Tocilizumab and Active Antibody-Mediated Rejection in Kidney Transplantation: A Literature Review
IntroductionChronic kidney disease (CKD) is a major public-health problem that increases the risk of end-stage kidney disease (ESKD), cardiovascular diseases, and other complications. Kidney transplantation is a renal-replacement therapy that offers better survival compared to dialysis. Antibody-med...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-04-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.839380/full |
| _version_ | 1818059500521783296 |
|---|---|
| author | Lara Cabezas Thomas Jouve Thomas Jouve Paolo Malvezzi Benedicte Janbon Diane Giovannini Diane Giovannini Lionel Rostaing Lionel Rostaing Johan Noble Johan Noble |
| author_facet | Lara Cabezas Thomas Jouve Thomas Jouve Paolo Malvezzi Benedicte Janbon Diane Giovannini Diane Giovannini Lionel Rostaing Lionel Rostaing Johan Noble Johan Noble |
| author_sort | Lara Cabezas |
| collection | DOAJ |
| description | IntroductionChronic kidney disease (CKD) is a major public-health problem that increases the risk of end-stage kidney disease (ESKD), cardiovascular diseases, and other complications. Kidney transplantation is a renal-replacement therapy that offers better survival compared to dialysis. Antibody-mediated rejection (ABMR) is a significant complication following kidney transplantation: it contributes to both short- and long-term injury. The standard-of-care (SOC) therapy combines plasmapheresis and Intravenous Immunoglobulins (IVIg) with or without steroids, with or without rituximab: however, despite this combined treatment, ABMR remains the main cause of graft loss. IL-6 is a key cytokine: it regulates inflammation, and the development, maturation, and activation of T cells, B cells, and plasma cells. Tocilizumab (TCZ) is the main humanized monoclonal aimed at IL-6R and appears to be a safe and possible strategy to manage ABMR in sensitized recipients. We conducted a literature review to assess the place of the anti-IL-6R monoclonal antibody TCZ within ABMR protocols.Materials and MethodsWe systematically reviewed the PubMed literature and reviewed six studies that included 117 patients and collected data on the utilization of TCZ to treat ABMR.ResultsMost studies report a significant reduction in levels of Donor Specific Antibodies (DSAs) and reduced inflammation and microvascular lesions (as found in biopsies). Stabilization of the renal function was observed. Adverse events were light to moderate, and mortality was not linked with TCZ treatment. The main side effect noted was infection, but infections did not occur more frequently in patients receiving TCZ as compared to those receiving SOC therapy.ConclusionTCZ may be an alternative to SOC for ABMR kidney-transplant patients, either as a first-line treatment or after failure of SOC. Further randomized and controlled studies are needed to support these results. |
| first_indexed | 2024-12-10T13:17:31Z |
| format | Article |
| id | doaj.art-75e6683ba27047e1a4491ec214b2bba4 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-10T13:17:31Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-75e6683ba27047e1a4491ec214b2bba42022-12-22T01:47:29ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-04-011310.3389/fimmu.2022.839380839380Tocilizumab and Active Antibody-Mediated Rejection in Kidney Transplantation: A Literature ReviewLara Cabezas0Thomas Jouve1Thomas Jouve2Paolo Malvezzi3Benedicte Janbon4Diane Giovannini5Diane Giovannini6Lionel Rostaing7Lionel Rostaing8Johan Noble9Johan Noble10Nephrology, Hemodialysis, Apheresis and Kidney Transplantation Department, University Hospital Grenoble, Grenoble, FranceNephrology, Hemodialysis, Apheresis and Kidney Transplantation Department, University Hospital Grenoble, Grenoble, FranceUniversity Grenoble Alpes, Grenoble, FranceNephrology, Hemodialysis, Apheresis and Kidney Transplantation Department, University Hospital Grenoble, Grenoble, FranceNephrology, Hemodialysis, Apheresis and Kidney Transplantation Department, University Hospital Grenoble, Grenoble, FranceUniversity Grenoble Alpes, Grenoble, FrancePathology Department, University Hospital Grenoble, Grenoble, FranceNephrology, Hemodialysis, Apheresis and Kidney Transplantation Department, University Hospital Grenoble, Grenoble, FranceUniversity Grenoble Alpes, Grenoble, FranceNephrology, Hemodialysis, Apheresis and Kidney Transplantation Department, University Hospital Grenoble, Grenoble, FranceUniversity Grenoble Alpes, Grenoble, FranceIntroductionChronic kidney disease (CKD) is a major public-health problem that increases the risk of end-stage kidney disease (ESKD), cardiovascular diseases, and other complications. Kidney transplantation is a renal-replacement therapy that offers better survival compared to dialysis. Antibody-mediated rejection (ABMR) is a significant complication following kidney transplantation: it contributes to both short- and long-term injury. The standard-of-care (SOC) therapy combines plasmapheresis and Intravenous Immunoglobulins (IVIg) with or without steroids, with or without rituximab: however, despite this combined treatment, ABMR remains the main cause of graft loss. IL-6 is a key cytokine: it regulates inflammation, and the development, maturation, and activation of T cells, B cells, and plasma cells. Tocilizumab (TCZ) is the main humanized monoclonal aimed at IL-6R and appears to be a safe and possible strategy to manage ABMR in sensitized recipients. We conducted a literature review to assess the place of the anti-IL-6R monoclonal antibody TCZ within ABMR protocols.Materials and MethodsWe systematically reviewed the PubMed literature and reviewed six studies that included 117 patients and collected data on the utilization of TCZ to treat ABMR.ResultsMost studies report a significant reduction in levels of Donor Specific Antibodies (DSAs) and reduced inflammation and microvascular lesions (as found in biopsies). Stabilization of the renal function was observed. Adverse events were light to moderate, and mortality was not linked with TCZ treatment. The main side effect noted was infection, but infections did not occur more frequently in patients receiving TCZ as compared to those receiving SOC therapy.ConclusionTCZ may be an alternative to SOC for ABMR kidney-transplant patients, either as a first-line treatment or after failure of SOC. Further randomized and controlled studies are needed to support these results.https://www.frontiersin.org/articles/10.3389/fimmu.2022.839380/fullkidney transplantationtocilizumabantibody-mediated rejectionchronic active antibody-mediated rejectionestimated glomerular filtration ratedonor-specific alloantibody |
| spellingShingle | Lara Cabezas Thomas Jouve Thomas Jouve Paolo Malvezzi Benedicte Janbon Diane Giovannini Diane Giovannini Lionel Rostaing Lionel Rostaing Johan Noble Johan Noble Tocilizumab and Active Antibody-Mediated Rejection in Kidney Transplantation: A Literature Review Frontiers in Immunology kidney transplantation tocilizumab antibody-mediated rejection chronic active antibody-mediated rejection estimated glomerular filtration rate donor-specific alloantibody |
| title | Tocilizumab and Active Antibody-Mediated Rejection in Kidney Transplantation: A Literature Review |
| title_full | Tocilizumab and Active Antibody-Mediated Rejection in Kidney Transplantation: A Literature Review |
| title_fullStr | Tocilizumab and Active Antibody-Mediated Rejection in Kidney Transplantation: A Literature Review |
| title_full_unstemmed | Tocilizumab and Active Antibody-Mediated Rejection in Kidney Transplantation: A Literature Review |
| title_short | Tocilizumab and Active Antibody-Mediated Rejection in Kidney Transplantation: A Literature Review |
| title_sort | tocilizumab and active antibody mediated rejection in kidney transplantation a literature review |
| topic | kidney transplantation tocilizumab antibody-mediated rejection chronic active antibody-mediated rejection estimated glomerular filtration rate donor-specific alloantibody |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.839380/full |
| work_keys_str_mv | AT laracabezas tocilizumabandactiveantibodymediatedrejectioninkidneytransplantationaliteraturereview AT thomasjouve tocilizumabandactiveantibodymediatedrejectioninkidneytransplantationaliteraturereview AT thomasjouve tocilizumabandactiveantibodymediatedrejectioninkidneytransplantationaliteraturereview AT paolomalvezzi tocilizumabandactiveantibodymediatedrejectioninkidneytransplantationaliteraturereview AT benedictejanbon tocilizumabandactiveantibodymediatedrejectioninkidneytransplantationaliteraturereview AT dianegiovannini tocilizumabandactiveantibodymediatedrejectioninkidneytransplantationaliteraturereview AT dianegiovannini tocilizumabandactiveantibodymediatedrejectioninkidneytransplantationaliteraturereview AT lionelrostaing tocilizumabandactiveantibodymediatedrejectioninkidneytransplantationaliteraturereview AT lionelrostaing tocilizumabandactiveantibodymediatedrejectioninkidneytransplantationaliteraturereview AT johannoble tocilizumabandactiveantibodymediatedrejectioninkidneytransplantationaliteraturereview AT johannoble tocilizumabandactiveantibodymediatedrejectioninkidneytransplantationaliteraturereview |