Successful Kidney Transplantation After Desensitization Using Plasmapheresis, Low-Dose Intravenous Immunoglobulin, and Rituximab in Highly Sensitized Patients: A Single-Center Experience

Jin, Myungwon; Cho, J.-H.; Kwon, Owen; Hong, Ki-Heon; Choi, Ji-Young; Yoon, Se-Hee; Park, S.-H.; Kim, Y.-L.; Kim, C.-D.

doi:10.1016/j.transproceed.2011.11.040

Cited by 24 publications

(11 citation statements)

References 13 publications

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“…Theoretically, cytokines or their receptor antagonists mainly lead to acute cellular rejection, while PRA facilitates acute humoral rejection. It is crucial for clinicians to take necessary measures to overcome sensitization using novel immunosuppressive protocols, including therapeutic plasma exchange, immunoadsorption, intravenous immunoglobulin, rituximab, bortezomib, and basiliximab [13,31–33]. …”

Section: Discussionmentioning

confidence: 99%

Association Between Cytokines and Their Receptor Antagonist Gene Polymorphisms and Clinical Risk Factors and Acute Rejection Following Renal Transplantation

Xie

Wan

2016

Med Sci Monit

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BackgroundAcute rejection (AR) after renal transplantation affects both patient and graft survival. There is growing evidence of the genetic association between cytokine or its receptor antagonist and AR in solid organ transplantation. The objectives of this study were to investigate the role of recipient TNF β, IL-10, IL-1β, and IL-1 receptor antagonist (ra) gene polymorphism, as well as traditional clinical variables such as panel-reactive antibody (PRA) levels, donor type, and HLA mismatches in AR following renal transplantation.Material/MethodsTNF β (+252A/G), IL-10 (−592A/C), IL-1β (−511C/T) and IL-1ra (86 bp VNTR) gene polymorphisms were determined in 195 renal allograft recipients with and without AR, using PCR. Both these genotypic variants and clinical risk factors were investigated for correlation with AR within the first year after renal transplantation.ResultsPatients with increased pre-transplant PRA levels (P<0.001) and donor type (P=0.012) were prone to the development of AR. After adjusting for all variables of P<0.2, a PRA level >10% (OR=4.515, 95% confidence intervals=1.738–11.727, P=0.002) and the receipt of a graft from a donation after cardiac death (DCD) donor (OR=2.437, 95% confidence intervals=1.047–5.673, P=0.039) remained significantly associated with AR in a multivariate logistic regression analysis. No correlation could be found between recipients with an episode and absence of acute rejection and the gene polymorphisms of these cytokines investigated in the present study.ConclusionsThis study shows that the presence of increased pre-transplant levels of PRA and the receipt of a graft from DCD donor other than cytokine gene polymorphisms are significant risk factors for AR in renal transplantation. To reduce the occurrence of AR, clinicians should take necessary measures to lower the PRA levels and pay more attention to patients who received a graft from a DCD donor.

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Section: Discussionmentioning

confidence: 99%

Association Between Cytokines and Their Receptor Antagonist Gene Polymorphisms and Clinical Risk Factors and Acute Rejection Following Renal Transplantation

Xie

Wan

2016

Med Sci Monit

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“…Although the risk of AMR is significantly higher in sensitized patients, studies in kidney transplantation have demonstrated improved survival rates in those undergoing desensitization followed by transplantation when compared with those that continue waiting for an organ on the list [32]. A combination of total plasma exchange (TPE) and intravenous immunoglobulin (IVIG) is an effective desensitization regimen in SOT with good long-term outcomes in kidney transplantation [33][34][35]. In addition, novel B-cell targeting agents, such as Rituximab or Bortezomib, and complement inhibitors have improved the management of theses patients [36][37][38].…”

Section: Key Pointsmentioning

confidence: 99%

Acute rejection in vascularized composite allotransplantation

Fischer

Lian

Kueckelhaus

et al. 2014

Current Opinion in Organ Transplantation

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Acute rejection is higher in VCA than in any other organ in the field of transplantation, although most episodes are controlled by high-dose steroids and optimization of maintenance immunosuppression. Because of limitations in patient number and the duration of follow-up, the long-term safety and effectiveness of VCA remain unclear. Moreover, the tests currently used to diagnose acute rejection are of limited value. Better diagnostic tools and a better understanding of the immunologic events during acute rejection are therefore needed to improve diagnosis, treatment and outcomes of this life-changing restorative surgery.

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“…(ii) treatment protocols; (iii) treatment endpoints; (iv) antibody evaluation; (v) crossmatch procedures; (vi) assessment of graft function; (vii) donor type (living or deceased); (viii) DSA strength pretreatment and at transplant; (ix) length of follow-up; and (x) additional risk factors such as repeated mismatches. Tables 1 and 2 give AMR rates and graft survival data, respectively, for selected studies representing variations of the high dose IVIG and PP/low dose IVIG protocols (35,39,40,65,71,75,(81)(82)(83)(84)(85)(86). Because of the variability noted above, these data cannot be taken as a meaningful comparison of the different protocols but, rather, show that despite the increased risk of AMR, good graft and patient survival can be achieved.…”

Section: Desensitization For Hla Antibodymentioning

confidence: 99%

Desensitization for solid organ and hematopoietic stem cell transplantation

Zachary

Leffell

2014

Immunological Reviews

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Desensitization protocols are being used worldwide to enable kidney transplantation across immunologic barriers, i.e. antibody to donor HLA or ABO antigens, which were once thought to be absolute contraindications to transplantation. Desensitization protocols are also being applied to permit transplantation of HLA mismatched hematopoietic stem cells to patients with antibody to donor HLA, to enhance the opportunity for transplantation of non-renal organs, and to treat antibody-mediated rejection. Although desensitization for organ transplantation carries an increased risk of antibody-mediated rejection, ultimately these transplants extend and enhance the quality of life for solid organ recipients, and desensitization that permits transplantation of hematopoietic stem cells is life saving for patients with limited donor options. Complex patient factors and variability in treatment protocols have made it difficult to identify, precisely, the mechanisms underlying the downregulation of donor-specific antibodies. The mechanisms underlying desensitization may differ among the various protocols in use, although there are likely to be some common features. However, it is likely that desensitization achieves a sort of immune detente by first reducing the immunologic barrier and then by creating an environment in which an autoregulatory process restricts the immune response to the allograft.

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Successful Kidney Transplantation After Desensitization Using Plasmapheresis, Low-Dose Intravenous Immunoglobulin, and Rituximab in Highly Sensitized Patients: A Single-Center Experience

Cited by 24 publications

References 13 publications

Association Between Cytokines and Their Receptor Antagonist Gene Polymorphisms and Clinical Risk Factors and Acute Rejection Following Renal Transplantation

Association Between Cytokines and Their Receptor Antagonist Gene Polymorphisms and Clinical Risk Factors and Acute Rejection Following Renal Transplantation

Acute rejection in vascularized composite allotransplantation

Desensitization for solid organ and hematopoietic stem cell transplantation

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