and Renal Transplantation Department, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain
| | - Federico Oppenheimer
- Nephrology and Renal Transplantation Department, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain
| | - Fritz Diekmann
- Nephrology and Renal Transplantation Department, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain
| | - Esteban Poch
- Nephrology and Renal Transplantation Department, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain
| | - Josep M Campistol
- Nephrology and Renal Transplantation Department, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain
| | - Miquel Blasco
- Nephrology and Renal Transplantation Department, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain
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31
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Kim H, Choe W, Shin S, Kim YH, Han D, Park S, Kwon S, Ko D. ABO‐incompatible kidney transplantation can be successfully conducted by monitoring
IgM
isoagglutinin titers during desensitization. Transfusion 2020; 60:598-606. [DOI: 10.1111/trf.15672] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2019] [Revised: 10/21/2019] [Accepted: 12/05/2019] [Indexed: 12/12/2022]
Affiliation(s)
- Hyungsuk Kim
- Department of Laboratory MedicineSeoul National University Hospital Seoul South Korea
| | - Wonho Choe
- Department of Laboratory MedicineEulji University School of Medicine Seoul South Korea
| | - Sung Shin
- Department of SurgeryUniversity of Ulsan College of Medicine and Asan Medical Center Seoul South Korea
| | - Young Hoon Kim
- Department of SurgeryUniversity of Ulsan College of Medicine and Asan Medical Center Seoul South Korea
| | - Duck‐Jong Han
- Department of SurgeryUniversity of Ulsan College of Medicine and Asan Medical Center Seoul South Korea
| | - Su‐Kil Park
- Division of Nephrology, Department of Internal MedicineUniversity of Ulsan College of Medicine and Asan Medical Center Seoul South Korea
| | - Seog‐Woon Kwon
- Department of Laboratory MedicineUniversity of Ulsan College of Medicine and Asan Medical Center Seoul South Korea
| | - Dae‐Hyun Ko
- Department of Laboratory MedicineUniversity of Ulsan College of Medicine and Asan Medical Center Seoul South Korea
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32
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Tiwari AK, Aggarwal G, Arora D, Bhardwaj G, Jain M, Bansal SB, Sethi SK. Immunoadsorption in ABO-incompatible kidney transplantation in adult and pediatric patients with follow-up on graft and patient survival: First series from India. Asian J Transfus Sci 2020; 14:13-18. [PMID: 33162699 PMCID: PMC7607981 DOI: 10.4103/ajts.ajts_82_19] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2019] [Revised: 03/01/2020] [Accepted: 03/22/2020] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND: There are no published reports on desensitization protocol for ABO-incompatible kidney transplants using Immuno-Adsorption (IA) plasmapheresis from India. IA offers certain advantages including processing of larger plasma volumes, quicker reduction of isoagglutinin titers and no requirement of replacement fluids. AIMS AND OBJECTIVES: Authors' center evaluated success of desensitization protocol, and graft/patient outcomes when IA procedures were performed for desensitization in adult and pediatric ABO-incompatible kidney transplant patients. METHODS: Patients undergoing ABO-incompatible kidney transplant with use of IA were evaluated at tertiary care center in north India. Patient records for 2-years were collated from hospital information system (HIS) and procedure forms. RESULTS: Sixteen IA procedures were performed in five patients who underwent successful ABO-incompatible kidney transplant. Initial isoagglutinin IgG titer ranged from 32-512. Mean number of IA procedures performed to achieve the desired pre-transplant IgG titer ≤8 was 3.2. New IA column was used for each patient (and re-used for the same patient, if needed, after sterilization with Low temperature steam of formaldehyde). Mean plasma volume processed during each IA procedure was 4.5 times. No adverse events were observed during any IA procedure. All patients achieved successful desensitization. All patients continue to do well clinically with mean follow-up period of 8.8 months. Although IA was expensive, it offered advantages like specificity, larger plasma volume processing with desired reduction in titer, no 'replacement fluid' requirements and no adverse events in present case series. CONCLUSION: IA plasmapheresis was universally successful in decreasing the ABO-isoagglutinin titers to desired level in all prospective ABO incompatible kidney transplant patients.
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Affiliation(s)
- Aseem Kumar Tiwari
- Department of Transfusion Medicine, Medanta-The Medicity, Gurgaon, Haryana, India
| | - Geet Aggarwal
- Department of Transfusion Medicine, Medanta-The Medicity, Gurgaon, Haryana, India
| | - Dinesh Arora
- Department of Transfusion Medicine, Medanta-The Medicity, Gurgaon, Haryana, India
| | - Gunjan Bhardwaj
- Department of Transfusion Medicine, Medanta-The Medicity, Gurgaon, Haryana, India
| | - Manish Jain
- Department of Nephrology, Medanta-The Medicity, Gurgaon, Haryana, India
| | | | - Sidharth K Sethi
- Department of Nephrology, Medanta-The Medicity, Gurgaon, Haryana, India
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33
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Ryzhov IM, Bovin NV. Synthesis of glycans functioning as antigens of the ABO blood group system. MENDELEEV COMMUNICATIONS 2019. [DOI: 10.1016/j.mencom.2019.11.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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34
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Salvadori M, Tsalouchos A. Therapeutic apheresis in kidney transplantation: An updated review. World J Transplant 2019; 9:103-122. [PMID: 31750088 PMCID: PMC6851502 DOI: 10.5500/wjt.v9.i6.103] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2019] [Revised: 10/02/2019] [Accepted: 10/15/2019] [Indexed: 02/05/2023] Open
Abstract
Therapeutic apheresis is a cornerstone of therapy for several conditions in transplantation medicine and is available in different technical variants. In the setting of kidney transplantation, immunological barriers such as ABO blood group incompatibility and preformed donor-specific antibodies can complicate the outcome of deceased- or living- donor transplantation. Postoperatively, additional problems such as antibody-mediated rejection and a recurrence of primary focal segmental glomerulosclerosis can limit therapeutic success and decrease graft survival. Therapeutic apheresis techniques find application in these issues by separating and selectively removing exchanging or modifying pathogenic material from the patient by an extracorporeal aphaeresis system. The purpose of this review is to describe the available techniques of therapeutic aphaeresis with their specific advantages and disadvantages and examine the evidence supporting the application of therapeutic aphaeresis as an adjunctive therapeutic option to immunosuppressive agents in protocols before and after kidney transplantation.
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Affiliation(s)
- Maurizio Salvadori
- Department of Transplantation Renal Unit, Careggi University Hospital, Florence 50139, Italy
| | - Aris Tsalouchos
- Nephrology and Dialysis Unit, Saints Cosmas and Damian Hospital, Pescia 51017, Italy
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35
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Alhabbab RY, Nova-Lamperti E, Aravena O, Burton HM, Lechler RI, Dorling A, Lombardi G. Regulatory B cells: Development, phenotypes, functions, and role in transplantation. Immunol Rev 2019; 292:164-179. [DOI: 10.1111/imr.12800] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2019] [Accepted: 08/27/2019] [Indexed: 12/15/2022]
Affiliation(s)
- Rowa Y. Alhabbab
- Infectious Disease Unit and Division of Applied Medical Sciences King Fahad Centre for medical research King Abdulaziz University Jeddah Saudi Arabia
- Peter Gorer Department of Immunobiology MRC Centre for Transplantation School of Immunology & Mucosal Biology King's College LondonKing's Health PartnersGuy's Hospital London UK
| | - Estefanía Nova-Lamperti
- Molecular and Translational Immunology Laboratory Department of Clinical Biochemistry and Immunology Pharmacy Faculty Universidad de Concepción Concepción Chile
| | - Octavio Aravena
- Programa Disciplinario de Immunología Instituto de Ciencias Biomédicas Facultad de Medicina Universidad de Chile Santiago Chile
| | - Hannah M. Burton
- Peter Gorer Department of Immunobiology MRC Centre for Transplantation School of Immunology & Mucosal Biology King's College LondonKing's Health PartnersGuy's Hospital London UK
| | - Robert I. Lechler
- Peter Gorer Department of Immunobiology MRC Centre for Transplantation School of Immunology & Mucosal Biology King's College LondonKing's Health PartnersGuy's Hospital London UK
| | - Anthony Dorling
- Peter Gorer Department of Immunobiology MRC Centre for Transplantation School of Immunology & Mucosal Biology King's College LondonKing's Health PartnersGuy's Hospital London UK
| | - Giovanna Lombardi
- Peter Gorer Department of Immunobiology MRC Centre for Transplantation School of Immunology & Mucosal Biology King's College LondonKing's Health PartnersGuy's Hospital London UK
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36
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Hourmant M, Figueres L, Gicquel A, Kimmel C, Garandeau C. New rules of ABO-compatibility in kidney transplantation. Transfus Clin Biol 2019; 26:180-183. [DOI: 10.1016/j.tracli.2019.06.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2019] [Accepted: 06/06/2019] [Indexed: 12/20/2022]
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37
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Alhamoud I, Huang R, Lacelle C, Burguete D, Hendricks AR, Torrealba JR, Seikaly MG. Allograft outcomes of treated children with kidney transplant who developed plasma cell-rich acute rejection (PCAR): A single center's experience. Pediatr Transplant 2019; 23:e13500. [PMID: 31437388 DOI: 10.1111/petr.13500] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2018] [Revised: 10/10/2018] [Accepted: 10/15/2018] [Indexed: 12/17/2022]
Abstract
INTRODUCTION PCAR is a rare form of ACR that may compromise renal allografts. This review evaluates the outcomes of a protocol used to treat PCAR (Study group), and compares these outcomes with a matched cohort with ACR (Control group). METHODS A retrospective analysis of 138 of pRTRs who underwent renal allograft biopsies between January 2008 and November 2016. RESULTS Seven biopsies revealed in situ hybridization of EBER-negative PCAR (5%). Three Study group pRTRs lost their grafts within 3 months after rejection (43%). None of the Control group pRTRs lost their graft during this period. At the time of rejection, eGFR was different between the Control and Study groups (27.0 ± 19.9 mL/min per m2 vs 40.0 ± 10.6 mL/min/1.73 m2 , respectively; P < 0.05). Among Study group pRTRs with functioning allografts (n = 4), treatment resulted in an increase in eGFR from nadir levels (27.0 ± 19.9 vs 55.6 ± 18.3 mL/min/1.73 m2 , P < 0.05). In the Study group, complications included neutropenia, BK and EBV viremia, and infusion-related hypotension and hypertension. SUMMARY (a) Graft loss in Study group while remaining high (43%) was lower than that reported in the published pediatric literature. (b) Our protocol was associated with improvement in eGFR in all surviving pRTRs within the Study group. (c) No life-threatening complications or malignancy were reported during the observation period.
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Affiliation(s)
- Issa Alhamoud
- Division of Pediatric Nephrology, University of Texas Southwestern Medical Center, Dallas, Texas.,Children's Medical Center, Dallas, Texas
| | - Rong Huang
- Children's Medical Center, Dallas, Texas
| | - Chantale Lacelle
- Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Daniel Burguete
- Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Allen R Hendricks
- Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Jose R Torrealba
- Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Mouin G Seikaly
- Division of Pediatric Nephrology, University of Texas Southwestern Medical Center, Dallas, Texas.,Children's Medical Center, Dallas, Texas
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38
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Single cohort study: ABO-incompatible kidney transplant recipients have a higher risk of lymphocele formation. Langenbecks Arch Surg 2019; 404:999-1007. [DOI: 10.1007/s00423-019-01812-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2018] [Accepted: 08/05/2019] [Indexed: 12/26/2022]
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39
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Speer C, Kälble F, Nusshag C, Pego da Silva L, Schaier M, Becker LE, Klein K, Sommerer C, Beimler J, Leo A, Waldherr R, Mehrabi A, Süsal C, Zeier M, Morath C. Outcomes and complications following ABO‐incompatible kidney transplantation performed after desensitization by semi‐selective immunoadsorption ‐ a retrospective study. Transpl Int 2019; 32:1286-1296. [DOI: 10.1111/tri.13482] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2019] [Revised: 02/11/2019] [Accepted: 07/16/2019] [Indexed: 12/18/2022]
Affiliation(s)
- Claudius Speer
- Department of Nephrology University of Heidelberg Heidelberg Germany
| | - Florian Kälble
- Department of Nephrology University of Heidelberg Heidelberg Germany
| | - Christian Nusshag
- Department of Nephrology University of Heidelberg Heidelberg Germany
| | | | - Matthias Schaier
- Department of Nephrology University of Heidelberg Heidelberg Germany
| | | | - Katrin Klein
- Department of Nephrology University of Heidelberg Heidelberg Germany
| | - Claudia Sommerer
- Department of Nephrology University of Heidelberg Heidelberg Germany
| | - Jörg Beimler
- Department of Nephrology University of Heidelberg Heidelberg Germany
| | - Albrecht Leo
- Institute for Clinical Transfusion Medicine and Cell Therapy University of Heidelberg Heidelberg Germany
| | - Rüdiger Waldherr
- Institute of Pathology University of Heidelberg Heidelberg Germany
| | - Arianeb Mehrabi
- Department of General, Visceral and Transplantation Surgery University of Heidelberg Heidelberg Germany
| | - Caner Süsal
- Department of Transplantation Immunology University of Heidelberg Heidelberg Germany
| | - Martin Zeier
- Department of Nephrology University of Heidelberg Heidelberg Germany
| | - Christian Morath
- Department of Nephrology University of Heidelberg Heidelberg Germany
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40
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Chauhan K, Mehta AA. Rituximab in kidney disease and transplant. Animal Model Exp Med 2019; 2:76-82. [PMID: 31392300 PMCID: PMC6600632 DOI: 10.1002/ame2.12064] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2019] [Accepted: 03/04/2019] [Indexed: 12/14/2022] Open
Abstract
Rituximab is a chimeric monoclonal antibody that binds to CD20 antigen of B-cells. It depletes the level of mature B-cells by various mechanisms such as mediation of antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, and B-cell apoptosis. Rituximab is a USFDA approved drug for clinical use in non-Hodgkin's B-cell lymphoma (NHL), rheumatoid arthritis, chronic lymphocytic leukemia (CLL), granulomatosis with polyangiitis and pemphigus vulgaris. It is also known for its "off label" use in renal disease and renal transplant worldwide. However, the exact mechanisms by which it exerts its effect in the aforementioned condition remain unclear but may be related to its long-term effects on plasma cell development and the impact on B-cell modulation of T cell responses. This review discusses the current use of rituximab in renal disease and renal transplantation, and its potential role in novel therapeutic protocols.
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Affiliation(s)
- Kajal Chauhan
- Medical ServicesTorrent PharmaceuticalsAhmedabadIndia
| | - Anita A. Mehta
- Department of PharmacologyL. M. College of PharmacyAhmedabadGujaratIndia
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41
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Agrawal S, Chowdhry M, Makroo RN, Nayak S, Gajulapalli SP, Thakur UK, Agrawal A. Therapeutic Immunoadsorption and Conventional Plasma Exchange in ABO-incompatible Renal Transplant: An Exculpatory Evidence. Cureus 2019; 11:e4787. [PMID: 31367505 PMCID: PMC6666925 DOI: 10.7759/cureus.4787] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Aim The objective of this study was to compare the efficacy of immunoadsorption (IA) with conventional therapeutic plasma-exchange (cTPE) in ABO-incompatible (ABOi) renal transplant. Methods Data of patients from July 2015 to June 2017 (category-I, number of patients (N) = 11; IA±cTPE) on the average length of stay (ALOS), number of cTPE/IA, antibody-titers (AT), creatinine, patient and graft survival at one year were compared retrospectively with patients in period from February 2012 to June 2015 (category-II, N = 29; cTPE only). AT of patients not decreasing to less than one fold after two cTPE were shifted for IA. For patients undergoing IA, real-time AT was done and IA stopped after target titer (TT <1:8) was achieved. Post-transplant cTPE was done if, titers rebounded to ≥1:8. Intravenous immunoglobulin (IVIG) was given after every cTPE/IA. Cost comparisons were made. Results In category-I, seven patients (63.63%) were shifted to IA from cTPE. The mean cTPE procedures in category I and II are 3.5 ± 2.4 and 4.8 ± 2.5, respectively (p = 0.206). The mean IA procedures in category-I are 1.6 ± 0.5. The number of patients requiring post-operative TPE was less in category-I than category-II, i.e., N = 5, 45.5% vs N = 20, 69%, respectively (p = 0.171). The expense of IA in category-I vs cTPE in category-II was statistically not significant (p = 0.422) but had significant lesser ALOS (p = 0.044). Expenses, when a patient undergoes both cTPE and IA (category-I), are significantly higher to category-II (p = 0.003). The two groups were comparable in AT, creatinine value, graft and patient survival rates at one year. Conclusion Contrary to the general judgment of IA being expensive than cTPE, this study shows equivalent expenditures with comparable therapeutic outcomes.
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Affiliation(s)
- Soma Agrawal
- Transfusion Medicine, Indraprastha Apollo Hospitals, New Delhi, IND
| | - Mohit Chowdhry
- Transfusion Medicine, Indraprastha Apollo Hospitals, New Delhi, IND
| | - Raj N Makroo
- Transfusion Medicine, Indraprastha Apollo Hospitals, New Delhi, IND
| | - Sweta Nayak
- Transfusion Medicine, Fortis Hospital, Faridabad, IND
| | | | - Uday K Thakur
- Transfusion Medicine, Indraprastha Apollo Hospitals, New Delhi, IND
| | - Ankit Agrawal
- Internal Medicine, Saint Peter's University Hospital - Rutgers Robert Wood Johnson Medical School, New Brunswick, USA
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42
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Hirose T, Iwami D, Hotta K, Sasaki H, Higuchi H, Shinohara N. Percentage of CD19 + Cells in Peripheral Blood Lymphocytes After Rituximab-Based Desensitization as a Predictor of Acute Antibody-Mediated Rejection in ABO-Incompatible Kidney Transplantation. Transplant Proc 2019; 51:1382-1386. [PMID: 31027828 DOI: 10.1016/j.transproceed.2019.01.127] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2018] [Accepted: 01/03/2019] [Indexed: 02/02/2023]
Abstract
BACKGROUND Rituximab (RIT) is effective as a part of the desensitization therapy before ABO-incompatible kidney transplantation (ABOi-KTx), and a single dose of RIT at 375 mg/m2 or less is recommended. However, adequate RIT dose recommendations have not yet been established for individual recipients. Therefore, we evaluated the relationship between the proportion of B cells in peripheral blood and acute antibody-mediated rejection (AAMR). METHODS Forty-four consecutive ABOi-KTx recipients were enrolled in this retrospective study. Before transplantation, subjects were treated with RIT at various doses, ranging from 65 to 400 mg/body (46-263 mg/m2), followed by plasmapheresis and intravenous immunoglobulin as a desensitization therapy. The percentage of CD19+ cells in the total peripheral blood lymphocytes population (%CD19) was determined the day before transplantation. Transplant recipients were divided into 2 groups according to pretransplant %CD19, as follows: low %CD19 group, ≤ 1.2% (n = 35) and high %CD19 group, > 1.2% (n = 9). The relationship between %CD19 and incidence of AAMR was evaluated, and the predicting factors for AAMR incidence were determined by univariate and multivariate analyses. RESULTS The incidence of AAMR was significantly higher in the high %CD19 group than in the low %CD19 group (44.4% vs 5.7%, P = .006). Furthermore, multivariate analysis showed that %CD19 > 1.2% was the only independent factor to predict AAMR, with an odds ratio of 14.31 (P = .038). CONCLUSION High %CD19 values after rituximab administration in ABOi-KTx recipients implies insufficient depletion of B cells, which can lead to AAMR.
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Affiliation(s)
- T Hirose
- Department of Renal and Genitourinary Surgery, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - D Iwami
- Department of Renal and Genitourinary Surgery, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
| | - K Hotta
- Department of Renal and Genitourinary Surgery, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - H Sasaki
- Department of Renal and Genitourinary Surgery, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - H Higuchi
- Department of Renal and Genitourinary Surgery, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - N Shinohara
- Department of Renal and Genitourinary Surgery, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
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43
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Okumi M, Kakuta Y, Unagami K, Takagi T, Iizuka J, Inui M, Ishida H, Tanabe K. Current protocols and outcomes of ABO-incompatible kidney transplantation based on a single-center experience. Transl Androl Urol 2019; 8:126-133. [PMID: 31080772 DOI: 10.21037/tau.2019.03.05] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
ABO-incompatible living kidney transplantation (ABO-ILKT) is an effective option for increasing living kidney transplant opportunities. ABO-ILKT has been conducted in our institution since 1989 to widen the indication for living kidney transplantation. ABO-ILKT is considered to require extra treatment, and it has increased risks compared with ABO-compatible living kidney transplantation (ABO-CLKT). In the past two decades, some protocols have removed anti-blood-type antibodies to prevent the production of antibodies. Additionally, we have made considerable changes to our ABO-ILKT protocol as new immunosuppressive agents have been developed. Consequently, increased immunosuppression and immunological understanding have helped shape recent desensitization protocols. Herein, we review the history, therapeutic strategy, pathology, and future directions of ABO-ILKT. Our standard immunosuppressive regimen and desensitization protocol for ABO-ILKT recipients consist of low doses of tacrolimus (TAC), mycophenolate mofetil (MMF), and rituximab; several sessions of double filtration plasmapheresis; and basiliximab induction. We do not use thymoglobulin induction, intravenous immunoglobulin, or prophylactic post-transplant plasmapheresis. Recently, ABO-ILKT has been recognized as a useful alternative therapy for end-stage kidney disease with ABO-incompatibility, and its outcome is comparable to that of ABO-CLKT.
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Affiliation(s)
- Masayoshi Okumi
- Department of Urology, Tokyo Women's Medical University, Tokyo, Japan
| | - Yoichi Kakuta
- Department of Urology, Tokyo Women's Medical University, Tokyo, Japan
| | - Kohei Unagami
- Department of Nephrology, Tokyo Women's Medical University, Tokyo, Japan.,Department of Organ Transplant Medicine, Tokyo Women's Medical University, Tokyo, Japan
| | - Toshio Takagi
- Department of Urology, Tokyo Women's Medical University, Tokyo, Japan
| | - Junpei Iizuka
- Department of Urology, Tokyo Women's Medical University, Tokyo, Japan
| | - Masashi Inui
- Department of Urology, Tokyo Women's Medical University, Tokyo, Japan
| | - Hideki Ishida
- Department of Urology, Tokyo Women's Medical University, Tokyo, Japan.,Department of Organ Transplant Medicine, Tokyo Women's Medical University, Tokyo, Japan
| | - Kazunari Tanabe
- Department of Urology, Tokyo Women's Medical University, Tokyo, Japan
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Shah Y, Almeshari K, Broering D, Aleid H, Brockmann J, Alhumaidan H, Hammad E, Elgamal H, Alahmadi I, Hussein M, Ibrahim I, Ali T. ABO-Incompatible Kidney Transplantation: Low Rates of Infectious Complications and Excellent Patient Survival. Transplant Proc 2019; 51:512-516. [PMID: 30879579 DOI: 10.1016/j.transproceed.2019.01.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND A significant gap exists between demand and supply of organs for patients with end-stage renal disease. To increase the donor pool, kidney transplantation is performed across ABO- and HLA-incompatible barriers. ABO-incompatible kidney transplant (ABOi-KT) recipients are at increased risk of antibody-mediated rejection, infection, and mortality. Hypogammaglobulinemia secondary to immunosuppression is highly prevalent after solid organ transplantation, and intravenous immunoglobulin (IVIG) has been reported to reduce the risks of infections in various settings. We use high-dose IVIG in ABOi-KT recipients perioperatively. We aimed to determine the rate of infectious complications along with graft and patient survival in our ABOi-KT recipients. METHODS We included all adult patients who underwent ABOi-KT from the year 2007 to 2016. Patients received rituximab, plasma exchange, and IVIG (2 g/kg body weight). Thymoglobulin and intravenous methylprednisolone were used as induction treatment. Oral prednisone, mycophenolate mofetil, and tacrolimus were used as maintenance therapy. RESULTS A total of 77 ABOi-KTs were performed, and the recipients were followed up for a median of 1557 days. Two patients were diagnosed as having BK nephropathy. No patients were diagnosed as having pneumocystis infection, cytomegalovirus disease, herpes simplex, varicella zoster, or fungal infection. One-year graft and patient survival was 94.8% and 100%, respectively. CONCLUSIONS In our series of ABOi-KTs, we observed a low risk of infectious complications and excellent patient survival. High-dose IVIG might have reduced infections.
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Affiliation(s)
- Y Shah
- King Faisal Specialist Hospital & Research Center, Department of Kidney and Pancreas Transplant, Riyadh, Saudi Arabia
| | - K Almeshari
- King Faisal Specialist Hospital & Research Center, Department of Kidney and Pancreas Transplant, Riyadh, Saudi Arabia
| | - D Broering
- King Faisal Specialist Hospital & Research Center, Department of Kidney and Pancreas Transplant, Riyadh, Saudi Arabia
| | - H Aleid
- King Faisal Specialist Hospital & Research Center, Department of Kidney and Pancreas Transplant, Riyadh, Saudi Arabia
| | - J Brockmann
- King Faisal Specialist Hospital & Research Center, Department of Kidney and Pancreas Transplant, Riyadh, Saudi Arabia
| | - H Alhumaidan
- King Faisal Specialist Hospital & Research Center, Department of Kidney and Pancreas Transplant, Riyadh, Saudi Arabia
| | - E Hammad
- King Faisal Specialist Hospital & Research Center, Department of Kidney and Pancreas Transplant, Riyadh, Saudi Arabia
| | - H Elgamal
- King Faisal Specialist Hospital & Research Center, Department of Kidney and Pancreas Transplant, Riyadh, Saudi Arabia
| | - I Alahmadi
- King Faisal Specialist Hospital & Research Center, Department of Kidney and Pancreas Transplant, Riyadh, Saudi Arabia
| | - M Hussein
- King Faisal Specialist Hospital & Research Center, Department of Kidney and Pancreas Transplant, Riyadh, Saudi Arabia
| | - I Ibrahim
- King Faisal Specialist Hospital & Research Center, Department of Kidney and Pancreas Transplant, Riyadh, Saudi Arabia
| | - T Ali
- King Faisal Specialist Hospital & Research Center, Department of Kidney and Pancreas Transplant, Riyadh, Saudi Arabia.
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45
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Outcomes of Pediatric ABO-incompatible Living Kidney Transplantations From 2002 to 2015: An Analysis of the Japanese Kidney Transplant Registry. Transplantation 2018; 102:1934-1942. [DOI: 10.1097/tp.0000000000002259] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Abstract
Rituximab is a chimeric anti-CD20 monoclonal protein used in various clinical scenarios in kidney transplant recipients. However, its evidence-based use there remains limited due to lack of controlled studies, limited sample size, short follow-up and poorly defined endpoints. Rituximab is indicated for CD20+ posttransplant lymphoproliferative disorder. It may be beneficial for treating recurrent membranous nephropathy and recurrent allograft antineutrophilic cytoplasmic antibody vasculitis and possibly for recurrent focal segmental glomerulosclerosis. Rituximab, in combination with IVIg/plasmapheresis, appears to decrease antibody level and increase the odds of transplantation in sensitized recipients. The role of Rituximab in ABOi transplant remains unclear, as similar outcomes are achieved without its use. Rituximab is not efficacious in antibody-mediated rejection/chronic antibody-mediated rejection. Strict randomized control trials are necessary to elucidate its true role in these settings.
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47
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Increased but stable isoagglutinin titers in hemodialysis patients. J Nephrol 2018; 32:121-127. [DOI: 10.1007/s40620-018-0512-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2018] [Accepted: 07/04/2018] [Indexed: 12/18/2022]
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48
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Desensitization with the Use of an Antibody Removal–Free Protocol in ABO-Incompatible Kidney Transplant Recipients with a Low Anti-A/B Antibody Titer. Transplant Proc 2018; 50:982-986. [DOI: 10.1016/j.transproceed.2018.01.032] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2017] [Revised: 01/06/2018] [Accepted: 01/30/2018] [Indexed: 12/30/2022]
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49
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Sethi SK, Bansal SB, Wadhwani N, Tiwari A, Arora D, Sharma R, Nandwani A, Yadav DK, Mahapatra AK, Jain M, Jha P, Ghosh P, Bhan A, Dhaliwal M, Raghunathan V, Kher V. Pediatric ABO-incompatible kidney transplantation: Evolving with the advancing apheresis technology: A single-center experience. Pediatr Transplant 2018; 22:e13138. [PMID: 29380556 DOI: 10.1111/petr.13138] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/28/2017] [Indexed: 12/11/2022]
Abstract
Recent literature has endorsed favorable outcomes following ABOi kidney transplantation in pediatric population. Nevertheless, reluctance to pursue an ABOi still remains pervasive. This could be ascribed to various legitimate reasons, namely less extensive pediatric ABOi data, technical difficulties encountered during PP, cost restraints, and concerns regarding higher rates of antibody-mediated rejection, infectious complications, and post-transplant lymphoproliferative disorder as compared to adults. However, given the similar excellent outcomes of both ABOi and ABOc kidney transplantation, clinicians should consider this option sooner if a compatible donor or swap is not available. Here, we describe the outcomes of three pediatric ABOi performed at our institute in India (from 2014 till now), wherein distinct apheresis modalities had been employed in each desensitization protocol, and our techniques evolved with advancing science in apheresis. This case series includes India's first published pediatric ABO-incompatible transplant (Case 2) and the youngest child to undergo ABO-incompatible renal transplant in SAARC nations (Case 3).
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Affiliation(s)
- Sidharth Kumar Sethi
- Kidney and Renal Transplant Institute, Medanta, The Medicity Hospital, Gurgaon, India
| | - Shyam Bihari Bansal
- Kidney and Renal Transplant Institute, Medanta, The Medicity Hospital, Gurgaon, India
| | - Nikita Wadhwani
- Kidney and Renal Transplant Institute, Medanta, The Medicity Hospital, Gurgaon, India
| | - Aseem Tiwari
- Blood Transfusion Department, Medanta, The Medicity Hospital, Gurgaon, India
| | - Dinesh Arora
- Blood Transfusion Department, Medanta, The Medicity Hospital, Gurgaon, India
| | - Reetesh Sharma
- Kidney and Renal Transplant Institute, Medanta, The Medicity Hospital, Gurgaon, India
| | - Ashish Nandwani
- Kidney and Renal Transplant Institute, Medanta, The Medicity Hospital, Gurgaon, India
| | - Dinesh Kumar Yadav
- Kidney and Renal Transplant Institute, Medanta, The Medicity Hospital, Gurgaon, India
| | - Amit Kumar Mahapatra
- Kidney and Renal Transplant Institute, Medanta, The Medicity Hospital, Gurgaon, India
| | - Manish Jain
- Kidney and Renal Transplant Institute, Medanta, The Medicity Hospital, Gurgaon, India
| | - Pranaw Jha
- Kidney and Renal Transplant Institute, Medanta, The Medicity Hospital, Gurgaon, India
| | - Prasun Ghosh
- Urology Department, Medanta, The Medicity Hospital, Gurgaon, India
| | - Anil Bhan
- Cardiothoracic Surgery, Medanta, The Medicity Hospital, Gurgaon, India
| | - Maninder Dhaliwal
- Pediatric Critical Care, Medanta, The Medicity Hospital, Gurgaon, India
| | - Veena Raghunathan
- Pediatric Critical Care, Medanta, The Medicity Hospital, Gurgaon, India
| | - Vijay Kher
- Kidney and Renal Transplant Institute, Medanta, The Medicity Hospital, Gurgaon, India
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50
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Alhabbab R, Blair P, Smyth LA, Ratnasothy K, Peng Q, Moreau A, Lechler R, Elgueta R, Lombardi G. Galectin-1 is required for the regulatory function of B cells. Sci Rep 2018; 8:2725. [PMID: 29426942 PMCID: PMC5807431 DOI: 10.1038/s41598-018-19965-z] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2017] [Accepted: 01/04/2018] [Indexed: 12/11/2022] Open
Abstract
Galectin-1 (Gal-1) is required for the development of B cells in the bone marrow (BM), however very little is known about the contribution of Gal-1 to the development of B cell regulatory function. Here, we report an important role for Gal-1 in the induction of B cells regulatory function. Mice deficient of Gal-1 (Gal-1−/−) showed significant loss of Transitional-2 (T2) B cells, previously reported to include IL-10+ regulatory B cells. Gal-1−/− B cells stimulated in vitro via CD40 molecules have impaired IL-10 and Tim-1 expression, the latter reported to be required for IL-10 production in regulatory B cells, and increased TNF-α expression compared to wild type (WT) B cells. Unlike their WT counterparts, T2 and T1 Gal-1−/− B cells did not suppress TNF-α expression by CD4+ T cells activated in vitro with allogenic DCs (allo-DCs), nor were they suppressive in vivo, being unable to delay MHC-class I mismatched skin allograft rejection following adoptive transfer. Moreover, T cells stimulated with allo-DCs show an increase in their survival when co-cultured with Gal-1−/− T2 and MZ B cells compared to WT T2 and MZ B cells. Collectively, these data suggest that Gal-1 contributes to the induction of B cells regulatory function.
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Affiliation(s)
- R Alhabbab
- Infectious Disease Unit & Division of Applied Medical Sciences, King Fahad Centre for medical research, King Abdulaziz University, Jeddah, Saudi Arabia. .,Division of Transplantation Immunology & Mucosal Biology, King's College London, King's Health Partners, Guy's Hospital, London, SE1 9RT, UK.
| | - P Blair
- Division of Transplantation Immunology & Mucosal Biology, King's College London, King's Health Partners, Guy's Hospital, London, SE1 9RT, UK.,Centre for Rheumatology, Division of Medicine, University College London, London, WC1E 6JF, UK
| | - L A Smyth
- Division of Transplantation Immunology & Mucosal Biology, King's College London, King's Health Partners, Guy's Hospital, London, SE1 9RT, UK.,School of Health, Sports and Biosciences, University of East London, Stratford, E15 4LZ, UK
| | - K Ratnasothy
- Division of Transplantation Immunology & Mucosal Biology, King's College London, King's Health Partners, Guy's Hospital, London, SE1 9RT, UK
| | - Q Peng
- Division of Transplantation Immunology & Mucosal Biology, King's College London, King's Health Partners, Guy's Hospital, London, SE1 9RT, UK
| | - A Moreau
- Division of Transplantation Immunology & Mucosal Biology, King's College London, King's Health Partners, Guy's Hospital, London, SE1 9RT, UK.,Centre de Recherche en Transplantation et Immunologie UMR 1064, INSERM, Université de Nantes, CHU, Nantes, France
| | - R Lechler
- Division of Transplantation Immunology & Mucosal Biology, King's College London, King's Health Partners, Guy's Hospital, London, SE1 9RT, UK
| | - R Elgueta
- Division of Transplantation Immunology & Mucosal Biology, King's College London, King's Health Partners, Guy's Hospital, London, SE1 9RT, UK.
| | - G Lombardi
- Division of Transplantation Immunology & Mucosal Biology, King's College London, King's Health Partners, Guy's Hospital, London, SE1 9RT, UK.
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