ABO-incompatible Kidney Transplantation Research Articles

Plasma exchange therapy in the critically ill patient.

Introduction: Plasmapheresis has been used with different levels of evidence in neurology, nephrology, and rheumatology. Management guidelines have evolved with the development of randomized clinical trials; however, the low prevalence of some conditions that can benefit from this intervention is a limitation. Objective of the review: This article is a narrative review that reviews the basic principles of plasma exchange therapy, establishes the levels of evidence, and identifies entities that may benefit from this treatment. Essential points of the review: In category I, the conditions are established where the therapy is first-line; in category II, plasmapheresis is the second treatment option; in category III, the optimal role has yet to be established; and in category IV, it is an ineffective treatment. Among the category I renal indications are Goodpasture syndrome with diffuse alveolar hemorrhage, recurrent focal and segmental glomerulosclerosis in kidney transplant, vasculitis associated with ANCA, rapidly progressive, ABO incompatible kidney transplant. Conclusion: Due to the lack of clinical studies, some pathologies remain with indications category II to IV. Due to the low prevalence and incidence in intensive care, the collective work of the scientific community is required.

Successful Kidney Transplantation Using Elderly Living Donor with Extremely Large Renal Cyst and Double Arteries.

The authors describe a kidney transplant procedure using a living donor with a large cyst and double arteries. Due to the lack of regular transplant activity from a deceased donors, we decided to use the, so called, expanded criteria living donors, which means older age (more than 65 years), hypertension, some structural anomalies of the kidneys (cysts, multiple renal arteries), ABO incompatible kidney transplant, etc. The surgical procedure was the unroofing of a large cyst and wadding with perirenal fat. The 10 years survival rate is quite successful and we can recommend it.

#2390 Does incompatible kidney transplantation provide a reliable alternative? An updated meta-analysis

Abstract Background and Aims The ABO system often poses one of the challenges to kidney transplantation, but due to the scarcity of organs, ABO incompatible kidney transplantation (ABOi-kTx) has gained the clinical attention. So, we aim in this study to evaluate the impact of ABO incompatible kidney transplantation on patients' clinical outcomes in comparison with ABO compatible kidney transplantation (ABOc-kTx). Method We searched six electronic databases: PubMed, Scopus, WOS, Cochrane, Embase, and Medline to identify relevant studies published until October 8th 2023, with no filters applied during the research process. After screening of 8562 studies, we included observational studies that compared any clinical outcomes of ABO incompatible kidney transplantation with ABO compatible kidney transplantation across various age groups. Synthesized odds ratios (ORs) with 95% confidence intervals (CIs) are used to present the differences between the two groups based on random-effects models. Results Our comprehensive search according to the eligible criteria of this study resulted in 102 studies including 254 496 patients in both groups. Due to the clinical heterogeneity, we used random effects models for quantitative synthesis of the eligible studies. Our meta-analysis showed that there was a statistically significant higher mortality ratio after one year, 3 years and 5 years (odds ratio [OR] 2.21 [95% CI 1.56–3.14], P < .00001; I² = 53%), (OR 1.86 [1.35–2.75], P = .0001; I² = 61%), (OR 1.69 [1.20–2.40], P = .003; I² = 75%), respectively. While there was no statistically significant difference at 8-years after transplantation (OR 1.05 [0.76–1.46], P = .77; I² = 58%). Pooled data of graft failure from our studies revealed higher incidence in ABOi-kTx group after one year (OR 2.44 [1.81–3.28], P < .00001; I² = 64%), 3 years (OR 1.57 [1.24–1.98], P < .00001; I² = 54%) and after 5 years (OR 1.57 [1.23–2.01], P = .0003; I² = 76%), There was not any statistically significant difference between both groups after 8 years. Acute anti-body mediated rejections were noticed to be statistically higher in ABOi-kTx group (OR 2.51 [2.12–2.97], (P < .00001); I² = 20%). Also, there was a significantly higher incidence of CMV infection in ABOi-kTx group (OR 1.27 [1.08–1.48], (P = .003); I² = 58%). Conclusion Although that ABOi-kTx is inferior to ABOc-kTx in the first 5 years after the transplantation in patient and graft mortality. Both groups are similar in both outcomes after 8 years post transplantation. Considering the higher incidence of acute rejection in the ABOi-kTx group and increased infection rate, desensitization techniques should be furtherly developed for better survival and complication outcomes.

ABO-incompatible kidney transplantation using immunoadsorption columns: First experiences in South Africa

Background. ABO-incompatible kidney transplantation gives patients with chronic kidney disease requiring dialysis and without a blood group-compatible donor an alternative option for a kidney transplant. Objectives. To describe our first experiences and outcomes with 3 patients using Glycosorb ABO immunoadsorption (IA) columns in performing ABO-incompatible living-donor kidney transplants. This is the first time this technique has been used in Africa. Methods. As per the protocol, patients needed between 1 and 4 sessions of IA and received rituximab ~ one month before transplantation. Results. All the patients achieved the target isohaemagglutinin antibody titre of 1:4 pretransplant. Only 1 patient with the highest initial screening titre (1:256) needed IA post-transplant. None of the patients experienced clinical rejection, and all had good graft kidney function at discharge and at the time of writing. Conclusion. Glycosorb ABO IA is an effective technique in enabling ABO-incompatible living-donor kidney transplants to be performed successfully in a South African setting.

Polyomavirus Nephropathy in ABO Blood Group-Incompatible Kidney Transplantation: Torque Teno Virus and Immunosuppressive Burden as an Approximation to the Problem

IntroductionEarlier reports suggest that patients after ABO-incompatible kidney transplantation (ABOi) are at enhanced risk to develop BK-virus (BKV) nephropathy (BKPyVAN). It remains elusive whether this is a result of more intense immunosuppression or an ABOi-associated ‘intrinsic attribute’. To address this question, we measured Torque-Teno-Virus (TTV) loads as a quantitative proxy for immunosuppressive depth in ABOi recipients and compared them to HLA-incompatible (HLAi, i.e. pre-transplant donor-specific antibody-positive) and standard-risk transplant recipients. MethodsOur retrospective study screened 2256 consecutive kidney transplantations performed between 2007-2020 at the Medical University of Vienna. Out of 629 in-principle eligible transplantations, we were able to include 465 patients: 42 ABOi, 106 HLAi and 317 control recipients. Longitudinal TTV- and BKV-PCR was carried out at pre-defined timepoints and ranged from pre-transplant until month 24 post-transplantation. TTV loads and immunosuppression were evaluated in the context of BKV-associated-complications. ResultsABOi recipients had a higher TTV load compared to HLAi and controls both at month three (median 1.5x109 vs. 2.4x108 vs. 9.1x107, p=0.010) and month six (3.1x109 vs. 1.4x107 vs. 6.4x107, p=0.014) post-transplantation. Tacrolimus exposure was significantly higher in ABOi patients compared to HLAi and control patients (ABOi vs. HLAi: p=0.007, ABOi vs. controls: p<0.0001). Biopsy-proven BKPyVAN was more frequent in ABOi recipients when compared to HLAi- and control-recipients (11.9% vs. 2.8% vs. 4.1%, p=0.046). ConclusionOur data support the assumption that ABOi patients are indeed at higher risk to develop BKPyVAN. A higher TTV load and immunosuppressive burden suggest that intense immunosuppression, rather than an ‘intrinsic attribute’ conferred by ABOi, may contribute to this finding.

Outcome of ABO-incompatible living-donor kidney transplants : Aplea for crossover living-donor kidney transplantation

The lack of postmortem donated organs is the background to varyingly high rates of living-donor kidney transplants worldwide. ABO blood group-incompatible living-donor kidney transplants have also been established for at least 20years. The equivalence of the results of ABO-incompatible and ABO-compatible transplants has recently been questioned. In the sense of acritical reflection of our own kidney transplant program, we were interested in comparing ABO-incompatible with ABO-compatible living-donor kidney transplants. Aretrospective analysis of the long-term outcomes of all living-donor kidney transplants performed at our center since the first ABO-incompatible transplants were performed in 2005 up to and including 2022 was performed. Between 2005 and 2022, 1099 living kidney transplants were performed at the authors' center. Among them were 241ABO-incompatible transplants. Transplant survival was significantly lower after ABO-incompatible donation than after ABO-compatible donation. This effect consisted of an increased mortality of the recipients, especially in the early phase, and areduced longevity of the grafts. Including ABO-incompatible pairs for living-donor kidney transplants in crossover programs can improve medical outcomes and reduce costs.

The Effect of Induction Therapy on Antibody-Mediated Rejection in Kidney Transplantation: A Network Meta-Analysis Using Recent Data

Various induction regimens are available for kidney transplantation (KT); however, which is superior remains unclear. Moreover, although the induction regimens are effective and important for reducing side effects, their respective relationships with antibody-mediated rejection (AMR) after transplantation remain unclear. Therefore, this study aimed to elucidate the most effective induction regimen for AMR reduction through network analysis. We performed a comprehensive search of databases, including basiliximab, alemtuzumab, antithymocyte globulin (ATG), and daclizumab as induction regimens for KT from inception to September 1, 2022. Using a network meta-analysis, we investigated the priorities of 5 induction regimens for patient survival, graft failure, and graft rejection after ABO-incompatible KT. In total, 25 studies comprising 1768 people were included in this network meta-analysis. The primary outcome was the AMR rate of other induction regimens compared with that of basiliximab, whereas the secondary outcomes were heart failure, stroke, hospitalization, peripheral artery disease, myocardial infarction, anemia, leukopenia, herpes zoster, or adverse events. Notably, ATG reduced the AMR rate by 59% (odds ratio, 0.41; 95% credible interval, 0.20-0.90), whereas the other drugs did not show statistical significance. Furthermore, secondary outcomes did not significantly differ between the induction regimens. ATG is widely used in KT induction regimens. Our results showed that ATG reduced the risk of AMR in KT recipients when compared with other induction drugs; therefore, it appears to be an efficient choice of induction regimen to reduce AMR after KT.

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.

High-Dose Intravenous Immunoglobulin to Treat Anti-Thymocyte Globulin Induction–Related BK Virus and Cytomegalovirus Infection in Patients with ABO-Incompatible Kidney Transplantation

ABO-incompatible (ABOi) transplantation is a novel method transplantation method that carries a heightened risk of infection caused by the use of high immunosuppressant doses. This elevated risk is particularly concerning for viral infections, such as cytomegalovirus (CMV) and the BK virus (BKV) increases. Herein, we present a case where high-dose intravenous immunoglobulin (IVIG) was effective in treating viral infections after transplantation. A 41-year-old man underwent an ABOi transplantation. The initial isoagglutinin titer was 1:32. The patient received 200 mg of rituximab, and 3 rounds of plasmapheresis were performed. Subsequently, renal function remained normal; however, 7 months later, the renal function declined, and BK nephropathy and CMV infection were diagnosed through biopsy and serologic tests. The FK level was reduced, and mycophenolate mofetil was discontinued. Although ciprofloxacin and leflunomide were administered, their effects were minimal. Therefore, high-dose IVIG (1 g/kg) was administered 5 times over 5 weeks, which led to a reduction in BK viral load and CMV infectivity in the serum. High-dose IVIG may serve as a promising alternative treatment to mitigate early transplant rejection and BKV and CMV infections.

Effect of Induction Therapy Dose on Survival in Abo-Incompatible Kidney Transplantation: A Network Meta-Analysis Using Recent Data

Rituximab is an essential induction immunosuppressant for ABO-incompatible kidney transplantation (KT) (ABOi-KT). However, studies on the optimal dose of rituximab are insufficient, and there are dosage differences between transplant centers and countries. Therefore, we conducted a study to determine the survival outcomes of patients receiving the most effective and safe dose of rituximab during ABOi-KT. Studies on rituximab dose were divided into four groups: ABO compatible, 1) placebo, 2) rituximab 200 mg, 3) rituximab 200-500 mg, and 4) rituximab 500 mg. We searched the CENTRAL, MEDLINE, EMBASE, and Science Citation Index Expanded databases from 1970 to February 2022.9 . The inclusion criteria were adult patients (>18 years old). Reviews, observational studies, and clinical trials that did not clearly define outcomes or that did not have graft failure as an outcome were excluded. We performed direct and indirect network meta-analyses using Bayesian models and ranked different rituximab doses using a generation mixed treatment comparison (GeMTC) and Stata version 13. The NMA approach was evaluated using the GRADE framework, which specifies four levels of certainty for a given result: high, moderate, low, and very low. The outcomes included patient survival, graft failure, and bacterial and viral infections. Twenty-five trials, including 5,378 subjects, were divided into the following four groups: 1) placebo, 2) rituximab 200 mg, 3) rituximab 200-500 mg, and 4) rituximab 500 mg. We focused on survival outcomes according to the dose of rituximab when patients received induction therapy for ABOi-KT. The mortality rate was significantly lower in the ABO-compatible and rituximab 200 mg groups (odds ratio [OR] 0.27, 95% CrI: 0.071-0.91 and OR 0.14, 95% CrI 0.036-0.47), compared with that in the placebo group. We found that low-dose rituximab in ABO-i KT was effective compared to the high-dose and placebo in maintaining the survival rate. However, large-scale and long-term data are necessary for further validation of our findings. Additionally, the use of smaller doses of rituximab will require further discussion.

Pre-transplant donor specific antibodies in ABO incompatible kidney transplantation - data from the Swiss transplant cohort study.

Living donor (LD) kidney transplantation in the setting of ABO blood group incompatibility (ABOi) has been previously reported to be associated with increased risk for antibody-mediated rejection (ABMR). It is however unclear if the presence of pre-transplant donor specific antibodies (DSA) works as an additive risk factor in the setting of ABOi and if DSA positive ABOi transplants have a significantly worse long-term outcome as compared with ABO compatible (ABOc) DSA positive transplants. We investigated the effect of pre-transplant DSA in the ABOi and ABOc setting on the risk of antibody-mediated rejection (ABMR) and graft loss in a cohort of 952 LD kidney transplants. We found a higher incidence of ABMR in ABOi transplants as compared to ABOc transplants but this did not significantly affect graft survival or overall survival which was similar in both groups. The presence of pre-transplant DSA was associated with a significantly increased risk of ABMR and graft loss both in the ABOi and ABOc setting. We could not detect an additional risk of DSA in the ABOi setting and outcomes were comparable between DSA positive ABOi and ABOc recipients. Furthermore, a combination of DSA directed at both Class I and Class II, as well as DSA with a high mean fluorescence intensity (MFI) showed the strongest relation to ABMR development and graft loss. The presence of pre-transplant DSA was associated with a significantly worse long-term outcome in both ABOi and ABOc LD kidney transplants and our results suggests that the risk associated with pre-transplant DSA is perhaps not augmented in the ABOi setting. Our study is the first to investigate the long-term effects of DSA in the ABOi setting and argues that pre-transplant DSA risk could potentially be evaluated similarly regardless of ABO compatibility status.

Advances in the management of chronic kidney disease – a South African perspective

Abstract Chronic kidney disease (CKD) represents a significant public health problem globally, and there is evidence to suggest that the prevalence of CKD in sub-Saharan Africa is comparable to elsewhere. For many South African patients who progress to kidney failure (KF), life-sustaining kidney replacement therapy (KRT) is inaccessible due to strict rationing in a resource-limited public healthcare sector, upon which most South Africans are reliant. This shortage brings into focus the need for strategies for delaying CKD progression. This review aims to highlight significant developments in the management of CKD over the last few decades and to discuss these advances within a South African context. That is, to consider the profile of kidney disease locally and issues surrounding access to newer therapeutic agents. We summarise the mechanisms by which the newer therapeutic agents confer renal protection and the major trials supporting their efficacy. Notable advances include newer anti-diabetic agents such as sodium-glucose-transporter-2 (SGLT-2) inhibitors, endothelin-receptor antagonists (ERAs), and nonsteroidal mineralocorticoid antagonists (MRAs). In addition, experimental, targeted therapies in the setting of various glomerular diseases, polycystic kidney disease and APOL-1-mediated kidney disease are briefly discussed. We also highlight several locally relevant advances pertinent to patients on KRT, including newer therapies for managing anaemia in CKD and local experiences with ABO-incompatible kidney transplantation. Although many newer therapies for managing CKD have robust data supporting their use, many barriers exist to implementing them into daily clinical practice. Key messages Although there is a significant burden of CKD in South Africa many patients are unable to access life-sustaining kidney replacement therapy (KRT) due to the strict rationing of dialysis in a resource-limited public healthcare sector. Newer therapies such as sodium-glucose-transporter-2 (SGLT-2) inhibitors, non-steroidal mineralocorticoid receptor antagonists (MRAs) and endothelin receptor antagonists (ERAs) delay the progression of CKD, which is crucial in patients with CKD who may not be able to access KRT. It is therefore paramount that we address the barriers limiting access to these newer therapies.

I-JAMM-(I): A survey providing an insight into the practices of isoagglutinin titration in ABO incompatible kidney and liver transplantation

Background and objectivesABO-incompatible transplantations allow patients to receive timely transplants. Isoagglutinin titration to ascertain levels of incompatible antibodies in the recipient is important in determining patient selection and transplant survivability. To find out the prevalent trends in India, the largest, first of its kind survey was carried out among the transplant centers regarding their practices in isoagglutinin titration. MethodsThe survey was drafted by a working group of Transfusion and Transplant Immunology specialists from six different centers. Data was obtained via the use of an online questionnaire. ResultsResults were categorized into four categories, Hospital information, Titration methodology, Role of transfusion specialists and cut-off titers. Most centers had a well-established solid-organ transplant program with considerable number of ABO-incompatible transplantations. Most centers performed isoagglutinin titration in Transfusion Medicine department. Column Agglutination Technique (CAT) was the most common method, using EDTA blood samples and freshly-prepared in-house pooled cells. Most centers had a turn-around time of less than 12 h. While the policy for ascertaining baseline and threshold titers is well-defined in ABO-incompatible renal transplants, variations from center to center still exist for ABO-incompatible liver transplants. Most centers required a Transfusion Medicine consultation for the patients before such transplants. ConclusionWith increasing ABO-incompatible kidney and liver transplants across the country, the role of Transfusion medicine specialists has become vital in pre-conditioning regimes enabling the viability and success of such transplants. This was a unique survey that provided a snapshot of current trends and practices of isoagglutinin titration for ABO-incompatible transplants in India.

Pretransplant immunologic risk assessment in high baseline ABO antibody titers and donor-specific anti-human leukocyte antigen antibodies in ABO incompatible kidney transplantation

Pretransplant immunologic risk assessment in high baseline ABO antibody titers and donor-specific anti-human leukocyte antigen antibodies in ABO incompatible kidney transplantation

Emphasizing long-term isoagglutinin monitoring after ABO-incompatible kidney transplant: lessons from a case series on late antibody-mediated rejection

Emphasizing long-term isoagglutinin monitoring after ABO-incompatible kidney transplant: lessons from a case series on late antibody-mediated rejection

Comparison of the effectiveness and safety of rabbit anti-thymocyte globulin and basiliximab as induction agents in ABO-incompatible kidney transplants: a Korean Organ Transplantation Registry-based study

Comparison of the effectiveness and safety of rabbit anti-thymocyte globulin and basiliximab as induction agents in ABO-incompatible kidney transplants: a Korean Organ Transplantation Registry-based study

ABO-incompatible kidney transplantation: a single-center experience

ABO-incompatible kidney transplantation: a single-center experience

Comparison of clinical and pathological features of rejection in ABO-incompatible and ABO-compatible kidney transplantation

Comparison of clinical and pathological features of rejection in ABO-incompatible and ABO-compatible kidney transplantation