Pilot conversion trial from mycophenolic acid to everolimus in ABO-incompatible kidney-transplant recipients with BK viruria and/or viremia.

Immunosuppression using everolimus (EVR) plus low-dose tacrolimus (Tac) is commonly used in organ transplantation. EVR has potential antiviral effects. Herein, the long-term outcomes and impacts of Tac-EVR on the BK virus are reported in ABO-incompatible kidney-transplant recipients. The initial immunosuppressive regimen combined steroids, Tac, and mycophenolic acid (MPA). At a median of 141 (34-529) days post-transplantation, seven stable ABO-incompatible kidney-transplant recipients were converted from MPA to EVR because of active BK replication, and compared with a reference group of fourteen ABO-incompatible patients receiving classical Tac plus MPA. At 1 month before conversion, at 1, 3 months after, and at last follow-up, clinical and biological parameters were monitored. The median time from conversion to the last follow-up was 784 (398-866) days. Conversion to EVR caused no change to rejection episodes or immunological status (isoagglutinin titers, anti-HLA antibodies). At last follow-up, median eGFR was similar in the Tac-MPA versus Tac-EVR group (40 [range: 14-56] vs. 54.5 ml/min/1.73 m(2) [range: 0-128], P = 0.07). The major adverse event was dyslipidemia. Interestingly, conversion from MPA to EVR decreased BK viral load in five patients. ABO-incompatible kidney-transplant recipients with an active BK virus infection may benefit from conversion to EVR.

[Lyme nephritis in humans: Physio-pathological bases and spectrum of kidney lesions]. / La néphrite de Lyme chez l'homme : bases physiopathologiques et spectre lésionnel rénal.

Known in less than half a century, borreliosis, or Lyme disease, is a zoonosis caused by the tick bite. It is the most common vector disease in Europe and the United States. Borrelia burgdorferi sensu lato, the bacterium in question, is fitted with a "cunning device" that allows it to trick the immune system and implant the infection chronically. It causes multi-system tissue damage mediated by the inflammatory response of the host. Renal involvement is rarely reported and is better known in dogs as Lyme nephritis. The first case of kidney impairment in the human being was described in 1999, and since then eight other cases have been reported. The involvement is preferentially glomerular; the histological forms vary between immune complex nephropathy and podocytopathy. The pathophysiological mechanisms appear to be triple: immune complex deposits, podocytic hyper-expression of the B7-1 membrane protein, and renal infiltration of inflammatory cells. On the basis of the accumulated knowledge of the disease in just over 40 years, this review aims at establishing the physio-pathological hypotheses of renal involvement in order to better define the histological lesions.

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.

Successful Transplantation in ABO- and HLA-Incompatible Living Kidney Transplant Patients: A Report on 12 Cases.

Few studies have assessed the outcomes of ABOi/HLAi living-kidney transplantation. We report a single-center experience of 12 ABOi/HLAi living-kidney recipients. Twenty-seven donor-specific alloantibodies (DSAs) (1-6 per patient) were found with fluorescence intensities of 1500-15 000. Desensitization was based on IVIg, two doses of rituximab (375 mg/m2 ), tacrolimus-based (0.2 mg/kg) immunosuppression (started on day-10 pretransplant), and 11 (6-27) pretransplant apheresis sessions (plasmapheresis, specific or semi-specific immunoadsorption). By day 0, 17 of the 27 DSAs had become undetectable. After 19 (3-51) months, patient- and graft-survival rates were 100% and 91.6%, respectively. One patient had an acute humoral rejection whereas three had a chronic antibody-mediated rejection (CAMR). At the last follow-up, kidney biopsies were nearly normal in seven cases (58.3%) and renal function was excellent except for the three cases of CAMR. Four patients had a BK virus infection. We conclude that ABOi/HLAi living-kidney transplantation is a reasonable option for highly sensitized patients.

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).

Immunoadsorption and hemodialysis as a tandem procedure: a single-center experience of more than 60 procedures.

PURPOSE: We have designed a desensitization program that gives good results and is cost effective for kidney-transplant patients who have a potential living donor, who are ABO incompatible (ABOi), and who may or may not have donor-specific alloantibodies (DSAs). METHODS: Desensitization at pretransplant is based on immunosuppressants (such as rituximab, tacrolimus, and mycophenolic acid) and apheresis to retrieve potentially detrimental isoagglutinins and DSAs from blood. In 2011, we implemented immunoadsorption (IA) instead of plasmapheresis in our center as part of the desensitization protocol. Because IA is very tedious and time-consuming, we decided to perform IA and hemodialysis (HD) in tandem instead of performing these methods sequentially. Herein, we report on more than 100 of these tandem procedures and compare the results to those obtained when IA was performed before a HD session. RESULTS: The tandem process resulted in nursing time being cut by half: from almost 10h30 min/patient to 6 h/patient. When IA was performed alone, body-weight gain was 1 kg (range 0 to 1.75) and the median volume of plasma treated per session was 6500 mL (range 4500 to 10 600). Conversely, during a tandem IA + HD session, the net median weight gain was -1.5 kg (range -4.1 to 0) and the median volume of plasma treated per session was 5000 mL (range 4000 to 8600). In addition, the tandem procedure was as well tolerated as that for IA followed by HD. CONCLUSIONS: Tandem IA plus HD is a safe and cost-effective procedure.

Efficacy of immunoadsorption to reduce donor-specific alloantibodies in kidney-transplant candidates.

OBJECTIVES: We implemented a desensitization program at our center to enable transplant in kidney-transplant candidates who have a living human-leukocyte antigen-incompatible (HLAi) donor. We report on the efficacy of semispecific immunoadsorption to allow HLAi kidney transplant in 6 highly sensitized patients. MATERIALS AND METHODS: We chose immunoadsorption as the apheresis technique coupled to hemodialysis as a means to decrease donor-specific alloantibodies in kidney transplant candidates submitted to a pretransplant desensitization program to remove detrimental antibodies. RESULTS: Six highly sensitized kidney-transplant patients (5 females), awaiting their first (n = 1) or second (n = 5) kidney transplant from a living donor, were enrolled in this desensitization program. They had 1 (n = 2), 2 (n = 1), 3 (n = 2), or 4 (n = 1) donor-specific alloantibodies; their mean fluorescent intensities at predesensitization ranged from 1200 to 19 000. Each patient underwent between 10 and 16 immunoadsorption sessions. At the time of transplant, donor-specific alloantibodies were undetectable in 2 patients (A24, DR3); donorspecific alloantibodies decreased by > 50% in 8 patients (A11, B44, DR3, DR11, DQ3 thrice, DQ5); donor-specific alloantibodies remained unchanged in 2 patients (B50, DR13); and mean fluorescent intensities were slightly increased in 2 patients (Cw6, DQ8). In the analysis of final outcomes, 2 patients experienced no rejection (1 experienced donor-specific alloantibody elimination, and 1 experienced a > 50% decrease in donor-specific alloantibodies). One patient presented with acute antibody-mediated rejection, which required immunoadsorption sessions and eculizumab therapy (donor-specific alloantibodies between 5000 and 19 000). Two patients presented with subacute antibody-mediated rejection; 1 was treated by plasmapheresis/rituximab therapy, and the other was treated with plasmapheresis/ methylprednisolone pulses. Another patient presented with chronic antibody-mediated rejection, which was treated unsuccessfully with plasmapheresis/rituximab; a tentative of rescue therapy with eculizumab was attempted without success. CONCLUSIONS: Desensitization of the humanleukocyte antigen using this immunoadsorption procedure effectively reduced or eliminated donorspecific alloantibodies in 71% of patients undergoing kidney transplant, at the time of transplant.

Non-tolerability of double-filtration plasmapheresis in antibody-incompatible kidney transplant candidates.

Few studies have reported the use of double-filtration plasmapheresis (DFPP) in antibody-incompatible kidney transplantation. To assess the efficiency and tolerability of DFPP, we prospectively studied four chronic hemodialysis patients from two centers undergoing antibody-incompatible kidney transplantation. DFPP was used for ABO-incompatible transplantation (n = 1), for high human leukocyte antigen (HLA) immunization levels (n = 2) or for the presence of a donor-specific antibody (DSA) against a potential living donor (n = 1). In all the patients, the DFPP program was discontinued because of the adverse effects. Low blood pressure occurred during the first hour of the session in all the patients. A significant loss of plasma proteins, clotting factors and immunoglobulins also occurred during this treatment. In addition, fistula thrombosis was diagnosed in two patients. Three patients experienced gastrointestinal symptoms. The DFPP reduced the titers of the anti-B antibodies and reduced the levels of DSA in one patient, but had no effect on anti-HLA antibodies in the remaining two patients. Our study highlights the non-tolerability and poor efficacy of DFPP prior to antibody-incompatible kidney transplantation that limit its extensive use in the desensitization protocols.

Efficacy and safety of tandem hemodialysis and immunoadsorption to desensitize kidney transplant candidates.

OBJECTIVES: We conducted a desensitization program in our center in patients undergoing kidney transplant for end-stage renal disease. These patients had a living-donor either ABO incompatible and/or human-leukocyte antigen-incompatible. The safety and efficacy of this program were evaluated. MATERIALS AND METHODS: A pretransplant desensitization program relies on immunosuppressants and apheresis to remove detrimental antibodies. We chose immunoadsorption as the apheresis technique, and coupled this with hemodialysis in a tandem procedure. RESULTS: We report on the efficacy of this new method in 120 procedures performed in 20 patients (14 ABO incompatible, 6 ABO incompatible/human leukocyte antigen-incompatible). The tandem procedure was well tolerated, and saved time compared with conducting sequential immunoadsorption and hemodialysis (6 h vs 10 h). The tandem procedure was associated with significantly decreased isoagglutinin titers and donor-specific alloantibodies (assessed by mean fluorescence intensity). Dialysance was effective (183, 102-264). The biochemical and hematologic parameters were similar to those observed after a conventional hemodialysis session, with the exception of protidemia; this might be related to some degree of albumin loss during the immunoadsoprtion procedure. The posttransplant events included 1) one ABO incompatible / human leukocyte antigenincompatible patient with vein thrombosis and ultimate kidney loss; 2) two patients with steroidsensitive cellular acute rejection; and 3) two patients with acute antibody-mediated rejection, which was successfully treated with apheresis and steroid pulses, plus rituximab in one and eculizumab in the other. CONCLUSIONS: We conclude that the tandem immunoadsorption-hemodialysis procedure is efficient at desensitizing patients with end-stage renal disease who are candidates for a living ABO incompatible and/or human leukocyte antigenincompatible donor-kidney transplant.

How to implement immunoadsorption in a polyvalent dialysis unit: a review.

BACKGROUND: Many kidney-transplant candidates have anti-HLA alloantibodies (HLAi): these make transplantation difficult, even from a living kidney (LK) donor, because of the presence of donor-specific anti-HLA alloantibodies. Due to the shortage of deceased kidney donors, the number of LK transplants is increasing, but is potentially limited by ABO incompatibility (ABOi). OBJECTIVES: To make ABOi and/or HLAi patients suitable for kidney transplantation they need to be desensitised: this strategy is mainly based on rituximab therapy combined with either plasmapheresis (PP) or immunoadsorption (IA). IA can be more efficient than PP because greater plasma volumes can be treated within a single session than a PP session (>4 vs. 1.5-2). IA can be specific (ABOi setting) or non-specific (HLAi). DESIGN: We describe how we designed and implemented a desensitisation programme based on IA. This was started in the first trimester of 2010 within the Acute Polyvalent Haemodialysis and Apheresis Unit in Toulouse University Hospital, France. So far, we have performed >200 IA sessions with good results. RESULTS: The IA sessions were associated with a net body-weight gain of ∼1 kg. Normally, IA is performed first and then haemodialysis on the same or next day; however, we have been able to, for the first time, couple IA with haemodialysis. Moreover, we can now carry out this procedure 24 hours a day, seven days a week. CONCLUSION: This procedure has improved patient care and reduced costs. The IA desensitisation programme has enabled successful transplantation in 24 patients to date.