autosomal recessive polycystic kidney disease, PKHD1-related

What Is Autosomal Recessive Polycystic Kidney Disease, PKHD1-Related?

Autosomal recessive polycystic kidney disease (ARPKD), is an inherited condition caused by mutations in the PKHD1 gene in which clusters of fluid-filled sacs (cysts) form in the kidneys, often leading to kidney failure by the age of 10 and a reduced lifespan. Children with ARPKD may have underdeveloped lungs, leading to breathing problems or lung infections. Without treatment, 30% of children with ARPKD die within the first year of life. However, with treatments to aid breathing and/or kidney transplantation, about 80% of infants will survive.

The majority of infants with ARPKD show enlarged, cyst-filled kidneys within the first month of life. These cysts will impair the kidneys' ability to filter waste from the body. About 50% of infants with ARPKD will also have an enlarged liver. These anomalies are often detectable through an ultrasound before the child is born. More than half of the children will develop kidney failure by the age of 10. Without dialysis or transplantation, the disease is often fatal.

Extremely high blood pressure is common in people with ARPKD. They are also prone to urinary tract infections, frequent urination, low blood-cell counts, pain in the back or the sides, varicose veins, and hemorrhoids. Many affected individuals are also smaller in stature than normal.

A minority of people with ARPKD do not show symptoms of the disease until later in childhood or early in adulthood, with liver disease being the dominant symptom. In these people, the kidney disease is often mild.

How Common Is Autosomal Recessive Polycystic Kidney Disease, PKHD1-Related?

The prevalence of ARPKD is 1 in 10,000 to 1 in 40,000 infants. However, the disease may actually be more common than these estimates suggest because people with milder forms of the disease may not be diagnosed without genetic testing. Mutations in the PKHD1 gene account for about 75% of ARPKD cases.

How Is Autosomal Recessive Polycystic Kidney Disease, PKHD1-Related Treated?

The initial concern with infants who have ARPKD is to protect their ability to breathe. Stabilizing respiratory function through mechanical ventilation may be required. Eating a nutritious diet can aid growth, and in some cases, growth hormones are recommended. Infants and children may require feeding tubes in order to ensure proper growth.

If faced with kidney failure, people with ARPKD frequently undergo dialysis (a “cleansing” of the blood through a machine that removes waste) or kidney transplantation. If the liver is extremely damaged, transplantation of this organ may also be recommended. Some individuals with ARPKD must undergo dialysis or kidney transplantation in infancy. Treatments to minimize dehydration and medications to lower blood pressure and to treat urinary tract infections may also be necessary.

What Is the Prognosis for a Person with Autosomal Recessive Polycystic Kidney Disease, PKHD1-Related?

Without treatment, approximately 30% of infants with ARPKD die within the first year of life due to breathing difficulties or lung infections. However, with treatments to aid breathing and/or kidney transplantation, about 80% of affected individuals will survive past infancy. Of those who survive infancy, about 82% survive to age 10, and 73% live past the age of 15. In one study, 58% of individuals required dialysis or kidney transplantation by age 20. As transplantation methods improve, it is expected that people with ARPKD will live longer lives.