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. 2022 Sep;35(7):1831-1840.
doi: 10.1007/s40620-022-01341-w. Epub 2022 Sep 8.

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

Naiane do Nascimento Gonçalves #  1 , Heloisa Cristina Caldas #  1 , Greiciane Maria da Silva Florim  1 , Giovanna Mattiello Sormani  1 , Lidia Maria Rebolho Batista Arantes  2 , Bruna Pereira Sorroche  2 , Maria Alice Sperto Ferreira Baptista  1 , Ida Maria Maximina Fernandes-Charpiot  1 , Carlos Henrique Viese Nascimento-Filho  3 , Rogério Moraes de Castilho  3 , Mario Abbud-Filho  4
Affiliations

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

Naiane do Nascimento Gonçalves et al. J Nephrol. 2022 Sep.

Abstract

Background: Epigenetic mechanisms may affect the ideal and non-ideal kidneys selected for transplantation and their inflammatory gene expression profile differently and may contribute to poor clinical outcomes.

Objective: Study the Global DNA methylation and the expression profiles of the DNA methyltransferases (DNMTs) and nuclear factor kappa B (NF-κB) in preimplantation kidney biopsies from ideal and non-ideal kidneys (expanded criteria donor (ECD) and with KDPI > 85%).

Methods: In a sample consisting of 45 consecutive pre-implantation biopsies, global DNA methylation levels were detected by LINE-1 repeated elements using bisulfite pyrosequencing. DNMT gene expression was assessed by real-time quantitative polymerase chain reaction, and NF-κB protein expression by immunofluorescence.

Results: ECD kidneys displayed increased methylation levels in LINE-1, and DNMT1 and DNMT3B expression was upregulated when comparing ECD to standard criteria donor kidneys. Similarly, kidneys with KDPI > 85% exhibited increased LINE-1 methylation and DNMT1 upregulation when compared to a KDPI ≤ 85%. NF-κB protein expression levels were greatly increased in both types of non-ideal kidneys compared to ideal kidneys. Moreover, hypermethylation of LINE-1 was associated with cold ischemia time > 20 h and ECD kidney classification.

Conclusions: This study shows that global DNA hypermethylation and high expression of NF-κB occurred in both types of non-ideal kidneys and were associated with prolonged cold ischemia time. Global DNA methylation can be a useful tool to assess non-ideal kidneys and hence, could be used to expand the pool of kidneys donors.

Keywords: Donor kidneys; Kidney; Methylation; Transplantation.

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References

    1. Mittal S, Adamusiak A, Horsfield C et al (2017) A re-evaluation of discarded deceased donor kidneys in the UK: are usable organs still being discarded? Transplantation 101(7):1698–1703 - DOI
    1. Wong G, Howell M, Patrick E, Yang J (2017) Taking kidneys for granted? Time to reflect on the choices we make. Transplantation 101(12):2812–2813 - DOI
    1. McKay DB (2011) The role of innate immunity in donor organ procurement. Semin Immunopathol 33(2):169–184 - DOI
    1. Zhao H, Alam A, Soo AP, George AJT, Ma D (2018) Ischemia-reperfusion injury reduces long term renal graft survival: mechanism and beyond. EBioMedicine 28:31–42 - DOI
    1. Mazeti-Felicio CM, Caldas HC, Fernandes-Charpiot IMM, Dezotti CZ, Baptista MASF, Abbud-Filho M (2017) Preimplantation kidney biopsies of extended criteria donors have a heavier inflammatory burden than kidneys from standard criteria donors. Transplant Direct 3(7):e180 - DOI

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