ABO-incompatible Kidney Transplant Recipients Research Articles

Distribution of Anti-ABO Immunoglobulin G Subclass and C1q Antibody in ABO-incompatible Kidney Transplantation

IntroductionTo investigate the correlation between serum anti-ABO immunoglobulin G (IgG) and IgG subclasses, anti-ABO IgG subclasses were measured by flow cytometry (FCM) in ABO-incompatible (ABOi) kidney transplant recipients. We also evaluated baseline anti-ABO C1q antibody. MethodBaseline anti-ABO IgG titers were measured by both FCM and column agglutination technique methods in 18 ABOi kidney transplant recipients. The mean florescence intensity (MFI) ratios of baseline anti-ABO IgG subclasses and anti-ABO C1q antibody were obtained by FCM and followed-up after rituximab treatment, each plasmapheresis (PP) session, and kidney transplantation. Correlation between the values of IgG subclass and total IgG titer was analyzed. ResultsThe baseline MFI ratios of total IgG, IgG1, IgG2, IgG3, and IgG4 were 202.46, 62.41, 30.01, 1.04, and 1.13, respectively. The MFI ratios of IgG1, IgG2, and total IgG measured at baseline and pre-PP were positively correlated with the baseline ABO titer was measured using the column agglutination technique. The numbers of PP sessions to reach the target titer were correlated with the baseline IgG and IgG1 levels. IgG1 and IgG2 as well as total IgG were removed effectively after serial PP. Anti-ABO C1q antibody was neither detected nor correlated with total IgG and any IgG subclasses. ConclusionsOur findings suggest that IgG1 and IgG2 are the dominant IgG subclass in ABOi kidney transplant recipients. Baseline levels of IgG1 and IgG2 were correlated with baseline total IgG titer. However, anti-ABO C1q antibody was not detected in the present study.

VDJ Gene Usage of B Cell Receptors in Peripheral Blood of ABO-incompatible Kidney Transplantation Patients

IntroductionB cell subtypes and immunoglobulin variable (V), diversity (D), joining (J) gene segment usage of B cell receptors in ABO-incompatible (ABOi) kidney transplantation (KT) in comparison to ABO-compatible KT have not been studied. The aims of this study were to analyze the VDJ gene segment usages of B cell receptors in peripheral blood of ABOi KT recipients. MethodsEighteen ABOi KT patients with accommodation (ABOiA), 10 ABO-compatible stable KT patients (ABOcS), and 10 ABOi KT patients with biopsy-proven acute antibody-mediated rejection (ABOiR) at day 10 after transplantation were selected. Complete transcriptomes of their peripheral blood samples were sequenced and analyzed through RNA sequencing. ResultsBy family, immunoglobulin heavy chain variable 3 (IGHV3), immunoglobulin light kappa chain variable 1 (IGKV1), immunoglobulin light lambda chain variable 2 (IGLV2), and immunoglobulin light lambda chain joining 3 (IGLJ3) gene segments were most frequently used in all groups, and their usage was not statistically different among the three groups except for IGHV3 and IGKV1. IGKV1 was more frequently used in the ABOiA group than in the ABOcS group. According to individual gene segments, IGHV3-7, IGHV3-15, IGHV4-59, IGKV3-11, IGLV1-44, IGLV2-14, IGLV4-69, and IGLV7-46 were more frequently used in the ABOcS group than other groups, and IGKV3-7 was more frequently used in the ABOiR group than other groups. IGLV5-52 and IGLV7-43 were more frequently used in the ABOiA group than in ABOcS group. ConclusionsOur findings suggest that RNA sequencing transcriptomic analyses of peripheral blood can provide information on the VDJ gene usage of B cell receptors and the mechanisms of accommodation and immune reaction in ABOi KT.

Desensitization with the Use of an Antibody Removal–Free Protocol in ABO-Incompatible Kidney Transplant Recipients with a Low Anti-A/B Antibody Titer

BackgroundDesensitization for ABO-incompatible (ABOi) kidney transplantation mainly comprises removal of antibodies with the use of apheresis and suppression of antibody (Ab) production with the use of rituximab. This study aimed to estimate the outcomes of ABOi kidney transplantation with the use of an Ab removal–free protocol to avoid complications associated with apheresis. MethodsA total of 32 de novo consecutive adults who underwent ABOi living-donor kidney transplantation were retrospectively evaluated. Our protocol for ABOi recipients was stratified and fixed according to the anti-A/B Ab titer at baseline before desensitization. Desensitization was performed before transplantation with 0–4 sessions of plasmapheresis or double-filtration plasmapheresis and 1–2 administrations of rituximab at 100 mg/body. Graft outcomes, anti-A/B Ab titer, and plasma fibrinogen level were compared between the Ab removal (n = 21) and Ab removal–free (n = 11) groups. ResultsBetween the Ab removal and Ab removal–free groups, the graft loss rate (4.8% vs 0.0%; P = 1.0), acute rejection rate (19.0% vs 0.0%; P = .14), and serum creatinine level (1.74 vs 1.40 mg/dL, P = .53) were similar. The anti-A/B Ab titer was maintained at a low level until postoperative month 12 in both groups. The plasma fibrinogen level on the operation day was significantly lower in the Ab removal group than in the Ab removal–free group (163.4 vs 250.2 mg/dL; P < .001). ConclusionsDesensitization with the use of an antibody removal–free protocol for ABOi kidney transplant recipients with a low anti-A/B Ab titer can maintain excellent graft outcomes and avoid postoperative bleeding risk.

Efficacy of Ultralow-Dose Valganciclovir Chemoprophylaxis for Cytomegalovirus Infection in ABO-Incompatible Kidney Transplantation Recipients

BackgroundCytomegalovirus (CMV) infection can increase morbidity and mortality in kidney transplant (KT) patients. Chemoprophylaxis with valganciclovir (VGCV) is recommended for ABO-incompatible (ABOi) KT patients as it significantly reduces CMV disease and infection. The recommended dose of VGCV for prevention of CMV in a KT recipient is 900 mg once daily, and the treatment duration is 6 months. However, because it is expensive, sufficient amounts might not be administered. MethodsWe investigated whether ultralow-dose VGCV (450 mg every other day) and short dosing period (3 months) was sufficient to prevent CMV infection after ABOi KT. We retrospectively evaluated 74 adult CMV-seropositive donor/CMV-seropositive recipient (D+/R+) ABOi KT recipients from June 2009 to July 2016 who received ultralow-dose VGCV prophylaxis for 3 months. The primary outcome was occurrence of CMV infection. Secondary outcomes were leukopenia and thrombocytopenia. ResultAll patients received intravenous rituximab 200 mg once and plasmapheresis for reduction of anti-A/B antibodies and interleukin-2 antibodies before undergoing ABOi KT. Mean prophylaxis and follow-up durations were 3 and 52 months, respectively. One patient died of bacterial pneumonia. Four patients lost graft function and were undergoing hemodialysis; 3 cases were caused by antibody-mediated rejection, and 1 was due to mechanical complication after surgery. Fortunately, CMV infection did not occur in any patient. ConclusionUltralow-dose VGCV is an effective prophylaxis for D+/R+ ABOi KT recipients. Especially, ultralow-dose VGCV CMV infection prevention protocol in Asian populations reduced the side effects and cost.

Steroid Withdrawal Using Everolimus in ABO-Incompatible Kidney Transplant Recipients With Post-Transplant Diabetes Mellitus

BackgroundThe effectiveness of everolimus (EVR) for ABO-incompatible (ABOi) kidney transplantation is unknown. We evaluated outcomes of conversion from steroid to EVR in ABOi kidney transplant recipients. MethodsWe performed a retrospective observational cohort study of 33 de novo consecutive adult ABOi living donor kidney transplant recipients. Desensitization was performed using 0 to 4 sessions of plasmapheresis and 1 to 2 doses of 100 mg rituximab according to the anti-A/B antibody titer. ABOi recipients were administered a combination of tacrolimus, mycophenolate mofetil, and methylprednisolone. Diabetic patients were converted from methylprednisolone to EVR at 1 to 15 months post-transplantation to prevent diabetes progression. Graft outcomes, hemoglobin A1c (HbA1c) levels, and cytomegalovirus infection rates were compared between the EVR (n = 11) and steroid (n = 22) groups. ResultsMean postoperative duration was 814 and 727 days in the EVR and steroid groups, respectively (P = .65). Between the 2 groups, graft survival rate (100% vs 95.5%, P > .99), acute rejection rate (9.1% vs 18.2%, P = .64), and serum creatinine levels (1.46 mg/dL vs 1.68 mg/dL, P = .66) were comparable. Although HbA1c levels were elevated in the steroid group (5.47%, 5.87%; P = .003), no significant deterioration was observed in the EVR group without additional insulin administration (6.10%, 6.47%; P = .21). Cytomegalovirus infection rate was significantly lower in the EVR group than in the steroid group (18.2% vs 63.6%, P = .026). ConclusionConversion from steroid to EVR in ABOi kidney transplant recipients maintained excellent graft outcomes and avoided diabetes progression and cytomegalovirus infection.

Passenger Lymphocyte Syndrome in the ABO-Incompatible Kidney Transplant Recipient Receiving Rituximab

Passenger lymphocyte syndrome is a rare but important disease in which the donor lymphocytes produce antibodies to the red blood cell antigens of the recipient, causing alloimmune hemolysis. It occurs in ABO blood group-mismatched solid-organ and/or bone marrow transplant. We report a case of passenger lymphocyte syndrome occurring after ABO-incompatible kidney transplant. The recipient received rituximab as a desensitization protocol. On posttransplant day 18, the recipient showed a fall in her hemoglobin levels without identifiable bleeding source and an elevation of total bilirubin. Although hemolytic anemia was suspected, schizocytes on the peripheral smear were not observed. Anti-B-type antibodies were detected, and a diagnosis of passenger lymphocyte syndrome was confirmed. The patient was successfully treated with steroid pulse therapy, an increase of mycophenolate mofetil to 2 g/day, and conversion from cyclosporine to tacrolimus. To our knowledge, this is the first demonstration of passenger lymphocyte syndrome in an ABO-incompatible kidney recipients receiving rituximab.

Comparative Analysis of Effectiveness and Safety between High and Low Dose Rituximab in ABO-Incompatible Kidney Transplant Recipients

Comparative Analysis of Effectiveness and Safety between High and Low Dose Rituximab in ABO-Incompatible Kidney Transplant Recipients

Prospective Analyses of Circulating B Cell Subsets in ABO-Compatible and ABO-Incompatible Kidney Transplant Recipients.

Immunosuppressive strategies applied in renal transplantation traditionally focus on T cell inhibition. B cells were mainly examined in the context of antibody-mediated rejection, whereas the impact of antibody-independent B cell functions has only recently entered the field of transplantation. Similar to T cells, distinct B cell subsets can enhance or inhibit immune responses. In this study, we prospectively analyzed the evolution of B cell subsets in the peripheral blood of AB0-compatible (n = 27) and AB0-incompatible (n = 10) renal transplant recipients. Activated B cells were transiently decreased and plasmablasts were permanently decreased in patients without signs of rejection throughout the first year. In patients with histologically confirmed renal allograft rejection, activated B cells and plasmablasts were significantly elevated on day 365. Rituximab treatment in AB0-incompatible patients resulted in long-lasting B cell depletion and in a naïve phenotype of repopulating B cells 1 year following transplantation. Acute allograft rejection was correlated with an increase of activated B cells and plasmablasts and with a significant reduction of regulatory B cell subsets. Our study demonstrates the remarkable effects of standard immunosuppression on circulating B cell subsets. Furthermore, the B cell compartment was significantly altered in rejecting patients. A specific targeting of deleterious B cell subsets could be of clinical benefit in renal transplantation.

Outcome after Desensitization in HLA or ABO-Incompatible Kidney Transplant Recipients: A Single Center Experience

BackgroundThe shortage of deceased donors led to an increase of living donor kidney (LDK) transplantations performed in the presence of donor-specific antibodies (DSA) or ABO incompatibility (ABOi) using various desensitization protocols.MethodsWe herein analyzed 26 ABOi and 8 Luminex positive DSA patients who were successfully desensitized by anti-CD20, antigen-specific immunoadsorption and/or plasmapheresis to receive an LDK transplant. Twenty LDK recipients with non-donor-specific HLA-antibodies (low risk) and 32 without anti-HLA antibodies (no risk) served as control groups.Results1-year graft survival rate and renal function was similar in all 4 groups (creatinine: 1.63 ± 0.5 vs 1.78 ± 0.6 vs 1.64 ± 0.5 vs 1.6 ± 0.3 mg/dl in ABOi, DSA, low risk and no risk group). The incidence of acute T-cell mediated rejections did not differ between the 4 groups (15% vs 12, 5% vs 15% vs 22% in ABOi, DSA, low risk and no risk), while antibody-mediated rejections were only found in the DSA (25%) and ABOi (7.5%) groups. Incidence of BK nephropathy (BKVN) was significantly more frequent after desensitization as compared to controls (5/34 vs 0/52, p = 0.03).ConclusionWe demonstrate favorable short-term allograft outcome in LDK transplant recipients after desensitization. However, the desensitization was associated with an increased risk of BKVN.

Ongoing higher infection rate in ABO-incompatible kidney transplant recipient: is it a serious problem? A single-center experience.

PurposeAdditional clinical experience and knowledge regarding the barrier to transplantation of ABO blood type incompatibility could reduce the higher rate of infectious complications in ABO-incompatible kidney transplantation.MethodsA total of 79 ABO-incompatible kidney transplantation (ABOiKT) patients were compared with 260 ABO-compatible kidney transplantation (ABOcKT) patients for basic clinical characteristics, infectious complications, rejection episodes, and graft survival.ResultsThere were no significant differences in baseline characteristics, rejection rates, or graft survival between the ABOiKT and ABOcKT patients. No significant difference in the infection rate was shown for cytomegalovirus (26.6% vs. 30.0%; P = 0.672), BK virus (19.0% vs. 21.5%; P = 0.752), herpes disease (10.1% vs. 5.0%; P = 0.082), pneumonia (5.3% vs. 3.8%; P = 0.746), or urinary tract infection (8.9% vs. 10.0%; P > 0.999). Female sex (hazard ratio [HR], 2.20; P = 0.003), advanced age (≥60 years) (HR, 2.5; P = 0.019), history of rejection episodes (HR, 2.28; P = 0.016), and history of surgical complications (HR, 4.64; P = 0.018) were significant risk factors for infection. ABO incompatibility demonstrated a tendency toward higher infection risk without statistical significance (HR, 1.74; P = 0.056).ConclusionIn spite of immunosuppressant protocol modification, the rate of infectious complications following ABOiKT is still higher than with ABOcKT when a modified desensitization protocol is used. However, this was not sufficient to avoid ABOiKT.

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.

Outcomes Following ABO-Incompatible Kidney Transplantation Performed After Desensitization by Nonantigen-Specific Immunoadsorption

For desensitization of ABO-incompatible kidney transplant recipients we recently proposed nonantigen-specific immunoadsorption (IA) and rituximab. We now compared clinical outcomes of 34 ABO-incompatible living-donor kidney recipients who were transplanted using this protocol with that of 68 matched ABO-compatible patients. In addition, we analyzed efficacy and cost of nonantigen-specific as compared to blood group antigen-specific IA. Before desensitization, the median isoagglutinin titer of 34 ABO-incompatible patients was 1:64 (Coombs technique). Patients received a median of 7 preoperative IA treatments. Twenty-four patients had a median of 2 additional plasmapheresis treatments to reach the preoperative target isoagglutinin titer of 1:8 or less. After a median postoperative follow-up of 22 months, overall graft survival in the ABO-incompatible group was not significantly different from that in ABO-compatible patients (log-rank P = 0.20), whereas patient survival tended to be lower (log-rank P = 0.05). The incidence of rejection episodes was 15% in both groups. The ABO-incompatible kidney recipients had a higher incidence of BK virus replication (P = 0.04) and nephropathy (P = 0.01) and showed more often colonization with multidrug resistant bacteria (P = 0.02). In comparison to blood group antigen-specific IA, nonantigen-specific IA showed equal efficacy but was associated with reduction in cost. Clinical outcomes of ABO-incompatible patients desensitized with a nonantigen-specific IA device and rituximab do not differ from that of matched ABO-compatible patients although a trend toward reduced patient survival was noted. Special attention must be paid to the higher incidence of BK virus infection in recipients of ABO-incompatible grafts.

ABO desensitization affects cellular immunity and infection control after renal transplantation.

The impact of ABO desensitization on overall immunity, infectious control, and alloreactivity remains unknown. We compared 35 ABO-incompatible kidney transplant recipients (KTRs) to a control of 62 ABO compatible KTRs. Samples were collected before, at +1, +2, +3, +6, and +12 months post-transplantation. CMV-, BKV-specific, and alloreactive T cells were measured using an interferon-γ ELISPOT assay. The extent of immunosuppression was quantified by enumeration of lymphocyte subpopulations and cytokines. No differences were observed for 5-year allograft survival and function between both groups (P > 0.05). However, ABO-incompatible KTRs were more likely to develop CMV infection, BKV-associated nephropathy, and severe sepsis (P = 0.001). Interestingly, ABO-incompatible KTRs with poor HLA-match showed the highest rates of infections and inferior allograft function (P < 0.05). CD3+, CD4+ T-cell counts, interferon-γ and IL-10 levels were lower in ABO-incompatible KTRs early post-transplantation (P < 0.05). Likewise, ABO-incompatible KTRs showed impaired BKV- and CMV-specific T-cell immunity (P < 0.05). ABO-incompatible KTRs showed lower frequencies of alloreactive T cells (P < 0.05). Our data suggest T-cell depletion due to ABO desensitization, which may contribute to the increased risk of T-cell-dependent infections. Elimination of B cells serving as antigen-presenting cells, thereby causing impaired T-cell activation, plays a significant role in both impaired infection control and reduced alloreactive T-cell activation.

How can we minimize bleeding complications in ABO-incompatible kidney transplant recipients?

How can we minimize bleeding complications in ABO-incompatible kidney transplant recipients?

Post-transplantation immunoadsorption can be safely withheld in ABO-incompatible kidney transplant recipients

Post-transplantation immunoadsorption can be safely withheld in ABO-incompatible kidney transplant recipients

Alemtuzumab induction in ABO-incompatible kidney transplant recipients

Alemtuzumab induction in ABO-incompatible kidney transplant recipients

ABO-incompatible kidney transplant recipients have a higher bleeding risk after antigen-specific immunoadsorption

Pretransplant removal of antiblood group ABO antibodies is the cornerstone of all current ABO-incompatible (ABOi) transplantation programmes. In our protocol, plasmapheresis (PP) is performed with a plasmafilter followed by immunoadsorption (IA) of anti-ABO antibodies. The bleeding complications of this technique are not known. We analysed the data of all 65 consecutive ABOi kidney transplantations between March 2006 and October 2013 and compared these with matched 130 ABO-compatible (ABOc) kidney transplantations. Cases differed from controls in the pre-operative regimen, which included IA-PP and rituximab, tacrolimus, mycophenolate mofetil, prednisone and immunoglobulines. Data on platelet count, blood loss and red blood cell (EC) transfusions during 48h postoperatively were collected. ABOi patients received EC transfusions more frequently than controls (29% vs. 12%, P=0.005). Intra-operative blood loss was higher (544 vs. 355ml, P<0.005) and they experienced more major bleeding (≥3 EC within 24h, 15% vs. 2%, P<0.0005). Platelet count decreased by 28% after the pre-operative IA. In a multivariate model, only the number of pre-operative IAs was associated with the number of ECs given (OR per IA 1.9, P<0.05). ABOi kidney transplant recipients have a high postoperative bleeding risk, correlating with the number of pre-operative IA sessions performed.

Clinical Outcome of DSA Positive Alone in Kidney Transplantation.

Cell based assay (CDC or FCXM) methods, can identify antibodies that can mediated acute humoral rejection. Furthermore recent new solid phase assay, by single bead PRA (Luminex®) is more sensitive method for detection of anti-donor antibody. However the need and benefit of desensitization for DSA positive but FCXM negative patients are controversial. From Aug 2012 to Dec 2013 we had performed 481 kidney transplantations. Among them 29 patients were DSA positive alone patients (FCXM negative). Eight patients were excluded because they were ABO incompatible kidney transplant recipients who need preoperative desensitization. In these 21 patients simulect® induction followed by triple immunosuppressant was used without preoperative desensitization. Eleven (52.3%) patients were male, 7(33%) from deceased donor, and five retransplant patients. Mean FCXM MFI value was 1.1(reference value; positive ≥2.0). Mean PRA class I and II was 53% and 55% respectively. DSA MFI value was 2039 (1008-5744) in Class I and 3356 (1073-9933) in class II HLA antigen. One year patient and graft survival were 95.2% each (1 case of mortality from infection). During mean 344 ±142 days of follow up, 5 rejection episodes were developed (23.8% 1 year rejection rate). Among whom, 2 case of antibody mediated rejection, 2 case of cellular rejection and one case of mixed rejection were developed. Interestingly rejections were developed during relatively early postoperative period (Median 17 days) and relatively severe rejection (IB, IIA and IIB), but all reversed by plasmapheresis, rituximab and IVIG. In the analysis of the risk factor for rejection, we could not detect any factors affecting rejection, such as the intensity of DSA or value of cPRA. Although all the rejections were was reversible by rescue therapy and majority of patients does not developed acute rejection, DSA positive alone patients had relative higher rejection rate. Careful follow up and monitoring may be mandatory in this category patients, and desensitization might be needed in some patients according to further analysis.

Late-Onset Neutropenia and Acute Rejection in ABO-Incompatible Kidney Transplant Recipients Receiving Rituximab.

Recently, a new avenue in the management of ABO-incompatible kidney transplantation has been presented with the introduction of an anti-CD20 monoclonal antibody, rituximab. In May 2006, we started our program using this antibody for ABO-incompatible kidney transplantations. Using rituximab, we have experienced successful ABO-incompatible renal transplantations without splenectomy as well as in recipients with high pre-transplant anti-A/B antibody titers. At our institution, rituximab (150 mg/m2) was administered twice at 2 weeks priorto and on the day of transplantation except for elderly recipients. The recipients aged 65 years and older received only a single dose of 150 mg/m2 rituximab at 2 weeks prior to transplantation. An increasingly recognized toxicity of rituximab is late-onset neutropenia (LON), defined as unexplained grade III-IV neutropenia occurring at least 4 weeks after the last dose of rituximab in the absence of an alternative explanation. Patients and Methods Between May 2006 and December 2011, 25 patients who received rituximab underwent successful ABO-incompatible kidney transplantations. These 25 cases were enrolled as the subjects in this study. LON was defined as grade III to IV neutropenia after the last administration of rituximab, in the absence of any alternative reason to explain its occurrence. Results Twelve recipients (48%) experienced LON 1-11 months after transplantation. Five of the 12 patients (41.6%) who developed LON had an episode of biopsy-confirmed acute cellular rejection, as compared with one of the remaining 13 patients (7.7%) who did not develop LON. Moreover, 3 patients who experienced LON developed steroid and deoxyspergualin-resistant acute cellular rejection, and they required OKT-3 administration. Conclusion The frequency of acute cellular rejection tended to be higher in ABO-incompatible kidney transplant recipients with LON than in those without LON. Our findings suggest that recipients who develop LON after rituximab administration may be at an increased risk for acute cellular rejection.

ABO Incompatible Kidney Transplantation Without Plasmapheresis and/or Plasma Exchange, Immunoadsorption and IVIG.

[Aim] The aim of this study is to evaluate whether ABO incompatible kidney transplant (ABOi) recipients with low titer of anti-donor blood group antibody (ADBGAB) need plasmapheresis (PP) and/or plasma exchange (PE), immunoadsorption (IA) and IVIG pre- and post-transplantation (Tx). [Methods] Ten ABOi recipients were entered in this study. The low titer of ADBGAB was defined below 32 folds or equal (≤ x32). As desensitization, rituximab 100mg was administered 10 days and 1 day before Tx. Mycophenolate mofetile (MMF) 20mg/kg/day, methylprednisolone (MP) 8-16 mg/day and cyclosporine (CyA) or tacrolimus (FK) were given from 10 to 0 day before Tx. CyA and FK doses were adjusted in terms of trough level, 200 and 10 ng/ml, respectively pre-Tx. All 10 recipients never had PP and/or PE, IA and IVIG pre- and post-Tx. Immunosuppression was consisted of basiliximab, CyA (n=5) or FK (n=5), MMF and MP post-Tx. Clinical acute rejection, subclinical rejection and viral infections were studied. [Patient Background] The recipient and the donor ages at Tx were 31.4 ± 16.0 (4˜52) and 50.4 ± 10.0 (37˜60) years, respectively. The recipient and the donor genders were 8 and 3 males, respectively. No recipients had donor specific HLA antibody. ABO incompatible matches were 4 (A to B), 2(B to O), 1 (A to O), 2 (AB to B) and 1 (AB to A). The titers of ADBGAB pre-Tx were x32 in 1, x8 in 1, x2 in 3, and x1 in 5 recipients. The relations of donor to recipient were 4 mothers, 2 fathers, 2 wives, 1 brother and 1 sister. HLA mismatches were 5 in 1, 3 in 3, 2 in 4, 1 in 1 and 0 in 1 recipients. [Result] All 10 recipients have so far survived and kept good renal function (recent serum Cr; 0.3 ˜ 1.67mg/dl). The mean of post-Tx period was 14 months (2˜40 months). The highest titers of ADBGAB were x8 in 2 and x1 in 8 recipients post-Tx. All 10 recipients never had clinical acute rejection. Protocol biopsy showed borderline change in 1 recipient at 3 and 12 months post-Tx. CMV infection without any symptoms was diagnosed by antigenemia method in 1 recipient. BK virus was positive in urine but not in blood in 1 recipient. One recipient had herpes zoster infection. Leukopenia (WBC≤2000) occurred in 2 recipients. [Conclusion] ABOi recipients with low titer of ADBGAB do not need PP and/or PE, IA and IVIG pre- and post-Tx.