TY - JOUR
T1 - Insights Into the Molecular Mechanisms of Polycystic Kidney Diseases
AU - Vasileva, Valeriia Y.
AU - Sultanova, Regina F.
AU - Sudarikova, Anastasia V.
AU - Ilatovskaya, Daria V.
N1 - Funding Information:
This work was supported by the NIDDK R00DK105160, NHLBI R01HL148114, and the PKD Foundation award 221G18a (all to DI).
Publisher Copyright:
© Copyright © 2021 Vasileva, Sultanova, Sudarikova and Ilatovskaya.
PY - 2021/9/8
Y1 - 2021/9/8
N2 - 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.
AB - 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.
KW - calcium
KW - cilia
KW - microbiome
KW - mitochondria
KW - polycystic kidney disease
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U2 - 10.3389/fphys.2021.693130
DO - 10.3389/fphys.2021.693130
M3 - Review article
AN - SCOPUS:85115350075
SN - 1664-042X
VL - 12
JO - Frontiers in Physiology
JF - Frontiers in Physiology
M1 - 693130
ER -