[Pathophysiology, epidemiology, clinical presentation, diagnosis and treatment options for autosomal dominant polycystic kidney disease]

Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is the leading genetic cause of end-stage renal disease (ESRD) worldwide. Its prevalence is evaluated according to studies and population between 1/1000 and 1/4000 live births and it accounts for 6 to 8% of incident ESRD patients in developed countries. ADPKD is characterized by numerous cysts in both kidneys and various extrarenal manifestations that are detailed in this review. Clinico-radiological and genetic diagnosis are also discussed. Mutations in the PKD1 and PKD2 codifying for polycystin-1 (PC-1) and polycystin-2 (PC-2) are responsible for the 85 and 15% of ADPKD cases, respectively. In primary cilia of normal kidney epithelial cells, PC-1 and PC-2 interact forming a complex involved in flow- and cilia-dependant signalling pathways where intracellular calcium and cAMP play a central role. Alteration of these multiple signal transduction pathways leads to cystogenesis accompanied by dysregulated planar cell polarity, excessive cell proliferation and fluid secretion, and pathogenic interactions of epithelial cells with an abnormal extracellular matrix. The mass effect of expanding cyst is responsible for the decline in glomerular filtration rate that occurs late in the course of the disease. For many decades, the treatment for ADPKD aims to lessen the condition's symptoms, limit kidney damage, and prevent complications. Recently, the development of promising specific treatment raises the hope to slow the growth of cysts and delay the disease. Treatment strategies targeting cAMP signalling such as vasopressin receptor antagonists or somatostatin analogs have been tested successfully in clinical trials with relative safety. Newer treatments supported by preclinical trials will become available in the next future. Recognizing early markers of renal progression (clinical, imaging, and genetic markers) to identify high-risk patients and multidrug approaches with synergistic effects may provide new opportunities for the treatment of ADPKD.

Keywords: Antagoniste du récepteur de la vasopressine; Autosomal dominant polycystic kidney disease; Polycystin; Polycystine; Polykystose rénale autosomique dominante; Somatostatin; Somatostatine; Vasopressin receptor antagonists.