Reviewing the pathogenesis of antibody-mediated rejection and renal graft pathology after kidney transplantation

Diagnostic criteria and treatment protocols for acute antibody-mediated rejection (AMR) of kidney allograft remain controversial. We report the case of early severe AMR after primary kidney transplantation. The graft removal was considered in the absence of treatment efficacy and in the presence of systemic infl ammatory response syndrome. However, at surgery the graft looked normal and it was not removed. The repeated treatment course (plasmapheresis, antithymocyte globulin, intravenous immunoglobulin and rituximab) was effective. The patient has good and stable graft function in 1 year after transplantation.

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Thrombotic microangiopathy after kidney transplantation: causes, clinical specifics and outcomes

Almanac of Clinical Medicine ◽

10.18786/2072-0505-2020-48-022 ◽

2020 ◽

Vol 48 (3) ◽

pp. 177-186

Author(s):

E. I. Prokopenko ◽

E. O. Shcherbakova ◽

R. O. Kantaria ◽

V. A. Stepanov

Keyword(s):

Kidney Transplantation ◽

Renal Transplant ◽

Graft Survival ◽

Thrombotic Microangiopathy ◽

De Novo ◽

Renal Transplant Recipients ◽

Post Transplant ◽

Antibody Mediated Rejection ◽

Renal Graft ◽

Kidney Transplantations

Background: Thrombotic microangiopathy (TMA) is a clinical and morphological phenomenon characterized by specific microvascular injury, microangiopathic hemolytic anemia, and damage of various target organs. TMA after kidney transplantation (post-renal transplant TMA) is a serious complication affecting the recipient and graft survival.Aim: To analyze the timing, causes, specifics of the clinical course and outcomes of TMA in renal transplant recipients.Materials and methods: This one-center study was based on a comprehensive examination and follow-up of 697 patients who had undergone 728 kidney transplantations (KT) from deceased donors in 2003–2019. Post-transplant TMA of the renal graft was confirmed morphologically in all cases.Results: We identified 32 episodes of post-transplant TMA in 32 patients; thus, the incidence of TMA was 4.4%. All cases developed after KT de novo; no recurrent TMA was observed. TMA was systemic in 37.5% and locally renal in 62.5% of the patients. The median time to the development of post-transplant TMA was 0.55 (range, 0.1 to 51.6) months. The patients with TMA did not differ from those without by gender, age, body mass index, underlying disorders, type and duration of dialysis before KT, protocols of immunosuppressive therapy, incidence of surgical, urological, infectious, cardiovascular and oncological complications. The patients with TMA were significantly more likely to have graft rejection (25.0% vs 11.2%, p = 0.035) and a never-functioning transplant (28.1% vs 4.9%, p < 0.001). The presence of TMA negatively affected the transplantation outcomes. The cumulative 1-year graft survival in the patients without and with TMA was 91% and 44%, respectively, whereas their 5-year survival rates were 68% and 25% (p < 0.001). The leading causes of TMA were: donor pathology (31.2%), antibody-mediated rejection (28.1%), and cyclosporine/tacrolimus nephrotoxicity (21.9%); the proportion of other causes was 18.8%. A combination of TMA etiological factors was identified in 68.7% of the recipients. The recipients with of calcineurin inhibitors nephrotoxicity had a more favorable prognosis compared to those with other causes of TMA.Conclusion: Post-renal transplant TMA is an infrequent but serious complication that worsens the graft survival and often is life-threatening for recipients. In most cases, TMA develops in the early post-operative period; however, it can occur any time thereafter. To improve the outcome of TMA, early diagnosis is necessary based on clinical suspicion and a prompt biopsy of the renal graft with suspected TMA. Treatment should be started quickly with consideration of the cause of the complication.

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Acute Rejection Following Kidney Transplantation: State-of-the-Art and Future Perspectives

Current Pharmaceutical Design ◽

10.2174/1381612826666200610184433 ◽

2020 ◽

Vol 26 (28) ◽

pp. 3468-3496

Author(s):

Emilio Rodrigo ◽

Marcio F. Chedid ◽

David San Segundo ◽

Juan C.R. San Millán ◽

Marcos López-Hoyos

Keyword(s):

Kidney Transplantation ◽

Acute Rejection ◽

Rescue Therapy ◽

Standard Of Care ◽

Rejection Rate ◽

New Drugs ◽

High Dose ◽

Current Standard ◽

Antibody Mediated Rejection ◽

Cellular Rejection

: Although acute renal graft rejection rate has declined in the last years, and because an adequate therapy can improve graft outcome, its therapy remains as one of the most significant challenges for pharmacists and physicians taking care of transplant patients. Due to the lack of evidence highlighted by the available metaanalyses, we performed a narrative review focused on the basic mechanisms and current and future therapies of acute rejection in kidney transplantation. : According to Kidney Disease/Improving Global Outcomes (KDIGO) guidelines, both clinical and subclinical acute rejection episodes should be treated. Usually, high dose steroids and basal immunosuppression optimization are the first line of therapy in treating acute cellular rejection. Rabbit antithymocytic polyclonal globulins are used as rescue therapy for recurrent or steroid-resistant cellular rejection episodes. Current standard-of-care (SOC) therapy for acute antibody-mediated rejection (AbMR) is the combination of plasma exchange with intravenous immunoglobulin (IVIG). Since a significant rate of AbMR does not respond to SOC, different studies have analyzed the role of new drugs such as Rituximab, Bortezomib, Eculizumab and C1 inhibitors. Lack of randomized controlled trials and heterogenicity among performed studies limit obtaining definite conclusions. Data about new direct and indirect B cell and plasma cell depleting agents, proximal and terminal complement blockers, IL-6/IL-6R pathway inhibitors and antibody removal agents, among other promising drugs, are reviewed.

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B-cell activating factor BAFF as a novel alert marker for the immunological risk stratification after kidney transplantation

Immunologic Research ◽

10.1007/s12026-021-09205-4 ◽

2021 ◽

Author(s):

Antonia Margarete Schuster ◽

N. Miesgang ◽

L. Steines ◽

C. Bach ◽

B. Banas ◽

...

Keyword(s):

Kidney Transplantation ◽

B Cell ◽

Graft Function ◽

Risk Profile ◽

Kidney Transplant Recipients ◽

Post Transplantation ◽

Antibody Mediated Rejection ◽

B Cell Activating Factor ◽

Medium Risk ◽

Patients At Risk

AbstractThe B cell activating factor BAFF has gained importance in the context of kidney transplantation due to its role in B cell survival. Studies have shown that BAFF correlates with an increased incidence of antibody-mediated rejection and the development of donor-specific antibodies. In this study, we analyzed a defined cohort of kidney transplant recipients who were treated with standardized immunosuppressive regimens according to their immunological risk profile. The aim was to add BAFF as an awareness marker in the course after transplantation to consider patient’s individual immunological risk profile. Included patients were transplanted between 2016 and 2018. Baseline data, graft function, the occurrence of rejection episodes, signs of microvascular infiltration, and DSA kinetics were recorded over 3 years. BAFF levels were determined 14 d, 3 and 12 months post transplantation. Although no difference in graft function could be observed, medium-risk patients showed a clear dynamic in their BAFF levels with low levels shortly after transplantation and an increase in values of 123% over the course of 1 year. Patients with high BAFF values were more susceptible to rejection, especially antibody-mediated rejection and displayed intensified microvascular inflammation; the combination of high BAFF + DSA puts patients at risk. The changing BAFF kinetics of the medium risk group as well as the increased occurrence of rejections at high BAFF values enables BAFF to be seen as an awareness factor. To compensate the changing immunological risk, a switch from a weaker induction therapy to an intensified maintenance therapy is required.

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Safety and Efficacy of Tandem Hemodialysis and Selective Plasma Exchange in Pretransplant Desensitization of ABO-Incompatible Kidney Transplantation

Blood Purification ◽

10.1159/000512713 ◽

2021 ◽

pp. 1-8

Author(s):

Ako Hanaoka ◽

Toshihide Naganuma ◽

Daijiro Kabata ◽

Daichi Morii ◽

Yoshiaki Takemoto ◽

...

Keyword(s):

Kidney Transplantation ◽

Plasma Exchange ◽

Treatment Time ◽

Venous Pressure ◽

Transmembrane Pressure ◽

Safety And Efficacy ◽

Antibody Mediated Rejection ◽

Tandem Therapy ◽

Internal Pressures ◽

Over Time

Introduction: In patients requiring both hemodialysis (HD) and apheresis, the 2 treatments can be performed simultaneously. At our hospital, selective plasma exchange (SePE) is often performed along with HD for removal of isoagglutinins before ABO-incompatible (ABOi) kidney transplantation. The 2 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 and efficacy of tandem HD and SePE. Methods: A total of 58 SePE sessions in 30 ABOi kidney transplant recipients were investigated. The SePE circuit was connected in parallel with the HD circuit, and tandem HD and SePE therapy was performed using filtration methods. The SePE sessions were divided into 2 groups: those with SePE monotherapy (group S, n = 20) and those with tandem therapy (group T, n = 38). Changes in transmembrane pressure (TMP), arterial pressure (AP), venous pressure (VP), and decrease in isoagglutinin titers over time were compared between the groups with adjustment for background data. Results: The internal pressures (AP and VP) were higher in group T, and there were significant differences in changes of TMP and AP over time between groups T and S. Membrane exchange was required in 1 case in group T due to coagulation. There was a more significant decrease of immunoglobulin G isoagglutinin titers in group T compared to group S. No case had antibody-mediated rejection after transplantation. Discussion/Conclusion: In HD/SePE tandem therapy, internal pressures were higher and TMP and AP tended to increase more compared to SePE monotherapy, but we were able to perform the 2 treatments without any functional problems. Tandem therapy was also effective in decreasing isoagglutinin titers, which suggests that this may be a beneficial treatment modality as apheresis before ABOi kidney transplantation.

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Treatment of antibody‐mediated rejection with double‐filtration plasmapheresis, low dose IVIg plus rituximab after kidney transplantation

Journal of Clinical Apheresis ◽

10.1002/jca.21897 ◽

2021 ◽

Author(s):

Hamza Naciri Bennani ◽

Mélanie Daligault ◽

Johan Noble ◽

Béatrice Bardy ◽

Lionel Motte ◽

...

Keyword(s):

Kidney Transplantation ◽

Low Dose ◽

Antibody Mediated Rejection ◽

Double Filtration Plasmapheresis ◽

Double Filtration

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Acute Antibody-Mediated Rejection in Kidney Transplantation: Clinical and Therapeutic Aspects

Journal of Nephrology & Therapeutics ◽

10.4172/2161-0959.1000146 ◽

2014 ◽

Vol 04 (01) ◽

Cited By ~ 1

Author(s):

Salvadori M Bertoni E

Keyword(s):

Kidney Transplantation ◽

Antibody Mediated Rejection

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Defining the phenotype of antibody-mediated rejection in kidney transplantation: Advances in diagnosis of antibody injury

Transplantation Reviews ◽

10.1016/j.trre.2017.08.005 ◽

2017 ◽

Vol 31 (4) ◽

pp. 257-267 ◽

Cited By ~ 15

Author(s):

Neetika Garg ◽

Milagros D. Samaniego ◽

Dana Clark ◽

Arjang Djamali

Keyword(s):

Kidney Transplantation ◽

Antibody Mediated Rejection

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Infectious complications and graft outcome following treatment of acute antibody-mediated rejection after kidney transplantation: A nationwide cohort study

PLoS ONE ◽

10.1371/journal.pone.0250829 ◽

2021 ◽

Vol 16 (4) ◽

pp. e0250829

Author(s):

Nancy Perrottet ◽

Mario Fernández-Ruiz ◽

Isabelle Binet ◽

Michael Dickenmann ◽

Suzan Dahdal ◽

...

Keyword(s):

Cohort Study ◽

Kidney Transplantation ◽

Real Life ◽

Severe Infection ◽

Intravenous Immunoglobulins ◽

Infectious Complications ◽

Treatment Recommendation ◽

Accurate Information ◽

Significant Heterogeneity ◽

Antibody Mediated Rejection

Acute antibody-mediated rejection (AMR) remains a challenge after kidney transplantation (KT). As there is no clear-cut treatment recommendation, accurate information on current therapeutic strategies in real-life practice is needed. KT recipients from the multicenter Swiss Transplant Cohort Study treated for acute AMR during the first post-transplant year were included retrospectively. We aimed at describing the anti-rejection protocols used routinely, as well as patient and graft outcomes, with focus on infectious complications. Overall, 65/1669 (3.9%) KT recipients were treated for 75 episodes of acute AMR. In addition to corticosteroid boluses, most common therapies included plasmapheresis (56.0%), intravenous immunoglobulins (IVIg) (38.7%), rituximab (25.3%), and antithymocyte globulin (22.7%). At least one infectious complication occurred within 6 months from AMR treatment in 63.6% of patients. Plasmapheresis increased the risk of overall (hazard ratio [HR]: 2.89; P-value = 0.002) and opportunistic infection (HR: 5.32; P-value = 0.033). IVIg exerted a protective effect for bacterial infection (HR: 0.29; P-value = 0.053). The recovery of renal function was complete at 3 months after AMR treatment in 67% of episodes. One-year death-censored graft survival was 90.9%. Four patients (6.2%) died during the first year (two due to severe infection). In this nationwide cohort we found significant heterogeneity in therapeutic approaches for acute AMR. Infectious complications were common, particularly among KT recipients receiving plasmapheresis.

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