ABO-incompatible Kidney Transplant Recipients Research Articles

Non-antigen-specific Immunoadsorption Is a Risk Factor for Severe Postoperative Infections in ABO-Incompatible Kidney Transplant Recipients.

ABO-incompatible (ABOi) living kidney transplantation (KTx) is an established procedure to address the demand for kidney transplants with outcomes comparable to ABO-compatible KTx. Desensitization involves the use of immunoadsorption (IA) to eliminate preformed antibodies against the allograft. This monocentric retrospective study compares single-use antigen-selective Glycosorb® ABO columns to reusable non-antigen-specific Immunosorba® immunoglobulin adsorption columns regarding postoperative infectious complications and outcome. It includes all 138 ABOi KTx performed at Freiburg Transplant Center from 2004-2020. We compare 81 patients desensitized using antigen-specific columns (sIA) to 57 patients who received IA using non-antigen-specific columns (nsIA). We describe distribution of infections, mortality and allograft survival in both groups and use Cox proportional hazards regression to test for the association of IA type with severe infections. Desensitization with nsIA tripled the risk of severe postoperative infections (adjusted HR 3.08, 95% CI: 1.3-8.1) compared to sIA. nsIA was associated with significantly more recurring (21.4% vs. 6.2%) and severe infections (28.6% vs. 8.6%), mostly in the form of urosepsis. A significantly higher proportion of patients with sIA suffered from allograft rejection (29.6% vs. 14.0%). However, allograft survival was comparable. nsIA is associated with a two-fold risk of developing a severe postoperative infection after ABOi KTx.

Experience with Tandem Pre-Dilution Online Hemodiafiltration and Centrifugal Plasma Exchange in Pretransplant Desensitization for Abo-Incompatible Kidney Transplantation: A Case Report

In the use of therapeutic plasma exchange (TPE) as antibody removal therapy for ABO-incompatible (ABOi) kidney transplantation, it is technically possible to perform online hemodiafiltration (OHDF) and TPE simultaneously for patients who are receiving OHDF. In this study, we report tandem therapy of pre-dilution OHDF and centrifugal plasma exchange (cTPE), instead of membrane plasma exchange, which is the mainstay of TPE in Japan. A total of 14 sessions of tandem cTPE and pre-dilution OHDF were performed as preoperative antibody removal therapy for 6 ABOi kidney transplant recipients. cTPE intra-circuit pressure, decreased antibody titer, and adverse events were evaluated. The study was carried out following the ethical standards of the Declaration of Helsinki and Istanbul. Donors were not prisoners or individuals who were coerced or paid. The tandem therapy was completed safely in 12 of the 14 sessions, with no problems such as pressure upper and lower limit alarms or circuit coagulation. In 2 sessions, the tandem therapy had to be interrupted due to coagulation on the dialysis circuit side. Antibody titers were reduced by a median of 3-fold for both IgG and IgM. There was no acute antibody-associated rejection. In preoperative apheresis therapy for ABOi kidney transplantation, tandem therapy of pre-dilution OHDF and cTPE may be a useful treatment option that can be performed safely and results in sufficient reduction of antibody levels.

Detecting and exploring kidney-derived extracellular vesicles in plasma.

Extracellular vesicles (EVs) have received considerable attention as ideal biomarkers for kidney diseases. Most reports have focused on urinary EVs, that are mainly derived from the cells in the urinary tract. However, the detection and the application of kidney-derived EVs in plasma remains uncertain. We examined the kidney-derived small EVs (sEVs) in plasma that were supposedly released from renal mesangial and glomerular endothelial cells, using clinical samples from healthy controls and patients with kidney transplants. Plasma from healthy controls underwent ultracentrifugation, followed by on-bead flow cytometry, targeting α8 integrin, an antigen-specific to mesangial cells. To confirm the presence of kidney-derived sEVs in peripheral blood, plasma from ABO-incompatible kidney transplant recipients was ultracentrifuged, followed by western blotting for donor blood type antigens. Immunohistochemistry and immunoelectron microscopy confirmed α8 integrin expression in kidney mesangial cells and their sEVs. The CD9-α8 integrin double-positive sEVs were successfully detected using on-bead flow cytometry. Western blot analysis further revealed transplanted kidney-derived sEVs containing blood type B antigens in non-blood type B recipients, who had received kidneys from blood type B donors. Notably, a patient experiencing graft kidney loss exhibited diminished signals of sEVs containing donor blood type antigens. Our findings demonstrate the potential usefulness of kidney-derived sEVs in plasma in future research for kidney diseases.

Outcome of ABO-Incompatible Living Donor Kidney Transplantation: A Single Center Observational Study from Nepal

Introduction: Kidney transplantation is the most effective treatment for end-stage renal disease (ESRD) patients. However, the increasing number of ESRD patients and the limited availability of living and cadaveric donors has led to a growing waiting list for kidney transplantation. ABO-incompatible transplantation has emerged as an alternative for these patients in Nepal. Methods: This was an observational study of all the patients who underwent kidney transplantation from March 2017-Feb 2019. Data on demography of recipients and donor, blood group, human leukocyte antigen mismatch, induction agent, post-operative complications and creatinine clearance at discharge and one-year post-transplant were collected and analysed. Then we compared patient and kidney graft survival at one year between ABO incompatible and ABO compatible recipients. Results: During the study period, there were total of 124 kidney transplant recipients among them 12 were ABO incompatible and 112 were ABO compatible recipients. The study showed slightly lower patient and graft survival in ABO-incompatible recipients than ABO compatible recipients (83.3% vs 99.2%, p<0.001). However, death-censored graft survival were similar in both groups (100%,p<0.001). The graft function at one year measured by creatinine clearance was better in ABO-incompatible recipients than ABO-compatible recipients (67.1±11.75 vs 61.87±12.82, p<0.001). Postoperative complications were slightly higher, however, complications at one year were lower in ABO-incompatible recipients. Conclusion: The study showed that living donor ABO-incompatible kidney transplant recipients have a good outcome at one year but is associated with greater risks of patient and graft loss at early transplant period compared to ABO-compatible recipients.

Impact of pretransplant asplenia vaccination on anti‐A/B antibody titers in prospective ABO incompatible kidney transplant recipients

AbstractBackgroundAsplenia vaccination is employed before ABO‐incompatible (ABOi) transplantation in case splenectomy is needed. Pneumococcal vaccines have been reported, in different patient groups, to increase anti‐A/B titers, through cross‐reactivity to shared polysaccharide epitopes. We investigated the impact of pretransplant asplenia vaccinations on anti‐A/B antibody titers in prospective ABOi renal transplant recipients.MethodsPublished asplenia vaccine microbial structures were reviewed to assess expression of A/B antigens. All patients who underwent ABOi transplantation at Monash Medical Centre with anti‐A/B titers taken either side of asplenia vaccination were included in a retrospective cohort study between 2007 and 2021. Patients with paired titers without intervening vaccination were included as controls. Paired titers were compared within groups.ResultsA and B antigens were found to be expressed by vaccine specific pneumococcal serotypes. Thirty‐nine ABOi renal transplant recipients received vaccination including at least one pneumococcal vaccine. The most common donor to recipient combination was A1 to O. The median pre‐ and postvaccination anti‐A/B titers were 1:32 and there was no significant change in titers following vaccination (median change in titer 0 dilutions, range –2 to 3, P = 0.43). The same findings were apparent in the control group (n = 20). There was no significant change in titer by donor blood group or vaccine type. No transplants were canceled or delayed by a rise in anti‐A/B titers postvaccination.ConclusionPneumococcal vaccination had no clinically relevant impact on anti‐A/B titers before ABOi transplantation in this cohort. These results provide reassurance regarding the safety of asplenia vaccination before ABOi transplantation.

316.7: ABO – Incompatible Kidney Transplantation in COVID 19 Era: A Single Centre Experience

Introduction: Though there are multiple studies on outcome of ABO incompatible kidney transplants, we herein present the short term outcome of ABO-incompatible kidney transplantations done in the Covid-19 era. Methods: We analysed 40 consecutive ABO incompatible kidney transplant recipients undergone transplant from October 2020 till February 2022, followed up till March 2022.Included patients received rituximab 100 mg/200 mg depending on baseline anti ABO titre, plasma exchange and IVIG for desensitization. Target pre transplant anti ABO titre was ≤ 1:64.Patients received induction therapy with anti thymocyte globulin and IV methylprednisolone. Results: The median duration of follow up was 294 days. The highest baseline and pre transplant titre were 2048 and 64 respectively. The mean serum creatinine at discharge was 1.35±0.39 mg/dl and at follow up was 1.48 ± 0.59 mg/dl.The patient and death censored graft survival were 97.5% each. The single graft and patient loss was due to fungal pyelonephritis. 5 patients (12.5%) experienced episodes of biopsy proven rejection.3 patients (7.5%) had acute antibody mediated rejection and 2 patients (5%) suffered T Cell Mediated rejection. The post-transplant hospital stay was 12.79 ± 4.61 days. 5 patients needed hospitalisation for infection in the post transplant follow up period. 10 covid-19 recovered patients were transplanted after a mean duration of 88.4 days with mild to moderate severity. 3 patients (7.5%) acquired covid-19 post-transplantation, 2 in early post transplant (<3 months) and 1 patient at 5 months post-transplant period. Conclusion: There were no significant differences in the patient and graft survival in covid-19 era as compared to our pre covid studies. Rather, they had lower infection rates due to covid-19 related precautions. There was no increase in mortality or infection in a shorter term of follow up of our study period. Keywords: Short term outcome, ABO incompatible kidney transplantation, Covid19 Era.

Outcome of ABO-incompatible kidney transplantation using a modified desensitization protocol without plasmapheresis.

Several controversies regarding desensitization strategies for successful ABO-incompatible (ABOi) kidney transplantation still exist. This study aimed to investigate whether pretransplant anti-A/B antibody removal is mandatory in an ABOi kidney transplant recipient with low baseline isoagglutinin titers. We adopted a modified desensitization protocol with two doses of rituximab (RTX, 100 mg/body) without pretransplant antibody removal for ABOi kidney transplant recipients with a titer of ≤1:64 (group A; n = 35) and investigated the feasibility of this protocol by comparing it with the clinical outcomes of patients undergoing standard pretransplant plasmapheresis (group B; n = 21). There was no significant difference in the rate of antibody-mediated rejection within the first month after transplantation between the two groups (11.4% in group A vs. 2% in group B, p = 0.6019). Moreover, no differences were observed in the short- and long-term graft outcomes between the groups. However, two major critical acute antibody-mediated events occurred in group A; one patient lost the graftdue to hyperacute rejection, and the other patient developed thrombotic microangiopathy after surgery. Risk factors predicting these perioperative complications were not identified. We conclude that not only B-cell depletion using RTX but also pretransplant antibody removal is still recommended even for patients with low isoagglutinin titers. In addition, a new diagnostic tool is needed for accurate risk stratification.

Clinical Outcomes of Everolimus With Reduced-Dose Tacrolimus vs Mycophenolate Mofetil With Standard-Dose Tacrolimus in De Novo ABO-Incompatible Kidney Transplant Recipients: 1-Year Follow-up

One of the major barriers for long-term renal graft survival is considered to be calcineurin inhibitor nephrotoxicity, contributing to chronic graft dysfunction. Thus, recent immunosuppressive strategies are focused on regimens that can reduce or avoid exposure to calcineurin inhibitors. Herein, we carried out a small-scale pilot study to assess whether everolimus (EVR) with reduced-dose tacrolimus (Tac) is an acceptable immunosuppressive regimen for patients with de novo ABO-incompatible kidney transplant compared with mycophenolate mofetil (MMF) with standard-dose Tac. This retrospective single-center cohort study included patients who underwent ABO-incompatible kidney transplant at our institution between January 2016 and December 2019. Those whose immunosuppressive regimen was changed by reasons other than rejection during the 1-year follow-up period were excluded. A total of 24 patients were enrolled in this study: 10 patients who received an EVR with reduced-dose Tac regimen and 14 patients who received an MMF with standard-dose Tac regimen. Tac trough levels in the EVR group were significantly lower than those in the MMF group (P < .001). No patients died or lost their grafts during the follow-up period. There were no significant differences in renal function, proteinuria, and prevalence of hyperlipidemia between the 2 groups at 1 year after transplant. There were no significant differences in the incidence of rejection (acute cellular rejection, steroid-resistant acute cellular rejection, acute antibody-mediated rejection) and infection (cytomegalovirus viremia, cytomegalovirus disease, BK viremia, BK virus nephropathy) between the 2 groups. Comparable with MMF with standard-dose Tac, EVR with reduced-dose Tac might be an acceptable immunosuppressive regimen for patients with de novo ABO-incompatible kidney transplant.

A Tale of Survival: COVID-19, Disseminated Cryptococcus, and Cytomegalovirus Disease in an ABO-Incompatible Kidney Transplant Recipient

A Tale of Survival: COVID-19, Disseminated Cryptococcus, and Cytomegalovirus Disease in an ABO-Incompatible Kidney Transplant Recipient

Removal of Anti-Thymocyte Globulin by Plasma Exchange in ABO-Incompatible and Positive Crossmatch Kidney Transplant Recipients

BackgroundRecipients of ABO-incompatible (ABOI) and positive crossmatch (PXM) kidney transplants are at high risk for antibody-mediated acute rejection. Despite aggressive immunosuppression in high-risk patients, the incidence of acute rejection remains considerably higher than in other groups. No published studies have examined plasma concentrations of anti-thymocyte globulin (ATG) in patients undergoing plasma exchange. The objectives of this study were to compare plasma ATG concentrations before and after plasma exchange in ABOI and PXM kidney transplant patients to determine the amount removed. Materials and MethodsThis prospective pharmacokinetic evaluation enrolled 10 patients undergoing ABOI or PXM kidney transplant at an academic medical center. Blood and waste plasma samples from 5 patients were assayed for total and active ATG concentrations. Patient records were monitored for renal function and rejection rates in the first 6 months post-transplant. ResultsTotal ATG concentrations decreased a mean of 59.78 ± 13.91% after each plasma exchange session, and active ATG levels decreased a mean of 56.8 ± 17.08%. Mean daily concentrations reflect a lack of expected ATG accumulation. Only 1 of 4 patients had detectable ATG concentrations after 30 days. After 6 months, the incidence of acute rejection in this sample was 44% and graft survival was 89%. ConclusionsThis is the first study to show that plasma exchange removes a substantial amount of ATG in high-risk kidney transplant patients. Based on these results, we believe these high-risk patients have been traditionally underdosed.

P1745EFFECTS OF DESENSITIZATION THERAPY ON LYMPH NODES AND PERIPHERAL BLOOD TFH AND TFR CELLS IN ABO-INCOMPATIBLE KIDNEY TRANSPLANT RECIPIENTS

Abstract Background and Aims Desensitization therapy has enabled successful transplantation of renal allografts across the ABO blood group barrier, which significantly expands the living donor pool. Whether the B cell depletion induced by rituximab would affect the proportions of peripheral blood (PB) and lymph nodes (LN) T follicular helper (Tfh) and T follicular regulatory (Tfr) cells, whose survival depends on B cells, in ABO-incompatible kidney transplant recipients (ABOi-KTRs) is unknown. Method PB and LN samples were simultaneously collected on the day of transplantation from 14 ABOi-KTRs and 12 ABO-compatible KTRs (ABOc-KTRs) between January to October 2019. Additional PB from ABOi-KTRs was obtained before desensitization treatment (Rituximab+plasmapheresis+ immunosuppression). All recipients were undergone living donor transplantation. The frequency of B, Tfh (CD4+CXCR5+Foxp3-) and Tfr (CD4+CXCR5+Foxp3+) cells and the expression the PD-1, ICOS on Tfh and Tfr cells were quantified by flow cytometry. Results After desensitization treatment, significantly lower proportions of PB and LN B cells were observed in ABOi-KTRs (ABOi-a) when compared to ABOc and ABOi-b (ABOi-KTRs before desensitization) groups (Fig. A). Circulating Tfr cells decreased significantly after desensitization therapy, while no difference was found in LN Tfr cells (Fig. F). In addition, ABOi-a group showed higher expression of PD-1 on Tfr cell within PB, but lower within LN when compared to ABOi-b and ABOc groups, respectively (Fig. G). For Tfh proportion and its expression of PD-1 and ICOS within PB and LN, no significant difference was observed among groups (Fig. B-D). Significantly lower ratio of Tfr to Tfh was observed after ABO desensitization (Fig. E). Conclusion Our results indicated that ABO desensitization had significant suppression effects on B cells both within the PB and LN of ABOi-KTRs. In addition, the desensitization treatment mainly affected circulating Tfr cells, instead of Tfh cells, which shifted the balance between Tfr and Tfh cells towards Tfr cells in PB. Whereas, this treatment showed no influence on Tfh and Tfr populations within LN in ABOi-KTRs.

P1740KINETICS OF B-CELL SUBSETS RECONSTITUTION FOLLOWING RITUXIMAB TREATMENT IN ABO-INCOMPATIBLE KIDNEY TRANSPLANT RECIPIENTS

Abstract Background and Aims With the application of B-cell-depleting agent rituximab, plasmapheresis and powerful immunosuppression, ABO-incompatible kidney transplant recipients (ABOi-KT) have successfully overcome the ABO antibody barrier. As an important immune cell population, B cells are not only involved in antibody-mediated rejection, but also have been reported to have different immunoregulatory effects due to the existence of distinct B cell subsets. Therefore, comprehensively understanding the reconstitution of B-cell subsets in ABOi-KTRs is crucial to know the immune status that may be related to the subsequent complications. Method Fresh whole blood were collected from 22 ABOi-KTRs and 22 ABO-compatible recipients (ABOc-KTRs) at 0, 1week, 2 weeks ,1month, 3months, and 6 months post-transplantation between October 2018 and May 2019. In addition, pre-desensitization samples were also collected from ABOi-KTRs. B cell subsets including total, naïve, memory, plasma, plasma blast and regulatory B cells were determined by flow cytometry. Results The percentages of B cells in ABOi group remained extremely low and significantly lower than ABOc group through the first 6 months after rituximab treatment (Fig. A). Similar trends were observed in total memory and switched memory B cells whose frequencies increased within first 2 weeks, then decreased thereafter. Meanwhile, the significant differences between ABOi and ABOc groups disappeared at 6 months (Fig. B-D). In addition, plasma and plasma blast B cells increased 2 weeks after transplantation and were significantly higher in ABOi group compared to ABOc group (Fig. E, G), while Naïve B cells started to elevate 1 month after transplantation in ABOi-KTRs and significantly higher proportions were found in ABOc group through the entire 6 months (Fig. F). No obvious difference was observed between ABOi and ABOc groups regarding unswitched memory and regulatory B cell percentages (Fig. C, H). Conclusion Our preliminary results indicated that B-cell depletion therapy applied in ABOi-KTRs not only significantly reduced the number of B cells, but also changed the composition of B cell subsets in the remaining B cell population. Whether such alteration would be clinical significance requires further follow-up.

Early Steroid Withdrawal Protocol With Basiliximab and Rituximab in ABO-Incompatible Kidney Transplant Recipients

ObjectivesCorticosteroids remain an important component of immunosuppressive regimens in high-risk kidney transplants. In this study, we investigated the efficacy of early steroid withdrawal with basiliximab and rituximab in ABO–blood type incompatible (ABO-i) recipients of kidney transplants. MethodsBetween 2008 and 2019, 15 patients underwent ABO-i kidney transplantation. Seven of the 15 patients were treated with a steroid maintenance protocol and the remaining 8 with an early steroid withdrawal protocol. The immunosuppressive protocol consisted of tacrolimus, mycophenolate mofetil, and methylprednisolone (MP), with basiliximab administered as induction therapy. Rituximab was administered as a single 200-mg dose 1 to 4 weeks before kidney transplantation. Two to 4 sessions of either double-filtration plasmapheresis or regular plasmapheresis or both were performed to remove anti-AB antibodies before transplantation. During surgery, MP was administered at a dose of 500 mg; thereafter, the dosage was tapered rapidly, and the drug was discontinued on day 14 post transplant. ResultsIn the steroid maintenance group, 2 patients experienced acute antibody-mediated rejection (AMR). One patient with severe AMR had graft loss on postoperative day 4. Patient and graft survival rates in the steroid maintenance group were 100% and 86%, respectively. MP was successfully withdrawn in the steroid withdrawal group. In this group, there was no biopsy-proven rejection. Patient and graft survival rates were 100%, and when last measured, serum creatinine level ± SD was 1.6 ± 0.8 mg/dL. ConclusionsOur protocol successfully enabled the early withdrawal of steroids in recipients of ABO-i grafts; however, further follow-up is necessary to confirm our results.

SAT-083 SAFETY OF HEMODIALYSIS AND APHERESIS COMBINATION THERAPY AT PRE-TRANSPLANT DESENSITIZATION OF ABO-INCOMPATIBLE KIDNEY TRANSPLANTATION

In patients requiring both hemodialysis (HD) and apheresis, the two treatments can be performed simultaneously. At our hospital, apheresis is often performed along with HD for isoagglutinins removal before ABO-incompatible kidney transplantation. The two treatments can be completed within the HD schedule, which allows the treatment time to be shortened. This approach is also less stressful for patients because fewer punctures are required. In this study, we investigated the safety of HD and apheresis combination therapy. A total of 130 apheresis sessions in 37 ABO-incompatible kidney transplantation recipients between 2015 and 2018 were investigated. Differences in the time changes of arterial pressure, venous pressure, filtration pressure and transmembrane pressure (TMP) were examined in patients treated with combination therapy (Group C, n=90) and apheresis monotherapy (Group M, n=40). In combination therapy, after HD was initiated, apheresis treatment was started by connecting the apheresis circuit, and the same volume as the priming volume (100 to 200 ml) was added. The apheresis circuit was connected to the blood removal side sample port of the HD circuit and the liquid level adjustment line of the arterial chamber. Heparin was administered from the dialysis circuit alone by increasing the dose. Nafamostat mesylate was administered from both the dialysis and apheresis circuits. The blood was returned after apheresis treatment, and the apheresis circuit was disconnected. The two groups were compared using a mixed effects model (random effects) with adjustment of background factors (anticoagulant, machinery used, treatment mode, blood flow rate, filtration rate). Statistical analysis was performed using the R Ver. 3.3.2 rms package. The internal pressures were higher in Group C, but there were no significant differences in time changes compared to Group M and no functional problems (C vs. M for interaction, arterial pressure, venous pressure, filtration pressure, and TMP: P=0.337, 0.725, 0.222 and 0.498, respectively). Membrane exchange was required in one case in Group C due to coagulation. There were no differences in the rates of decrease of isoagglutinin titers between the two groups, and no case had antibody-mediated rejection after transplantation. In HD and apheresis combination therapy, care is required when securing vascular access for adequate removal of blood, establishing an effective blood flow, selecting the appropriate anticoagulant and administration method, and choosing the method of monitoring of circuit internal pressures. Provided that these approaches are performed correctly, our results suggest that combination therapy can be performed without any functional problems, compared to apheresis monotherapy.

Successful pregnancy after in vitro fertilization in an ABO-incompatible kidney transplant recipient receiving rituximab: a case report

BackgroundSuccessful pregnancy outcomes after in vitro fertilization in kidney transplant recipients have been reported, but few cases of successful pregnancy after ABO-incompatible kidney transplantation have been described. Herein, we report on a successful pregnancy after in vitro fertilization in an ABO-incompatible kidney transplant recipient with rituximab, focusing on the changes in immunity.Case presentationA 35-year-old woman with end-stage kidney disease caused by IgA nephropathy was referred for kidney transplantation and successfully underwent an ABO-incompatible living-donor kidney transplant using rituximab from her 66-year-old father at the age of 36. Because she and her husband desired childbearing, they received fertility treatments, and embryo cryopreservation was performed before transplantation. Two years after the transplant, she desired pregnancy. Although immunoglobulin levels such as IgG, IgA and IgM had recovered to almost normal range, the peripheral CD19+ cells and CD20+ cells remained depleted. At 6 months after conversion from mycophenolate mofetil to azathioprine, frozen embryo transfer was performed during the hormone replacement cycle.At 37 weeks and 4 days gestation, a healthy baby girl weighing 2220 g was delivered by cesarean section for arrest of labor. There were no complications in both the recipient and her baby during the perinatal period. At 5 years after the transplant, the recipient has had no major complications including rejection or infection.ConclusionsIt is possible for women receiving ABO-incompatible kidney transplantation with rituximab to successfully become pregnant and deliver a heathy baby after in vitro fertilization, if IgG levels recover to normal range despite depleted peripheral blood B cells.

ABO-Incompatible Kidney Transplantation: Low Rates of Infectious Complications and Excellent Patient Survival

BackgroundA significant gap exists between demand and supply of organs for patients with end-stage renal disease. To increase the donor pool, kidney transplantation is performed across ABO- and HLA-incompatible barriers. ABO-incompatible kidney transplant (ABOi-KT) recipients are at increased risk of antibody-mediated rejection, infection, and mortality. Hypogammaglobulinemia secondary to immunosuppression is highly prevalent after solid organ transplantation, and intravenous immunoglobulin (IVIG) has been reported to reduce the risks of infections in various settings. We use high-dose IVIG in ABOi-KT recipients perioperatively. We aimed to determine the rate of infectious complications along with graft and patient survival in our ABOi-KT recipients. MethodsWe included all adult patients who underwent ABOi-KT from the year 2007 to 2016. Patients received rituximab, plasma exchange, and IVIG (2 g/kg body weight). Thymoglobulin and intravenous methylprednisolone were used as induction treatment. Oral prednisone, mycophenolate mofetil, and tacrolimus were used as maintenance therapy. ResultsA total of 77 ABOi-KTs were performed, and the recipients were followed up for a median of 1557 days. Two patients were diagnosed as having BK nephropathy. No patients were diagnosed as having pneumocystis infection, cytomegalovirus disease, herpes simplex, varicella zoster, or fungal infection. One-year graft and patient survival was 94.8% and 100%, respectively. ConclusionsIn our series of ABOi-KTs, we observed a low risk of infectious complications and excellent patient survival. High-dose IVIG might have reduced infections.

Efficacy of 2 Doses of Rituximab on B-Cell and Antidonor Antibody and Outcomes of ABO-Incompatible Living-Donor Pediatric Kidney Transplant.

Rituximab treatment strategies vary in ABOincompatible pediatric kidney transplant recipients. Here, we present the efficacy of 2 doses of rituximab and subsequent outcomes in ABO-incompatible pediatric kidney transplant patients. Our study of ABO-incompatible pediatric kidney transplant recipients included 21 who were pretreated with desensitization that included 2 doses of 100 mg rituximab (rituximab group) at 10 and 1 day pretransplant and 14 who received splenectomy without rituximab (splenectomy group). Both groups received immunosuppression. Basiliximab was administered during transplant and 4 days posttransplant. Double-filtration plasmapheresis and/or plasma exchange procedures were performed pretransplant in those with higher antidonor antibody titers. CD19-positive and CD20-positive B cells were measured sequentially in the rituximab group. Maximum titers of antidonor antibody pre- and posttransplant, patient and graft survival, biopsy-proven rejection, and complications/infections were compared between groups. In the rituximab group, CD19- and CD20-positive B cells were depleted on transplant, persistently depleted at 3 months, and under 5% until 1 year posttransplant. Maximum titers of antidonor antibodies decreased significantly posttranplant in the rituximab (P < .001) but not in the splenectomy group (P = .174), with maximum titers posttransplant significantly lower than shown in the splenectomy group (P < .001). No rituximab patients had clinical rejection, but 5 splenectomy group patients had clinical T-cell-mediated rejection, with 2 also having antibody-mediated rejection. Six in the rituximab group had cytomegalovirus viremia but no cytomegalovirus disease; however, 5 splenectomy group recipients had cytomegalovirus disease and viremia. In the rituximab group, 3 had late-onset neutropenia. One child died of hypertrophic cardio myopathy with a functioning graft; all others survived with no failed grafts. All splenectomy group children survived, although 2 had deteriorated graft function. Two doses of rituximab were effective in long-term B-cell depletion to suppress antidonor antibodies. The possibility of late-onset neutropenia must be considered.

Comparative analysis of ABO-incompatible kidney transplantation with ABO-compatible transplantation: A single-center experience from Eastern India

This study aimed to compare the outcomes of ABO-incompatible kidney transplantation (ABOiKT) with ABO-compatible kidney transplantation (ABOcKT) in a singlecenter study. A total of 30 consecutive ABOiKT recipients (ABOiKTR) from April 2014 to June 2015 were included in this study. All the patients received rituximab 200 mg/body for B-cell depletion. Plasmapheresis was done for anti-ABO antibody removal. The target anti-ABO titer was kept at <1:8. The outcomes of this group of patients were compared with that of thirty ABOcKT recipients. Both the groups received similar induction therapy with antithymocyte globulin and methylprednisolone. After a follow-up period of one year, the outcomes of both the groups were compared in terms of patient survival, graft survival, graft function, incidence of rejections, infective complications, and duration of posttransplant hospital stay. The patient survival in both the groups of patients was 96.67%. The death-censored graft survival was 96.67% in both the groups. The average serum creatinine level, estimated glomerular filtration rate, incidence of rejections, infective episodes, and posttransplant hospital stay were comparable in both the groups. The outcomes of ABOiKT were comparable with ABOcKT and as such, this modality can expand the living donor pool substantially.

Pilot Conversion Study From Mycophenolate Mofetil to Everolimus in Stable ABO-Incompatible Kidney Transplant Recipients: Analysis of 1-Year Follow-Up Data.

Here, we report our 1-year follow-up data of stable ABO-incompatible kidney transplant recipients who converted from mycophenolate mofetil plus a standard dose of a calcineurin inhibitor to everolimus plus low exposure to calcineurin inhibitors. Our study included 17 recipients of ABO-incompatible kidney transplant procedures performed at our institution. At baseline and at 3 and 12 months after conversion, graft biopsies were performed to check for acute rejection and C4d deposition. Treatment with everolimus was stopped due to adverse events in 8 patients (47.1%). Conversion to everolimus with calcineurin inhibitor minimization did not induce acute rejection or C4d deposition at 3 and 12 months after conversion in ABO-incompatible kidney transplant recipients in whom everolimus was maintained or stopped within 1 year after conversion. Everolimus elicited no acute rejection and no C4d deposition, whether everolimus was maintained or stopped within 1 year after conversion, in ABO-incompatible kidney transplant recipients.

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

Introduction To investigate the correlation between serum anti-ABO immunoglobulin G (IgG) and IgG subtypes, anti-ABO IgG subclasses were measured by flow cytometry (FCM) in ABO-incompatible (ABO-i) kidney transplant recipients (KTRs). We also evaluated baseline anti-ABO C1q antibody of KTRs. Method Baseline anti-ABO IgG titers were measured with both FCM and column agglutination technique (CAT) methods in 18 ABO-i KTRs. The mean florescence intensity (MFI) ratios of baseline Anti-ABO IgG subclasses were obtained by FCM method and followed up after rituximab (RTX), each plasmapheresis (PP) session and kidney transplantation. Correlation between the values of IgG subclass and total IgG titer were analyzed. Baseline anti-ABO C1q antibody was measured by FCM methods. Result The 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 measured by CAT (rho, baseline; 0.641, 0.638, 0.663, PP; 0.662, 0.581, 0.662). However, Spearman correlation analysis revealed that baseline ABO titer did not show any correlation with the values after final PP and transplantation. IgG1 and IgG2 as well as total IgG were removed effectively after serial PP. However, anti-ABO C1q antibody was not detected and neither correlated with total IgG and any IgG subclasses. Conclusion Our findings suggest that IgG1 and IgG2 are dominant IgG subtypes in ABO-i KTRs. The mean 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. Further study is warranted to evaluate the function of each IgG subtype to activate complement pathway.