Chairs: S. Schmaldienst (Vienna, Austria), G. Böhmig (Vienna, Austria)
|Apheresis techniques in ABO-incompatible kidney transplantation
1 University Hospital Heidelberg, Transplantation Center, Heidelberg, Germany
Abstract text :
ABO incompatible kidney transplantation has long time been considered a contraindication to successful kidney transplantation. Due to an increasing organ shortage, however, several groups have developed strategies to overcome the ABO antibody barrier in recent years. Today, ABO incompatible kidney transplantation has become a standard procedure with death-censored graft survival rates that are not different from rates in compatible patients. Desensitization is achieved by apheresis with or without B cell-depleting therapies that are accompanied by powerful immunosuppressive therapy. Anti-A/B antibodies are aimed to be below a certain threshold at the time of ABO incompatible kidney transplantation and during the first 2 weeks after surgery. Thereafter, even a rebound of anti-A/B antibodies does not appear to harm the kidney transplant, a phenomenon that is called accommodation. While the general desensitization protocol does not differ substantially in transplant centers around the world, the method of antibody depletion varies from center to center. Plasmapheresis, double-filtration plasmapheresis, and antibody-specific or unspecific immunoadsorption are used for anti-A/B antibody depletion before incompatible kidney transplantations. Each procedure has its specific advantages and disadvantages and, therefore, many centers even use a combination of procedures to accomplish the incompatible procedure.
|AB0 incompatible kidney transplantation – Freiburg experience
1 University Hospital Freiburg, General Surgery - Transplant Section, Freiburg, Germany
Abstract text :
Introduction: Dramatic shortage of deceased donor organs in Germany stimulated us to start AB0
incompatible kidney transplantation in our transplant center to expand the living donor
transplantation options. In 2004 we introduced this program in Germany. Since the beginning more
than 1000 patients were transplanted in 26 German centers offering this method. Meanwhile it is
established procedure which expands the living donor pool.
Method: In period between April 2004 and December 2015 100 AB0 incompatible and 118 AB0
compatible kidney transplantations have been performed in our center. The immunosuppressive
therapy consisted induction with Basiliximab, Tacrolimus, Mycophefon acid and corticosteroids. The
recipients in AB0 incompatible group became four weeks for planned transplantation once Rituximab
375mg/sqm. The additionaly the regular therapy with antigen specific immunoadsorption columns
(Glycorex Sweden) and since 2012 non-specific immunoglobulin adsorption columns (Immunosorba ,
Fresenius Medical Care) depending of isohaemagglutinin titer titers (target IgM, IgG Titer < 1 : 4).
Classic triple immunosuppressive therapy was given in the preoperative phase. We compared both
groups concerning patient survival and death-censored graft survival, graft function, graft rejections,
infectious and surgical complications. The only significant fact was lymphocele formation with 23,0 %
in recipients in AB0 incompatible group in comparison to patients in AB0 compatible cohort. Ten
years patient survival of 99 % and death censored graft survival of 94% in this group was comparable
with data from Japan.
Conclusion: AB0 incompatible living kidney transplantation is established and safe method of
treatment for patients with End Stage Renal Disease who do not have blood group compatible
|Apheresis techniques to counteract ABMR
1 FR263 800 302, , GRENOBLE, France
Abstract text :
|REFRACTORY ACUTE ABMR: EFFECTIVE TREATMENT BY A NOVEL STRATEGY OF MEMBRANE FILTRATION PLUS IMMUNOADSORPTION FOR CLASSICAL COMPLEMENT INTERFERENCE IN ADDITION TO ANTIBODY DEPLETION
1 Medical University of Vienna, Internal Medecine III / Division of Nephrology, Vienna, Austria
Abstract text :
BACKGROUND. Apheresis for IgG depletion represents an effective strategy for the prevention and treatment of antibody-mediated rejection (ABMR). We have earlier shown that membrane filtration (MF), added to the circuit of conventional immunoadsorption (IA), may specifically interfere with alloantibody-triggered complement activation, by eliminating C1q, the key component of the classical pathway (CP). Here, we report on the effect of combined apheresis in four cases of severe refractory C4d-positive ABMR.
METHODS. For IA we used a semiselective double-column device (146-GAM peptide adsorber; 2-3 plasma volumes per session). For combined apheresis, a porous membrane filter (MONET®) was connected to the extracorporeal circuit. ABMR was classified and scored according to the Banff 2013 update.
RESULTS. Four kidney allograft recipients (transplantation between 2014 and 2016; two re-transplants, two female recipients, age 47-71 years, pre-Tx CDC-PRA 0-44%) were transplanted across preformed donor-specific antibodies (DSA, HLA class I and/or II) using a local standard protocol of peri-transplant IA and ATG induction. Despite desensitization, studied patients developed severe acute/active ABMR (g ptc score: 2-4; TMA in 3 cases) 14 to 17 days after transplantation (two of the patients were dialysis-dependent). Signs of intra-graft CP activation (diffuse C4d staining in all four cases) prompted us to add MF to IA treatment. Upon 2-8 combined treatment sessions, recipients showed reversal of rejection, two within the first week. Remarkably, follow-up allograft biopsies performed within 2 to 9 days after the last treatment session showed marked morphological improvement (g ptc: 0-1, no TMA), with negative C4d staining in three cases. Last serum creatinine 3-20 months post-Tx was 1.42 mg/dL (median; range: 0.97-3.1).
CONCLUSION. Our findings illustrate that MF as an add-on to IA may be an effective strategy to reverse refractory acute ABMR, presumably as a result of CP interference.
|ABO antigen-specific immunoadsorption in pure red cell aplasia following major and bidirectional ABO-incompatible, allogeneic hematopoietic stem cell transplantation
1 Medical University of Vienna, Department of Medicine III, Division of Nephrology and Dialysis, Vienna, Austria
2 Medical University of Vienna, Department of Medicine I, Bone marrow transplantation unit, Vienna, Austria
Abstract text :
Infectious complications are the leading cause of the increased mortality after hematopoietic stem cell transplantation (HSCT). Pure red cell aplasia (PRCA) further increases the mortality rate due to iron overload-related organ toxicity following polytransfusion. Caused by host isohemagglutinines directed against donor erythrocytes PRCA is treated by immunosuppressive agents or apheresis modalities, which so far unselectively removed all IgG and IgM from circulation, exposing the patient to increased susceptibility to infections. Glycosorb ABO immunoadsorption columns (Glycorex Transplantation AB, Lund, Sweden) selectively eliminate anti A- and/or anti B- isohemagglutinines without immunocompromising effect. The objective of this study was to assess the efficacy of IA using these ABO antigen-specific adsorbers for the treatment of PRCA.
Medical histories of all ABO-incompatible HSCT-recipients transplanted between 01/2002 and 06/2017 at the Medical University of Vienna were screened for the development of PRCA and the subsequent treatment with ABO-antigen specific immunoadsorption using Glycosorb ABO immunoadsorption columns.
Three subjects were treated with IA using Glycosorb ABO immunoadsorption columns due to PRCA following major or bidirectional ABO-incompatible, allogeneic unrelated donor-HSCT. IA was initiated between day 104 and 154 after major ABOi-HSCT and resolved PRCA in all three patients. A sustained increase in reticulocyte counts >32 G/L was observed after 20.7±15.6 (range: 6-37) days of treatment, during which 13.0±9.0 (range: 4-22) IAs were performed. As expected, hemoglobin levels increased soon after reticulocytosis was observed without further RBC transfusions and normal hemoglobin values were achieved few weeks after the discontinuation of ABO antigen-specific IA. Repeated measurements of CMV-, EBV- and parvovirus B19-PCR showed no reactivation or infection. None of the HSCT-recipients showed any signs of infection during the time of IA or in the first months therafter.
Our data demonstrated the successful recovery of PRCA in three recipients of an ABO-incompatible, allogeneic unrelated donor-HSCT by ABO-antigen specific IA. Of note, the time between initiation of the specific treatment and the recovery from PRCA was short and none of the patients showed any signs of infection during the time of IA or the first months thereafter.
|Outcomes following living donor kidney transplantation in patients with donor-specific HLA antibodies after desensitization with immunoadsorption
1 Nephrology Unit, University Hospital Heidelberg, Heidelberg, Germany
2 Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
3 Department of Transplantation Immunology, University Hospital Heidelberg, Heidelberg, Germany
Abstract text :
INTRODUCTION AND AIMS
Due to the current organ shortage, living donor kidney transplantation is increasingly performed over human leukocyte antigen (HLA) or ABO antibody barriers. Uncertainty still exists concerning the risk for antibody-mediated rejection episodes, possibly limiting long-term graft survival. The present study aimed to evaluate the outcomes of kidney transplantations performed after desensitization in patients with donor-specific HLA antibodies compared to standard risk recipients.
Thirty-seven sensitized patients were included in the study. Sixteen patients had a positive CDC and/or ELISA crossmatch result with their prospective living donor and 31 patients had Luminex-detected donor-specific HLA antibodies (DSA). Patients were successfully desensitized by immunoadsorption treatment (median of 8 treatments) and anti-CD20 antibody rituximab (N=32) combined with antithymocyte globulin (N=19) or anti-IL2 receptor antibody therapy (N=18). Eleven patients were additionally treated by plasmapheresis. All patients received a kidney transplant from a living donor. Postoperative apheresis was performed in 35 patients. The outcomes of the 37 patients were retrospectively compared to outcomes of 74 standard risk recipients (2:1 matching).
During a median of 8 pretransplant immunoadsorption treatments, IgG was reduced by 98% and IgM by 78% in sensitized patients. After transplantation, sensitized patients showed comparable death-censored graft survival and patient survival compared to standard risk recipients. Infectious complications, surgical complications and rejection rates (19% in both groups) were not significantly different between groups. Median 1-year serum creatinine was with 1.31 mg/dL in sensitized recipients not significantly different to the 1.38 mg/dL in standard risk recipients. One-year urinary protein excretion was also not significantly different with a low 10.8 and 10.5 g/mol creatinine, respectively.
Our desensitization protocol for sensitized living donor kidney transplant recipients results in good graft outcomes with comparable side effects and rejections rates to standard risk recipients.
|HLA desensitization using rituximab/ immunoadsorption before kidney transplantation
1 CHU Grenoble Alpes, Nephrology, Hemodialysis, Apheresis, and Transplantation, GRENOBLE, France
2 Clinique de Néphrologie, , GRENOBLE, France
3 , , ,
Abstract text :
Introduction: Many kidney-transplant (KT) candidates are sensitized against HLA-antigens, making it difficult to find a suitable HLA-compatible donor. Pretransplant HLA-desensitization strategies have shown improved patient survival after transplantation.