Autosomal Dominant Polycystic Kidney Disease

Autosomal dominant polycystic kidney disease, also called adult polycystic kidney disease, affects children and adults in the prime of life and accounts for 10% of persons who require treatment for end-stage renal diease. The disorder is transmitted as a dominant trait, which means thát there iš a 50% chance of children of an affected parent developing the disorder.

Three mutant genes have been implicated in the disease. A gene called ADPKDI, located on chromosome 16, is responsible for most cases. There is a high degree of penetrance for the defect; persons who inherit the gene are likely to develop the disorder. There is considerable variability in gene expression, and many affected persons do not develop clinical symptoms, or if they do, the symptoms occur late in life. A second gene, the ADPKD2 gene, which is located on chromosome 4, is responsible for a milder form of the disease. Evidence points to a third gene, ADPKD3, that also is responsible for the disease.

The pathogenesis of adult polycystic kidney disease is not fully understood. There is tubular dilatation caused by either obstruction or weakening of the tubule structure. Glomerular filtrate collects in the cyst while it is still part of the tubular lumen, or it is secreted into the cyst after it has separated from the tubule. As the fluid accumulates, the cysts gradually increase in size, some of which become as large as 5 cm in diameter. The kidneys of persons with polycystic kidney disease eventually become enlarged because of the presence of multiple cysts. Cysts may also be found in the liver and, less commonly, the pancreas and spleen. Also, there may be a weakness in the walls of the cerebral arteries that could lead to aneurysm formation. Subarachnoid hemorrhage occurs in about 10%. to 15% of persons with polycystic kidney disease. 

The manifestations, of polycystic kidney disease include pain from the enlarging cysts that may reach debilitating levels, episodes of gross hematuria from bleeding into a cyst, infected cysts from ascending urinary tract infection, and hypertension resulting from compression of intrarenal blood vessels with activation of the renin-angiotensin mechanism. Persons with polycystic kidney disease are also at risk for development of renal cell carcinoma. The progress of the disease is slow, and end-stage renal failure is uncommon before age 40. 

The diagnosis of autosomal polycystic kidney dis ease can be made by radiologic studies, such as excretory urography, and by ultrasonography or computed tomography (CT). Ultrasonography and CT have largely replaced excretory urography because they are betterable to detect small cysts. Ultrasonography is particularly useful as a screening test for the disease. It is recommended that first-degree relatives of affected persons be screened for polycystic disease if they are at least 20 years old. The sensitivity of ultrasonography in this age group is about 95%; before that age, false-negative 

results may occur because the cysts are too small to detect.3 Persons with a positive family history and no radiologically evident cysts can be further evaluated through gene-lixcage analysis. Two related persons who are affected must be included to establish the presence of the defective gene with 99% certainty It is also possible to diagnosis polycystic kidney disease prenatally using DNA obtained from amniocentesis or chorionic villus sampling.

The treatment of polycystic kidney disease is largely supportive. Control of hypertension and prevention of ascending urinary tract infections are important. The cysts may be surgically removed if the patient has refractory pain. Dialysis and kidney transplantation are reserved for those who progress to end-stage renal disease.

In summary about l0% of infants are born with potentially significant malformations of the urinary system. These abnormalities can range from bilateral renal agenesis, which is incompatible with life, to hypogenesis of one kidney, which usually causes no prthlems unless the function of the single kidney is impaired. The developmental process can result in kidneys that lie outside their normal position.

Because of the abnormal position, kinking of the ureters and obstruction of urine flow can occur. Renal cystic disease is a condition in which there is dilatation of tubular structures to form a cyst. Cysts may be single or multiple. Polycystic kidney disease is an inherited form of renal cystic disease;it can be inherited as an autosomal recessive or an autosomal dominant trait. Autosomal recessive poly-. cystic kidney disease is rare and usually presents as severe renal dysfunction during infancy. Autoso mal dominant polycystic disease usually does not become symptomatic until later in life, often after age 40.