Abstract
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a heritable renal disease that results in end-stage kidney disease, due to the uncontrolled bilateral growth of cysts throughout the kidneys. While it is known that a mutation within a PKD-causing gene is required for the development of ADPKD, the underlying mechanism(s) causing cystogenesis and progression of the disease are not well understood. Limited therapeutic options are currently available to slow the rate of cystic growth. Epigenetic modifications, including DNA methylation, are known to be altered in neoplasia, and several FDA-approved therapeutics target these disease-specific changes. As there are many similarities between ADPKD and neoplasia, we (and others) have postulated that ADPKD kidneys contain alterations to their epigenetic landscape that could be exploited for future therapeutic discovery. Here we summarise the current understanding of epigenetic changes that are associated with ADPKD, with a particular focus on the burgeoning field of ADPKD-specific alterations in DNA methylation.
Highlights
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common heritable renal disease in humans
It was theorised by Woo et al [75] that if the hypermethylation of the ADPKD genome was resulting in cystogenesis, pharmaceuticals, such as the DNA methyltransferase (DNMT) inhibitor decitabine, could be used for the treatment and management of ADPKD patients
Genes associated with DMFs in ADPKD patients identified by Representation Bisulfite Sequencing (RRBS) [77] were compared with the top genes identified in the epigenomic analysis of Chronic Kidney Disease (CKD) by Chu et al [85]
Summary
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common heritable renal disease in humans. The prevalence of intracranial aneurysms is higher in ADPKD patients than in the general population [9,10] Many of these extra-renal symptoms are caused by connective tissue defects [11]. Progression of ADPKD will inhibit renal function to the point of end-stage kidney disease (ESKD). One of the recently available therapeutic options is the vasopressin V2-receptor antagonist tolvaptan, which slows fluid accumulation in renal cysts. This drug has been approved for the treatment of ADPKD in several countries, as it attenuates the rate of cyst growth by half, delaying the onset of ESKD. There is a clear need for better treatments for the approximately 2.4 million people worldwide who are affected by ADPKD
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