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      Treatment of large plasma volumes using specific immunoadsorption to desensitize ABO-incompatible kidney-transplant candidates

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          Abstract

          Background

          ABO-incompatible (ABOi) kidney-transplantation has very good long-term results, i.e. similar to those observed for living-kidney ABO-compatible transplantation. This is because patients are desensitized at pretransplant using apheresis and rituximab therapy, with tacrolimus-based immunosuppression.

          Objectives

          To assess the efficacy of a single, pretransplant (Day –1), specific immunoadsorption session using Glycosorb® columns (anti-A or anti-B; Glycorex Sweden) to treat large volumes of plasma (up to 18 L).

          Patients and Methods

          Prospective single-center study evaluating 12 consecutive patients (6 males), aged 40 (23–59) years. Incompatibilities were A into 0 (8), B into 0 (3), and AB into 0 (1). Pretransplant desensitization relied on rituximab (D–30), tacrolimus, mycophenolic acid, and steroids (all started on D–13), and a single session of specific immunoadsorption on D–1. Immunoadsorption was coupled in tandem with a hemodialysis session.

          Results

          Overall, 15 L (11–18) of plasma were treated per patient, i.e., 0.2 (0.11–0.36 L/kg). Isoagglutinin titers were 1/16 (1/5–1/64) before the procedure, decreasing after 6 hours to 1/5 (1/1–1/16 P = 0.008), and to 1/2 (1/1–1/8; P = 0.05) at completion of the session. The next day, i.e., the day of transplantation, there was no rebound of isoagglutinins [1/4 (1/1–1/5); P = ns]. The procedure was well tolerated with no side-effects and no significant changes in hemoglobin level, platelet counts, fibrinogen, or albumin levels.

          Conclusions

          For ABOi kidney-transplantation, a single, longer, specific immunoadsorption session was very efficient at 1-day pre-transplantation with no rebound. These results should be confirmed when isoagglutinin titers are higher (≥120).

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          Most cited references23

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          Three-year outcomes following 1420 ABO-incompatible living-donor kidney transplants performed after ABO antibody reduction: results from 101 centers.

          Reports from experienced centers suggest that recipients of an ABO-incompatible living-donor kidney transplant after reduction of ABO antibodies experience no penalty in graft and patient survival versus ABO-compatible transplants, but confirmation that these results can be widely replicated is lacking.
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            Outcomes of ABO-incompatible kidney transplantation in the United States.

            ABO incompatible (ABOi) kidney transplantation is an important modality to facilitate living donor transplant for incompatible pairs. To date, reports of the outcomes from this practice in the United States have been limited to single-center studies. Using the Scientific Registry of Transplant Recipients, we identified 738 patients who underwent live-donor ABOi kidney transplantation between January 1, 1995, and March 31, 2010. These were compared with matched controls that underwent ABO compatible live-donor kidney transplantation. Subgroup analyses among ABOi recipients were performed according to donor blood type, recipient blood type, and transplant center ABOi volume. When compared with ABO compatible-matched controls, long-term patient survival of ABOi recipients was not significantly different between the cohorts (P=0.2). However, graft loss was significantly higher, particularly in the first 14 days posttransplant (subhazard ratio, 2.34; 95% confidence interval, 1.43-3.84; P=0.001), with little to no difference beyond day 14 (subhazard ratio, 1.28; 95% confidence interval, 0.99-1.54; P=0.058). In subgroup analyses among ABOi recipients, no differences in survival were seen by donor blood type, recipient blood type, or transplant center ABOi volume. These results support the use and dissemination of ABOi transplantation when a compatible live donor is not available, but caution that the highest period of risk is immediately posttransplant.
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              ABO incompatible kidney transplantations without splenectomy, using antigen-specific immunoadsorption and rituximab.

              ABO incompatible kidney transplantations have previously only been performed after several preoperative sessions of plasmapheresis and splenectomy, with the conventional triple-drug immunosuppressive protocol being reinforced with antilymphocyte globulin and B-cell-specific drugs, such as cyclophosphamide or deoxyspergualine. We have designed a protocol without splenectomy, based on antigen-specific immunoadsorption, rituximab and a conventional triple-drug immunosuppressive protocol. The protocol calls for a 10-day pretransplantation conditioning period, starting with one dosage of rituximab and followed by full dose tacrolimus, mycophenolate mofetil and prednisolone. Antigen-specific immunoadsorption was performed on pretransplantation days -6, -5, -2 and -1. After the last session, 0.5 g/kg of intravenous immunoglobulin (IVIG) was administered. Postoperatively, three more apheresis sessions were given every third day. Furthermore, if there was a significant increase in the antibody titers, extra sessions were considered. Eleven patients have received transplants with this protocol. The ABO antibodies were readily removed by the antigen-specific immunoadsorption and were kept at a low level post-transplantation by further adsorptions. There were no side effects and all patients have normal renal transplant function. We conclude that after an infusion each of rituximab and IVIG, and antigen-specific immunoadsorption; blood group-incompatible renal transplantations can be performed with excellent results using standard immunosuppression and no splenectomy.
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                Author and article information

                Journal
                J Nephropathol
                J Nephropathol
                J Nephropathol
                J Nephropathol
                JNP
                Journal of Nephropathology
                Society of Diabetic Nephropathy Prevention
                2251-8363
                2251-8819
                July 2016
                29 June 2016
                : 5
                : 3
                : 90-97
                Affiliations
                1Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France
                2INSERM U563, IFR–BMT, CHU Purpan, Toulouse, France
                3Université Toulouse III Paul Sabatier, Toulouse, France
                4Department of Urology, Andrology, and Transplantation, CHU Rangueil, Toulouse, France
                5Etablissement Français du Sang de Midi-Pyrénées, CHU Purpan, Toulouse, France
                6Laboratory of Histopathology, CHU Rangueil, Toulouse, France
                7INSERM U1043, IFR-BMT, CHU Purpan, Toulouse, France
                Author notes
                [* ] Corresponding author: Professor Lionel Rostaing, Department of Nephrology and Organ Transplantation, CHU Rangueil, Toulouse, France lrostaing@ 123456chu-grenoble.fr
                Article
                10.15171/jnp.2016.17
                4961822
                27540536
                65c64fb7-cd15-465d-8fa5-83ddc5814f48
                © 2016 The Author(s)

                Published by Society of Diabetic Nephropathy Prevention. This is an open-access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 03 May 2016
                : 14 June 2016
                Page count
                Tables: 4, References: 23, Pages: 8
                Categories
                Original Article

                abo-incompatible kidney transplantation,specific immunoadsorption,glycosorb®,large plasma volumes

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