Present Status and Advances in Autosomal Dominant Polycystic Kidney Disease

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic disorder of the kidney. The mainly clinical manifestation is progressive cyst formation in bilateral kidneys, impairs normal renal parenchyma, and ultimately results in end-stage renal disease (ESRD). Extra-renal lesions include cystic liver or pancreas, brain aneurysm and cardiovascular defects. Mutations in either PKD1 or PKD2 genes result in the disease, but the former develops more severe clinical phenotypes than the latter. Currently, ADPKD still challenge vast clinicians on account of lacking effective and less side-effect therapy. Intensive study of molecular mechanism of the disease can establish theoretical basis for potential therapeutic targets and guide clinicians to develop new approaches in treatment of this disease. This review will focus on current advances of ADPKD pathogenesis which may benefit the translational therapy and precision medicine for the disease treatment. liver failure [25,26]. The prevalence of intracranial aneurysms (ICA) among ADPKD patients is about 12% [27]. A family history of intracranial hemorrhage can significantly increase the risk of ICA [28]. Therefore, examination and evaluation of extrarenal organ of ADPKD patients is also very important.At present, there is no safe and effective treatment of ADPKD in clinic. Therefore, understanding the pathogenesis of ADPKD may provide a new therapeutic target for the clinical treatment and lay the foundation for the development of various biological and drug treatments for ADPKD. [30,31]. Polycystin-1 is found in most segments of the nephron and is distributed in a variety of subcellular structures such as the primary cilia, cytoplasmic vesicles, plasma membrane at focal adhesions, desmosomes, adherens junctions, and possibly endoplasmic reticulum and nuclei. Among them, polycystin-1 distributed in primary cilia is considered to play an important role in the mechano/chemo-sensor function [32][33][34], whereas polycystin-1 distributed in the side wall and the basal body participates in the formation of intercellular adhesion and focal adhesion [35]. In addition, a cleavage product of polycystin-1 that includes the C-terminal tail can translocate to the nucleus and regulate gene transcription [36,37]. PKD Genes and Proteins