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

Long-term outcomes after ABO-incompatible kidney transplantation; a single-center French study

Background: ABO-incompatible (ABOi) is as efficient as ABO-compatible (ABOc) kidneytransplantation in the setting of live-donation. Objectives: To evaluate the long-term outcomes (i.e. >6 months) of 44 consecutive ABOi living-donor kidney-transplants (KTx). The results were compared to those from 44 ABOc KTx that were matched with ABOi-patients on age, gender, and date of transplantation. Patients and Methods: With regards to immunosuppression (IS) only ABOi-patients received pre-transplant IS, that included rituximab. Induction therapy relied significantly more frequently on basiliximab in ABOc- than in ABOi-patients 77.2% vs. 38.6% (P = 0.0002). Post-transplant IS relied only on tacrolimus/mycophenolic acid and steroids in ABOipatients, whereas some ABOc-patients were alternatively on cyclosporine (13.6%)/everolimus (11.3%) and no steroids (7%), respectively (P = 0.05). Results: In ABOi-patients there was no isoagglutinin titer rebound posttransplant. At last follow-up patient and graft survival was similar in the two groups, as well as kidneyallograft function. Acute rejection rates (cellular, humoral, or mixed) were similar across both groups (ABOi: 22.7%; ABOc: 20.4%). With regards to bacterial and viral infections the only significant difference between the two groups was that at month three there were significantly more BKV viruria in ABOi (25%) vs. 6.8% in ABOc (P = 0.03). De novo donor-specific alloantibody were detected in 13.6% ABOi and 4.5% ABOc patients (ns). Readmission rates in our department for less than two days were more frequent for ABOi conversely readmission rates for more than two days was similar across the groups. Conclusions: ABOi-kidney transplantation after desensitization provides in the long-term same results as those observed in live-donor ABOc-kidney transplantation

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

Jejak sekelompok pembaharu negeri di tanah cibugel

xx, 249 hlm.; ilus.; 25 cm

Jejak sekelompok pembaharu negeri di tanah cibugel

xx, 249 hlm.; ilus.; 25 cm

Low incidence of SARS-CoV-2, risk factors of mortality and the course of illness in the French national cohort of dialysis patients

International audienceThe aim of this study was to estimate the incidence of COVID-19 disease in the French national population of dialysis patients, their course of illness and to identify the risk factors associated with mortality. Our study included all patients on dialysis recorded in the French REIN Registry in April 2020. Clinical characteristics at last follow-up and the evolution of COVID-19 illness severity over time were recorded for diagnosed cases (either suspicious clinical symptoms, characteristic signs on the chest scan or a positive reverse transcription polymerase chain reaction) for SARS-CoV-2. A total of 1,621 infected patients were reported on the REIN registry from March 16th, 2020 to May 4th, 2020. Of these, 344 died. The prevalence of COVID-19 patients varied from less than 1% to 10% between regions. The probability of being a case was higher in males, patients with diabetes, those in need of assistance for transfer or treated at a self-care unit. Dialysis at home was associated with a lower probability of being infected as was being a smoker, a former smoker, having an active malignancy, or peripheral vascular disease. Mortality in diagnosed cases (21%) was associated with the same causes as in the general population. Higher age, hypoalbuminemia and the presence of an ischemic heart disease were statistically independently associated with a higher risk of death. Being treated at a selfcare unit was associated with a lower risk. Thus, our study showed a relatively low frequency of COVID-19 among dialysis patients contrary to what might have been assumed