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Erschienen in: Journal of Nephrology 2/2022

19.05.2021 | Review

Therapeutic advances in ADPKD: the future awaits

verfasst von: Ivana Capuano, Pasquale Buonanno, Eleonora Riccio, Maria Amicone, Antonio Pisani

Erschienen in: Journal of Nephrology | Ausgabe 2/2022

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Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is a heterogeneous genetic disorder included in ciliopathies, representing the fourth cause of end stage renal disease (ESRD), with an estimated prevalence between 1:1000 and 1:2500. It is mainly caused by mutations in the PKD1 and PKD2 genes encoding for polycystin 1 (PC1) and polycystin 2 (PC2), which regulate differentiation, proliferation, survival, apoptosis, and autophagy. The advances in the knowledge of multiple molecular pathways involved in the pathophysiology of ADPKD led to the development of several treatments which are currently under investigation. Recently, the widespread approval of tolvaptan and, in Italy, of long-acting release octreotide (octreotide-LAR), represents but the beginning of the new therapeutic management of ADPKD patients. Encouraging results are expected from ongoing randomized controlled trials (RCTs), which are investigating not only drugs acting on the calcium/cyclic adenosin monoposphate (cAMP) pathway, the most studied target so far, but also molecules targeting specific pathophysiological pathways (e.g. epidermal growth factor (EGF) receptor, AMP-activated protein kinase (AMPK) and KEAP1-Nrf2) and sphingolipids. Moreover, studies on animal models and cultured cells have also provided further promising therapeutic strategies based on the role of intracellular calcium, cell cycle regulation, MAPK pathway, epigenetic DNA, interstitial inflammation, and cell therapy. Thus, in a near future, tailored therapy could be the key to changing the natural history of ADPKD thanks to the vigorous efforts that are being made to implement clinical and preclinical studies in this field. Our review aimed to summarize the spectrum of drugs that are available in the clinical practice and the most promising molecules undergoing clinical, animal, and cultured cell studies.

Graphical abstract

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Metadaten
Titel
Therapeutic advances in ADPKD: the future awaits
verfasst von
Ivana Capuano
Pasquale Buonanno
Eleonora Riccio
Maria Amicone
Antonio Pisani
Publikationsdatum
19.05.2021
Verlag
Springer International Publishing
Erschienen in
Journal of Nephrology / Ausgabe 2/2022
Print ISSN: 1121-8428
Elektronische ISSN: 1724-6059
DOI
https://doi.org/10.1007/s40620-021-01062-6

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