Immunoadsorption and Its Application for Desensitizing Incompatible Kidney Transplant Candidates Who Have a Potential Living Donor

Background. Plasmapheresis is widely used to remove potential deleterious antibodies from the blood. Because the volume of treated plasma is limited, plasmapheresis can be replaced by immunoadsorption (IA), a more tedious but sophisticated technique that enables treatment of larger volumes of plasma, i.e., > 4 L vs. 1.5–2 L. We have implemented in our department IA technique to replace plasmapheresis when we launched our ABO-incompatible (ABOi) and HLA-incompatible (HLAi) kidney-transplant programs with living kidney donors. In this setting, isoagglutinin titers (ABOi) or donor-specific alloantibodies (HLAi) have to be decreased drastically at pretransplant by apheresis and immunosuppression. Methods. We designed a desensitization program based on IA, which was started in the first trimester of 2010 within the Acute Polyvalent Hemodialysis and Apheresis Unit (Toulouse University Hospital, France). We describe all the steps used to implement this IA technique. So far, we have performed > 225 IA sessions. Results and Conclusions. The IA sessions were associated with a net body-weight gain of ~ 1 kg. Normally, IA is performed first and then hemodialysis on the same or following day; however, we were able to simultaneously perform IA with hemodialysis (tandem procedure). This tandem procedure has reduced costs. Implementation of IA has enabled the successful transplantation of 32 kidney patients

Rituximab and hypogammaglobulinemia in the setting of ABO-incompatible kidney transplantation

Background: ABO-incompatible (ABOi) kidney transplantation can be achieved by desensitizing the recipient using apheresis plus rituximab-based immunosuppression. Objectives: We sought to ascertain the factors that contributed to low immunoglobulin levels at post-ABOi kidney transplantation. Patients and Methods: This single-center study included 43 ABO-i kidney-transplant recipients desensitized with rituximab-based therapy. Posttransplant immunoglobulin levels (IgG, IgA, and IgM) were prospectively monitored within 2 years. If severe hypogammaglobulinemia occurred, i.e., IgG levels <4 g/L, patients received polyvalent immunoglobulin (IVIg substitution). Results: Within 1-year posttransplantation, 25% of patients experienced at least once severe hypogammaglobulinemia. On D –30 (pre-transplantation), IgG, IgA, and IgM levels were within normal ranges: 10 ± 4.4, 1.9 ± 1.2, and 0.8± 0.5 g/L, respectively. IgG levels were significantly decreased at D0 (4.2 ± 3.8 g/L) compared to D–30. At D15, IgG levels did not significantly differ from those on D0 or D –30. Conversely, beyond month-1 posttransplant IgG levels were within normal ranges and were significantly higher than levels measured on D0. Within three months posttransplantation, 11 patients required IVIg because IgG levels were <4 g/L (IVIg+ group). When these patients were compared with those that did not receive IVIg within 3 months posttransplantation (IVIg– group), IgG levels were similar at D –30 in both groups. Conversely, at D0, IgG levels were significantly lower in the Ig+ group (2.4 ± 2 vs. 5.5± 4.2 g/L; P = 0.009); t he d ifference remained significant until D15 posttransplantation (Ig+: 3.4 ± 1.7, Ig–: 6.6 ± 2 g/L; P = 0.0002). There was no statistical difference between the two groups after D15. Infectious complications did not significantly vary between patients with or without hypogammaglobulinemia. Conclusions: We conclude that hypogammaglobulinemia occurred frequently after ABOincompatible kidney transplantation but did not cause more infectious complications

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

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)

Early post-transplant complications following ABO-incompatible kidney transplantation

Background: Living-kidney transplantation is increasing because of the scarcity of kidneys from deceased donors and the increasing numbers of patients on waiting lists for a kidney transplant. Living-kidney transplantation is now associated with increased long-term patient- and allograft-survival rates. Objectives: The purpose of this retrospective study was to identify, in a cohort of 44 ABO-incompatible (ABOi) live-kidney transplant patients, the main complications that occurred within 6 months post-transplantation, and to compare these findings with those from 44 matched ABO-compatible (ABOc) live-kidney transplant patients who were also from our center. Patients and Methods: This single-center retrospective study assessed post-transplantation complications in 44 ABO-i versus 44 matched ABO-c patients. All patients were comparable at baseline except that ABO-i patients had greater immunological risks. Results: During the 6-month post-transplant period, more ABO-i patients presented with postoperative bleeds, thus requiring significantly more blood transfusions. Bleeds were associated with significantly lower values of fibrinogen, platelets, prothrombin time, and hemoglobin levels. Surgical complications, patient- and graft-survival rates, and kidney-function statuses were similar between both groups at 6 months post-transplantation. Conclusions: We conclude that impairment of hemostatic factors at pre-transplant explained the increased risk of a post-transplant bleed in ABO-i patients

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xx, 249 hlm.; ilus.; 25 cm