By Beatrice Goilav, MD, Lisa M. Saltin, MD, and Jeffrey M. Saland, MD

There are two major types of polycystic kidney disease (PKD) that can affect children. These are both genetic diseases, caused by abnormal changes (mutations) in the DNA. The autosomal dominant (ADPKD) form implies that one of the parents has the disease as well, although they may not know it when their child is diagnosed. The autosomal recessive (ARPKD) form is caused by a gene that both parents carry, but does not cause the disease in either of them, because only the combination of the two abnormal genes leads to illness. ARPKD is a relatively rare disease, diagnosed in only 1 out of 20,000 newborns, whereas ADPKD is much more common, present in 1 out of as many as 1000 newborns.

The clinical manifestations of AR- and ADPKD can be highly variable. However, ARPKD is typically more likely to cause severe disease in children than ADPKD. In fact, information from the United States Renal Data System shows there are three times as many children with kidney failure from ARPKD than from ADPKD.

Even before birth, ARPKD often affects the fetus. Reduced kidney function reduces the amount of amniotic fluid and this, along with kidney enlargement, may be detected on prenatal sonograms. In some cases, these problems do not allow normal lung development leading to immediate, life-threatening breathing problems at birth. In the past, many babies with ARPKD did not survive the first 24 hours of life. ARPKD is characterized by severe kidney enlargement as the normal kidney structure is destroyed by numerous fluid-filled cysts (small sacs). The liver can be damaged by congenital hepatic fibrosis, a “scarring” of the liver and subsequent loss of function, which may require a liver transplant.
Drainage of bile from the liver to the intestine can be impaired, putting the child at risk for infection and gallstones. Frequently, children with ARPKD have very high blood pressure. Polycystic kidneys may fail to conserve water and salt, therefore placing children, especially the youngest, at risk of dehydration. As the kidney function worsens, the child with ARPKD may develop anemia and require intermittent injections of erythropoietin, a hormone normally produced by the kidney, which stimulates the production of red blood cells. Almost all children with ARPKD have problems with growth. Not only does kidney failure itself slow growth, but children with kidney insufficiency or failure need more calories than healthy children. In addition, the enlarged cystic kidneys can, by pressing on the intestines and stomach, cause loss of appetite, a situation that occasionally necessitates removal of a kidney.

Although the abnormal gene that causes ADPKD is present at birth, the disease does not typically manifest until 30-40 years of age. Patients with ADPKD can develop cysts in the kidneys, liver and pancreas. Bleeding into cysts is a common problem for patients with ADPKD. A small percentage of families with ADPKD also have intracranial aneurysms, which are bulges in the blood vessels inside the brain, which can burst and lead to a stroke. ADPKD may be discovered in a child because the kidneys may be big enough to be felt as a lump in the belly, sides or back. Some children are diagnosed after their pediatrician detects an abnormal urine or blood test or high blood pressure. A child with ADPKD can also develop fever and flank pain if a cyst becomes infected. Kidney insufficiency or failure from ADPKD could make a child become pale or weak from anemia or have stunted growth.

Fortunately, major breakthroughs in prenatal and neonatal care have improved the survival of affected children significantly. Prenatal sonogram technology continues to improve and has become more routine, allowing doctors to diagnose many cases of PKD prior to birth. Accordingly, the birth of an affected child is better planned so the necessary specialists can be alerted. Importantly, the doctors are able to discuss with the parents what they should expect once the baby is born, advising them that the infant may need a breathing tube, may require dialysis, may have severe liver disease, and will require multiple evaluations and treatments to deal with associated complications. Indeed, it is in the area of neonatal intensive care that major advances in the care of PKD have been made. Particularly encouraging is recent data indicating that infants with ARPKD surviving the first month of life are likely to reach adulthood.

Pediatric nephrologists are the main specialists in the care of children with PKD from before birth until adulthood. An important advance in treating childhood PKD is the realization that hypertension worsens the disease. Because the last 10-15 years have seen an increase in the availability and safety data for medications used to treat pediatric hypertension, particularly ACE inhibitors, this aspect of care has greatly improved. Still, as PKD progresses, kidney removal may be required if the child has uncontrollable high blood pressure. Pediatric nephrologists also supervise dialysis in children, which may be required if the kidneys fail or if they are removed.

One of the goals of care is to maintain a good quality of life, particularly focused on helping the child grow and develop as normally as possible. There are many potential hurdles to overcome for children with PKD and usually an entire team of medical specialists is formed including nephrologists, surgeons, liver specialists, lung specialists, nutritionists and others. The medical team must be firmly anchored by the family itself and it is clear the active involvement of school and community organizations is integral to the child’s overall well-being.

The ultimate treatment of kidney failure for patients with PKD is kidney transplantation. Family members without PKD or even unrelated healthy people may be able to donate a kidney, and children can enter the waiting list for a kidney transplant from a deceased donor. It is technically very difficult to perform a kidney transplant in babies and generally an infant must be helped to grow for the future possibility of a successful transplant. Sometimes, the infant needs to be provided extra calories given through a tube inserted directly into the stomach. Many centers now perform kidney transplants in children as young as 1-2 years of age. If a child with ARPKD has severe liver disease, a liver transplant (regardless of age) may also be required.

The care of children with PKD in the last decades has greatly improved. Not only do the majority of children with severe kidney disease survive the critical neonatal period, but they are also able to lead more normal lives with few hospitalizations and better growth and development. Improved care of pediatric hypertension and the development of novel therapies, including some medications now under investigation to slow or stop cyst growth, are likely to have a major impact in the future.

Beatrice Goilav, MD, Lisa M. Saltin, MD, and Jeffrey M. Saland, MD, are members of the Mount Sinai School of Medicine, Department of Pediatrics, Division of Pediatric Nephrology in New York, NY.

This article originally appeared in the November 2007 issue of aakpRENALIFE.

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