Longitudinal genome-wide DNA methylation changes in response to kidney failure replacement therapy

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Anna Witasp1, Karin Luttropp2,3, Abdul Rashid Qureshi1

  • 1Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital, M99, 141 86, Stockholm, Sweden.

Scientific Reports
|January 11, 2022
PubMed

Insights

Chronic kidney disease (CKD) alters DNA methylation. Kidney replacement therapies like dialysis or transplantation partially reverse these epigenome changes over 12 months.

Area of Science:

  • Epigenetics and Genomics
  • Nephrology and Public Health

Background:

  • Chronic kidney disease (CKD) is a growing public health concern with high mortality.
  • The uremic environment in CKD disrupts essential cellular processes, including DNA methylation.
  • Understanding epigenome modifications in CKD is crucial for developing effective treatments.

Purpose of the Study:

  • To investigate the impact of dialysis and kidney transplantation on epigenome-wide DNA methylation signatures in CKD patients.
  • To analyze changes in DNA methylation patterns over a 12-month treatment period.

Main Methods:

  • Utilized the Infinium HumanMethylation450 BeadChip assay on whole blood samples.
  • Compared DNA methylation profiles of CKD patients (dialysis or transplantation) with age- and sex-matched controls.
  • Analyzed methylation patterns at baseline and after 12 months of treatment.

Main Results:

  • Significant differences in CpG methylation were observed at baseline between CKD patients and controls, particularly in genes related to inflammation, aging, and vascular calcification.
  • After 12 months, the global DNA methylation patterns in treated patients showed a trend towards normalization, resembling those of the control group.
  • A subset of 413 CpG sites remained differentially methylated in both treatment groups compared to controls at follow-up.

Conclusions:

  • The uremic milieu significantly drives genome-wide DNA methylation changes in CKD.
  • Kidney failure replacement therapies partially reverse these epigenome-wide alterations.
  • Persistently differentially methylated CpG sites may represent key targets for understanding kidney disease pathogenesis.

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