Polycystic kidney disease

Other Names: PKD; Polycystic kidneys; ADPKD; Autosomal dominant polycystic kidney disease

Polycystic kidney disease is a disorder that affects the kidneys and other organs. Clusters of fluid-filled sacs, called cysts, develop in the kidneys and interfere with their ability to filter waste products from the blood. The growth of cysts causes the kidneys to become enlarged and can lead to kidney failure. Cysts may also develop in other organs, particularly the liver.

Epidemiology

Polycystic kidney disease is a fairly common genetic disorder. It affects about 500,000 people in the United States. The autosomal dominant form of the disease is much more common than the autosomal recessive form. Autosomal dominant polycystic kidney disease affects 1 in 500 to 1,000 people, while the autosomal recessive type occurs in an estimated 1 in 20,000 to 40,000 people.

Forms

The two major forms of polycystic kidney disease are distinguished by the usual age of onset and their pattern of inheritance: (1) Autosomal dominant polycystic kidney disease (ADPKD) is the most common form that usually causes symptoms between the ages of 30 and 40; but they can begin earlier, even in childhood. ADPKD can be further divided into type 1 and type 2, depending on the underlying genetic cause. (2) Autosomal recessive polycystic kidney disease (ARPKD) is a rare form that usually causes symptoms in infancy and early childhood and is often lethal early in life. Some people with ARPKD do not develop symptoms until later in childhood or even adulthood.

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Cause

Mutations in the PKD1, PKD2, and PKHD1 genes cause polycystic kidney disease. Mutations in either the PKD1 or PKD2 gene can cause autosomal dominant polycystic kidney disease; PKD1 gene mutations cause ADPKD type 1, and PKD2 gene mutations cause ADPKD type 2. These genes provide instructions for making proteins whose functions are not fully understood. Researchers believe that they are involved in transmitting chemical signals from outside the cell to the cell's nucleus. The two proteins work together to promote normal kidney development, organization, 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, particularly women, typically have a less severe form of the disease than people with PKD1 mutations. The signs and symptoms, including a decline in kidney function, tend to appear later in adulthood in people with a PKD2 mutation. Mutations in the PKHD1 gene cause autosomal recessive polycystic kidney disease. This gene provides instructions for making a protein whose exact function is unknown; however, the protein likely transmits chemical signals from outside the cell to the cell nucleus. Researchers have not determined how mutations in the PKHD1 gene lead to the formation of numerous cysts characteristic of polycystic kidney disease. Although polycystic kidney disease is usually a genetic disorder, a small percentage of cases are not caused by gene mutations. These cases are called acquired polycystic kidney disease. This form of the disorder occurs most often in people with other types of kidney disease who have been treated for several years with hemodialysis (a procedure that filters waste products from the blood).

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Inheritance

Most cases of polycystic kidney disease have an autosomal dominant pattern of inheritance. People with this condition are born with one mutated copy of the PKD1 or PKD2 gene in each cell. In about 90 percent of these cases, an affected person inherits the mutation from one affected parent. The other 10 percent of cases result from a new mutation in one of the genes and occur in people with no history of the disorder in their family. Although one altered copy of a gene in each cell is sufficient to cause the disorder, an additional mutation in the second copy of the PKD1 or PKD2 gene may make cysts grow faster and increase the severity of the disease. The rate at which cysts enlarge and cause a loss of kidney function varies widely, and may be influenced by mutations in other genes that have not been identified. Polycystic kidney disease also can be inherited in an autosomal recessive pattern. People with this form of the condition have two altered copies of the PKHD1 gene in each cell. The parents of a child with an autosomal recessive disorder are not affected but are carriers of one copy of the altered gene.

Signs and symptoms

Signs and symptoms vary greatly from person to person. But affected individuals typically develop multiple cysts in both kidneys, which impair their ability to filter waste products from the blood. Later in the disease, the cysts cause the kidneys to become enlarged and can lead to kidney failure. Cysts may also develop in other organs, particularly the liver. Frequent complications of polycystic kidney disease include dangerously high blood pressure (hypertension), severe pain in the back or sides, blood in the urine (hematuria), recurrent urinary tract infections, kidney stones, and heart valve abnormalities. People with this condition also have an increased risk an aortic aneurysm in the brain (an abnormal bulging of the large blood vessel at the base of the brain). Aneurysms can be life-threatening if they tear or rupture.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Decreased glomerular filtration rate
• Elevated serum creatinine(Elevated creatinine)
• Hepatic [[cysts](Liver cysts)
• Renal cyst(Kidney cyst)

30%-79% of people have these symptoms

• Abnormal urinary electrolyte concentration
• Albuminuria
• Hematuria(Blood in urine)
• Hypertension
• Pain
• Stage 5 chronic kidney disease

5%-29% of people have these symptoms

• Aortic root aneurysm(Bulge in wall of root of large artery that carries blood away from heart)
• Arachnoid cyst(Fluid-filled sac located in membrane surrounding brain or spinal cord)
• Dilatation of the cerebral artery
• Enlarged kidney(Large kidneys)
• Mitral valve prolapse
• Nephrolithiasis(Kidney stones)
• Pancreatic cysts
• Polycystic liver disease
• Pyelonephritis
• Recurrent urinary tract infections(Frequent urinary tract infections)
• Reduced sperm motility

1%-4% of people have these symptoms

• Cerebral berry aneurysm
• Mitral regurgitation
• Pituitary growth hormone cell adenoma

Diagnosis

Polycystic kidney disease can be ascertained via a CT scan of abdomen, as well as, an MRI and ultrasound of the same area. A physical exam/test can reveal enlarged liver, heart murmurs and elevated blood pressure.

Treatment

Polycystic Kidney Disease, Autosomal Recessive Management of affected neonates centers on stabilization of respiratory function by mechanical ventilation and (rarely) unilateral or bilateral nephrectomy if massive kidney enlargement impairs diaphragmatic excursion. Neonates with oliguria or anuria may require peritoneal dialysis within the first days of life, and early recognition and treatment of dehydration and hypertension is critical. Affected children with significant chronic kidney disease should be treated with all modalities of modern pediatric ESRD therapy.

Treatment of biliary dysfunction focuses on (1) malabsorption of nutrients and fat-soluble vitamins and (2) the risk for ascending cholangitis, and includes administration of synthetic bile acids and early recognition and treatment of ascending cholangitis. In those with progressive portal hypertension, endoscopy with sclerotherapy or banding of varices may be required. Portosystemic shunting and/or consideration of liver transplantation may be required. Those with ESRD and severe portal hypertension may be candidates for dual renal/liver transplantation.

Polycystic Kidney Disease, Autosomal Dominant Vasopressin V2 receptor antagonists (e.g., tolvaptan) to slow disease progression. Treatment for hypertension may include ACE inhibitors or angiotensin II receptor blockers and diet modification. Conservative treatment of flank pain includes nonopioid agents, tricyclic antidepressants, narcotic analgesics, and splanchnic nerve blockade. More aggressive treatments include cyst decompression with cyst aspiration and sclerosis, laparoscopic or surgical cyst fenestration, renal denervation, and nephrectomy. Cyst hemorrhage and/or gross hematuria is usually self-limiting.

Treatment of nephrolithiasis is standard. Treatment of cyst infections is difficult, with a high failure rate. Therapeutic agents of choice may include trimethoprim-sulfamethoxazole, fluoroquinolones, clindamycin, vancomycin, and metronidazole. The diagnosis of malignancy requires a high index of suspicion. Therapeutic interventions aimed at slowing the progression of ESRD in ADPKD include control of hypertension and hyperlipidemia, dietary protein restriction, control of acidosis, and prevention of hyperphosphatemia. Most individuals with PLD have no symptoms and require no treatment, but rare severe cases may require surgical resection or even liver transplantation. The mainstay of therapy for ruptured or symptomatic intracranial aneurysm is surgical clipping of the ruptured aneurysm at its neck; however, for some individuals, endovascular treatment with detachable platinum coils may be indicated. Thoracic aortic replacement is indicated when the aortic root diameter exceeds established size.

NIH genetic and rare disease info

• NIH info on Polycystic kidney disease

Polycystic kidney disease is a rare disease.

Polycystic kidney disease Resources
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