Autosomal dominant (AD) and autosomal recessive (AR)
polycystic kidney diseases (PKD) are severe multisystem
genetic disorders characterized with formation and uncontrolled growth of fluid-filled
cysts in the kidney, the spread of which eventually leads to the loss of renal function. Currently, there are no treatments for
ARPKD, and
tolvaptan is the only FDA-approved
drug that alleviates the symptoms of
ADPKD. However,
tolvaptan has only a modest effect on
disease progression, and its long-term use is associated with many side effects. Therefore, there is still a pressing need to better understand the fundamental mechanisms behind PKD development. This review highlights current knowledge about the fundamental aspects of PKD development (with a focus on
ADPKD) including the PC1/PC2 pathways and cilia-associated mechanisms, major molecular cascades related to metabolism, mitochondrial bioenergetics, and systemic responses (hormonal status, levels of
growth factors, immune system, and microbiome) that affect its progression. In addition, we discuss new information regarding non-pharmacological
therapies, such as
dietary restrictions, which can potentially alleviate PKD.