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

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.

Molecular Markers of Kidney Transplantation Outcome: Current Omics Tools and Future Developments

“…Although our study focused only on the four fundamental pillars, other omics technologies exist. These other omics, including epigenomic, fluxomic, inomic, or lipidomic, could bring a novel perspective to the field of transplantation [ 62 , 63 ].…”

Correlation of Different Serum Biomarkers with Prediction of Early Pancreatic Graft Dysfunction Following Simultaneous Pancreas and Kidney Transplantation

“…Furthermore, few current convincing studies identified cell-free DNA (circulating/donor-derived) as well as EVs, specifically kidneyspecific parameters (aquaporin, CD133, clusterin, PODXL, SYT17 as well as multiple mRNA signatures), as promising markers for early graft dysfunction in several clinical KTA settings [54,55]. Notably, in the field of genomic and transcriptomic profiling, the assessment of DNA methylation seems to become a potential new and sensitive clinical biomarker in the detection of early graft dysfunction during KTA and consecutively targeting therapy for the future [58]. However, further research is needed to evaluate the significance of these new approaches for early graft dysfunction in SPKT, with the pancreas-specific lipase and alterations of CRP being by far the most specific IRI and graft dysfunction markers for the pancreas graft yet.…”

Monitoring of Serological, Cellular and Genomic Biomarkers in Transplantation, Computational Prediction Models and Role of Cell-Free DNA in Transplant Outcome

“…CXCL-10. It is a chemokine secreted by renal graft leukocytes that regulate angiogenesis in conditions such as wound healing, ischemia and neoplasia [ 37 ]. It is also a sign of inflammation.…”

“…It is also a sign of inflammation. CXCL-10 (uCXCL-10) in urine appears to be more sensitive and specific than creatinine in serum [ 37 ]. Its levels can aid in the detection of early signs of acute renal failure as well as the diagnosis of noninvasive kidney disease [ 38 ].…”

“…Lastly, epigenetics has also been associated with post-transplant evolution with DNA methylation phenomena regulating processes and pathways involved in its evolution [ 36 , 37 ]. Surely this field will be especially novel for future studies.…”