Autosomal Recessive Polycystic Kidney Disease

Autosomal recessive polycystic kidney disease (ARPKD) is a rare genetic disorder characterized by the formation of fluid-filled sacs (cysts) in the kidneys. Most affected infants have enlarged kidneys during the newborn (neonatal) period and some cases may be fatal at this time. ARPKD is not simply a kidney disease and additional organ systems of the body may also be affected, especially the liver. High blood pressure (hypertension), excessive thirst, frequent urination and feeding difficulties may also occur. Some affected children may also have distinctive facial features and incomplete development of the lungs (pulmonary hypoplasia) causing breathing (respiratory) difficulties. The severity of the disorder and the specific symptoms that occur can vary greatly from one person to another. Some affected children eventually develop end-stage renal disease sometime during the first decade of life. In some patients, symptoms do not develop until adolescence or even adulthood. ARPKD is caused by changes (mutations) in the PKHD1 gene.[rx]

Types of ARPKD

There is one main type of ARPKD, which is a genetic condition present from birth. It can affect individuals in various ways, with symptoms ranging from mild to severe. ARPKD is caused by mutations in the PKHD1 gene, which is responsible for the proper development of the kidneys and liver.

Causes of ARPKD

ARPKD is caused by specific genetic mutations in the PKHD1 gene. To develop ARPKD, an individual must inherit two mutated copies of the gene, one from each parent. When both parents carry one copy of the mutated gene (but do not have ARPKD themselves), there is a 25% chance that their child will inherit two mutated copies and develop the disease.

ARPKD is caused by mutations of the PKHD1 gene and is inherited in an autosomal recessive pattern.

Recessive genetic disorders occur when an individual inherits a non-working gene from each parent. If an individual receives one working gene and one non-working gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the non-working gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier, like the parents, is 50% with each pregnancy. The chance for a child to receive working genes from both parents is 25%. The risk is the same for males and females.

PKHD1 is a large gene and many different mutations to this gene cause ARPKD. The PKHD1 gene contains instructions for creating (encoding) a protein known as fibrocystin (or polyductin). If patients have two mutations that result in no protein being generated, the result is usually lethal. However, in the majority of patients at least one copy of the gene generates some functional protein and these cases are usually viable. The exact role and function of this protein in the body is unknown.[rx]

The ARPKD protein may be involved in the proper development or function of cilia, a hair-like structure found on most cells in the body. Cilia are classified as motile or immotile. Motile cilia have specific mechanical functions such as to move or propel mucus over the cell in the respiratory tract, while immotile (primary) cilia were believed to play a sensory or mechano-sensory role. Immotile cilia are active structures required for normal health and development that are involved in sensing the environment outside of the cell and sending related signals into the cell. The exact relationship between the ARPKD protein and the cilia and their ultimate roles in proper kidney function and health is not fully understood. More research is necessary to determine the complex, underlying mechanisms that ultimately cause ARPKD.

The symptoms of ARPKD result from the development and continued enlargement of cysts in the kidneys and other organ systems of the body. Cysts within the kidneys form within nephrons, which are small tubules that serve as the basic filtering units of the kidneys and help to remove waste from the blood. Cysts form at the tips or ends of the nephrons, a section known as the collecting tubules. Specifically, a cyst is a widened (dilated) collecting tubule that has swollen or ballooned. Because of the numerous cysts that form, the kidneys become enlarged and normal nephrons are destroyed, eventually eliminating kidney function. In a normal kidney, the nephrons and collecting tubules help to regulate the amount of water and acid in the body.

The liver symptoms of ARPKD result from the improper development of the network of bile ducts found within the liver. Bile ducts may be widened (dilated) and duplicated and surrounding tissue may become inflamed, ultimately causing scarring in the affected area. This scarring process is known as congenital hepatic fibrosis. All children with ARPKD have congenital hepatic fibrosis, but not all children develop clinically evident liver disease.[rx]

Symptoms of ARPKD

Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by the formation of cysts within the kidneys

ARPKD symptoms can vary widely, but they often become noticeable in infancy or childhood. Here are some common symptoms:

Enlarged Kidneys: The kidneys become enlarged and filled with fluid-filled sacs called cysts.
High Blood Pressure: Children with ARPKD may develop high blood pressure at a young age.
Kidney Problems: The cysts in the kidneys can lead to kidney dysfunction, including kidney failure in severe cases.
Liver Issues: Some individuals with ARPKD may have liver problems, such as an enlarged liver or liver fibrosis.
Breathing Problems: Large kidneys can press on the lungs, causing difficulty breathing.
Urinary Tract Infections: Children with ARPKD are at a higher risk of urinary tract infections.
Growth Delays: ARPKD can affect a child’s growth and development.
Portal Hypertension: In some cases, ARPKD can lead to portal hypertension, which affects blood flow in the liver.
Jaundice: Yellowing of the skin and eyes (jaundice) can occur due to liver involvement.
Abdominal Pain: Enlarged organs may cause discomfort or pain in the abdominal area.
Frequent Urination: Children with ARPKD may urinate more frequently than usual.
Constipation: Digestive issues can lead to constipation in some cases.
Increased Thirst: Some individuals may feel very thirsty.
Protein in Urine: Kidney dysfunction may result in proteinuria, which is the presence of excess protein in the urine.
Poor Appetite: Children with ARPKD may have a reduced appetite.
Pale Skin: Anemia (low red blood cell count) can cause pale skin.
Swollen Ankles and Feet: Fluid retention may cause swelling in the lower extremities.
Headaches: High blood pressure can lead to headaches.
Fatigue: Kidney dysfunction can cause fatigue.
Developmental Delays: Some children with ARPKD may experience developmental delays.

Diagnostic Tests for ARPKD

To diagnose ARPKD, doctors may use various tests, including:

Ultrasound: An ultrasound of the abdomen can reveal enlarged kidneys with cysts.
Genetic Testing: Genetic testing can identify mutations in the PKHD1 gene.
Blood and Urine Tests: These tests may show signs of kidney dysfunction.
Liver Function Tests: To check for liver involvement.
Biopsy: In some cases, a tissue sample may be taken for further evaluation.
Imaging: MRI or CT scans can provide detailed images of the kidneys and liver.
Fetal Ultrasound: ARPKD can sometimes be detected during prenatal ultrasounds.

Treatment for ARPKD

While there is no cure for ARPKD, treatment aims to manage symptoms and complications. Here are some common approaches:

Blood Pressure Management: Medications can help control high blood pressure.
Dialysis: In severe cases of kidney failure, dialysis may be necessary to filter waste and excess fluid from the blood.
Kidney Transplant: Some individuals with ARPKD may require a kidney transplant.
Liver Care: Regular monitoring and management of liver issues.
Nutrition: A special diet may be recommended to support growth and kidney function.
Antibiotics: To treat and prevent urinary tract infections.
Pain Management: Medications can help alleviate pain and discomfort.
Supportive Care: Addressing specific symptoms as they arise, such as respiratory support.
Physical Therapy: To improve mobility and muscle strength.
Psychological Support: ARPKD can be emotionally challenging, so counseling and support groups can be helpful.

Medications can be used to control and manage high blood pressure, specifically angiotensin-converting enzyme (ACE) inhibitors. In some individuals, high blood pressure can be resistant to therapy (refractory) and severe enough to require more than one medication. Antibiotics may be used to treat urinary tract infections or cholangitis.

Some children may require nutritional supplements including vitamin D, iron, bicarbonate and citrate. Adequate fluid and salt supplementation may also be necessary. Because of feeding difficulties and growth delays, some children may require the insertion of a tube through a small surgical opening in the stomach (gastrostomy) or a tube through the nose, down the esophagus and into the stomach (nasogastric tube). These tubes are used to directly provide essential nutrients. In severe cases, growth hormone therapy may be necessary.[rx]

Medications for ARPKD

While there is no specific medication to treat ARPKD itself, several medications may be prescribed to manage its symptoms and complications:

Antihypertensive Medications: To control high blood pressure.
Antibiotics: To treat and prevent infections.
Pain Relief Medications: For pain management.
Medications to Manage Liver Issues: Depending on the severity of liver involvement.
Growth Hormone Therapy: To support growth in children with ARPKD.
Iron Supplements: To address anemia.
Diuretics: To reduce fluid retention.
Anti-nausea Medications: To alleviate nausea and vomiting.
Immunosuppressants: For individuals who undergo kidney transplantation.
Erythropoietin (EPO): To stimulate red blood cell production.

In Conclusion

Autosomal Recessive Polycystic Kidney Disease (ARPKD) is a rare genetic disorder that affects the kidneys and liver. It is caused by mutations in the PKHD1 gene and can lead to a range of symptoms and complications. Early diagnosis and appropriate management are essential to improve the quality of life for individuals with ARPKD. While there is no cure, various treatments and medications can help manage the condition and its associated symptoms. If you or your child has ARPKD or you suspect you may be a carrier of the gene mutation, it is crucial to consult with healthcare professionals who specialize in the condition for personalized guidance and care.

Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, previous medical history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. Thank you for giving your valuable time to read the article.

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