Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Feb 7;14(1):20.
doi: 10.1186/s13148-022-01241-7.

The applications of DNA methylation as a biomarker in kidney transplantation: a systematic review

Iacopo Cristoferi  1   2   3 , Tommaso Antonio Giacon  4   5   6   7 , Karin Boer  8   9 , Myrthe van Baardwijk  10   11   8 , Flavia Neri  4 , Manuela Campisi  5 , Hendrikus J A N Kimenai  10   8 , Marian C Clahsen-van Groningen  11   8   12 , Sofia Pavanello  5 , Lucrezia Furian  4 , Robert C Minnee  10   8
Affiliations

The applications of DNA methylation as a biomarker in kidney transplantation: a systematic review

Iacopo Cristoferi et al. Clin Epigenetics. .

Abstract

Background: Although kidney transplantation improves patient survival and quality of life, long-term results are hampered by both immune- and non-immune-mediated complications. Current biomarkers of post-transplant complications, such as allograft rejection, chronic renal allograft dysfunction, and cutaneous squamous cell carcinoma, have a suboptimal predictive value. DNA methylation is an epigenetic modification that directly affects gene expression and plays an important role in processes such as ischemia/reperfusion injury, fibrosis, and alloreactive immune response. Novel techniques can quickly assess the DNA methylation status of multiple loci in different cell types, allowing a deep and interesting study of cells' activity and function. Therefore, DNA methylation has the potential to become an important biomarker for prediction and monitoring in kidney transplantation.

Purpose of the study: The aim of this study was to evaluate the role of DNA methylation as a potential biomarker of graft survival and complications development in kidney transplantation. MATERIAL AND METHODS: A systematic review of several databases has been conducted. The Newcastle-Ottawa scale and the Jadad scale have been used to assess the risk of bias for observational and randomized studies, respectively.

Results: Twenty articles reporting on DNA methylation as a biomarker for kidney transplantation were included, all using DNA methylation for prediction and monitoring. DNA methylation pattern alterations in cells isolated from different tissues, such as kidney biopsies, urine, and blood, have been associated with ischemia-reperfusion injury and chronic renal allograft dysfunction. These alterations occurred in different and specific loci. DNA methylation status has also proved to be important for immune response modulation, having a crucial role in regulatory T cell definition and activity. Research also focused on a better understanding of the role of this epigenetic modification assessment for regulatory T cells isolation and expansion for future tolerance induction-oriented therapies.

Conclusions: Studies included in this review are heterogeneous in study design, biological samples, and outcome. More coordinated investigations are needed to affirm DNA methylation as a clinically relevant biomarker important for prevention, monitoring, and intervention.

Keywords: Biomarker; DNA methylation; Kidney transplantation; Reperfusion injury; Systematic review.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Flow diagram of the systematic literature search
Fig. 2
Fig. 2
Overview of the summarization strategy. Abbreviations: cSCC, Cutaneous squamous cell carcinoma; DGF, Delayed graft function; DNAm, DNA methylation; KA, Kidney allograft; KTR, Kidney transplant recipient; IRI, Ischemia–reperfusion injury; TSDR, Treg-specific demethylated region
Fig. 3
Fig. 3
Overview of the proposed biomarker discovery pipelines. a Workflow of a proposed DNA methylation analysis pipeline for the discovery of differentially methylated regions associated with eGFR slope for the development of a limited panel that could be the base of a potential clinical tool. b Workflow of a proposed DNA methylation analysis pipeline for the development of a deep-learning-based prediction system. Abbreviations: DMR: Differentially methylated regions; eGFR: Estimated glomerular filtration rate; KT: Kidney transplantation
See this image and copyright information in PMC

References

    1. Wolfe RA, et al. Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. N Engl J Med. 1999;341(23):1725–1730. - PubMed
    1. Mas VR, Le TH, Maluf DG. Epigenetics in kidney transplantation: Current evidence, predictions, and future research directions. Transplantation. 2016;100(1):23–38. - PMC - PubMed
    1. Moreso F, Hernandez D. Has the survival of the graft improved after renal transplantation in the era of modern immunosuppression? Nefrología (English Edition) 2013;33(1):14–26. - PubMed
    1. Dupont PJ, Manuel O, Pascual M. Infection and chronic allograft dysfunction. Kidney Int Suppl. 2010;78(119):S47–S53. - PubMed
    1. Campistol JM, et al. Chronic allograft nephropathy: a clinical syndrome: early detection and the potential role of proliferation signal inhibitors. Clin Transplant. 2009;23(6):769–777. - PubMed

Publication types

MeSH terms