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Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a highly prevalent hereditary renal disorder in which fluid-filled cysts are appeared in both kidneys. Main causative genes of ADPKD are PKD1 and PKD2, encoding for polycystin-1 (PC1) and polycystin-2 (PC2) respectively. Those proteins are localized on primary cilia and function as mechanosensor in response to the fluid flow, translating mechanistic stimuli into calcium signaling. With mutations either of PKD1 or PKD2, hyper-activated renal tubular epithelial cell proliferation is observed, followed by disrupted calcium homeostasis and aberrant intracellular cyclic AMP (cAMP) accumulation. Increased cell proliferation with fluid secretion leads to the development of thousands of epithelial-lined, fluid-filled cysts in kidneys. It is also accompanied by interstitial inflammation, fibrosis, and finally reaching end-stage renal disease (ESRD). In human ADPKD, the age at which renal failure typically occurs is later in life, however no specific targeted medications are available to cure ADPKD. Recently, potential therapeutic targets or surrogate diagnostic biomarkers for ADPKD are proposed with the advances in the understanding of ADPKD pathogenesis, and some of them were attempted for clinical trials. Herein, we will summarize genetic and epi-genetic molecular mechanisms in ADPKD progression, and overview the currently available biomarkers or potential therapeutic reagents suggested.
Presents key challenges in the study of Autosomal dominant polycystic kidney disease (ADPKD) Covers basic cellular mechanisms and clinical trials in ADPKD research Opens the door for the development of biomarkers and therapeutic targets for ADPKD
Klappentext
This book covers the mechanisms of renal cyst development as well as the aberrant signaling pathways which are involved in Autosomal Dominant Polycystic Kidney Disease (ADPKD). ADPKD is a genetic disease in which cysts appear in the epithelial lining of both kidneys. End stage ADPKD patients experience renal failure and require dialysis or a renal transplantation. There are no specific targeted therapies for ADPKD currently available, making it important to understand the basic cellular mechanisms underlying the onset and progression of ADPKD, in order to identify potential therapeutic targets for the disease.
Several therapeutic approaches that have been attempted to date are reviewed. This work provides a broad overview of ADPKD and highlights the key challenges currently faced by researchers in this field. Furthermore, it provides insight into ADPKD to facilitate the development of novel biomarkers for ADPKD and to direct future research into this challenging pathology.
This book is suitable for clinicians who have encountered patients with ADPKD, for clinicians / researchers working in the field of ADPKD and more generally on the kidney and kidney related disorders and for students of medicine with an interest in internal medicine.
Inhalt
Part I ADPKD Overview.- Chapter 1 Recent Trends in ADPKD Research.- Chapter 2 Genetic Mechanisms of ADPKD.- Part II Cystogenesis Mechanisms.- Chapter 3 Cell Proliferation and Apoptosis in ADPKD.- Chapter 4 Inflammation and Fibrosis in ADPKD.- Chapter 5 Functional Study of the Primary Cilia in ADPKD.- Chapter 6 Epigenetic Regulation in Cystogenesis.- Part III Therapeutic Approaches and Diagnostic Markers for ADPKD.- Chapter 7 Validation of Effective Therapeutic Targets for ADPKD using Animal Models.- Chapter 8 Diagnostic Evaluation as a Biomarker in Patients with ADPKD.- Chapter 9 Clinical Trials and a View toward the Future of ADPKD.
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