The gray area between operational tolerance and overt rejection in kidney transplantation

Operational tolerance in kidney transplantation is characterized by stable serum creatinine < 1.7 mg/dL and proteinuria < 1 g/day in the absence of immunosuppression or immunodeficiency for over one year. However, simultaneous donor specific antibodies are common and serum creatinine is a poor surrogate of early lesions. Consequently, subclinical rejections will meet operational tolerance criteria if serum creatinine remains stable. We report a patient with operational tolerance criteria followed by biopsy-proven chronic active antibody mediated rejection, discussing the intricate challenges of immunosuppression management.

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Intensity of de novo DSA detected by Immucor Lifecodes assay and C3d fixing antibodies are not predictive of subclinical ABMR after Kidney Transplantation

PLoS ONE ◽

10.1371/journal.pone.0249934 ◽

2021 ◽

Vol 16 (4) ◽

pp. e0249934

Author(s):

Dominique Bertrand ◽

Rangolie Kaveri ◽

Charlotte Laurent ◽

Philippe Gatault ◽

Maïté Jauréguy ◽

...

Keyword(s):

Kidney Transplantation ◽

Prognostic Value ◽

De Novo ◽

Added Value ◽

Multicentric Study ◽

Specific Antibodies ◽

Antibody Mediated Rejection ◽

Single Antigen ◽

Donor Specific Antibodies ◽

Allograft Loss

De novo donor-specific antibodies (dnDSA) are associated with antibody-mediated rejection (ABMR) and allograft loss. We tested Immucor* (IM) Luminex Single-antigen beads (LSAB) assay and C3d-fixing antibodies in the setting of dnDSA and subclinical (s) ABMR. This retrospective multicentric study included 123 patients biopsied because of the presence of subclinical de novo DSA detected by One Lamda* Labscreen (MFI > 1000). In 112 patients, sera of the day of the biopsy were available and tested in a central lab with IM Lifecodes LSAB and C3d fixing antibodies assays. In 16 patients (14.3%), no DSA was detected using Immucor test. In 96 patients, at least one DSA was determined with IM. Systematic biopsies showed active sABMR in 30 patients (31.2%), chronic active sABMR in 17 patients (17.7%) and no lesions of sABMR in 49 KT recipients (51%). Intensitity criteria (BCM, BCR and AD-BCR) of DSA were not statistically different between these 3 histological groups. The proportion of patients with C3d-fixing DSA was not statistically different between the 3 groups and did not offer any prognostic value regarding graft survival. Performing biopsy for dnDSA could not be guided by the intensity criteria of IM LSAB assay. C3d-fixing DSA do not offer added value.

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Antibody-Mediated Rejection With and Without HLA Donor-Specific Antibodies in Kidney-Transplantation

Transplantation Journal ◽

10.1097/01.tp.0000542869.07515.27 ◽

2018 ◽

Vol 102 ◽

pp. S211-S212 ◽

Cited By ~ 1

Author(s):

Marta Crespo ◽

Dolores Redondo ◽

Carrie Butler ◽

Javier Gimeno ◽

Carme Garcia ◽

...

Keyword(s):

Kidney Transplantation ◽

Specific Antibodies ◽

Antibody Mediated Rejection ◽

Donor Specific Antibodies

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Safety and efficacy of eculizumab for the prevention of antibody‐mediated rejection after deceased‐donor kidney transplantation in patients with preformed donor‐specific antibodies

American Journal of Transplantation ◽

10.1111/ajt.15397 ◽

2019 ◽

Vol 19 (10) ◽

pp. 2865-2875 ◽

Cited By ~ 21

Author(s):

Denis Glotz ◽

Graeme Russ ◽

Lionel Rostaing ◽

Christophe Legendre ◽

Gunnar Tufveson ◽

...

Keyword(s):

Kidney Transplantation ◽

Deceased Donor ◽

Donor Kidney ◽

Safety And Efficacy ◽

Specific Antibodies ◽

Antibody Mediated Rejection ◽

Deceased Donor Kidney ◽

Donor Specific Antibodies ◽

Donor Kidney Transplantation ◽

Deceased Donor Kidney Transplantation

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Pretransplant Donor-Specific Anti-HLA Antibodies and the Risk for Rejection-Related Graft Failure of Kidney Allografts

Journal of Transplantation ◽

10.1155/2020/5694670 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10

Author(s):

Michiel G. H. Betjes ◽

Kasia S. Sablik ◽

Henny G. Otten ◽

Dave L. Roelen ◽

Frans H. Claas ◽

...

Keyword(s):

T Cell ◽

Graft Survival ◽

Survival Data ◽

Graft Failure ◽

Graft Loss ◽

Specific Antibodies ◽

Antibody Mediated Rejection ◽

Early Graft ◽

Donor Specific Antibodies ◽

One Year

Background. The presence of donor-specific antibodies (DSAs) against HLA before kidney transplantation has been variably associated with decreased long-term graft survival. Data on the relation of pretransplant DSA with rejection and cause of graft failure in recipients of donor kidneys are scarce. Methods. Patients transplanted between 1995 and 2005 were included and followed until 2016. Donor-specific antibodies before transplantation were determined retrospectively. For cause, renal transplant biopsies were reviewed. Results. Pretransplant DSAs were found in 160 cases on a total of 734 transplantations (21.8%). In 80.5% of graft failures, a diagnostic renal biopsy was performed. The presence of pretransplant DSA (DSApos) increased the risk of graft failure within the first 3 months after transplantation (5.2% vs. 9.4%) because of rejection with intragraft thrombosis (p<0.01). One year after transplantation, DSApos recipients had an increased hazard for antibody-mediated rejection at 10 years (9% DSAneg vs. 15% DSApos, p=0.01) with significant decreased graft survival at 10 years (79% DSAneg vs. 69% DSApos, p=0.02). This could largely contribute to an increased graft loss because of antibody-mediated rejection in the DSApos group. The incidence and graft loss because of T cell-mediated rejection was not affected by the presence of pretransplant DSA. Conclusions. Pretransplant DSAs are a risk factor for early graft loss and increase the incidence for humoral rejection and graft loss but do not affect the risk for T cell-mediated rejection.

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ABO-incompatibility and donor-specific antibodies existence effect on antibody-mediated rejection in kidney transplantation

Korean Journal of Transplantation ◽

10.4285/atw2021.op-1066 ◽

2021 ◽

Vol 35 (1) ◽

pp. S81-S81

Author(s):

Kwang Woo Choi ◽

Sangil Min ◽

Eun-Ah Jo ◽

Ahram Han ◽

Sanghyun Ahn ◽

...

Keyword(s):

Kidney Transplantation ◽

Specific Antibodies ◽

Antibody Mediated Rejection ◽

Abo Incompatibility ◽

Donor Specific Antibodies

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P1785KIDNEY TRANSPLANTATION ACROSS VERY HIGH DONOR SPECIFIC ANTIBODIES(DSA) - A SINGLE CENTER EXPERIENCE OF A TERTIARY LEVEL HOSPITAL FROM INDIA

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p1785 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Jayanta Kumar Hota

Keyword(s):

Kidney Transplantation ◽

Serum Creatinine ◽

Graft Function ◽

Hla Antigens ◽

Class Ii ◽

Class I ◽

Specific Antibodies ◽

Donor Specific Antibodies ◽

Very High ◽

High Donor

Abstract Background and Aims Kidney Transplantation across very high donor specific antibodies (DSA) poses a significant challenge even today . With our current understanding and precise desensitization techniques, we are now able to do kidney transplantation across such high DSA . Here we are reporting ten such cases where baseline DSA were more than 10,000 mean fluroscent intensity (MFI) on Single Antigen Bead (SBA) Luminex. Method: It is a retrospective analiysis of ten kidney transplant patients from January 2017 to March 2019 . Patients with MFI more than 10,000 to class II HLA antigens at baseline with negative CDC and flow cytometry cross match were included in this study. All patients were treated with 1 dose of Rituximab (375mg/M? before plasma exchanges (PLEX) were started . Each session of PLEX was followed by 10 grams of intravenous human immunoglobulin (IVIg). Solid based SBA Luminex for both class I and II antigens was repeated after the third exchange and fifth exchange and seventh exchange depending on the level of MFI . Results Ten patients ( seven males three females ) of age 37± 7 years were included in this study . History of blood transfusion with 5±2 units was present in 7 patients . All females were multiparous ( 3±1children). Mean solid based SBA Luminex for class I HLA antigens was 12000 ± 1500 and for II HLA antigens with MFI 16500 ± 3500 (Chart 1). Mean number of PLEX needed was 5 ± 2 . All patients had solid based SBA MFI was 1500±300 and for class II antigens 2500 ± 1500 before transplantation(Chart 2).There was no incidence of acute antibody mediated rejection . Baseline serum creatinine at discharge was1.35±0.35mg%. There were 3 (30%) biopsy proven cases of acute cellular rejection . There was evidence of BK viremia in 3(30%) patients, CMV infection in 1 (10%) patient, Klebsiella pneumonia in 1(10%) patient and cryptosporium infection in 1 (10%) patient each . There was no mortality and mean serum creatinine at 6 months follow-up was 1.55±1.05mg%. All 3 patients of BK Viremia were treated with modification of immunosupression with substitution of leflunamide for mycophenolate and all are doing well with good graft function with a mean serum creatinine of 1.75±0.55mg% . Other infections were treated accordingly. Conclusion: Transplantation across very high donor specific antibodies is possible with excellent immediate and short term graft function with judicious de-sensitization techniques . There was increase in infection rate but none was life threatening and can be managed with proper care.

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Clinical Case: Patient with Mixed Graft Rejection Four Days after Kidney Transplantation Developed Specific Antibodies against Donor Bw4 Specificities

Antibodies ◽

10.3390/antib10030028 ◽

2021 ◽

Vol 10 (3) ◽

pp. 28

Author(s):

Claudia M. Muñoz-Herrera ◽

Juan Francisco Gutiérrez-Bautista ◽

Miguel Ángel López-Nevot

Keyword(s):

Kidney Transplantation ◽

Graft Rejection ◽

Human Leukocyte ◽

Case Patient ◽

Specific Antibodies ◽

Antibody Mediated Rejection ◽

Leukocyte Antigens ◽

Hla Genotypes ◽

Donor Specific Antibodies ◽

Hla Genotype

Kidney transplantation, like other transplants, has the risk of producing graft rejection due to genetic differences between donor and recipient. The three known types of renal rejection are listed in the Banff classification: T-cell-mediated rejection (TCMR), antibody-mediated rejection (ABMR), and mixed rejection. The human leukocyte antigens (HLA) are highly polymorphic and may be the targets of donor-specific antibodies, resulting in ABMR. Therefore, prior to transplantation, it is necessary to analyze the HLA genotype of the donor and recipient, as well as the presence of DSA, in order to avoid hyperacute rejection. However, due to the shortage of kidneys, it is very difficult to find a donor and a recipient with completely matched HLA genotypes. This can trigger a future rejection of the kidney, as is reported in this work. We describe a patient who received a kidney transplant after a negative DSA test, who developed graft rejection with antibodies against the donor’s HLA-Bw4 public epitope and lymphocytic infiltrate four days after transplantation, whose differential diagnosis was mixed rejection.

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