Incompatible Kidney Transplantation Research Articles

Optimal acceptance of incompatible kidneys

Incompatibility between patient and donor is a major barrier in kidney transplantation (KT). The increasing shortage of kidney donors has driven the development of desensitization techniques to overcome this immunological challenge. Compared with compatible KT, patients undergoing incompatible KTs are more likely to experience rejection, infection, malignancy, and graft loss. We study the optimal acceptance of possibly incompatible kidneys for individual end-stage kidney disease patients. To capture the effects of incompatibility, we propose a Markov Decision Process (MDP) model that explicitly includes compatibility as a state variable. The resulting higher-dimensional model makes it more challenging to analyze, but under suitable conditions, we derive structural properties including control limit-type optimal policies that are easy to compute and implement. Numerical examples illustrate the behavior of the optimal policy under different mismatch levels and highlight the importance of explicitly incorporating the incompatibility level into the acceptance decision when desensitization therapy is an option.

C1q Binding Ability for Prior Risk Assessment of Acute Antibody-Mediated Rejection in ABO-Incompatible Kidney Transplantation.

In ABO blood group incompatible kidney transplantation (ABO-I), potential issues on acute antibody-mediated rejection (ABMR) remain to be solved. This study aimed to assess the risk factors of acute ABMR using recipient- or donor-derived specimens. Quantitative analysis of A/B antigen expression was conducted in 104 donor kidney tissues (Kt), platelets (Plt), and red blood cells (RBC) by immunohistochemical staining or flow cytometry (FCM). ABO-I pre-transplant recipient serum samples (ABMR = 12, non-ABMR = 27) were extracted by propensity score matching. Anti-A antibody titers of IgM, IgG and IgG subclasses, and C1q binding ability (%) on antibody were measured using RBC-FCM. No association was observed between ABMR and A/B antigen expression levels in donor's Plt, RBC, or Kt. In recipient's sample, C1q-IgG binding ability was significantly higher in the ABMR group than in the non-ABMR group (C1q-IgG: 9.04% vs. 5.93% p = 0.049). Neither the A/B antigen expression level in donors (grafts) nor anti-blood group IgG/IgM antibodies in recipient sera before desensitization seemed to influence ABMR incidence in ABO-I. In contrast, C1q-IgG binding ability could be a potential predictor for ABMR in ABO-I.

Human Leukocyte Antigen (HLA)-Incompatible Kidney Transplantation Shows Similar Outcomes Compared with HLA-Compatible Kidney Transplantation after Early Rejection

Human Leukocyte Antigen (HLA)-Incompatible Kidney Transplantation Shows Similar Outcomes Compared with HLA-Compatible Kidney Transplantation after Early Rejection

260.7: Comparison of thymoglobulin and grafalon as induction agents in ABO- incompatible kidney transplantation – A single centre retrospective study.

260.7: Comparison of thymoglobulin and grafalon as induction agents in ABO- incompatible kidney transplantation – A single centre retrospective study.

260.5: Current status of ABO incompatible kidney transplantation in Japan: Based on statistical data of renal transplantation in Japan.

260.5: Current status of ABO incompatible kidney transplantation in Japan: Based on statistical data of renal transplantation in Japan.

Terapia de recambio plasmático en el paciente críticamente enfermo.

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.

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.

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.

Increasing Access to Kidney Transplantation for Black and Asian Patients Through Modification of the Current A2 to B Allocation Policy.

The rate of A2 to B incompatible (ABO-i) kidney transplant continues to be low despite measures in the new Kidney Allocation System (KAS) to facilitate such transplants. This paper shows how the number of ABO-i transplants could increase if KAS policies were utilized to their fullest extent through a boost in ABO-i priority points. Predicting transplant outcomes using the Kidney Pancreas Simulated Allocation Model (KPSAM), preloaded with national data of 2010. We used this simulation to compare KAS to a new intervention in which priority equal to cPRA=100 has been given to blood type B candidate who are willing to accept an A blood type organ. The number of African American recipients increased by 375 (from 35% of recipient population to 38.7%), the number of blood type B African Americans increased by 65 (from 8% of recipient population to 9%), and the number of blood type B African Americans receiving blood type A kidneys increased by 49 (from 2% of recipient population to 2.5%). The same change occurred for Asians, particularly blood type B Asians (from 0.54% of the recipient population to 0.7%). Average wait time notably decreased by 27 days for blood type B African Americans. In the proposed scenario, 263 blood type B African Americans received blood type A organ (2.5% of recipient population) while only 181 (1.1%) of such transplants were performed in 2021. These results signify a considerable opportunity loss of ABO-i transplants for African American patients. If this policy was universally adopted, we would expect to see an overall increase of A2 to B transplantation, but in reality, not all centers perform ABOi transplantation. Thus, adopting this policy would incentivize other centers to perform more subtyping of A-type kidneys, and it would increase access to organs for blood type B Asian and African Americans in centers where ABOi transplantation already takes place.

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

A Case of Self-Limited Thrombotic Microangiopathy (TMA) After an ABO Incompatible (ABOi) Kidney Transplant (KT)

A Case of Self-Limited Thrombotic Microangiopathy (TMA) After an ABO Incompatible (ABOi) Kidney Transplant (KT)

WITHDRAWN: Therapeutic apheresis in renal transplantation: An update

Therapeutic apheresis (TA) plays a significant role in various aspects of renal transplantation. It has been a necessary preconditioning component in ABO incompatible kidney transplants and an important modality in the removal of anti-human leukocyte antigen (HLA) antibodies both in the context of desensitization protocols that have been developed to allow highly sensitized kidney transplant candidates to be successfully transplanted and as treatment of antibody mediated rejection episodes post transplantation. In addition, TA has been used with various results for the management of recurrent focal segmental glomerulosclerosis. The purpose of this review is to examine the evidence supporting the application of TA as an adjunctive therapeutic option to immunosuppressive agents in protocols both before and after kidney transplantation.

Risk Factors and Causality of Early Graft Loss in Kidney Transplanted Patients in Northwestern Iran: A 10-Year Retrospective Study

Background: Early graft loss (EGL) is one of the rare complications of kidney transplantation. Several factors play a role in the occurrence of EGL in kidney transplant recipients, which must be identified and limited. Objectives: This ten-year retrospective study was conducted in a single center on 32 kidney transplant recipients with EGL to determine the reasons for and risk factors of kidney transplant rejection in Iran. Methods: This descriptive-analytical study’s population included 605 kidney transplant recipients receiving kidneys during the last ten years in our center. The diagnosis of EGL was based on renal allograft biopsy examination and primary clinical complications, including a rapid increase in serum creatinine. The age, gender, blood group, and rhesus (Rh) of both donors and recipients, as well as the kinship between the donor and recipient (relative and non-relative), right/left-sided living donor/recipient kidneys, primary kidney disease, the presence of underlying disease in the recipient, dialysis duration, the year of kidney transplantation, transplant survival time, patient survival time, and complications (surgery and others) were gathered. The data were analyzed using SPSS version 18. Results: In this study, 32 out of 605 kidney transplant recipients (5.28%) experienced EGL (53.1% male and 46.9% female, average age of 41.12 years). The duration of kidney function after transplantation was 5.56 ± 0.13 days. The transplanted kidneys were functional between 72 hours and one week after transplantation in 34.4% of the patients. The causes of EGL were found to be tissue rejection in 31.3% of the patients and vascular thrombosis and hyperacute rejection in 21.8%. Nephrectomy occurred in 41% of the patients, and 43.75% died because of a heart attack. Conclusions: Our findings supported previous studies' results, suggesting that EGL is associated with receiving an incompatible kidney transplant and surgery-related complications, including bleeding and thrombosis.

ABO Incompatible Kidney Transplantation Without B-cell Depletion is Associated With Increased Early Acute Rejection: A Single-Center Australian Experience.

We performed a single-center retrospective cohort study of 66 consecutive ABO incompatible kidney transplants (ABOiKT) performed without B-cell depleting therapy. Outcomes were compared to an earlier era performed with rituximab (n = 18) and a contemporaneous cohort of ABO compatible live donor transplants (ABOcKT). Acute rejection within 3months of transplant was significantly more common after rituximab-free ABOiKT compared to ABOiKT with rituximab (OR 8.8, p = 0.04) and ABOcKT (OR 2.9, p = 0.005) in adjusted analyses. Six recipients of rituximab-free ABOiKT experienced refractory antibody mediated rejection requiring splenectomy, and a further two incurred early graft loss with no such episodes amongst ABOiKT with rituximab or ABOcKT cohorts. Patient and graft survival were similar between groups over a median follow-up of 3.1years. This observational evidence lends strong support to the continued inclusion of rituximab in desensitization protocols for ABOiKT.

Humoral response to SARS-CoV-2 mRNA vaccine on in ABO blood type incompatible kidney transplant recipients treated with low-dose rituximab

We aimed to evaluate the humoral response after the second and third doses of SARS-CoV-2 mRNA vaccine in ABO blood type incompatible kidney transplant (KT) recipients treated with rituximab. This retrospective study conducted between June 2021 and June 2022 included 131 KT recipients and 154 nontransplant controls who had received mRNA vaccines. We compared the seropositivity (anti-SARS-CoV-2 spike IgG antibody titer ≥ 0.8 U/mL) after the second and third vaccinations. Furthermore, we evaluated the impact of pretransplant vaccination for seropositivity. Of the 131 KT recipients, 50 had received the third dose of mRNA vaccine. The antibody titer was significantly increased after the third dose of mRNA vaccine. The seropositivity rate after the third dose of mRNA vaccine increased from 36 to 70%. We observed no significant difference in seropositivity after the third dose of mRNA vaccine in ABO incompatibility, rituximab use, mycophenolate mofetil use, and age at KT. Of the nine recipients who had received the second or third dose of the mRNA vaccine prior to the KT, eight of the recipients were seropositive both before and after the KT. Our results suggest that ABO incompatibility or rituximab use was not significantly associated with seropositivity.

ABO Incompatible Kidney Transplant in a Patient With Atypical Hemolytic Uremic Syndrome: Case Report

Kidney transplant (KT) or renal transplant is 1 of the preferred treatment options for patients with end-stage renal disease, but the presence of atypical hemolytic uremic syndrome (aHUS) further increases the risk of reoccurrence with graft rejection, and poor outcomes. ABO incompatibility further adds to the rejection risk. Here, we present a case of a young adult with a history of aHUS undergoing a successful ABO-incompatible (ABOi) renal transplant. ABO incompatibility desensitization was carried out, and the antibody titer was reduced to nullify the risk of rejection. Graft acceptance was facilitated by triple immunosuppression (steroid, tacrolimus, and mycophenolate mofetil), and 4-month serum creatinine follow-up indicated the absence of antibody-mediated rejection and recurrence of aHUS. This case demonstrates that in patients with aHUS, ABOi renal transplant can be performed successfully.

The Questionable Burden of AB0 Incompatible Kidney Transplantation

Abstract Background AB0 incompatible kidney transplantation has become a genuine treatment for end-stage renal disease. Non-inferiority in long term graft function compared to AB0 compatible transplantation has been shown. However, the assumed burden due to complications owing to increased immunosuppression inherent to AB0 incompatible transplantation has not yet been quantified. Aims The aim of the study was to determine if AB0 incompatible recipients have additional morbidity and whether this burden is justified or whether kidney paired donation programs should be advocated. Methods From January 2000 to March 2020 46 AB0 incompatible living kidney transplantations were performed. Patients were matched with AB0 compatible recipients according to sex, age, underlying disease, year of transplantation, and duration of dialysis. Number and duration of readmissions, surgical complication rates according to Clavien-Dindo and its comprehensive complication index (CCI), kidney function, occurrence of new onset diabetes, as well as tumor incidence were analyzed. Results Readmission rate was not higher in AB0 incompatible recipients. The median difference in length of hospital stay for readmissions, CCI during primary hospital stay, and CCI for readmissions at 3, 6, 12 and >12 months after transplantation were comparable. Incidence of tumor and new onset diabetes after transplantation was not increased in incompatible recipients. Conclusions AB0 incompatible recipients do not suffer from a higher burden compared to AB0 compatible recipients. We currently recommend not delaying transplantation in AB0 incompatible pairs.

Translation of therapeutic strategies to modulate B cell reponses from non-human primate models to human kidney transplantation.

Using novel drugs targeting lymphocyte costimulation, cytokines, antibody, complement, and plasma cells, we have developed strategies in a non-human primate model to modulate the B cell response to incompatible kidney transplants. After more than two decades of research supported by mechanistic studies, this has resulted in clinically relevant approaches that are currently enrolling in clinical trials or preparing for such. In this manner, we aim to address the problems of HLA sensitization for very highly sensitized patients awaiting transplantation and the unmet need of effective treatment for antibody-mediated rejection.