PKD1

About PKD1

PKD1 on chromosome 16p13.3 encodes polycystin 1, a large membrane protein with an extracellular region involved in cell to cell and cell to matrix interactions. Polycystin 1 forms a complex with polycystin 2 in the primary cilium of kidney tubule cells, where it is thought to act as a sensor that regulates calcium signaling, cell proliferation, and tubule diameter. Pathogenic variants cause autosomal dominant polycystic kidney disease, the most common inherited kidney disease, which affects roughly 1 in 1,000 people or more. PKD1 accounts for most cases, and PKD2 for most of the remainder, with PKD1 disease generally being more severe and progressing to kidney failure earlier. ADPKD causes numerous fluid filled cysts that progressively enlarge both kidneys, leading in many people to kidney failure in middle or later adulthood. Features include high blood pressure, blood in the urine, flank pain, kidney stones, urinary tract infections, liver cysts, and an increased risk of intracranial aneurysms. Cyst growth involves cyclic AMP signaling, and tolvaptan, a vasopressin V2 receptor antagonist, slows kidney enlargement and functional decline in people at risk of rapid progression. Management also includes blood pressure control, dialysis, and kidney transplantation for kidney failure.