DNA Methylation Dysfunction in Chronic Kidney Disease

Abstract

Renal disease is the common denominator of a number of underlying disease conditions, whose prevalence has been dramatically increasing over the last two decades. Two aspects are particularly relevant to the subject of this review: (I) most cases are gathered under the umbrella of chronic kidney disease since they require—predictably for several lustrums—continuous clinical monitoring and treatment to slow down disease progression and prevent complications; (II) cardiovascular disease is a terrible burden in this population of patients, in that it claims many lives yearly, while only a scant minority reach the renal disease end stage. Why indeed a review on DNA methylation and renal disease? As we hope to convince you, the present evidence supports the role of the existence of various derangements of the epigenetic control of gene expression in renal disease, which hold the potential to improve our ability, in the future, to more effectively act toward disease progression, predict outcomes and offer novel therapeutic approaches.

Blood pressure and the kidney cortex transcriptome response to high sodium diet challenge in female nonhuman primates

“…Network analysis of the highest BP animals versus the lowest BP animals on the HS diet showed activation of processes related to inflammation and fibrosis, and decreased ion homeostasis, vascular remodeling, vascular flexibility, hypoxic response, sex hormones, and lipid metabolism. For example, the network included EZH2, a pro-fibrotic and anti-angiogenic gene 37 and included estrogens, androgens, and their receptors, which have been shown to play a roles in renal ion homeostasis affecting the RAAS 38,39 . Furthermore, network genes TP53, MYC, ID2, RB1, GATA2, EP300, MITF, CTNNB1, and SNAI1 play roles in proliferation, remodeling, and fibrosis, potentially leading to less vascular flexibility 40 .…”

Are Alterations in DNA Methylation Related to CKD Development?

“…Heritability has been estimated to account for 20-80% of interindividual differences in CKD [15]. A relatively high prevalence of CKD (approximately 10% of the general population) is associated with increased incidence of other diseases, such as hypertension, diabetes, glomerulonephritis and chronic pyelonephritis, lupus, and other autoimmune diseases, as well as repeated urinary infections in which progression is associated with the development of renal impairment or failure [1,16,17]. Diabetes mellitus and hypertension are considered to be the main causes of CKD (accounting for 60% of the cases) [18].…”

“…The rate of premature deaths among patients with CKD is high as a result of complications (e.g., cardiovascular disease, anemia). The incidence of complications in this group of patients correlates with changed DNA methylation patterns and subsequent dysregulated expression of genes subjected to such regulation [1]. Therefore, the analysis of epigenetic modifications is needed to uncover the mechanisms underlying the worsening of eGFR and the onset of CKD.…”

“…However, the occurrence of acute renal failure (as a result of toxic drug-induced tubular necrosis, ureter obstruction, contrast use or the thrombosis of the renal artery) could also evolve towards CKD. This disease is associated with inflammatory, metabolic, and cardiovascular diseases [1]. The advancement in research methods enabled the shift from single-gene studies toward genome-wide linkage studies [2].…”

Roles and Mechanisms of DNA Methylation in Vascular Aging and Related Diseases

“…Chronic kidney disease (CKD) refers to abnormalities in chronic kidney structure or function caused by various reasons for more than 3 months ( Ingrosso and Perna, 2020 ). CKD is characterized by the development of renal fibrosis subsequent renal failure.…”