Polycystic Kidney Disease Causes
For the most part, polycystic kidney disease is caused by mutations in the PKD1, PKD, and PKHD1 genes. Mutations in these genes cause both autosomal dominant polycystic kidney disease and autosomal recessive polycystic kidney disease. Acquired cystic kidney disease is nonhereditary -- it most often occurs in people with long-term kidney damage.
Mutations in the PKD1, PKD2, and PKHD1 genes are the primary cause of polycystic kidney disease (PKD). The type of disease (see Polycystic Kidney Disease Types) is determined by which combination of these genes is affected.
Mutations in the PKD1 and PKD2 genes cause autosomal dominant polycystic kidney disease. The PKD1 gene is located on chromosome 16; the PKD2 gene is located on chromosome 4.
The functions of the proteins made by these genes are not fully understood, but it is known that they are involved in transmitting chemical signals from the outside of the cell to the cell's nucleus. Polycystic kidney disease research scientists believe that the two proteins work together to promote normal kidney development and function.
Mutations in the PKD1 or PKD2 gene lead to the formation of thousands of cysts, which disrupt the normal functions of the kidneys and other organs. People with mutations in the PKD2 gene typically have a less severe form of the disease than people with PKD1 mutations.
In about 90 percent of autosomal dominant PKD cases, an affected person inherits a mutation in the PKD1 or PKD2 gene from one affected parent. The other 10 percent of cases may result from new mutations in one of the genes. These cases occur in people with no history of the disorder in their family.
People with autosomal dominant polycystic kidney disease are born with one mutated copy of the PKD1 or PKD2 gene in each cell. Then, during their lifetime, a second mutation occurs in the other copy of the gene in kidney cells (or cells in other organs), triggering cyst formation. The rate at which cysts enlarge and cause a loss of kidney function varies widely; it may be accelerated by a second mutation in PKD1 or PKD2, or by mutations in other important genes.