ARPKD: Autosomal Recessive Polycystic Kidney Disease

You asked. We answered. Below you’ll find important information on ARPKD straight from some of the nation’s top nephrologists.

What is ARPKD?
Autosomal recessive polycystic kidney disease, ARPKD, is a rare genetic disorder, occurring in approximately 1 in 20,000 individuals. It affects boys and girls equally and often causes significant mortality in the first month of life.

If the child survives the newborn period, the chances of survival are good. For these children, approximately one-third will need dialysis or transplantation by the age of 10.

What causes ARPKD?
In recessive disorders such as ARPKD, the child must inherit a copy of the disease gene from each parent in order to be affected. Since the parents each have only one copy of the disease gene, they do not have the disease and are referred to as “carriers.” For carrier parents, there is a 25 percent chance in each pregnancy that both copies of the disease gene will be transmitted to the baby.

What is the kidney problem in ARPKD?
In ARPKD patients, small cysts form in the last section of the nephron called the collecting tubule. A cyst is a balloon-like widening of the tubule. In ARPKD, the abnormality always involves both kidneys. Due to the numerous nephrons with small balloon-like dilatations, the kidneys can become quite enlarged. In addition, the normal function of the collecting tubule is disrupted. In the normal kidney, the collecting tubule fine-tunes the amount of water and acid in the tubular fluid so that the body retains an appropriate amount of water and eliminates excess amounts of acid. In ARPKD patients, the cystic collecting ducts cannot retrieve water efficiently, causing much more urine production than in children with normal kidneys.

For ARPKD patients, the size of the kidneys and the degree to which their function is abnormal depends upon how many of the collecting ducts are cystic. For reasons that are not completely understood, the majority of ARPKD patients have a progressive loss of kidney function. However, the age at which kidney failure develops varies greatly among patients.

View a presentation on Chronic Kidney Disease and ARPKD (PDF) from the 2007 National Convention on PKD.

Are only the kidneys affected in ARPKD?
ARPKD affects both kidneys and the liver. Affected children may have significant kidney involvement at the time of birth, meaning very enlarged kidneys and decreased urine production. In utero, urine production is a critical factor in maintaining normal amniotic fluid levels. When amniotic fluid levels are very low, lung development can be impaired. In some newborns with low levels of amniotic fluid, impaired lung development can result in serious breathing difficulties that ultimately can cause death.

Children with ARPKD often produce very large volumes of urine and must urinate much more frequently than children with normal kidneys. Given the kidney abnormality, urine production in ARPKD children does not slow down at night or even when liquid intake is limited.

About one-third of children with ARPKD who live beyond the newborn period will require dialysis and kidney transplantation by 10 years of age. High blood pressure is very common in children with ARPKD, and current information indicates that untreated high blood pressure can lead to kidney failure more quickly than if the blood pressure is kept within the normal range with medications.

Children with ARPKD also have the liver abnormality called congenital hepatic fibrosis that may lead eventually to enlargement of the liver and spleen. In the liver, the abnormality can impede the return of blood from the intestine to the liver. This condition, called portal hypertension, can lead to distention (varices) and increased pressure in the veins around the esophagus, the stomach, and the intestine. These varices can rupture, leading sometimes to life-threatening gastro-intestinal bleeding. In addition, portal hypertension can cause splenic enlargement and hypersplenism, with resulting low red blood cell, white blood cell and platelet counts.

To learn more, download a presentation on Liver Disease and ARPKD (PDF) from the 2007 National Convention on PKD.

At the convention, there was also a presentation on Nutrition and ARPKD (PDF), which may be helpful.

How is ARPKD diagnosed in affected fetuses?
Typically in ARPKD, the kidneys appear to be larger than normal. In some babies, prenatal ultrasound can detect the enlarged kidneys as early as 18 weeks after conception.

Prenatal genetic testing is possible using samples from either chorionic villus sampling or amniocentesis. These genetic tests can either involve a direct search of the gene for mutations or an indirect association using linkage analysis. For linkage analysis, DNA samples are required from the fetus, a previously affected child, and the parents.

Another option for pre-natal diagnosis is a recently developed procedure called pre-implantation genetic diagnosis, or PGD. This is an early form of genetic diagnosis that involves the detection of specific genetic abnormalities in single cells taken from fertilized human embryos. The PGD procedure involves in vitro fertilization whereby eggs harvested from a mother are fertilized in a laboratory with the father’s sperm. Then, the fertilized embryos are tested for a specific genetic disorder (such as ARPKD) by removing one or two cells for genetic analysis. Embryos that are diagnosed as free of the disorder are then placed in the uterus with the intent to initiate a pregnancy; embryos that test positive for the disorder are destroyed.

If my child does not have ARPKD but is a carrier of the disease gene, what does that mean?

At the present time, the conventional wisdom is that carriers of the disease gene will not experience any of the typical features of ARPKD.

What is the transplant process like for a child with ARPKD?
Children with ARPKD who are kidney transplant candidates undergo the same evaluation as any other child with kidney failure who is in need of a transplant. The evaluation will include the performance of a physical examination, laboratory tests, and radiology tests (X-rays). The child will need to be seen by a dentist to make sure that their oral health is good, and they will require an assessment of their nutritional status by a dietitian. If the child’s immunization status is not up to date, additional vaccines will be given prior to the transplant to minimize the risk for infection. Especially pertinent for the child with ARPKD is the decision regarding removal of their native kidneys. The kidneys may be removed prior to or at the time of the transplant to help control high blood pressure and/ or to permit room for the transplant in patients with extremely large kidneys. Finally, a social work/psychology evaluation is necessary to evaluate readiness for transplant and to provide support because of the psychosocial stress that may have developed in the child and family surrounding the development of kidney failure and the preparation for transplantation.

The child will generally remain in the hospital for 1-2 weeks following the kidney transplant. They will be started on a variety of medications, including those which help prevent rejection of the kidney and others which help prevent infection. Education of the child and caregiver will also take place at this time and will address such issues as the roles of the different medications, the importance of regular blood pressure assessment at home, the schedule for blood tests following hospital discharge and the quantity of fluid that the child is expected to take every day.

Regular follow-up of the child by his/her physician and the transplant team following receipt of a kidney transplant is imperative. Laboratory studies will be obtained frequently to monitor the function of the kidney and repeated assessments of growth and nutritional status will take place. The success of kidney transplantation and the prolonged survival of children with ARPKD who develop kidney failure also makes it imperative that monitoring for the development of complications related to congenital hepatic fibrosis (CHF), such as portal hypertension, occurs. Complications of CHF have occurred in as many 80% of transplanted patients with ARPKD.

How can family members become kidney donors for my child with ARPKD and how soon should testing begin?
Family members who are interested in becoming a kidney donor for a child with ARPKD should inform the child’s medical team about their interest. Education about the donation process will be provided. Testing of potential donors will typically occur under the direction of the transplant team and can begin whenever there is evidence of progressive kidney failure in the affected child that will result in the need for a kidney transplant either before or following the initiation of dialysis. Typically, the donor must be at least 18 years of age. In the case of the individual who is felt to be an excellent candidate, an extensive evaluation will take place and will include a physical examination, as well as a laboratory, radiology and psychological assessment. Family members who are acceptable as donors must be in excellent health.

Will my child be able to have children and if so, will their children also have ARPKD?
Since ARPKD does not directly involve the reproductive system, merely having the disorder does not decrease the chances of having children. However, the presence of medical complications of ARPKD such as kidney failure can decrease the likelihood of a successful pregnancy. The child born to a parent with ARPKD can only develop ARPKD themselves if their other parent is a carrier for the disorder. Overall, the chance that a child born to a parent with ARPKD will NOT have the disorder themselves is > 99%.

How many children with ARPKD die in the first month of life? If they survive the first month, what is their life expectancy?
Approximately 70% of newborns diagnosed with ARPKD survive the first month of life. Those who do not survive are typically the patients who are born with extremely underdeveloped lungs (pulmonary hypoplasia) that result from the presence of massively enlarged kidneys. The largest study available which has evaluated the long-term course of patients with ARPKD who survived the neonatal (first month) period, found that patient survival was 82% at 10 years.

If my child dies from ARPKD, should I have his/her cord blood preserved for genetic testing?
Although the gene responsible for ARPKD has been identified and cloned, a simple diagnostic test that can be used clinically to assist in the diagnosis of the disorder is not available. In part, this is related to the very large size of the gene. However, while it may not currently be recommended to preserve cord blood or DNA from a child at risk for having ARPKD for diagnostic purposes, frequent improvements in genetic testing capabilities makes this a question that should be posed to your physician.

Will all of my children have ARPKD?
Parents of a child with ARPKD should be informed that each new child they have will have a one in four chance of developing the disorder and a one in two chance of being a carrier of the disorder. Those children who are carriers are unaffected by ARPKD and males and females are equally at risk for the its development.

How can I know whether my next child will have ARPKD?
Prenatal diagnosis of ARPKD is possible in “at-risk” families, or those families in whom there has already been at least one child with the diagnosis of ARPKD, by using a genetic testing technique called linkage analysis. Most important is the fact that this is an indirect approach to the diagnosis and the accuracy of the technique is completely dependent on confirmation of the diagnosis in the previously affected sibling. The prenatal diagnosis may also be suggested after 24 weeks of gestation in severe cases by the antenatal ultrasound findings of enlarged kidneys, little amniotic fluid and the absence of urine in the bladder.

How will ARPKD affect my child’s experience in school, academically and socially?
Many children with ARPKD or another chronic illness are forced to miss class for doctor visits, and frequent absences may lead to academic challenges. Socially, children may be self-conscious about how they look compared to other children their age. Short stature and enlarged abdomens are common appearance issues children with ARPKD may face.

Also, children with ARPKD often have to urinate frequently and sometimes have accidents. This can be avoided by encouraging children to use the bathroom every two hours. Finally, some high blood pressure medications can cause sleepiness, which can be a problem in the classroom. Currently, there isn’t any research on whether high blood pressure and blood-pressure control medications causes behavior problems. Parents and children can get help dealing with these academic and social issues by speaking with a developmental specialist.

Can my child play sports?
Contact sports such as football, hockey and basketball can place children at increased risk for popping or tearing a cyst. For children with extremely large kidneys, even running can be uncomfortable. However, there are ARPKD patients who are cyclists, runners and swimmers. Sports are not out-of-the-question but should be considered on an individual basis, depending on the child’s health and the intensity of the sport. Regardless of the athletic endeavor, it is very important for children to stay well-hydrated.

What kinds of medications might my child need to take on a daily and weekly basis?
ARPKD children will likely have to take blood pressure medication daily. Other common supplements include Vitamin D, iron, bicarbonate and citrate. Anemic children may need additional medications. Children experiencing growth problems may take growth hormones, if proper nutrition isn’t helping.

How often will my child need to see a doctor?
Your pediatric nephrologist will tailor the frequency of visits to your child’s needs, but most children will need several visits a year. If a child’s blood pressure needs a lot of attention, he or she may need to be seen more often. When the kidney function has fallen to levels where dialysis or transplantation is necessary, extra visits will be required.

What kinds of doctors might my child need to see?
A pediatric nephrologist is a specialist who has been trained in the care of children with kidney diseases. It is important that this type of doctor is involved with your child, since ARPKD is such an uncommon disease. If your child also has liver disease, they will also need to see a hepatologist. Sometimes ARPKD children require a lung specialist too. But first and foremost, you should have a good general pediatrician who can do most of the medical check-ups and coordinate your child’s health care team.

How can I find doctors experienced in treating children with ARPKD?
Your child’s pediatrician is your first point of reference and should refer you to an experienced pediatric neprhologist in your area. Very often it is necessary to travel to see the pediatric nephrologist for an initial evaluation and then to visit at intervals. Between those visits the pediatric nephrologist and your pediatrician can coordinate your child’s specific care. It is very important that your pediatrician be skilled in handling high blood pressure in children. If your pediatrician can’t refer you to a pediatric nephrologist or you’d like a second opinion, you may want to contact the Coordinators of the PKD Foundation’s National ARPKD Chapter, Julia Roberts and Kirsten Sclater-Booth. Julia can be reached at 404-636-9382 or julia@robertsresource.com, and Kirsten can be reached at 914-763-3795 or kirstensb@yahoo.co.uk.

How often do children with ARPKD need a transplant?
As a general rule, the earlier kidney failure sets in, the sooner the child will require a transplant. Some ARPKD children will not require a transplant until adulthood; others, who are born with high blood pressure and advanced kidney problems, for example, may need a transplant in childhood. Transplantation typically last between 15 and 20 years, so children who receive transplants will likely need another one sometime in that time frame.

What age can I expect my child to either need dialysis or a kidney transplant?
For those children who survive the newborn period, dialysis or transplantation can be offered when kidney failure occurs. The best treatment option depends on the age of the child, other health problems and whether there is a center nearby that can care for children with this disorder. It is advisable to have infants on dialysis until the child has grown enough to perform a transplant. It is usually best for small children to receive transplants in a hospital center that has extensive pediatric transplant experience. When children develop kidney failure at an older age, dialysis and transplantation tends to be an easier process.

What is dialysis and how does it work for a child with ARPKD?
Dialysis is a treatment that can only remove waste products from the body; it does not allow the body to completely replace all of the functions of a normal kidney. Some of the important hormones and other factors that the kidney produces can be taken by pill or injection. Often, it is necessary to offer tube feeding when a small child is undergoing dialysis to assure adequate nourishment for good growth. For these reasons, transplantation is usually a better long-term treatment than dialysis. As noted, though, it may be better to offer dialysis until the child grows to a larger size, which will increase the chances of successful transplantation.

Thanks to the Following Pediatric Nephrologists:

Lisa M. Guay-Woodford, M.D., is a Pediatric Nephrologist, Professor of Medicine and Director of the Division of Genetic and Translational Medicine at the University of Alabama at Birmingham. She is also a member of the PKD Foundation’s Scientific Advisory Committee.

Jeff Saland, M.D., is an Assistant Professor of Pediatrics at the Mount Sinai School of Medicine (MSSM) and the director of the pediatric nephrology fellowship training program at that institution.

Lisa Satlin, M.D., is a Professor of Pediatrics and Medicine at the Mount Sinai School of Medicine (MSSM), where she is the Chief of the Division of Pediatric Nephrology and Co-Director of the MD/PhD Training Program. She is also a member of the PKD Foundation’s Scientific Advisory Committee.

Bradley A. Warady, M.D., is Chief of Nephrology and Director of Dialysis and Transplantation at The Children's Mercy Hospital, and Professor of Pediatrics at the University of Missouri-Kansas City School of Medicine.

For information on the ARPKD Chapter please click here or email
ARPKDchapter@pkdcure.org.