Autosomal Recessive Polycystic Kidney Disease (ARPKD)

The severity and progression? of ARPKD can vary greatly from one person to another, even among members of the same family. In severe? cases, ARPKD can cause life-threatening complications during infancy. In other cases, affected individuals may not develop symptoms until later during childhood or adolescence. Some children may need a kidney (renal) transplant early in childhood; others may not need a transplant until early adulthood, or not at all. In rare cases, individuals may not develop symptoms until young adulthood. Generally, individuals who develop ARPKD later in life have milder kidney disease, but more severe liver disease.

Most of the medical literature on ARPKD, especially those written before the identification of the ARPKD disease gene, disproportionately focused on the most severe cases. Therefore, much of the literature may give the incorrect impression that ARPKD is a uniformly fatal or debilitating disease. Researchers now know that ARPKD can range from mild to severe. Consequently, it is important to note that affected individuals will not have all of the symptoms discussed below. Affected individuals should talk to their physician and medical team about their specific case, associated symptoms, and overall prognosis.

The characteristic finding of ARPKD is the development of fluid-filled sacs (cysts) in the kidneys. All affected individuals develop cysts in the kidneys, but the number, size, progression, and severity of cyst development varies greatly from one person to another. In most affected individuals, renal cysts grow and multiply in utero causing abnormal enlargement of the kidneys. Enlarged kidneys may be apparent at birth or during the newborn period. In these infants, the kidneys are firm and can be felt (palpated) on both flanks. Additional symptoms associated with cystic kidneys include high blood pressure (hypertension) and flank pain. High blood pressure is common in children with ARPKD and can be widespread, severe, and difficult to manage.

In severe cases of ARPKD, affected infants may face life-threatening complications shortly after birth, especially breathing (respiratory) insufficiency or failure. Breathing difficulties usually occur due to deficient levels of amniotic fluid (oligohydramnios) during pregnancy. Massively enlarged kidneys, which prevent the proper development of the lungs, may also contribute to respiratory insufficiency or failure. Although some children do not survive the newborn period (approximately 30 percent by most estimates), the majority of children survive.

Children who survive beyond the newborn period usually develop worsening kidney function, although the kidneys may reduce in size. Most children do not develop chronic renal insufficiency until late childhood, adolescence, or young adulthood. Renal insufficiency refers to the impaired ability of the kidneys to perform their basic functions. The kidneys are two bean-shaped organs located under the ribcage. The kidneys have several functions including filtering and excreting waste products from the blood and body, creating certain hormones, and helping maintain the balance of certain chemicals in the body such as potassium, sodium, chloride, calcium, and other electrolytes. Damage to the kidneys in ARPKD may be slowly progressive and can cause a variety of symptoms including weakness and fatigue, changes in appetite, puffiness or swelling, back pain, poor digestion, excessive thirst, and frequent urination. Eventually, many children progress to end-stage renal disease.

In severe cases of ARPKD, affected infants have extremely enlarged kidneys and decreased urine production at birth. Decreased urine production in utero contributes to a deficiency of amniotic fluid (oligohydramnios), the fluid that surrounds a developing fetus. In addition to protecting and cushioning a fetus, the amniotic fluid contains growth factors and other substances that are vital to fetal development. Low amniotic fluid levels can impair lung development and, consequently, some affected infants may have underdeveloped lungs (pulmonary hypoplasia). These infants can experience severe, life-threatening breathing (respiratory) complications during the newborn period. Infants with oligohydramnios may also develop distinctive facial features including deep-set eyes, a flattened nose, a small jaw (micrognathia), and abnormal, low-set ears. The physical findings associated with oligohydramnios are sometimes referred to as Potter’s sequence.

In addition to the kidneys, the liver is also commonly affected in children and adults with ARPKD. The liver performs many functions in the body including converting food into energy and nutrients, storing vitamins, and filtering toxins from the body. Children with ARPKD develop a liver condition known as congenital hepatic fibrosis, in which excess fiber-like connective tissue spreads throughout the liver. Although all children have congenital hepatic fibrosis, not all children develop liver dysfunction. Liver abnormalities that can occur in ARPKD include enlargement of the liver (hepatomegaly), inflammation and infection of the tubes (bile ducts) that carry bile from the liver to the gallbladder and intestines (cholangitis), and high blood pressure of the main vein of the liver (portal hypertension).

Portal hypertension can cause increased pressure and swelling (distention) of veins (varices) of the esophagus, the stomach, and intestines. These veins can rupture and potentially cause life-threatening gastrointestinal bleeding (variceal bleeding). Affected children may experience progressive liver dysfunction and scarring (cirrhosis) and ultimately liver failure.

Children with ARPKD may also experience feeding difficulties due to poor kidney function or from compression of the stomach by enlarged kidneys, liver, and/or spleen. Feeding difficulties and chronic renal failure may contribute to poor growth in affected individuals. Some children may be prone to urinary tract infections and have problems with water and salt balance.

Some children with ARPKD may also experience enlargement of the spleen (splenomegaly). Splenomegaly can potentially result in low levels of red blood cells (anemia), platelets (thrombocytopenia), and white blood cells (leukopenia). Anemia can cause fatigue, pale skin, irregular heartbeat, and shortness of breath. Thrombocytopenia can result in easy bruising, prolonged bleeding from cuts, spontaneous nosebleeds, and superficial bleeding in the skin (petechiae). Leukopenia decreases the body’s ability to fight infection and disease.