Current epigenetic aspects the clinical kidney researcher should embrace

Abstract

Chronic kidney disease (CKD), affecting 10-12% of the world's adult population, is associated with a considerably elevated risk of serious comorbidities, in particular, premature vascular disease and death. Although a wide spectrum of causative factors has been identified and/or suggested, there is still a large gap of knowledge regarding the underlying mechanisms and the complexity of the CKD phenotype. Epigenetic factors, which calibrate the genetic code, are emerging as important players in the CKD-associated pathophysiology. In this article, we review some of the current knowledge on epigenetic modifications and aspects on their role in the perturbed uraemic milieu, as well as the prospect of applying epigenotype-based diagnostics and preventive and therapeutic tools of clinical relevance to CKD patients. The practical realization of such a paradigm will require that researchers apply a holistic approach, including the full spectrum of the epigenetic landscape as well as the variability between and within tissues in the uraemic milieu.

Methyl Donor Nutrients in Chronic Kidney Disease: Impact on the Epigenetic Landscape

“…Such epigenetic changes regulate and coordinate access for transcriptional machinery to adjust gene expression, thus enabling changes in phenotype without changes in genotype. Additionally, at a non-canonical level, reciprocal regulatory networks of non-coding RNAs integrate canonical features within the greater epigenetic landscape (4,6).…”

“…As changes to the methylome are, context dependent, typically in response to dynamic environmental cues, it is worth discussing the impact of nutrition and how this may lead to observed differences in distinct clinical cohorts (3,4,5). A range of nutritional factors feeding into one carbon metabolism will be discussed and evaluated for their capacity to influence changes in the epigenetic landscape.…”

“…A particular element of the microbiomes function, which is crucial to its host is its ability to provide a means of metabolising otherwise inaccessible nutrients needed for example, for the production of short chain fatty acids during energy metabolism (78,88). The microbiome also produce metabolites, which are necessary for amino acid production essential to the host, and in turn is associated with maintaining our epigenetic landscape (3,4).…”

“…Interindividual variation in disease progression and response to therapy remains substantial and the underlying factors contributing to this variation remain largely unknown. One potential source of this variation resides in epigenetic differences and in particular, the epigenetic landscape of ageing (3,4), as CKD manifests as a disease of accelerated ageing (5). The epigenetic landscape of ageing refers to the interplay, over the life course, between the environment and canonical features of the genomic methylome and chromatin structure, along with non-canonical features, such as the co-ordinated regulation of a broad range of cellular biochemistry by non-coding RNAs (3,4,5).…”

MicroRNA as novel biomarkers and therapeutic targets in diabetic kidney disease: An update

“…Many drugs targeting the pathogenic signaling such as inflammation and TGF‐β1 for treatment of DKD (mostly through protein‐coding genes) are under development . However, because of the limited number of protein‐coding genes, noncoding RNAs including miRNAs are attracting more attention as potential new drug targets . Distinct features of miRNAs including short sequence and their high homology across multiple vertebrate species make them potentially suitable as therapeutic agents .…”