Autosomal Dominant Polycystic Kidney: Pathophysiology

Pathophysiology: The cilia-centrosome complex of renal tubular epithelial cells plays a central role in the pathophysiology of cyst formation in autosomal dominant polycystic kidney disease (ADPKD). The tubular epithelial cells contain a single non-motile primary cilium that projects into the tubular lumen. It acts as a mechanosensor that regulates intracellular calcium in response to changes in the urine flow through the tubule. Polycystin-1 and polycystin-2 are localized to the primary cilium where they form a heterodimer complex that plays a key role in this process. In PKD-mutated kidneys, polycystin complex is missing or aberrant which disrupts intracellular Ca+2 levels. This disrupts several downstream pathways, including cAMP, ERK, and mTOR pathways. The end result is increased cellular proliferation and enhanced secretory activity from tubular epithelium, leading to formation and progressive enlargement of cysts.