Reducing De Novo Donor-Specific Antibody Levels during Acute Rejection Diminishes Renal Allograft Loss

Everly, Matthew J; Everly, J; Arend, Lois J.; Brailey, Paul; Süßkind, B.; Govil, Amit; Rike, Adele; Roy‐Chaudhury, Prabir; Mogilishetty, G.; Alloway, Rita R.; Tevar, Amit D.; Woodle, E. Steve

doi:10.1111/j.1600-6143.2009.02577.x

Cited by 194 publications

(147 citation statements)

References 17 publications

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“…We performed predefined stratified analyses to examine for the effect of RMM on outcomes considering certain biologically anticipated risk groups. Given the increasing evidence that class 2 antigen differences 9-11 and class 2 HLA antibodies [18][19][20] specifically affect graft survival, the effect of class 2 RMM versus only class 1 was explored, and we found that the presence of class 2 RMM was associated with graft loss, specifically in sensitized recipients. This information may be of value in further refining the classification of immunologic risk in recipients with RMM, such that unsensitized recipients with class 2 RMM may be considered at lower risk than their sensitized counterparts.…”

Section: Discussionmentioning

confidence: 99%

Re-Examining Risk of Repeated HLA Mismatch in Kidney Transplantation

Tinckam

Rose

Hariharan

et al. 2016

JASN

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Kidney retransplantation is a risk factor for decreased allograft survival. Repeated mismatched HLA antigens between first and second transplant may be a stimulus for immune memory responses and increased risk of alloimmune damage to the second allograft. Historical data identified a role of repeated HLA mismatches in allograft loss. However, evolution of HLA testing methods and a modern transplant era necessitate re-examination of this role to more accurately risk-stratify recipients. We conducted a contemporary registry analysis of data from 13,789 patients who received a second kidney transplant from 1995 to 2011, of which 3868 had one or more repeated mismatches. Multivariable Cox proportional hazards modeling revealed no effect of repeated mismatches on all-cause or death-censored graft loss. Analysis of predefined subgroups, however, showed that any class 2 repeated mismatch increased the hazard of death-censored graft loss, particularly in patients with detectable panel-reactive antibody before second transplant (hazard ratio [HR], 1.15; 95% confidence interval [95% CI], 1.02 to 1.29). Furthermore, in those who had nephrectomy of the first allograft, class 2 repeated mismatches specifically associated with all-cause (HR, 1.30; 95% CI, 1.07 to 1.58) and death-censored graft loss (HR, 1.41; 95% CI, 1.12 to 1.78). These updated data redefine the effect of repeated mismatches in retransplantation and challenge the paradigm that repeated mismatches in isolation confer increased immunologic risk. We also defined clear recipient categories for which repeated mismatches may be of greater concern in a contemporary cohort. Additional studies are needed to determine appropriate interventions for these recipients. 27: 283327: -284127: , 201627: . doi: 10.1681 Kidney retransplantation is generally viewed to increase risk for immunologic damage and graft loss. The increased risk is attributed to the formation of T and B memory cells to mismatched HLA antigens in the original donors. Re-exposure to a repeated HLA antigen mismatched (RMM) in a subsequent donor potentially invokes alloimmune memory responses, resulting in earlier allograft damage and loss. J Am Soc NephrolThe nature and magnitude of this potential risk have changed with reanalysis over time. Whereas a number of studies have described worse allograft survival when repeated antigens are mismatched at the HLA-DR locus, 1-3 with RMM at class 1 (HLA-A or -B) not influencing outcomes, others have shown a beneficial effect of RMM on graft survival 4,5 or a neutral effect. 6,7 A more recent analysis showed an effect of class 1 RMM on graft survival, with no differences seen with class 2 RMM. 8

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Section: Discussionmentioning

confidence: 99%

Re-Examining Risk of Repeated HLA Mismatch in Kidney Transplantation

Tinckam

Rose

Hariharan

et al. 2016

JASN

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“…It has been shown that a fast reduction of DSAs results in better graft survival [60,61]. The most important trial studying the treatment of CAMR in children was carried out by Toenshoff and Billing.…”

Section: Chronic Antibody-mediated Rejection (Camr)mentioning

confidence: 99%

Acute and chronic antibody-mediated rejection in pediatric kidney transplantation

et al. 2014

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Acute antibody-mediated rejection is a diagnostic challenge in renal transplantation medicine. However, it is an important diagnosis to make, since chronic antibody-mediated rejection (CAMR) is the main cause of long-term graft loss. Antibody-mediated rejection is diagnosed by detecting donorspecific antibodies (DSAs) in the blood in combination with observing typical histomorphological signs in kidney biopsy, as described in the Banff classification. Therapy is based on the removal of DSAs by administering intravenous immunoglobulins (IVIGs), plasmapheresis, or immunoadsorption. Reoccurrence of antibodies is diminished by the use of rituximab, increased immunosuppression, and in some cases additional experimental substances. A combination of these techniques has been shown to be successful in the majority of cases of acute and chronic antibody-mediated rejection. Routine DSA monitoring is warranted for early detection of antibody-mediated rejection.

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“…This has led to recent observations that aABMR significantly reduces renal allograft survival compared with T-cell-mediated rejection. 16,17 Over the past decade, the diagnostic precision for aABMR in kidney transplant recipients has improved significantly. The phenotypes of early and late aABMR may differ.…”

Section: Discussionmentioning

confidence: 99%

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Gheith

Al-Otaibi

Halim³

et al. 2017

Exp Clin Transplant

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Objectives: There are no comparable trials concerning the use of rituximab among renal transplant recipients with acute antibody-mediated rejection. Here, we compared early and late acute antibody-mediated rejection in renal transplant recipients in terms of response to rituximab therapy. Materials and Methods: Of 1230 kidney transplants performed at Hamed Al-Essa Organ Transplant Center (Kuwait) over the past 10 years, 103 recipients developed acute antibody-mediated rejections and were subcategorized into 4 groups according to the onset of rejection and rituximab treatment. All patients received the standard treatment for acute antibody-mediated rejection according to our protocol (plasma exchange and intravenous immunoglobulin). We added rituximab to the treatment regimen in 2 groups of patients: 27 patients with early rejection (group 1) and 38 patients with late rejection (group 2). Groups 3 and 4 represented nonrituximab groups, with 20 patients with early (group 3) and 18 patients with late rejection (group 4). We compared the 4 groups regarding graft and patient outcomes. Results: All patients were comparable regarding patient age, sex, pretransplant type of dialysis, viral profile, type of induction, donor criteria, and pretransplant comorbidities. We observed that delayed and slow graft function were significantly higher in groups 1 and 3 (P = .016); however, we found no significant differences in the 4 groups regarding new-onset diabetes after transplant, BK viral infection, and malignancy. Graft outcomes were significantly better in groups 1 and 2 than in groups 3 and 4 (P = .028). However, patient outcomes were comparable in the 4 groups (P > .05). Conclusions: Early acute antibody-mediated rejection in renal transplant recipients had significantly better outcomes when rituximab was added to the standard treatment regimen.

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Reducing De Novo Donor-Specific Antibody Levels during Acute Rejection Diminishes Renal Allograft Loss

Cited by 194 publications

References 17 publications

Re-Examining Risk of Repeated HLA Mismatch in Kidney Transplantation

Re-Examining Risk of Repeated HLA Mismatch in Kidney Transplantation

Acute and chronic antibody-mediated rejection in pediatric kidney transplantation

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