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      Complication from Desensitization

      chapter-article
      Kidney Transplantation in Sensitized Patients
      Desensitization, Adverse effects, Kidney transplantation

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          Abstract

          Sensitization to human leukocyte antigens (HLAs) has been one of the major clinical challenges for successful kidney transplantation. In end-stage renal disease, kidney transplantation provides benefits compared with dialysis in terms of improved patient survival better quality of life, and lower ongoing costs after the first year. Living donor kidney transplantation has an advantage with improved allograft survival, and performed earlier and electively compared with deceased donor transplantation. However sensitized patients are increasing in number on transplant waiting lists, and their prospect of getting a transplant is less than nonsensitized patients due to immunological incompatibility with the donor. Strategy for sensitized patients are listing for a compatible deceased donor transplant or, if they have a living donor, either selecting a kidney exchange program or undergoing a desensitization procedure. Desensitization procedures may be undertaken to increase access to either living or deceased donor transplants, and in some situations may also be employed to facilitate participation in a kidney exchange, in less immunological barrier to be overcome. The question of whether individuals are better off with a desensitization treatment followed by HLA-incompatible living donor transplantation or waiting on the deceased donor kidney transplant list for a compatible transplant has recently been addressed by two large multicenter studies, with conflicting results. A multicenter study from the United States published in the New England Journal of Medicine [365;318 326.2011] concluded that there was a strong survival benefit for sensitized patients undergoing desensitization followed by HLA-incompatible living donor kidney transplant compared with those remaining on the waiting list. Of interest, a second study, published in the Lancet, [389;727 734.2017] found no significant survival advantage for desensitized patients compared with similar patients remaining on the waiting list in the United Kingdom. Controversies still remain regarding how desensitization can be achieved and which techniques are effective and safe.

          In this chapter various complications from the desensitization will be dealt with in current use of medications or armamentum.

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          Most cited references67

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          Assessment of Tocilizumab (Anti-Interleukin-6 Receptor Monoclonal) as a Potential Treatment for Chronic Antibody-Mediated Rejection and Transplant Glomerulopathy in HLA-Sensitized Renal Allograft Recipients.

          Extending the functional integrity of renal allografts is the primary goal of transplant medicine. The development of donor-specific antibodies (DSAs) posttransplantation leads to chronic active antibody-mediated rejection (cAMR) and transplant glomerulopathy (TG), resulting in the majority of graft losses that occur in the United States. This reduces the quality and length of life for patients and increases cost. There are no approved treatments for cAMR. Evidence suggests the proinflammatory cytokine interleukin 6 (IL-6) may play an important role in DSA generation and cAMR. We identified 36 renal transplant patients with cAMR plus DSAs and TG who failed standard of care treatment with IVIg plus rituximab with or without plasma exchange. Patients were offered rescue therapy with the anti-IL-6 receptor monoclonal tocilizumab with monthly infusions and monitored for DSAs and long-term outcomes. Tocilizumab-treated patients demonstrated graft survival and patient survival rates of 80% and 91% at 6 years, respectively. Significant reductions in DSAs and stabilization of renal function were seen at 2 years. No significant adverse events or severe adverse events were seen. Tocilizumab provides good long-term outcomes for patients with cAMR and TG, especially compared with historical published treatments. Inhibition of the IL-6-IL-6 receptor pathway may represent a novel approach to stabilize allograft function and extend patient lives.
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            IgG Endopeptidase in Highly Sensitized Patients Undergoing Transplantation

            Donor-specific antibodies create an immunologic barrier to transplantation. Current therapies to modify donor-specific antibodies are limited and ineffective in the most highly HLA-sensitized patients. The IgG-degrading enzyme derived from Streptococcus pyogenes (IdeS), an endopeptidase, cleaves human IgG into F(ab')2 and Fc fragments inhibiting complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity, which suggests that IdeS might be useful for desensitization. We report on the combined experience of two independently performed open-label, phase 1-2 trials (conducted in Sweden and the United States) that assessed the efficacy of IdeS with regard to desensitization and transplantation of a kidney from an HLA-incompatible donor.
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              Systematic review: the effect of preventive lamivudine on hepatitis B reactivation during chemotherapy.

              Lamivudine is increasingly being used to prevent hepatitis B reactivation in patients with cancer who test positive for hepatitis B surface antigen (HBsAg) and are undergoing chemotherapy. To determine whether preventive lamivudine reduces chemotherapy-induced hepatitis B virus (HBV)-related morbidity and mortality in patients with cancer who test positive for HBsAg. MEDLINE, Ovid MEDLINE, TOXNET, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials were searched in all languages until June 2007. Clinical trials and cohort studies that reported the efficacy of preventive lamivudine versus control on HBV reactivation in patients who tested positive for HBsAg and were receiving chemotherapy were included. Additional requirements included minimum sample size (>5 participants per treatment group) and reported HBV-related morbidity and mortality data. Two investigators independently did literature searches and data extraction, and 2 other investigators independently confirmed study eligibility and data retrieval. Fourteen studies (2 randomized, controlled trials; 8 prospective cohort studies; and 4 retrospective cohort studies) met the predefined criteria for analysis. There were 275 patients in the preventive lamivudine group and 475 control participants for the primary end point of HBV reactivation. With preventive lamivudine, the relative risk for both HBV reactivation and HBV-related hepatitis ranged from 0.00 to 0.21. None of the patients in the preventive lamivudine group developed HBV-related hepatic failure (0 of 108 patients vs. 21 of 162 patients), and only 4 deaths were attributable to HBV (4 of 208 patients vs. 27 of 394 patients) in the preventive lamivudine group. Lamivudine was well tolerated, and no adverse effects were noted. The studies included in the meta-analysis did not consistently report all of the outcomes of interest. Sample sizes were small and only 2 studies had a randomized, controlled design. Preventive therapy with lamivudine for patients who test positive for HBsAg and are undergoing chemotherapy may reduce the risk for HBV reactivation and HBV-associated morbidity and mortality.
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                Author and article information

                Contributors
                djhan@amc.seoul.kr
                djhan@amc.seoul.kr
                Journal
                978-981-10-7046-4
                10.1007/978-981-10-7046-4
                Kidney Transplantation in Sensitized Patients
                Kidney Transplantation in Sensitized Patients
                978-981-10-7045-7
                978-981-10-7046-4
                01 December 2019
                : 63-89
                Affiliations
                GRID grid.413967.e, ISNI 0000 0001 0842 2126, Department of General Surgery, , Asan Medical Center, ; Seoul, Korea (Republic of)
                GRID grid.413967.e, ISNI 0000 0001 0842 2126, Department of General Surgery, , Asan Medical Center, ; Seoul, South Korea
                Article
                6
                10.1007/978-981-10-7046-4_6
                7122531
                d50bf4b1-738f-4b0f-99f3-24dedb4a08b4
                © Springer Nature Singapore Pte Ltd. 2020

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

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                © Springer Nature Singapore Pte Ltd. 2020

                desensitization,adverse effects,kidney transplantation

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