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Epigenetic Mechanisms and Kidney Diseases

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In recent years, molecular research has brought to light a series of mechanisms involved in the regulation of gene function without altering the DNA sequence. These mechanisms are described with the term “epigenetics” and include modifications in the structure of the human genome, leading to heritable and potentially reversible changes in gene expression. There is now increasing evidence suggesting that several characteristic features of chronic kidney disease such as hyperhomocysteinemia, subclinical inflammation, increased oxidative stress and others may affect the human epigenome. In addition, animal studies have suggested a possible link between nutrition and environmental exposure during the periconceptional period and epigenetic changes in the expression of major genes implicated in kidney organogenesis; these changes result in a diminished number of nephrons in the developing kidney, which predisposes to an increased risk for hypertension and chronic kidney disease in future life. The understanding of the role of epigenetic phenomena in the pathogenesis of chronic kidney disease opens new avenues for future therapeutic strategies, through the development of pharmaceutical agents that target directly with the changes in the human epigenome. Such epigenetic drugs are already in clinical use for the treatment of cancer as well as under investigation for the use in other diseases. This review will summarize the existing data on the link between epigenetic mechanisms and chronic uremic milieu, as well as the promising results of ongoing research in the field of epigenetic drugs that could represent additional options in our therapeutic armamentarium for patients with chronic kidney disease.





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Keywords: Chronic kidney disease; diabetic nephropathy; environmental exposure; epigenetics; genome; hyperhomocysteinemia; kidney organogenesis; subclinical; transplantation

Document Type: Research Article

Publication date: 2011-04-01

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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