Materiały źródłowe

• #1 Autosomal Recessive Polycystic Kidney Disease – NIDDK

  https://www.niddk.nih.gov/health-information/kidney-disease/polycystic-kidney-disease/autosomal-recessive-pkd

  Autosomal recessive polycystic kidney disease (ARPKD) is a rare genetic disorder that affects 1 in 20,000 children. A fetus or baby with ARPKD has fluid-filled kidney cysts that may make the kidneys too big, or enlarged. ARPKD can cause a child to have poor kidney function, even in the womb. Poor kidney function can cause breathing problems that can threaten the life of a fetus or baby. About 30 percent of newborns with ARPKD die within their first week of life. A baby with ARPKD who survives birth and the first few weeks of life has a good chance of surviving into adulthood. However, children or young adults with ARPKD will likely need medical treatment their whole life. […] How quickly ARPKD progresses to kidney failure is different for each child. The sooner a fetus is diagnosed in the womb, the better the child’s outlook. Getting good prenatal care is important for increasing a child’s survival rate.

• #1

  https://www.nhs.uk/conditions/autosomal-recessive-polycystic-kidney-disease-arpkd/symptoms/

  The symptoms of autosomal recessive polycystic kidney disease (ARPKD) can vary significantly, even within the same family. […] Generally, however, the main symptoms of ARPKD differ, depending on when the condition first becomes apparent. […] In many cases, potential signs of ARPKD can be detected before birth during routine ultrasound scans. […] If your baby has the condition, an ultrasound scan may show that: they have enlarged kidneys; their lungs are underdeveloped; there’s a lack of amniotic fluid surrounding your baby. […] When your baby is born, there may be clearer signs that suggest they have ARPKD, such as: significant breathing difficulties this is caused by the lungs being underdeveloped; a swollen tummy (abdomen) caused by enlargement of the kidneys; Potter’s syndrome where a lack of amniotic fluid leads to deformities of the limbs, face and ears; Potter’s syndrome is a possibility in severe cases of ARPKD.

• #1

  https://www.nhs.uk/conditions/autosomal-recessive-polycystic-kidney-disease-arpkd/symptoms/

  For children with ARPKD, a number of problems affecting the liver can also develop. […] Internal bleeding can be rapid and severe, causing your child to vomit blood or pass stools that are very dark or tar-like. […] In ARPKD, the small tubes (tubules) that make up the kidneys can develop abnormally, causing bulges and fluid-filled sacs called cysts to form within them. […] This can lead to: polyuria where your child will need to pee frequently and may wet the bed; polydipsia an excessive and prolonged thirst. […] These symptoms increase the risk of dehydration, particularly if the child also has a high temperature, is vomiting, or has diarrhoea. […] Your child may have problems feeding because their enlarged kidneys take up most of the space in their abdomen. […] Some children with ARPKD do not grow at a normal rate.

• #1

  https://www.nhs.uk/conditions/autosomal-recessive-polycystic-kidney-disease-arpkd/symptoms/

  Most people with ARPKD lose a significant amount of kidney function. […] Symptoms of kidney failure can include: poor appetite and weight loss; swollen ankles, feet or hands (oedema); shortness of breath; an increased need to urinate, particularly at night (nocturia); itchy skin; feeling sick. […] Most children with ARPKD will develop kidney failure by the time they’re 15 to 20 years old.

• #1 Autosomal Recessive Polycystic Kidney Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK537137/

  Autosomal recessive polycystic kidney disease (ARPKD) is a rare genetic disorder primarily affecting the kidneys and liver. Clinicians should recognize early signs such as enlarged, echogenic kidneys in utero or during infancy. ARPKD most commonly results from mutations in PKHD1, causing renal cysts and congenital hepatic fibrosis early in life. About half of the patients with ARPKD develop end-stage renal failure requiring renal replacement therapy (dialysis or kidney transplantation) within the first 2 decades of life. In addition, hepatic function must be closely followed, as portal hypertension, splenomegaly, and cholangitis are common, especially in older patients. […] The clinical presentation of ARPKD varies significantly, with some patients diagnosed at a young age having more severe symptoms than those diagnosed when older. ARPKD is always associated with liver bile duct malformations, both intrahepatic and extrahepatic. Liver manifestations vary from mild cholestasis to hepatic fibrosis, portal vein hypertension, esophageal varices, cholangitis, and cirrhosis.

• #1 Autosomal Recessive Polycystic Kidney Disease – NIDDK

  https://www.niddk.nih.gov/health-information/kidney-disease/polycystic-kidney-disease/autosomal-recessive-pkd

  The early signs of ARPKD often appear during the first few months of life and in the womb. Early signs of ARPKD in the womb can cause serious health problems. […] An early sign of ARPKD is an enlarged kidney. Enlarged kidneys put pressure on a fetus or child’s lungs, which can make lung growth and breathing harder. […] Due to decreased kidney and lung function, children with ARPKD are usually smaller-than-average size, a condition called growth failure. […] Decreased kidney function can cause low levels of amniotic fluid in a mother’s womb. Low levels of amniotic fluid can cause breathing problems in the fetus. […] Some people with ARPKD do not develop signs or symptoms until later in childhood, or even adulthood. […] Children with ARPKD who survive birth often have kidney and liver problems that can affect their breathing.

• #1 Symptoms – Polycystic kidney disease | PKD treatment research | PKD Foundation

  https://pkdcure.org/about-the-disease/arpkd/what-are-the-symptoms-2/

  In autosomal recessive polycystic kidney disease (ARPKD), symptoms can begin prenatally when small cysts form in a microscopic tube in the kidney called the collecting tubule. […] The majority of children with ARPKD experience progressive loss of kidney function. However, the age at which kidney failure develops varies greatly among patients. […] Prenatal ARPKD Symptoms: Diminished amniotic fluid levels, Enlarged kidneys, Lung underdevelopment, Lung functioning issues. […] Post-Birth ARPKD Symptoms: Enlarged kidneys, Breathing problems, Excessive urine production, Hypertension, Growth problems, Congenital hepatic fibrosis, Enlarged spleen, Low red and white blood cell count, Low platelet counts.

• #1 Polycystic Kidney Disease | Children’s Hospital of Philadelphia

  https://www.chop.edu/conditions-diseases/polycystic-kidney-disease

  Autosomal recessive PKD is a rare, inherited form of polycystic kidney disease thought to be caused by a particular genetic flaw that is different from the genetic flaw that causes autosomal dominant PKD. Parents who do not have the disease can have a child with the disease if both parents carry the abnormal gene and both pass the gene to their child. Carrier parents have a 25 percent chance with each pregnancy to have a child with this type of PKD. Males and females are equally affected. Autosomal recessive PKD is sometimes detected prenatally (before birth) using a fetal ultrasound. […] Symptoms of autosomal recessive PKD can begin before birth. In most cases, the earlier the onset, the more severe the outcome. There are four different types of autosomal recessive PKD, depending on the child’s age when symptoms become evident: perinatal form (present at birth), neonatal form (presents within the first month of life), infantile form (presents between age 3 months and 6 months), juvenile form (presents after age 1).

• #1

  https://www.nhs.uk/conditions/autosomal-recessive-polycystic-kidney-disease-arpkd/

  The outlook for children with ARPKD can vary considerably depending on the severity of the condition. […] But in general, ARPKD is a severe condition and around 1 in 3 babies will die from severe breathing difficulties during the first 4 weeks after birth. […] About 9 out of 10 babies with ARPKD who survive the first month of life will live until they’re at least 5 years old. […] It’s difficult to predict exactly how long a child with ARPKD will live because there’s very little data showing long-term survival rates.

• #1 ARPKD basics

  https://pkdcharity.org.uk/arpkd/what-is-arpkd/arpkd-basics

  ARPKD is a rare disease that affects the kidneys and liver. It is usually diagnosed in babies and young children and occurs in roughly one in every 20,000 live births. ARPKD causes cysts sacs filled with fluid to develop in the small tubes of the kidneys. These tubes produce and transport urine. ARPKD also causes problems with the liver, including the formation of cysts, scar tissue (called fibrosis), and a swollen bile duct. The bile duct is a tube involved in producing and transporting bile, a fluid that aids digestion. […] Over time, ARPKD causes damage to the kidneys, stopping them working properly, and eventually leading to kidney failure, often during childhood or young adulthood. It can also cause complications in the liver and bile duct, such as infections. […] ARPKD symptoms, severity of disease and the age that problems occur vary between different people. For example, some babies have serious lung and kidney problems, but others do not; and some children and adults have mainly kidney symptoms, while others have mainly liver problems.

• #1 ARPKD basics

  https://pkdcharity.org.uk/arpkd/what-is-arpkd/arpkd-basics

  The severity of a child’s liver problems can vary from mild impairment to serious complications that can be life-threatening. […] Unfortunately, there are no proven treatments that can slow the progression of ARPKD. It’s possible that controlling blood pressure carefully might help to delay damage to the kidneys, but experts are not yet sure. […] The outlook for each child with ARPKD depends on the severity of their disease. As a general guide, the earlier the disease is diagnosed, the more severe it is. For example, a baby with obvious kidney problems at the routine scan will usually have a poorer outlook than a child who is diagnosed later in childhood. […] In general, ARPKD is a very severe disease: about 1 in every 3 babies with suspected or confirmed ARPKD dies from breathing problems during the first 4 weeks after birth. But, about 9 in ten 10 (89%) who survive the first 4 weeks of life are still alive at 5 years old. Encouragingly, most children now survive into adulthood and can live full and productive lives.

• #2

  https://www.nhs.uk/conditions/autosomal-recessive-polycystic-kidney-disease-arpkd/

  Autosomal recessive polycystic kidney disease (ARPKD) is a rare inherited childhood condition where the development of the kidneys and liver is abnormal. Over time, these organs may fail. […] The condition often causes serious problems soon after birth, although less severe cases may not become obvious until a child is older. […] ARPKD can cause a wide range of problems, including: underdeveloped lungs, which can cause severe breathing difficulties soon after birth; high blood pressure (hypertension); excessive peeing and thirst; problems with blood flow through the liver, which can lead to serious internal bleeding; a progressive loss of kidney function, known as chronic kidney disease (CKD). […] When these problems develop and how severe they are can vary considerably, even between family members with the condition.

• #2 Symptoms – Polycystic kidney disease | PKD treatment research | PKD Foundation

  https://pkdcure.org/about-the-disease/arpkd/what-are-the-symptoms-2/

  In autosomal recessive polycystic kidney disease (ARPKD), symptoms can begin prenatally when small cysts form in a microscopic tube in the kidney called the collecting tubule. […] The majority of children with ARPKD experience progressive loss of kidney function. However, the age at which kidney failure develops varies greatly among patients. […] Prenatal ARPKD Symptoms: Diminished amniotic fluid levels, Enlarged kidneys, Lung underdevelopment, Lung functioning issues. […] Post-Birth ARPKD Symptoms: Enlarged kidneys, Breathing problems, Excessive urine production, Hypertension, Growth problems, Congenital hepatic fibrosis, Enlarged spleen, Low red and white blood cell count, Low platelet counts.

• #2 Autosomal Recessive Polycystic Kidney Disease: ERKNet voor Patiënten

  https://www.erknet.org/patients/nl/your-kidney-disease/arpkd/disease-information

  ARPKD can lead to progressive damage to the kidneys, resulting in impaired kidney function over time. […] Cysts in the kidneys are a hallmark of ARPKD. These cysts can cause the kidneys to become enlarged and dysfunctional. […] Some individuals with ARPKD may experience gastrointestinal issues such as poor appetite, vomiting, or diarrhea. […] Yellowing of the skin and eyes (jaundice) may occur due to liver involvement. […] The progressive loss of kidney function can lead to kidney failure, which may require dialysis or kidney transplantation, before reaching adulthood. […] Most children with ARPKD have high blood pressure. High blood pressure increases a child’s chances of heart disease and stroke. High blood pressure can also further damage a child’s kidneys. […] ARPKD can also affect the liver, causing fibrosis (the formation of scar tissue) in the liver’s bile ducts. This can lead to liver problems, including hepatomegaly (enlarged liver) and, in severe cases, liver failure.

• #2 Polycystic Kidney Disease (PKD): Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/5791-polycystic-kidney-disease

  Polycystic kidney disease (PKD) causes cysts (fluid-filled growths) to develop in your kidneys. PKD causes chronic kidney disease, which can progress to kidney failure. PKD accounts for about 2% of all cases of kidney failure in the United States. Most people with PKD will need dialysis or a kidney transplant. […] Signs of autosomal recessive polycystic kidney disease (ARPKD) include low birth weight, swollen abdomen, high blood pressure at birth, and breathing problems. Signs of ARPKD in childhood could include growth failure, frequent UTIs, high blood pressure, and abdominal or low back pain. ARPKD can be fatal in babies who are born with a severe case of the disease. The first month of life is critical for babies born with ARKPD. […] The outlook for children with ARPKD isnt as positive. About one-third of all infants born with ARPKD dont survive. Babies who do survive will likely need medical treatment for the rest of their lives. About half of children who survive infanthood will have kidney failure by age 15 to 20.

• #2 Autosomal Recessive Polycystic Kidney Disease – NIDDK

  https://www.niddk.nih.gov/health-information/kidney-disease/polycystic-kidney-disease/autosomal-recessive-pkd

  Babies with the most severe cases of ARPKD often die hours or days after birth because they cannot breathe well enough to live. Their lungs do not develop as they should in the womb. […] Children born with ARPKD often develop kidney failure before reaching adulthood. […] Liver scarring occurs in all cases of ARPKD and is usually present at birth. Liver scarring can lead to decreased liver function and other liver problems. However, liver problems from ARPKD tend to become more of a concern over time. […] Most children with ARPKD have high blood pressure. High blood pressure increases a child’s chances of heart disease and stroke. High blood pressure can also further damage a child’s kidneys.

• #2 Autosomal Recessive Polycystic Kidney Disease: ERKNet voor Patiënten

  https://www.erknet.org/patients/nl/your-kidney-disease/arpkd/disease-information

  Infants and children with ARPKD may experience growth and developmental delays, possibly due to chronic illness and nutritional issues. […] Some individuals with ARPKD may face cognitive and behavioral challenges, which can vary in severity. […] In rare cases, ARPKD can be associated with neurological complications, including seizures.

• #2 Autosomal Recessive Polycystic Kidney Disease | Doctor

  https://patient.info/doctor/autosomal-recessive-polycystic-kidney-disease

  Autosomal recessive polycystic kidney disease (ARPKD) is one of the most common ciliopathies with kidney (nephromegaly, hypertension, renal dysfunction) and liver involvement (congenital hepatic fibrosis, dilated bile ducts). Pulmonary hypoplasia may also occur. Clinical features also include growth failure and neurocognitive impairment.1 […] The presentation of the disease can be highly variable, even within the same family. There are a number of classifications but this is the one that is used most often and is based on age at presentation which is, in turn, related to disease severity:5 […] Category 1 presents perinatally: Infants are born with a very large abdomen due to massive renal enlargement and this may complicate delivery. About 90% of the collecting ducts are dilated but the liver is scarcely involved. Severe renal impairment in utero produces oligohydramnios and subsequent pulmonary hypoplasia. Other clinical findings resulting from oligohydramnios include Potter’s facies (flattened nose, micrognathia and large, floppy, low-set ears) and club foot. Approximately 75% of cases result in the death of the baby within a week of birth.

• #2 Autosomal Recessive Polycystic Kidney Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK537137/

  Early identification of patients with ARPKD has increased tremendously in the last few decades, with routine antenatal ultrasound usually showing very large, echogenic kidneys. Sometimes the kidneys are so enlarged they can interfere with normal vaginal delivery. […] Symptoms that develop in early childhood include urinary tract infections, gross hematuria, and renal osteopathy. […] Earlier (neonatal) diagnosis is associated with more severe kidney disease, while a later presentation tends to demonstrate milder degrees of renal impairment but more severe liver disease with portal hypertension. […] The prognosis depends on the severity of the pulmonary, hepatic, and renal disease. Neonates born with severe renal disease may not survive due to pulmonary hypoplasia and insufficiency, which may occur in up to 40% of cases. Neonatal mortality has improved due to advances in neonatal care but remains at about 20%. Those who survive the neonatal period have 10-year survival rates estimated at 82% but often develop progressive renal failure, hypertension, hepatic fibrosis, portal hypertension, and end-stage renal disease.

• #2 Autosomal recessive polycystic kidney disease: late-onset renal enlargement and proteinuria with rare PKHD1 mutation—a case report | Egyptian Journal of Medical Human Genetics | Full Text

  https://jmhg.springeropen.com/articles/10.1186/s43042-024-00568-5

  Autosomal recessive polycystic kidney disease (ARPKD) is a genetically inherited pediatric disorder. It is caused by a mutation in the PKHD1 gene located on chromosome 6. The predominant phenotype is characterized by early-onset bilateral enlarged kidneys, as well as fibrocystic changes in the kidney and liver. Fetuses or infants usually present with Potter syndrome, and they are more likely to develop severe renal insufficiency. Generally, patients die perinatally or in infancy. Liver involvement has been reported in adults with ARPKD who have survived the neonatal period and childhood. However, renal involvement is rarely expected in adulthood. […] The clinical manifestations include nephromegaly, hypertension, portal hypertension, and fibrocystic abnormalities in both kidney and liver. The renal burden of ARPKD is thought to decrease in adults, while the hepatic symptoms become more common.

• #2 Clinical courses and complications of young adults with Autosomal Recessive Polycystic Kidney Disease (ARPKD) | Scientific Reports

  https://www.nature.com/articles/s41598-019-43488-w

  Signs of hepatic involvement and portal hypertension such as thrombocytopenia or splenomegaly may be helpful for clinical guidance. A high level of suspicion is required to identify adult ARPKD patients and a specific work-up of liver involvement including the search for signs of portal hypertension should be considered in adult patients with cystic kidney disease.

• #3

  https://www.nhs.uk/conditions/autosomal-recessive-polycystic-kidney-disease-arpkd/symptoms/

  The symptoms of autosomal recessive polycystic kidney disease (ARPKD) can vary significantly, even within the same family. […] Generally, however, the main symptoms of ARPKD differ, depending on when the condition first becomes apparent. […] In many cases, potential signs of ARPKD can be detected before birth during routine ultrasound scans. […] If your baby has the condition, an ultrasound scan may show that: they have enlarged kidneys; their lungs are underdeveloped; there’s a lack of amniotic fluid surrounding your baby. […] When your baby is born, there may be clearer signs that suggest they have ARPKD, such as: significant breathing difficulties this is caused by the lungs being underdeveloped; a swollen tummy (abdomen) caused by enlargement of the kidneys; Potter’s syndrome where a lack of amniotic fluid leads to deformities of the limbs, face and ears; Potter’s syndrome is a possibility in severe cases of ARPKD.

• #3 Autosomal Recessive Polycystic Kidney Disease: ERKNet voor Patiënten

  https://www.erknet.org/patients/nl/your-kidney-disease/arpkd/disease-information

  The clinical presentation of ARPKD can vary widely. Common symptoms and complications may include enlarged kidneys, high blood pressure, urinary tract infections, abdominal pain, and liver problems. […] The early signs of ARPKD often appear during the first few months of life and in the womb. Early signs of ARPKD in the womb can cause serious health problems. […] An early sign of ARPKD is an enlarged kidney. Enlarged kidneys put pressure on a fetus or child’s lungs, which can make lung growth and breathing harder. […] Due to decreased kidney and lung function, children with ARPKD are usually smaller-than-average size, a condition called growth failure. […] Decreased kidney function can cause prenatally low levels of amniotic fluid in a mother’s womb. Low levels of amniotic fluid can cause lung hypoplasia and with it connected breathing problems.

• #3 Autosomal Recessive Polycystic Kidney Disease – NIDDK

  https://www.niddk.nih.gov/health-information/kidney-disease/polycystic-kidney-disease/autosomal-recessive-pkd

  The early signs of ARPKD often appear during the first few months of life and in the womb. Early signs of ARPKD in the womb can cause serious health problems. […] An early sign of ARPKD is an enlarged kidney. Enlarged kidneys put pressure on a fetus or child’s lungs, which can make lung growth and breathing harder. […] Due to decreased kidney and lung function, children with ARPKD are usually smaller-than-average size, a condition called growth failure. […] Decreased kidney function can cause low levels of amniotic fluid in a mother’s womb. Low levels of amniotic fluid can cause breathing problems in the fetus. […] Some people with ARPKD do not develop signs or symptoms until later in childhood, or even adulthood. […] Children with ARPKD who survive birth often have kidney and liver problems that can affect their breathing.

• #3 Polycystic kidney disease – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/polycystic-kidney-disease/symptoms-causes/syc-20352820

  Polycystic kidney disease symptoms can include: […] High blood pressure. […] Belly, side or back pain. […] Blood in the urine. […] A feeling of fullness in the belly. […] Increased size of the belly from enlarged kidneys. […] Headaches. […] Kidney stones. […] Kidney failure. […] Urinary tract or kidney infections. […] The symptoms often appear soon after birth. Sometimes, symptoms don’t appear until later in childhood or during the teen years.

• #3 Autosomal Recessive Polycystic Kidney Disease – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK537137/

  Autosomal recessive polycystic kidney disease (ARPKD) is a rare genetic disorder primarily affecting the kidneys and liver. Clinicians should recognize early signs such as enlarged, echogenic kidneys in utero or during infancy. ARPKD most commonly results from mutations in PKHD1, causing renal cysts and congenital hepatic fibrosis early in life. About half of the patients with ARPKD develop end-stage renal failure requiring renal replacement therapy (dialysis or kidney transplantation) within the first 2 decades of life. In addition, hepatic function must be closely followed, as portal hypertension, splenomegaly, and cholangitis are common, especially in older patients. […] The clinical presentation of ARPKD varies significantly, with some patients diagnosed at a young age having more severe symptoms than those diagnosed when older. ARPKD is always associated with liver bile duct malformations, both intrahepatic and extrahepatic. Liver manifestations vary from mild cholestasis to hepatic fibrosis, portal vein hypertension, esophageal varices, cholangitis, and cirrhosis.

• #3 Molecular Pathophysiology of Autosomal Recessive Polycystic Kidney Disease

  https://www.mdpi.com/1422-0067/22/12/6523

  Although the disease is called “autosomal recessive polycystic kidney disease,” a cystic liver phenotype plays a significant role in the disease, which explains why the primary gene is entitled “polycystic kidney and hepatic disease 1 (PKHD1),” with polycystic liver disease (PLD) being the principal extrarenal manifestation. These histological changes are the consequences of a developmental defect of the hepatic ductal plate termed, ductal plate malformation (DPM). DPM is also a common feature of other ciliopathies. Liver disease appears with increasing age of the patient. The first manifestation appears as congenital hepatic fibrosis (CHF) with variable dilatations of both intra- and extrahepatic bile ducts (Caroli syndrome). Over the course of ARPKD, liver disease presents with two main manifestations: portal hypertension due to progressive hepatic fibrosis; and cholangitis. Complications related to portal hypertension can include splenomegaly, thrombocytopenia, and esophageal varices, producing severe bleeding complications. There is some link between adult patients with ARPKD (more than 40 years) and the risk of developing hepatic tumors, especially cholangiocarcinoma. Interestingly, the hepatocellular function normally remains stable, with serum liver enzymes in the normal range, except for cholestasis parameters. With the current clinical methods, this fact makes it difficult to monitor the severity and progression of liver disease.

• #3

  https://www.nhs.uk/conditions/autosomal-recessive-polycystic-kidney-disease-arpkd/symptoms/

  For children with ARPKD, a number of problems affecting the liver can also develop. […] Internal bleeding can be rapid and severe, causing your child to vomit blood or pass stools that are very dark or tar-like. […] In ARPKD, the small tubes (tubules) that make up the kidneys can develop abnormally, causing bulges and fluid-filled sacs called cysts to form within them. […] This can lead to: polyuria where your child will need to pee frequently and may wet the bed; polydipsia an excessive and prolonged thirst. […] These symptoms increase the risk of dehydration, particularly if the child also has a high temperature, is vomiting, or has diarrhoea. […] Your child may have problems feeding because their enlarged kidneys take up most of the space in their abdomen. […] Some children with ARPKD do not grow at a normal rate.

• #3 Polycystic Kidney Disease | Nationwide Children’s Hospital

  https://www.nationwidechildrens.org/conditions/polycystic-kidney-disease

  Symptoms of autosomal recessive PKD can begin before birth. In most cases, the earlier the onset, the more severe the outcome. There are four different types of autosomal recessive PKD, depending on the child’s age when symptoms become evident: […] Children born with autosomal recessive PKD may develop kidney failure within a few years and often experience the following: High blood pressure, Urinary tract infections, Frequent urination. […] The disease also usually affects the liver, spleen, and pancreas, resulting in low blood cell counts, varicose veins, and hemorrhoids.

• #3 Autosomal Recessive Polycystic Kidney Disease | Doctor

  https://patient.info/doctor/autosomal-recessive-polycystic-kidney-disease

  Category 2 presents neonatally: Infants have palpable kidneys at birth. About 60% of the kidney is affected and there is mild liver disease. As renal impairment is often less severe in utero there is less risk of pulmonary hypoplasia but the kidney disease is progressive, usually causing death within a few months. […] Category 3 presents in infancy: This tends to present when babies are a few months old. Approximately 25% of renal collecting ducts are dilated, with moderate hepatic periportal fibrosis. There are enlarged kidneys and hepatosplenomegaly on examination. Affected babies and children often develop chronic kidney disease with or without portal and systemic hypertension. The principal cause of mortality is end-stage kidney disease, usually in adolescence. […] Category 4 presents in childhood: There is marked liver disease. Fewer than 10% develop end-stage kidney disease. The disease usually presents between 6 months and 5 years. There is variable renal enlargement and hepatosplenomegaly. Significant liver involvement results in portal hypertension. Morbidity and mortality are usually due to portal hypertension, including variceal bleeding and thrombocytopenia or anaemia from hypersplenism. Mortality is the lowest of the four categories, with around 80% surviving beyond the age of 15 years.

• #3 Autosomal recessive polycystic kidney disease, PKHD1-related | Myriad Foresight® Carrier Screen

  https://myriad.com/womens-health/diseases/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.

• #3

  https://journals.lww.com/cjasn/fulltext/2022/10000/perspectives_on_drug_development_in_autosomal.19.aspx

  Autosomal recessive polycystic kidney disease (ARPKD) is a rare hepatorenal fibrocystic disease that often presents prenatally or in the first year of life and remains a major cause of morbidity and mortality in pediatric nephrology. […] Typical clinical symptoms include bilateral cystic kidney disease presenting with organ enlargement and a variable degree of functional CKD. Prenatal kidney disease may result in oligo-/anhydramnios with subsequent pulmonary hypoplasia and severe perinatal respiratory disease. […] Clinical symptoms and courses can be highly variable, and current genotype-phenotype correlations can only partly explain this variability. […] Patients with ARPKD and biallelic PKHD1 variants predicted to result in complete loss of function of fibrocystin are associated with severe kidney and liver phenotypes.

• #4

  https://111.wales.nhs.uk/encyclopaedia/k/article/kidneydisease,autosomalrecessivepolycystic/

  The symptoms of autosomal recessive polycystic kidney disease (ARPKD) can vary significantly, even within the same family. […] Generally, however, the main symptoms of ARPKD differ, depending on when the condition first becomes apparent. […] In many cases, potential signs of ARPKD can be detected before birth during routine ultrasound scans. […] If your baby has the condition, an ultrasound scan may show that they have enlarged kidneys; their lungs are underdeveloped; there’s a lack of amniotic fluid surrounding your baby. […] When your baby is born, there may be clearer signs that suggest they have ARPKD, such as significant breathing difficulties caused by the lungs being underdeveloped; a swollen tummy (abdomen) caused by enlargement of the kidneys; Potter’s syndrome where a lack of amniotic fluid leads to deformities of the limbs, face and ears.

• #4 Autosomal Recessive Polycystic Kidney Disease – MD Searchlight

  https://mdsearchlight.com/genetic-disorders/autosomal-recessive-polycystic-kidney-disease/

  In the first 30 days post-birth, newborns might suffer serious breathing problems due to underdeveloped lungs. This is mainly because their exceptionally big kidneys compress their thorax which reduces their vital capacity. Within the initial few months, 75% of these infants could develop kidney problems and high blood pressure, which can be severe. […] Young children affected by the disease usually present several symptoms including urinary tract infections, blood in urine, and kidney-related bone disease. It is important to note that their cognitive function remains unaffected. […] If a newborn is diagnosed with ARPKD, the kidney disease tends to be more severe. However, if diagnosed at a later stage, the kidney impairment might be milder, but liver disease with portal hypertension might be more intense.

• #4

  https://link.springer.com/article/10.1007/s00467-013-2634-1

  Systemic hypertension, which usually develops within the first few months of life, affects up to 80 % of ARPKD children. It is very common in both infants and adolescents, even in patients with normal renal function, and the majority of children with ARPKD are severely affected. The pathogenesis of systemic hypertension in ARPKD is not completely understood. […] Hypertension can be difficult to control in affected children and may require multidrug treatment. Angiotensin-converting enzyme (ACE) inhibitors are the standard of care in ARPKD patients, although they have never been formally studied. […] Pulmonary hypoplasia is the leading cause of death during the perinatal/neonatal period. Approximately 30 % of affected children diagnosed with ARPKD die shortly after birth from respiratory distress as a result of limited diaphragmatic excursion, pulmonary hypoplasia, and thoracic compression caused by bilateral kidney enlargement. […] There is currently no cure for ARPKD. Treatment focuses on managing the clinical complications derived either directly or indirectly from this disease, such as pulmonary hypoplasia, chronic renal insufficiency, arterial hypertension, and liver/biliary disease.

• #4 Autosomal recessive polycystic kidney disease (ARPKD) | Kidney Care UK

  https://kidneycareuk.org/kidney-disease-information/kidney-conditions/autosomal-recessive-polycystic-kidney-disease-arpkd/

  There are currently no treatments that can cure or slow the progression of ARPKD. Treatment therefore aims to manage the symptoms and should be led by a specialist team with expertise in ARPKD. […] About six in 10 children with ARPKD will have developed kidney failure by the age of 10 and need dialysis or a kidney transplant.

• #4 Autosomal Recessive Polycystic Kidney Disease: ERKNet voor Patiënten

  https://www.erknet.org/patients/nl/your-kidney-disease/arpkd/disease-information

  ARPKD can lead to progressive damage to the kidneys, resulting in impaired kidney function over time. […] Cysts in the kidneys are a hallmark of ARPKD. These cysts can cause the kidneys to become enlarged and dysfunctional. […] Some individuals with ARPKD may experience gastrointestinal issues such as poor appetite, vomiting, or diarrhea. […] Yellowing of the skin and eyes (jaundice) may occur due to liver involvement. […] The progressive loss of kidney function can lead to kidney failure, which may require dialysis or kidney transplantation, before reaching adulthood. […] Most children with ARPKD have high blood pressure. High blood pressure increases a child’s chances of heart disease and stroke. High blood pressure can also further damage a child’s kidneys. […] ARPKD can also affect the liver, causing fibrosis (the formation of scar tissue) in the liver’s bile ducts. This can lead to liver problems, including hepatomegaly (enlarged liver) and, in severe cases, liver failure.

• #4 Autosomal recessive polycystic kidney disease | nidirect

  https://www.nidirect.gov.uk/conditions/autosomal-recessive-polycystic-kidney-disease

  If your child has high blood pressure, they’ll usually need to take medication to lower it and prevent long-term damage to their heart and blood vessels. […] Kidney abnormalities cause cysts (fluid-filled sacs) to form affecting kidney function, causing loss of too much body fluid as urine leading to thirst and dehydration. […] Most children with ARPKD will develop kidney failure by the time they’re 15 to 20 years old. […] Enlarged kidneys can take up most of the space in the abdomen (tummy) causing vomiting after eating and they may only be able to eat small amounts at a time, leading to malnourishment. […] Some children with ARPKD don’t grow at a normal rate. […] For children with ARPKD, a number of problems affecting the liver can also develop. […] The small tubes that allow bile (a digestive fluid) to flow out of the liver may develop abnormally and cysts may grow inside them.

• #4 Polycystic Kidney Disease in Children – Conditions and Treatments | Children’s National Hospital

  https://www.childrensnational.org/get-care/health-library/polycystic-kidney-diseases

  The liver cysts in ARPKD can cause scarring (fibrosis) in the liver, which can lead to increased pressure in the blood vessels of the liver (portal hypertension), causing blood flow to back up into vessels that surround the esophagus, stomach and intestines. Children with ARPKD who develop portal hypertension have increased risk of bleeding from these swollen blood vessels (varices), as well as an increased risk of infection in the liver cysts (cholangitis). They should be monitored and treated by a pediatric hepatologist. Liver function remains relatively normally in these children and the need for liver transplantation is rare.

• #4 Autosomal Recessive Polycystic Kidney Disease | Doctor

  https://patient.info/doctor/autosomal-recessive-polycystic-kidney-disease

  Moderate presentation is seen rarely in adults with complications of liver disease or with renal manifestations, such as proteinuria, nephrolithiasis and renal insufficiency.6 […] ARPKD shows a range of severity, with 30% of individuals dying early and the majority having good prognosis if they survive the first year of life.3 However, those who survive to adulthood still see progressive deterioration of renal function and risk of hepatic complications. Disease progression may have organ-specific patterns. In those with pulmonary hypoplasia the outlook is very poor and even ventilation is unlikely to save lives. Only a subset of patients may be at risk for developing clinically significant manifestations of periportal fibrosis.12

• #4 ARPKD basics

  https://pkdcharity.org.uk/arpkd/what-is-arpkd/arpkd-basics

  The severity of a child’s liver problems can vary from mild impairment to serious complications that can be life-threatening. […] Unfortunately, there are no proven treatments that can slow the progression of ARPKD. It’s possible that controlling blood pressure carefully might help to delay damage to the kidneys, but experts are not yet sure. […] The outlook for each child with ARPKD depends on the severity of their disease. As a general guide, the earlier the disease is diagnosed, the more severe it is. For example, a baby with obvious kidney problems at the routine scan will usually have a poorer outlook than a child who is diagnosed later in childhood. […] In general, ARPKD is a very severe disease: about 1 in every 3 babies with suspected or confirmed ARPKD dies from breathing problems during the first 4 weeks after birth. But, about 9 in ten 10 (89%) who survive the first 4 weeks of life are still alive at 5 years old. Encouragingly, most children now survive into adulthood and can live full and productive lives.

• #4 Molecular Pathophysiology of Autosomal Recessive Polycystic Kidney Disease

  https://www.mdpi.com/1422-0067/22/12/6523

  While a majority of ARPKD patients show similar disease progression, there are atypical phenotypes; among the elderly population, some ARPKD cases were reported as moderately affected or even exclusive or predominant phenotypes of either the liver or kidneys. This is related to the fact that although ARPKD is a recessive disease, in which heterozygous carriers should not show any clinical manifestation of the disease, the data suggest heterozygous for PKHD1 mutations have an increased risk of PLD and mild PKD.

• #5 Autosomal Recessive Polycystic Kidney Disease – NIDDK

  https://www.niddk.nih.gov/health-information/kidney-disease/polycystic-kidney-disease/autosomal-recessive-pkd

  The early signs of ARPKD often appear during the first few months of life and in the womb. Early signs of ARPKD in the womb can cause serious health problems. […] An early sign of ARPKD is an enlarged kidney. Enlarged kidneys put pressure on a fetus or child’s lungs, which can make lung growth and breathing harder. […] Due to decreased kidney and lung function, children with ARPKD are usually smaller-than-average size, a condition called growth failure. […] Decreased kidney function can cause low levels of amniotic fluid in a mother’s womb. Low levels of amniotic fluid can cause breathing problems in the fetus. […] Some people with ARPKD do not develop signs or symptoms until later in childhood, or even adulthood. […] Children with ARPKD who survive birth often have kidney and liver problems that can affect their breathing.

• #5

  https://www.nhs.uk/conditions/autosomal-recessive-polycystic-kidney-disease-arpkd/symptoms/

  Underdeveloped lungs is the biggest problem immediately after birth, and breathing assistance with a ventilator is often needed. […] Around 1 in every 3 babies with ARPKD who develop breathing difficulties soon after birth will die within a few weeks or months. […] 9 in 10 babies who survive the first 4 weeks are still alive at 5 years old, and most children now live into adulthood. […] About 6 in 10 children with ARPKD will need dialysis or a kidney transplant by the age of 10. […] ARPKD tends to be less immediately life threatening in infants and older children, although the condition can still cause a wide range of serious problems. […] High blood pressure (hypertension) is a common problem for children with ARPKD. […] If your child has high blood pressure, they’ll usually need to take medication to lower it and prevent long-term damage to their heart and blood vessels.

• #5 Symptoms – Polycystic kidney disease | PKD treatment research | PKD Foundation

  https://pkdcure.org/about-the-disease/arpkd/what-are-the-symptoms-2/

  In autosomal recessive polycystic kidney disease (ARPKD), symptoms can begin prenatally when small cysts form in a microscopic tube in the kidney called the collecting tubule. […] The majority of children with ARPKD experience progressive loss of kidney function. However, the age at which kidney failure develops varies greatly among patients. […] Prenatal ARPKD Symptoms: Diminished amniotic fluid levels, Enlarged kidneys, Lung underdevelopment, Lung functioning issues. […] Post-Birth ARPKD Symptoms: Enlarged kidneys, Breathing problems, Excessive urine production, Hypertension, Growth problems, Congenital hepatic fibrosis, Enlarged spleen, Low red and white blood cell count, Low platelet counts.

• #5 Clinical courses and complications of young adults with Autosomal Recessive Polycystic Kidney Disease (ARPKD) | Scientific Reports

  https://www.nature.com/articles/s41598-019-43488-w

  Liver disease appeared to present later in life. Hepatic disease in ARPKD comes with two main presentations. On the one hand portal hypertension may develop as a consequence of progressive hepatic fibrosis. Splenomegaly was documented only in one third of patients based on clinical examination but in 57% according to ultrasound. Since 42% of this sub-cohort of patients without previous LTx showed thrombocytopenia as a marker of hypersplenism, sonographic detection of splenomegaly may be more sensitive and appropriate. In contrast to this, hepatomegaly was clinically diagnosed in 30% of the patients, but sonographically confirmed only in 11% of all patients without previous LTx. […] A second aspect of liver involvement in ARPKD is cholangitis. Almost 10% of reported patients suffered from recent cholangitis at the timepoint of the cross-sectional study. The late presentation of cholangitis in our cohort may appear to be a sign of weak hepatic involvement in the group analysed here. Nonetheless, six of the 45 patients received CLKTx or LTx during childhood and adolescence.

• #5

  https://www.nhs.uk/conditions/autosomal-recessive-polycystic-kidney-disease-arpkd/symptoms/

  For children with ARPKD, a number of problems affecting the liver can also develop. […] Internal bleeding can be rapid and severe, causing your child to vomit blood or pass stools that are very dark or tar-like. […] In ARPKD, the small tubes (tubules) that make up the kidneys can develop abnormally, causing bulges and fluid-filled sacs called cysts to form within them. […] This can lead to: polyuria where your child will need to pee frequently and may wet the bed; polydipsia an excessive and prolonged thirst. […] These symptoms increase the risk of dehydration, particularly if the child also has a high temperature, is vomiting, or has diarrhoea. […] Your child may have problems feeding because their enlarged kidneys take up most of the space in their abdomen. […] Some children with ARPKD do not grow at a normal rate.

• #5 Autosomal Recessive Polycystic Kidney Disease | Doctor

  https://patient.info/doctor/autosomal-recessive-polycystic-kidney-disease

  Category 2 presents neonatally: Infants have palpable kidneys at birth. About 60% of the kidney is affected and there is mild liver disease. As renal impairment is often less severe in utero there is less risk of pulmonary hypoplasia but the kidney disease is progressive, usually causing death within a few months. […] Category 3 presents in infancy: This tends to present when babies are a few months old. Approximately 25% of renal collecting ducts are dilated, with moderate hepatic periportal fibrosis. There are enlarged kidneys and hepatosplenomegaly on examination. Affected babies and children often develop chronic kidney disease with or without portal and systemic hypertension. The principal cause of mortality is end-stage kidney disease, usually in adolescence. […] Category 4 presents in childhood: There is marked liver disease. Fewer than 10% develop end-stage kidney disease. The disease usually presents between 6 months and 5 years. There is variable renal enlargement and hepatosplenomegaly. Significant liver involvement results in portal hypertension. Morbidity and mortality are usually due to portal hypertension, including variceal bleeding and thrombocytopenia or anaemia from hypersplenism. Mortality is the lowest of the four categories, with around 80% surviving beyond the age of 15 years.

• #5 Autosomal Recessive Polycystic Kidney Disease | Doctor

  https://patient.info/doctor/autosomal-recessive-polycystic-kidney-disease

  Moderate presentation is seen rarely in adults with complications of liver disease or with renal manifestations, such as proteinuria, nephrolithiasis and renal insufficiency.6 […] ARPKD shows a range of severity, with 30% of individuals dying early and the majority having good prognosis if they survive the first year of life.3 However, those who survive to adulthood still see progressive deterioration of renal function and risk of hepatic complications. Disease progression may have organ-specific patterns. In those with pulmonary hypoplasia the outlook is very poor and even ventilation is unlikely to save lives. Only a subset of patients may be at risk for developing clinically significant manifestations of periportal fibrosis.12

• #5 Autosomal Recessive Polycystic Kidney Disease – MD Searchlight

  https://mdsearchlight.com/genetic-disorders/autosomal-recessive-polycystic-kidney-disease/

  Severe cases can show Potters sequence which includes severe oligohydramnios, underdeveloped lungs, limb deformities from compression in the womb like clubfeet or dislocated hips, and Potters facies. […] The outcome of patients with complications like lung, liver, and kidney disease depends on the seriousness of these conditions. Newborns with severe kidney disease might not survive due to lung underdevelopment and failure, which can happen in up to 40% of such cases. […] Despite advancements in newborn care leading to better survival rates, neonatal mortality still lies around 20%. Those who do survive the early days of life generally have a ten-year survival rate of approximately 82%. However, these individuals often experience worsening kidney failure, high blood pressure, liver scarring, portal hypertension, and end-stage kidney disease. Some reports indicate that over 90% of those who survive the neonatal period live until at least their 20th birthday.

• #5 Clinical courses and complications of young adults with Autosomal Recessive Polycystic Kidney Disease (ARPKD) | Scientific Reports

  https://www.nature.com/articles/s41598-019-43488-w

  ARPKD typically is a disease of early childhood. Yet, given the progress in neonatal and pediatric care more and more patients reach adulthood. The clinical courses and complications in adulthood have not been described in detail. We may thus be facing novel challenges and even newly detected symptoms for this well-known disease as more and more adult ARPKD patients are being treated. […] Our cohort of 45 young adults included in the cross-sectional analysis showed body dimensions within normal range despite the long-term disease courses. Importantly, almost half of the cohort showed stable native renal function in CKD stages 1-3. While some degree of survivor bias cannot be excluded, these findings are in accordance with previous observations and suggest that kidney function in ARPKD may be better preserved than widely anticipated. The additional renal disease manifestations documented in our cohort also are consistent with previous descriptions. Hypertension was very common and multi-drug antihypertensive therapy was required in some patients.

• #6 Autosomal Recessive Polycystic Kidney Disease: ERKNet voor Patiënten

  https://www.erknet.org/patients/nl/your-kidney-disease/arpkd/disease-information

  The clinical presentation of ARPKD can vary widely. Common symptoms and complications may include enlarged kidneys, high blood pressure, urinary tract infections, abdominal pain, and liver problems. […] The early signs of ARPKD often appear during the first few months of life and in the womb. Early signs of ARPKD in the womb can cause serious health problems. […] An early sign of ARPKD is an enlarged kidney. Enlarged kidneys put pressure on a fetus or child’s lungs, which can make lung growth and breathing harder. […] Due to decreased kidney and lung function, children with ARPKD are usually smaller-than-average size, a condition called growth failure. […] Decreased kidney function can cause prenatally low levels of amniotic fluid in a mother’s womb. Low levels of amniotic fluid can cause lung hypoplasia and with it connected breathing problems.

• #6

  https://www.nhs.uk/conditions/autosomal-recessive-polycystic-kidney-disease-arpkd/

  The outlook for children with ARPKD can vary considerably depending on the severity of the condition. […] But in general, ARPKD is a severe condition and around 1 in 3 babies will die from severe breathing difficulties during the first 4 weeks after birth. […] About 9 out of 10 babies with ARPKD who survive the first month of life will live until they’re at least 5 years old. […] It’s difficult to predict exactly how long a child with ARPKD will live because there’s very little data showing long-term survival rates.

• #6

  https://www.nhs.uk/conditions/autosomal-recessive-polycystic-kidney-disease-arpkd/symptoms/

  For children with ARPKD, a number of problems affecting the liver can also develop. […] Internal bleeding can be rapid and severe, causing your child to vomit blood or pass stools that are very dark or tar-like. […] In ARPKD, the small tubes (tubules) that make up the kidneys can develop abnormally, causing bulges and fluid-filled sacs called cysts to form within them. […] This can lead to: polyuria where your child will need to pee frequently and may wet the bed; polydipsia an excessive and prolonged thirst. […] These symptoms increase the risk of dehydration, particularly if the child also has a high temperature, is vomiting, or has diarrhoea. […] Your child may have problems feeding because their enlarged kidneys take up most of the space in their abdomen. […] Some children with ARPKD do not grow at a normal rate.

• #6

  https://www.nhs.uk/conditions/autosomal-recessive-polycystic-kidney-disease-arpkd/symptoms/

  Most people with ARPKD lose a significant amount of kidney function. […] Symptoms of kidney failure can include: poor appetite and weight loss; swollen ankles, feet or hands (oedema); shortness of breath; an increased need to urinate, particularly at night (nocturia); itchy skin; feeling sick. […] Most children with ARPKD will develop kidney failure by the time they’re 15 to 20 years old.

• #6 Autosomal recessive polycystic kidney disease | nidirect

  https://www.nidirect.gov.uk/conditions/autosomal-recessive-polycystic-kidney-disease

  The liver can also develop fibrosis (a process similar to scarring) which blocks the blood flow through the liver and increases the pressure in its delicate blood vessels (portal hypertension). […] Blood bypasses the liver and is diverted into veins in the lower gullet (oesophagus). If the veins get too big they can bleed, causing vomiting of blood. […] Portal hypertension also diverts blood to the spleen, causing it to become bigger than normal. When enlarged it can filter too many cells from the blood (including ones that help blood clot), increasing the risk of bleeding.

• #6 Autosomal Recessive Polycystic Kidney Disease | Doctor

  https://patient.info/doctor/autosomal-recessive-polycystic-kidney-disease

  Autosomal recessive polycystic kidney disease (ARPKD) is one of the most common ciliopathies with kidney (nephromegaly, hypertension, renal dysfunction) and liver involvement (congenital hepatic fibrosis, dilated bile ducts). Pulmonary hypoplasia may also occur. Clinical features also include growth failure and neurocognitive impairment.1 […] The presentation of the disease can be highly variable, even within the same family. There are a number of classifications but this is the one that is used most often and is based on age at presentation which is, in turn, related to disease severity:5 […] Category 1 presents perinatally: Infants are born with a very large abdomen due to massive renal enlargement and this may complicate delivery. About 90% of the collecting ducts are dilated but the liver is scarcely involved. Severe renal impairment in utero produces oligohydramnios and subsequent pulmonary hypoplasia. Other clinical findings resulting from oligohydramnios include Potter’s facies (flattened nose, micrognathia and large, floppy, low-set ears) and club foot. Approximately 75% of cases result in the death of the baby within a week of birth.

• #6 Autosomal recessive polycystic kidney disease: late-onset renal enlargement and proteinuria with rare PKHD1 mutation—a case report | Egyptian Journal of Medical Human Genetics | Full Text

  https://jmhg.springeropen.com/articles/10.1186/s43042-024-00568-5

  Autosomal recessive polycystic kidney disease (ARPKD) is a genetically inherited pediatric disorder. It is caused by a mutation in the PKHD1 gene located on chromosome 6. The predominant phenotype is characterized by early-onset bilateral enlarged kidneys, as well as fibrocystic changes in the kidney and liver. Fetuses or infants usually present with Potter syndrome, and they are more likely to develop severe renal insufficiency. Generally, patients die perinatally or in infancy. Liver involvement has been reported in adults with ARPKD who have survived the neonatal period and childhood. However, renal involvement is rarely expected in adulthood. […] The clinical manifestations include nephromegaly, hypertension, portal hypertension, and fibrocystic abnormalities in both kidney and liver. The renal burden of ARPKD is thought to decrease in adults, while the hepatic symptoms become more common.

• #6 Kidney Disease Progression in Autosomal Recessive Polycystic Kidney Disease.

  https://scholarlyexchange.childrensmercy.org/papers/270/

  Annualized GFR change in subjects with ARPKD was -1.4 mL/min/1.73 m(2) (-6%), with greater decline in subjects age 10 years (-11.5%). […] However, overall rates of GFR decline did not differ significantly in subjects with ARPKD vs controls. […] The relatively slow rate of GFR decline in subjects with ARPKD and absence of significant proteinuria suggest that these standard clinical measures may have limited utility in assessing therapeutic interventions and highlight the need for other ARPKD kidney disease progression biomarkers.

• #7 Autosomal Recessive Polycystic Kidney Disease – NIDDK

  https://www.niddk.nih.gov/health-information/kidney-disease/polycystic-kidney-disease/autosomal-recessive-pkd

  Babies with the most severe cases of ARPKD often die hours or days after birth because they cannot breathe well enough to live. Their lungs do not develop as they should in the womb. […] Children born with ARPKD often develop kidney failure before reaching adulthood. […] Liver scarring occurs in all cases of ARPKD and is usually present at birth. Liver scarring can lead to decreased liver function and other liver problems. However, liver problems from ARPKD tend to become more of a concern over time. […] Most children with ARPKD have high blood pressure. High blood pressure increases a child’s chances of heart disease and stroke. High blood pressure can also further damage a child’s kidneys.

• #7

  https://link.springer.com/article/10.1007/s00467-013-2634-1

  Systemic hypertension, which usually develops within the first few months of life, affects up to 80 % of ARPKD children. It is very common in both infants and adolescents, even in patients with normal renal function, and the majority of children with ARPKD are severely affected. The pathogenesis of systemic hypertension in ARPKD is not completely understood. […] Hypertension can be difficult to control in affected children and may require multidrug treatment. Angiotensin-converting enzyme (ACE) inhibitors are the standard of care in ARPKD patients, although they have never been formally studied. […] Pulmonary hypoplasia is the leading cause of death during the perinatal/neonatal period. Approximately 30 % of affected children diagnosed with ARPKD die shortly after birth from respiratory distress as a result of limited diaphragmatic excursion, pulmonary hypoplasia, and thoracic compression caused by bilateral kidney enlargement. […] There is currently no cure for ARPKD. Treatment focuses on managing the clinical complications derived either directly or indirectly from this disease, such as pulmonary hypoplasia, chronic renal insufficiency, arterial hypertension, and liver/biliary disease.

• #7

  https://www.nhs.uk/conditions/autosomal-recessive-polycystic-kidney-disease-arpkd/symptoms/

  Most people with ARPKD lose a significant amount of kidney function. […] Symptoms of kidney failure can include: poor appetite and weight loss; swollen ankles, feet or hands (oedema); shortness of breath; an increased need to urinate, particularly at night (nocturia); itchy skin; feeling sick. […] Most children with ARPKD will develop kidney failure by the time they’re 15 to 20 years old.

• #7 Clinical courses and complications of young adults with Autosomal Recessive Polycystic Kidney Disease (ARPKD) | Scientific Reports

  https://www.nature.com/articles/s41598-019-43488-w

  ARPKD typically is a disease of early childhood. Yet, given the progress in neonatal and pediatric care more and more patients reach adulthood. The clinical courses and complications in adulthood have not been described in detail. We may thus be facing novel challenges and even newly detected symptoms for this well-known disease as more and more adult ARPKD patients are being treated. […] Our cohort of 45 young adults included in the cross-sectional analysis showed body dimensions within normal range despite the long-term disease courses. Importantly, almost half of the cohort showed stable native renal function in CKD stages 1-3. While some degree of survivor bias cannot be excluded, these findings are in accordance with previous observations and suggest that kidney function in ARPKD may be better preserved than widely anticipated. The additional renal disease manifestations documented in our cohort also are consistent with previous descriptions. Hypertension was very common and multi-drug antihypertensive therapy was required in some patients.

• #7 ARPKD basics

  https://pkdcharity.org.uk/arpkd/what-is-arpkd/arpkd-basics

  The severity of a child’s liver problems can vary from mild impairment to serious complications that can be life-threatening. […] Unfortunately, there are no proven treatments that can slow the progression of ARPKD. It’s possible that controlling blood pressure carefully might help to delay damage to the kidneys, but experts are not yet sure. […] The outlook for each child with ARPKD depends on the severity of their disease. As a general guide, the earlier the disease is diagnosed, the more severe it is. For example, a baby with obvious kidney problems at the routine scan will usually have a poorer outlook than a child who is diagnosed later in childhood. […] In general, ARPKD is a very severe disease: about 1 in every 3 babies with suspected or confirmed ARPKD dies from breathing problems during the first 4 weeks after birth. But, about 9 in ten 10 (89%) who survive the first 4 weeks of life are still alive at 5 years old. Encouragingly, most children now survive into adulthood and can live full and productive lives.

• #8 Autosomal Recessive Polycystic Kidney Disease – NIDDK

  https://www.niddk.nih.gov/health-information/kidney-disease/polycystic-kidney-disease/autosomal-recessive-pkd

  Babies with the most severe cases of ARPKD often die hours or days after birth because they cannot breathe well enough to live. Their lungs do not develop as they should in the womb. […] Children born with ARPKD often develop kidney failure before reaching adulthood. […] Liver scarring occurs in all cases of ARPKD and is usually present at birth. Liver scarring can lead to decreased liver function and other liver problems. However, liver problems from ARPKD tend to become more of a concern over time. […] Most children with ARPKD have high blood pressure. High blood pressure increases a child’s chances of heart disease and stroke. High blood pressure can also further damage a child’s kidneys.

• #8 Autosomal recessive polycystic kidney disease in children – UpToDate

  https://www.uptodate.com/contents/autosomal-recessive-polycystic-kidney-disease-in-children

  Severely affected neonates generally present with respiratory distress due to pulmonary insufficiency. These patients are often diagnosed prenatally, and oligohydramnios is a common antenatal finding. […] During the neonatal period, infants can present with the following kidney manifestations, which may or may not be accompanied by respiratory distress. […] For patients who survive the neonatal period, there is improvement of kidney function due to continued renal maturation. However, over time progressive deterioration of kidney function develops, which may be rapid or slow, and often results in ESKD. […] Kidney function initially improves for the first three years of life but is followed by progressive decline of kidney function, which may result in ESKD. […] The outcome of ARPKD is dependent on the degree of kidney and hepatic involvement, which is most often reflected by the age of presentation. Severe disease and poor prognosis are associated with the presence of biallelic truncating variants. The mortality rate is greatest for patients who present as neonates with severe kidney disease associated with pulmonary insufficiency, with reported rates of 30 percent.

• #8 Clinical courses and complications of young adults with Autosomal Recessive Polycystic Kidney Disease (ARPKD) | Scientific Reports

  https://www.nature.com/articles/s41598-019-43488-w

  Liver disease appeared to present later in life. Hepatic disease in ARPKD comes with two main presentations. On the one hand portal hypertension may develop as a consequence of progressive hepatic fibrosis. Splenomegaly was documented only in one third of patients based on clinical examination but in 57% according to ultrasound. Since 42% of this sub-cohort of patients without previous LTx showed thrombocytopenia as a marker of hypersplenism, sonographic detection of splenomegaly may be more sensitive and appropriate. In contrast to this, hepatomegaly was clinically diagnosed in 30% of the patients, but sonographically confirmed only in 11% of all patients without previous LTx. […] A second aspect of liver involvement in ARPKD is cholangitis. Almost 10% of reported patients suffered from recent cholangitis at the timepoint of the cross-sectional study. The late presentation of cholangitis in our cohort may appear to be a sign of weak hepatic involvement in the group analysed here. Nonetheless, six of the 45 patients received CLKTx or LTx during childhood and adolescence.

• #9 Autosomal Recessive Polycystic Kidney Disease (ARPKD) | Concise Medical Knowledge

  https://www.lecturio.com/concepts/autosomal-recessive-polycystic-kidney-disease/

  In the 1st 3 years, survivors of the neonatal period experience a temporary improvement of renal function, followed by a decline. Kidney manifestations include protruding abdomen due to bilaterally enlarged kidneys, polyuria and polydipsia (usually the 1st signs of renal insufficiency), hypertension, metabolic acidosis, recurrent urinary tract infections, and urinary abnormalities such as proteinuria, glucosuria, hyperphosphaturia, and increased magnesium excretion in urine. […] Progression to chronic kidney disease (CKD) is characterized by cyst formation and fibrosis, and decreased renal function. […] Affected largely by the degree of renal and hepatic involvement (usually dependent on the age of presentation). Worst prognosis (mortality rate of 30%): presentation as a neonate with severe renal disease and pulmonary insufficiency. Survival past the 1st month: 80% chance of survival past 15 years old.

• #9 Molecular Pathophysiology of Autosomal Recessive Polycystic Kidney Disease

  https://www.mdpi.com/1422-0067/22/12/6523

  Although the disease is called “autosomal recessive polycystic kidney disease,” a cystic liver phenotype plays a significant role in the disease, which explains why the primary gene is entitled “polycystic kidney and hepatic disease 1 (PKHD1),” with polycystic liver disease (PLD) being the principal extrarenal manifestation. These histological changes are the consequences of a developmental defect of the hepatic ductal plate termed, ductal plate malformation (DPM). DPM is also a common feature of other ciliopathies. Liver disease appears with increasing age of the patient. The first manifestation appears as congenital hepatic fibrosis (CHF) with variable dilatations of both intra- and extrahepatic bile ducts (Caroli syndrome). Over the course of ARPKD, liver disease presents with two main manifestations: portal hypertension due to progressive hepatic fibrosis; and cholangitis. Complications related to portal hypertension can include splenomegaly, thrombocytopenia, and esophageal varices, producing severe bleeding complications. There is some link between adult patients with ARPKD (more than 40 years) and the risk of developing hepatic tumors, especially cholangiocarcinoma. Interestingly, the hepatocellular function normally remains stable, with serum liver enzymes in the normal range, except for cholestasis parameters. With the current clinical methods, this fact makes it difficult to monitor the severity and progression of liver disease.

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