Preimplantation Kidney Biopsies of Extended Criteria Donors Have a Heavier Inflammatory Burden Than Kidneys From Standard Criteria Donors

Mazeti-Felicio, Camila M.; Caldas, Heloisa Cristina; Fernandes-Charpiot, Ida Maria Maximina; Dezotti, Camila Z.; Baptista, Maria Alice Sperto Ferreira; Abbud-Filho, Mário

doi:10.1097/txd.0000000000000671

Cited by 5 publications

(1 citation statement)

References 30 publications

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“…A recent study[42] confirmed that zero-time biopsies in ECDs showed a significant increase in the transcripts of MCP-1 , RANTES , TGF beta and IL 10 , documenting a higher gene expression of inflammatory cytokines in ECDs that could predict the post-transplant outcome.…”

Section: Histological Evaluation Of Donor Kidneysmentioning

confidence: 91%

Histological and clinical evaluation of marginal donor kidneys before transplantation: Which is best?

Salvadori¹,

Tsalouchos²

2019

WJT

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Organ shortage represents one of the major limitations to the development of kidney transplantation. To increase the donor pool and to answer the ever increasing kidney request, physicians are recurring to marginal kidneys as kidneys from older donors, from hypertensive or diabetic donors and from non-heart beating donors. These kidneys are known to have frequently a worse outcome in the recipients. To date major problem is to evaluate such kidneys in order to use or to discard them before transplantation. The use of such kidneys create other relevant question as whether to use them as single or dual transplant and to allocate them fairly according transplant programs. The pre-transplant histological evaluation, the clinical evaluation of the donor or both the criteria joined has been used and according the time each criterion prevailed over the others. Aim of this review has been to examine the advantages and the drawbacks of any criterion and how they have changed with time. To date any criterion has several limitations and several authors have argued for the development of new guidelines in the field of the kidney evaluation for transplantation. Several authors argue that the use of omic technologies should improve the organ evaluation and studies are ongoing to evaluate these technologies either in the donor urine or in the biopsies taken before transplantation.

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Section: Histological Evaluation Of Donor Kidneysmentioning

confidence: 91%

Histological and clinical evaluation of marginal donor kidneys before transplantation: Which is best?

Salvadori¹,

Tsalouchos²

2019

WJT

View full text Add to dashboard Cite

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Distinct global DNA methylation and NF-κB expression profile of preimplantation biopsies from ideal and non-ideal kidneys

et al. 2022

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Activation of HMGB1–TLR4 Pathway and Inflammasome Contribute to Enhanced Inflammatory Response in Extended Criteria and Kidneys With KDPI ≥85%

et al. 2020

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Background. Metrics for evaluating low-quality kidneys have failed to predict outcomes or reduce the kidney refusal and discard rates. Kidneys from extended-criteria donors (ECDs) and kidneys with ≥85% kidney donor profile indexes (KDPIs) might have different sensitivities to the proinflammatory milieu generated by brain death. We aimed to identify gene expression profile differences in innate immunity pathways between low-quality and ideal kidneys. Methods. Preimplantation kidney biopsies from ECD (n = 41) and standard-criteria donor (n = 39) were evaluated for real-time quantitative polymerase chain reaction gene expression using the TaqMan Gene Expression Array Plates system for genes Toll-like receptor-4 (TLR4), high-mobility group box 1, nuclear factor kappa beta, myeloid differentiation primary response 88, interferon (IFN)-γ, interleukin (IL)1-β, tumor necrosis factor alpha, caspase-1 (CASP1), intercellular adhesion molecule 1, IL-10, heme oxygenase 1 hypoxia-inducible factor 1 (HIF-1), monocyte chemotactic protein 1, transforming growth factor beta 1, TIR-domain containing adapter inducing interferon-β (TRIF), TRIF-related adaptor molecule, interferon regulatory factor 3 (IRF-3), receptor-interacting protein 1, IFNβ-1, and nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin protein 3 complex. Gene expression was also evaluated in kidneys with KDPI ≥85. Results. ECD biopsies showed significantly higher expression of IL-10, TLR4, high-mobility group box 1, IFN-γ, TRIF-related adapter molecule, IRF-3, HIF-1, nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin protein 3 complex, CASP1, and IL-1β (P < 0.05) compared with standard-criteria donor biopsies. IRF-3, HIF-1, and CASP1 were exclusively upregulated in ECD kidneys. Compared with kidneys with KDPIs <85%, kidneys with KDPIs ≥85% had very similar gene transcripts as those observed in ECD kidneys, except that tumor necrosis factor alpha and monocyte chemotactic protein 1 expression was only elevated in kidneys with KDPIs ≥85%. Significant positive correlations were found between the different genes upregulated and the increase in KDPIs. Conclusions. Our results showed that TLR4 and inflammasome pathways are enhanced in low-quality kidneys and suggest that blocking of some targets might improve transplant outcomes and reduce discard rates.

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Preimplantation Kidney Biopsies of Extended Criteria Donors Have a Heavier Inflammatory Burden Than Kidneys From Standard Criteria Donors

Cited by 5 publications

References 30 publications

Histological and clinical evaluation of marginal donor kidneys before transplantation: Which is best?

Histological and clinical evaluation of marginal donor kidneys before transplantation: Which is best?

Distinct global DNA methylation and NF-κB expression profile of preimplantation biopsies from ideal and non-ideal kidneys

Activation of HMGB1–TLR4 Pathway and Inflammasome Contribute to Enhanced Inflammatory Response in Extended Criteria and Kidneys With KDPI ≥85%

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