Combination of Peritubular C4d and Transplant Glomerulopathy Predicts Late Renal Allograft Failure

Kieran, Niamh E.; Wang, Xiaotong; Perkins, James D.; Davis, Connie L.; Kendrick, Elizabeth; Bakthavatsalam, Ramasamy; Dunbar, Nancy M.; Warner, Paul; Nelson, Karen; Smith, Kelly D.; Nicosia, Roberto F.; Alpers, Charles E.; Leca, Nicolae; Kowalewska, Jolanta

doi:10.1681/asn.2009020199

Cited by 72 publications

(81 citation statements)

References 42 publications

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“…This is important because CAMR is a major cause of chronic renal allograft loss. [36][37][38] One limitation of this study is that six patients who exhibited an acute cellular component to their rejection on biopsies were initiated on treatment with corticosteroids before blood sampling. Thus, more patients with rejection were on maintenance corticosteroids.…”

Section: Discussionmentioning

confidence: 99%

Immunologic Human Renal Allograft Injury Associates with an Altered IL-10/TNF-α Expression Ratio in Regulatory B Cells

Cherukuri

Rothstein²,

Clark

et al. 2014

Journal of the American Society of Nephrology

136

132

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Human B cells with immunoregulatory properties in vitro (Bregs) have been defined by the expression of IL-10 and are enriched in various B-cell subsets. However, proinflammatory cytokine expression in B-cell subsets is largely unexplored. We examined the cytokine profiles of human PBMCs and found that subsets of CD24 hi CD38 hi transitional B cells (TrBs), CD24 hi CD27 + memory B cells, and naïve B cells express IL-10 and the proinflammatory cytokine TNF-a simultaneously. TrBs had the highest IL-10/TNF-a ratio and suppressed proinflammatory helper T cell 1 (Th1) cytokine expression by autologous T cells in vitro more potently than memory B cells did, despite similar IL-10 expression. Whereas neutralization of IL-10 significantly inhibited TrB-mediated suppression of autologous Th1 cytokine expression, blocking TNF-a increased the suppressive capacity of both memory and naïve B-cell subsets. Thus, the ratio of IL-10/TNF-a expression, a measure of cytokine polarization, may be a better indicator of regulatory function than IL-10 expression alone. Indeed, compared with TrB cells from patients with stable kidney graft function, TrBs from patients with graft rejection displayed similar IL-10 expression levels but increased TNF-a expression (i.e., reduced IL-10/TNF-a ratio), did not inhibit in vitro expression of Th1 cytokines by T cells, and abnormally suppressed expression of Th2 cytokines. In patients with graft dysfunction, a low IL-10/TNF-a ratio in TrBs associated with poor graft outcomes after 3 years of follow-up. In summary, these results indicate that B cell-mediated immune regulation is best characterized by the cytokine polarization profile, a finding that was confirmed in renal transplant patients.

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Section: Discussionmentioning

confidence: 99%

Immunologic Human Renal Allograft Injury Associates with an Altered IL-10/TNF-α Expression Ratio in Regulatory B Cells

Cherukuri

Rothstein²,

Clark

et al. 2014

Journal of the American Society of Nephrology

136

132

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“…Graft survival was only 35% in AMR patients, suggesting the importance of prevention of AMR to reach better long-term outcomes in sensitized patients. After patients develop AMR or TGP, the prognosis is poor (48,49,(53)(54)(55).…”

Section: Current Problems In Desensitization Protocolsmentioning

confidence: 99%

Desensitization Protocols and Their Outcome

Marfo

Ling

et al. 2011

Clinical Journal of the American Society of Nephrology

235

184

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SummaryIn the last decade, transplantation across previously incompatible barriers has increasingly become popular because of organ donor shortage, availability of better methods of detecting and characterizing anti-HLA antibodies, ease of diagnosis, better understanding of antibody-mediated rejection, and the availability of effective regimens. This review summarizes all manuscripts published since the first publication in 2000 on desensitized patients and discusses clinical outcomes including acute and chronic antibody-mediated rejection rate, the new agents available, kidney paired exchange programs, and the future directions in sensitized patients. There were 21 studies published between 2000 and 2010, involving 725 patients with donor-specific anti-HLA antibodies (DSAs) who underwent kidney transplantation with different desensitization protocols. All studies were single center and retrospective. The patient and graft survival were 95% and 86%, respectively, at a 2-year median follow-up. Despite acceptable short-term patient and graft survivals, acute rejection rate was 36% and acute antibody-mediated rejection rate was 28%, which is significantly higher than in nonsensitized patients. Recent studies with longer follow-up of those patients raised concerns about long-term success of desensitization protocols. The studies utilizing protocol biopsies in desensitized patients also reported higher subclinical and chronic antibody-mediated rejection. An association between the strength of DSAs determined by median fluorescence intensity values of Luminex single-antigen beads and risk of rejection was observed. Two new agents, bortezomib, a proteasome inhibitor, and eculizumab, an anti-complement C5 antibody, were recently introduced to desensitization protocols. An alternative intervention is kidney paired exchange, which should be considered first for sensitized patients.

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“…Kieran, et al 19 concluyen en su estudio que el C4d por sí solo no predice la pérdida del injerto, pero sí cuando se encuentra junto con GT, siendo entonces un fuerte predictor de pérdida del injerto, con un riesgo relativo de 9.3. La combinación más poderosa para predecir la pérdida de injerto es GT, C4d positivo y CrS >2.3 mg/dl.…”

Section: Discussionunclassified