Impact of persistent and cleared preformed HLA DSA on kidney transplant outcomes

Redondo-Pachón, Dolores; Pérez‐Sáez, María José; Mir, Marisa; Gimeno, Javier; Llinás, Laura; García, Carmen; Hernández, Juan José Guardia; Yélamos, José; Pascual, Julio; Crespo, Marta

doi:10.1016/j.humimm.2018.02.014

Cited by 36 publications

(39 citation statements)

References 32 publications

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“…This confirms the suggestion from previous but much smaller studies that reported on resolution of preDSA after transplantation in 31%-67% of patients. 7,8,22 In addition, we confirmed that higher MFI values of the immunodominant preDSA were an independent determinant of preDSA persistence after transplantation. 7,8 Finally, and for the first time, we illustrated that predominantly DQ preDSA persisted after transplantation, which was not uncovered in prior studies potentially due to the lack of high-resolution or complete HLA typing data of the transplant pairs and preDSA misclassification.…”

Section: Discussionsupporting

confidence: 74%

Specificity, strength, and evolution of pretransplant donor-specific HLA antibodies determine outcome after kidney transplantation

Senev

Lerut

Sandt³

et al. 2019

American Journal of Transplantation

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In this cohort study (N = 924), we investigated the evolution and clinical significance of pretransplant donor-specific HLA antibodies (preDSA), detected in the singleantigen beads assay but complement-dependent cytotoxicity crossmatch-negative.Donor specificity of the preDSA (N = 107) was determined by high-resolution genotyping of donor-recipient pairs. We found that in 52% of the patients with preDSA, preDSA spontaneously resolved within the first 3 months posttransplant. PreDSA that persisted posttransplant had higher pretransplant median fluorescence intensity values and more specificity against DQ. Patients with both resolved and persistent DSA had a high incidence of histological picture of antibody-mediated rejection (ABMR h ; 54% and 59% respectively). Patients with preDSA that persisted posttransplant had worse 10-year graft survival compared to resolved DSA and preDSA-negative patients. Compared to cases without preDSA, Cox modeling revealed an increased risk of graft failure only in the patients with persistent DSA, in the presence (hazard ratio [HR] = 8.3) but also in the absence (HR = 4.3) of ABMR h . In contrast, no increased risk of graft failure was seen in patients with resolved DSA. We conclude that persistence of preDSA posttransplant has a negative impact on graft survival, beyond ABMR h . Even in the absence of antibody-targeting therapy, low median fluorescence intensity DSA and non-DQ preDSA often disappear early posttransplantation and are not deleterious for graft outcome. K E Y W O R D S alloantibody, antibody-mediated (ABMR), clinical research/practice, deceased, donors and donation, health services and outcomes research, histocompatibility, kidney transplantation/ nephrology, major histocompatibility complex (MHC), organ procurement and allocation, rejection, risk assessment/risk stratification 1 | INTRODUC TI ON With the introduction of the complement-dependent lymphocytoxicity crossmatching (CDC-XM), donor-specific antibodies (DSA) have been established as the main determinant of successful | 3101 SENEV Et al.

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Section: Discussionsupporting

confidence: 74%

Specificity, strength, and evolution of pretransplant donor-specific HLA antibodies determine outcome after kidney transplantation

Senev

Lerut

Sandt³

et al. 2019

American Journal of Transplantation

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“…In addition, Marfo et al demonstrated that recipients with persistent pDSAs experienced more acute and chronic rejection (p = 0.006) than recipients with reversed pDSA [18]. The independent risk factor associated with persistence of pDSA was pre-transplant MFI, as shown by Redondo-Pachon et al, and class II DSAs persisted more frequently [19]. Similarly, we found that persistent pDSAs possessed higher MFIs.…”

Section: Persistent Pdsassupporting

confidence: 82%

C3d-Positive Preformed DSAs Tend to Persist and Result in a Higher Risk of AMR after Kidney Transplants

Choi

Lee

Park

et al. 2020

JCM

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C3d-binding assays have been introduced as methods for the prediction of the presence of complement-binding functional antibodies; however, the prognostic value of C3d-positive preformed donor-specific antibodies (pDSAs) has not been fully evaluated. In this study, we performed a retrospective investigation of the association of pDSAs and their C3d-binding capacity with one-year clinical outcomes. pDSAs were defined as donor-specific antibodies (DSAs) that were produced before kidney transplants (KTs) (pre-pDSAs) or within the first four weeks after KTs, owing to rebound immune response (post-pDSAs). Of 455 adult KT recipients, pre-pDSAs and post-pDSAs were found in 56 (12.3%) and 56 (12.3%) recipients, respectively, and C3d-positive post-pDSAs were found in 13 recipients (2.9%) in total. Approximately half of the C3d-negative pre-pDSAs (37/73, 50.7%) disappeared after transplantation; however, all C3d-positive pre-pDSAs (8/8, 100%) persisted after transplantation despite desensitization (p = 0.008). C3d-positive pDSAs were significantly associated with a higher incidence and risk of AMR (p < 0.001, OR 94.467–188.934). Identification of the C3d-binding activity of pDSAs before and early after KT is important for predicting the persistence of pDSAs and the risk of AMR induced by the presence of pDSAs.

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“…The negative impact of preformed donor‐specific antibodies (DSAs) in isolated KT is well known, ( 1‐5 ) and the risk of hyperacute kidney rejection is high in the presence of a positive complement‐dependent cytotoxicity crossmatch (CDCXM). ( 6 ) Also, the presence of pretransplant DSAs has been associated with patient mortality.…”

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confidence: 99%

Kidney Graft Outcomes in High Immunological Risk Simultaneous Liver‐Kidney Transplants

et al. 2020

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Recipients of simultaneous liver‐kidney transplantations (SLKTs) have a lower risk of rejection compared with recipients of kidney transplants alone. However, there is disagreement about the impact of pretransplant anti–human leukocyte antigen sensitization on patient and kidney graft survival in the long term. The aim of the study was to evaluate the impact of the recipient immunological risk and comorbidities in renal graft outcomes on SLKT. We reviewed the SLKTs performed in our center from May 1993 until September 2017. Patient and graft survival were analyzed according to the immunological risk, comorbidities, liver and kidney rejection episodes, immunosuppression, and infections. A total of 20 recipients of SLKT were considered in the high immunological risk (HIR) group, and 68 recipients were included in the low immunological risk (LIR) control group. The prevalence of hepatitis C virus infection, second renal transplant, and time on dialysis prior to transplantation were significantly higher in the HIR group. The incidence of acute kidney rejection was higher in the HIR group (P<0.01). However, death‐censored kidney graft survival as well as the estimated glomerular filtration rate at follow‐up were not different between the 2 groups. Comorbidities, but not the immunological risk, impact negatively on patient survival. Despite the higher incidence of rejection in the HIR SLKT group, longterm renal function and graft survival were similar to the LIR group.

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Impact of persistent and cleared preformed HLA DSA on kidney transplant outcomes

Cited by 36 publications

References 32 publications

Specificity, strength, and evolution of pretransplant donor-specific HLA antibodies determine outcome after kidney transplantation

Specificity, strength, and evolution of pretransplant donor-specific HLA antibodies determine outcome after kidney transplantation

C3d-Positive Preformed DSAs Tend to Persist and Result in a Higher Risk of AMR after Kidney Transplants

Kidney Graft Outcomes in High Immunological Risk Simultaneous Liver‐Kidney Transplants

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