Dataset Information

Kidney Transplant With Low Levels of DSA or Low Positive B-Flow Crossmatch: An Underappreciated Option for Highly Sensitized Transplant Candidates.

ABSTRACT:

Background

Avoiding donor-specific antibody (DSA) is difficult for sensitized patients. Improved understanding of the risk of low level DSA is needed.

Methods

We retrospectively compared the outcomes of 954 patients transplanted with varied levels of baseline DSA detected by single antigen beads and B flow cytometric crossmatch (XM). Patients were grouped as follows: -DSA/-XM, +DSA/-XM, +DSA/low +XM, +DSA/high +XM, and -DSA/+XM and followed up for a mean of 4.1 ± 1.9 years (similar among groups, P = 0.49).

Results

Death-censored allograft survival was similar in all groups except the +DSA/high +XM group, which was lower at 79.1% versus 96.2% in the -DSA/-XM group (P < 0.01). The incidence of chronic antibody-mediated rejection (CAMR) based on surveillance biopsy was higher with increasing DSA (8.2% -DSA/-XM, 17.0% +DSA/-XM, 30.6% +DSA/low +XM, and 51.2% +DSA/high +XM, P < 0.01), but similar in groups without baseline DSA (8.1% -DSA/-XM vs 15.4% -DSA/+XM, P = 0.19). Having a calculated panel-reactive antibody (cPRA) of 80% or greater was independently associated with CAMR (hazard ratio, 5.2; P = 0.03) even when DSA was undetected at baseline. By 2 years posttransplant, the incidence of CAMR was 19.4% in patients with cPRA of 80% or greater and undetected DSA and negative XM at baseline.

Conclusions

Kidney transplantation with low-level DSA with or without a low positive XM is a reasonable option for highly sensitized patients and may be advantageous compared with waiting for a negative XM deceased donor. The risk for CAMR is low in patients with no DSA even if the XM is positive. Patients with cPRA of 80% or greater are at risk for CAMR even if no DSA is detected.

SUBMITTER: Schinstock CA

PROVIDER: S-EPMC5481511 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Publications

Kidney Transplant With Low Levels of DSA or Low Positive B-Flow Crossmatch: An Underappreciated Option for Highly Sensitized Transplant Candidates.

Schinstock Carrie A CA Gandhi Manish M Cheungpasitporn Wisit W Mitema Donald D Prieto Mikel M Dean Patrick P Cornell Lynn L Cosio Fernando F Stegall Mark M

Transplantation 20171001 10

<h4>Background</h4>Avoiding donor-specific antibody (DSA) is difficult for sensitized patients. Improved understanding of the risk of low level DSA is needed.<h4>Methods</h4>We retrospectively compared the outcomes of 954 patients transplanted with varied levels of baseline DSA detected by single antigen beads and B flow cytometric crossmatch (XM). Patients were grouped as follows: -DSA/-XM, +DSA/-XM, +DSA/low +XM, +DSA/high +XM, and -DSA/+XM and followed up for a mean of 4.1 ± 1.9 years (simila ...[more]

PMID: 28009780

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Project description:BackgroundPatients with broad HLA sensitization have poor access to donor organs, high mortality while waiting for kidney transplant, and inferior graft survival. Although desensitization strategies permit transplantation via lowering of donor-specific antibodies, the B cell-response axis from germinal center activation to plasma cell differentiation remains intact.MethodsTo investigate targeting the germinal center response and plasma cells as a desensitization strategy, we sensitized maximally MHC-mismatched rhesus pairs with two sequential skin transplants. We administered a proteasome inhibitor (carfilzomib) and costimulation blockade agent (belatacept) to six animals weekly for 1 month; four controls received no treatment. We analyzed blood, lymph node, bone marrow cells, and serum before desensitization, after desensitization, and after kidney transplantation.ResultsThe group receiving carfilzomib and belatacept exhibited significantly reduced levels of donor-specific antibodies (P=0.05) and bone marrow plasma cells (P=0.02) compared with controls, with a trend toward reduced lymph node T follicular helper cells (P=0.06). Compared with controls, carfilzomib- and belatacept-treated animals had significantly prolonged graft survival (P=0.02), and renal biopsy at 1 month showed significantly reduced antibody-mediated rejection scores (P=0.02). However, four of five animals with long-term graft survival showed gradual rebound of donor-specific antibodies and antibody-mediated rejection.ConclusionsDesensitization using proteasome inhibition and costimulation blockade reduces bone marrow plasma cells, disorganizes germinal center responses, reduces donor-specific antibody levels, and prolongs allograft survival in highly sensitized nonhuman primates. Most animals experienced antibody-mediated rejection with humoral-response rebound, suggesting desensitization must be maintained after transplantation using ongoing suppression of the B cell response.

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Dataset Information

Kidney Transplant With Low Levels of DSA or Low Positive B-Flow Crossmatch: An Underappreciated Option for Highly Sensitized Transplant Candidates.

Background

Methods

Results

Conclusions

Publications

Kidney Transplant With Low Levels of DSA or Low Positive B-Flow Crossmatch: An Underappreciated Option for Highly Sensitized Transplant Candidates.

Similar Datasets

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