Accommodation in renal transplantation: unanswered questions

Lynch, Raymond; Platt, Jeffrey L.

doi:10.1097/mot.0b013e32833b9c25

Cited by 48 publications

(44 citation statements)

References 40 publications

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“…One possibility is an interaction between BK virus and the immune system, which occurs at many different levels (21) and may be altered in the milieu of blood group incompatibility. The occurrence of a graft accommodation phenotype, an acquired resistance of an organ to immune-mediated damage, is more frequently observed in ABO-incompatible kidney recipients than in HLAincompatible recipients (22)(23)(24)(25). The results of this study suggest that ABO-incompatible kidney recipients who do not develop the accommodation phenotype are more likely to develop BKVAN than are HLA-incompatible and ABOcompatible patients.…”

Section: Discussionmentioning

confidence: 44%

Incidence and Outcomes of BK Virus Allograft Nephropathy among ABO- and HLA-Incompatible Kidney Transplant Recipients

Sharif

Alachkar²,

Bagnasco³

et al. 2012

Clinical Journal of the American Society of Nephrology

107

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SummaryBackground and objectives ABO-incompatible kidney transplant recipients may have a higher incidence of BK virus allograft nephropathy (BKVAN) compared with ABO-compatible recipients. It is unclear whether HLAincompatible recipients share this risk or whether this phenomenon is unique to ABO-incompatible recipients.Design, setting, participation, & measurements This study analyzed adult incompatible kidney transplant recipients from 1998 to 2010 (62 ABO-incompatible and 221 HLA-incompatible) and identified patients in whom BKVAN was diagnosed by biopsy (per protocol or for cause). This was a retrospective analysis of a prospectively maintained database that compared BKVAN incidence and outcomes between ABO-and HLA-incompatible recipients, respectively. BKVAN link to rejection and graft accommodation phenotype were also explored. The Johns Hopkins Institutional Review Board approved this study.Results Risk for BKVAN was greater among ABO-incompatible than HLA-incompatible patients (17.7% versus 5.9%; P=0.008). Of BKVAN cases, 42% were subclinical, diagnosed by protocol biopsy. ABO-incompatibility and age were independent predictors for BKVAN on logistic regression. C4d deposition without histologic features of glomerulitis and capillaritis (graft accommodation-like phenotype) on 1-year biopsies of ABO-incompatible patients with and without BKVAN was 40% and 75.8%, respectively (P=0.04). Death-censored graft survival (91%) and serum creatinine level among surviving kidneys (1.8 mg/dl) were identical in ABO-and HLAincompatible patients with BKVAN (median, 1399 and 1017 days after transplantation, respectively).Conclusions ABO-incompatible kidney recipients are at greater risk for BKVAN than HLA-incompatible kidney recipients. ABO-incompatible recipients not showing the typical graft accommodation-like phenotype may be at heightened risk for BKVAN, but this observation requires replication among other groups.

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Section: Discussionmentioning

confidence: 44%

Incidence and Outcomes of BK Virus Allograft Nephropathy among ABO- and HLA-Incompatible Kidney Transplant Recipients

Sharif

Alachkar²,

Bagnasco³

et al. 2012

Clinical Journal of the American Society of Nephrology

107

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“…The term 'accommodation' is mainly used for ABO-incompatible kidney transplants where the recipients continue to have stable kidney function without allograft injury despite circulating antibodies to ABO antigens after receiving desensitization treatment. 5 Clinical evidence has not documented accommodation in HLAincompatible transplantation, and it is suggested that the term 'protected' should be used instead of 'accommodated' if there is no allograft injury despite circulating DSA. The graft resistance to antibody-mediated damage may be due to upregulation of cytoprotective genes or complement regulatory proteins.…”

mentioning

confidence: 99%

Increased intragraft rejection–associated gene transcripts in patients with donor-specific antibodies and normal biopsies

Hayde

Broin

Bao

et al. 2014

Kidney International

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We investigated why some donor-specific antibody-positive patients do not develop antibody-mediated rejection. Of 71 donor-specific antibody-positive patients, 46 had diagnosis of antibody-mediated rejection and 25 had normal biopsies. Fifty donor-specific antibody-negative patients with normal biopsies were used as a control group. A subgroup of 61 patients with available biopsy and 64 with blood samples were analyzed by microarrays. Both donor-specific antibody-positive/antibody-mediated rejection-positive and negative biopsies showed increased expression of gene transcripts associated with cytotoxic T cells, natural killer cells, macrophages, interferon-gamma, and rejection compared to donor-specific antibody-negative biopsies. Regulatory T-cell transcripts were upregulated in donor-specific antibody-positive/antibody-mediated rejection-positive and B-cell transcripts in donor-specific antibody-positive/antibody-mediated rejection-negative biopsies. Whole-blood gene expression analysis showed increased immune activity in only donor-specific antibody-positive/antibody-mediated rejection-positive but not negative patients. During a median follow-up of 36 months, 4 donor-specific antibody-positive/antibody-mediated rejection-negative patients developed antibody-mediated rejection, 12 continued to have donor-specific antibody, but 9 lost their donor-specific antibody. Gene expression profiles did not predict the development of antibody-mediated rejection or the persistence of donor-specific antibody. Thus, donor-specific antibody-positive/antibody-mediated rejection-negative patients had increased rejection-associated gene transcripts in their allografts despite no histologic findings of rejection but not in their blood. This was found in both biopsy and blood samples of donor-specific antibody-positive/antibody-mediated rejection-positive patients.

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“…Complement regulation was thought to be essential for the survival of transplants over time and thus for accommodation to be manifested. C4d deposition without signs or symptoms of rejection can be observed in accommodated kidney (Lynch & Platt, 2010). The occurrence of complement activation means that antibody binding is intact in accommodated kidneys, and the lack of lysis means that some regulatory pathways are working for graft survival in the accommodation.…”

Section: Accommodationmentioning

confidence: 96%