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.