Renal agenesis is the failure of kidney formation during fetal development. Renal agenesis can be unilateral, with one kidney present, or bilateral, with no kidneys or very little kidney present. The two types of renal agenesis have very different clinical courses, with unilateral agenesis being more favorable.
Description
Kidneys perform many important bodily functions. Having at least one kidney is necessary for life. Kidneys filter waste and extra fluid from the blood, keep a healthy blood level of electrolytes and minerals, such as sodium, phosphorus, calcium, and potassium, help to maintain healthy blood pressure, and release hormones that are important for bodily functions. Normally, there are two fist-sized kidneys present, one on each side of the spinal column at the back just below the ribcage. Each kidney contains microscopic filter lobules called nephrons that transfer bodily waste products from the bloodstream to the urinary system. Functional nephrons are critical for maintaining bodily functions and for eliminating the buildup of waste products that can be life-threatening.
Unilateral renal agenesis
No treatment is necessary for unilateral renal agenesis other than controlling complications if they arise. Kidney function is monitored by regular physical examinations that check blood pressure and blood and urine tests. These tests are usually done once a year, and are designed to assess whether the unilateral kidney is functioning properly. Regular monitoring is critical because if the solitary kidney becomes diseased or damaged, there is no back-up kidney available to maintain life.
Normal blood pressure is defined as a measurement of 120/80 or lower. High blood pressure is defined as a measurement of 140/90 or higher. Individuals with unilateral renal agenesis are advised to maintain blood pressure levels below 130/80 to prevent kidney damage. If medication is required to control blood pressure, individuals with unilateral renal agenesis may need blood pressure medications that also protect kidney functions. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers are two classes of blood pressure medication that can also protect kidney function and reduce proteinuria. Diuretics may also be used to help lower blood pressure by removing excess fluid from the body.
Individuals with unilateral renal agenesis do not need to follow a special diet, but should limit daily sodium intake to avoid developing high blood pressure. While a special diet is not required, some methods of dieting are contraindicated. High-protein diets are not advised for individuals with unilateral renal agenesis. Because protein breakdown products add stress to the kidneys as they remove waste from the bloodstream, excessive protein intake puts an extra burden on the solitary kidney. Normal, moderate amounts of protein intake are recommended in unilateral renal agenesis. Alcohol and caffeine intake should also be limited. Individuals with unilateral renal agenesis are often advised to avoid contact sports unless protective gear is worn. Damage to the single functional kidney could quickly become life-threatening.
Bilateral renal agenesis
Neonates born with bilateral renal agenesis are immediately placed in the neonatal intensive care unit. The level of renal and respiratory function is immediately assessed. Evaluation is also made of any other malformations in bodily systems. Once the long-term prognosis of survival is determined, a treatment plan can be addressed. If a neonate with bilateral renal agenesis has severe respiratory distress from severe pulmonary hypoplasia, no further treatment may be the decided course of action. If lung development is sufficient to respond to treatment, mechanical ventilation can supply respiratory support. Management of renal failure involves a complex course of action taken to address all the consequent complications. Adequate nutrition with restricted sodium and fluid intake may be achieved through a nasogastric feeding tube. Medications and vitamin supplementation can be used to address electrolyte imbalances from lack of kidney function. Because the kidney is responsible for vitamin D formation, vitamin D therapy is important. Calcium carbonate is also supplemented because the kidneys are not present to regulate calcium levels in the blood.
Children with chronic renal failure often have poor growth and require supplemental human growth hormone (Genotropin, Humatrope, Nutropin). Human growth hormone stimulates the growth of bone, skeletal muscle, and organs. Human growth hormone acts in conjunction with another medication, erythropoietin, to increase the number of red blood cells and address the additional complication of anemia. Anemia occurs because the kidneys are not present to produce erythropoietin, which is responsible for the stimulation of red blood cell production in the bone marrow. Epoetin alfa (Epogen, Procrit) is a synthetic form of erythropoietin used in the treatment of bilateral renal agenesis. Anemia is also treated with iron supplements, which can be given orally or administered through an injection.
Renal failure causes hypertension; infants with bilateral renal agenesis may require hypertension medications in addition to restricted sodium and fluids. In renal failure, hypertension is caused by fluid overload. To treat the hypertension associated with bilateral renal agenesis, diuretic agents (Lasix) are used. Diuretic agents promote the excretion of water and electrolytes from the body. They decrease blood pressure by decreasing the amount of fluid present in the blood vessels. Other hypertensive medications may also be used, as is appropriate for the patient's age. Dialysis is required to function as a blood filter replacement for the kidney. Frequent dialysis treatments remain necessary until the infant is old enough to receive a kidney transplant.
Genetic profile
Bilateral renal agenesis (BRA) is a rare condition thought to occur in sporadic and autosomal recessive forms. Sporadic forms of BRA have an unknown cause that may or may not be genetic. It is thought that BRA can be inherited in an autosomal recessive form, caused by the inheritance of two defective copies of a gene. Each parent contributes one copy of a gene. In autosomal recessive inheritance, if both copies are defective, the result is disease. If only one defective copy is present, the disease does not occur, but the defective gene can still be passed on to subsequent generations. If both parents are carrying a defective gene, each offspring has a one in four (25%) chance of inheriting the disease. Populations with a high frequency of healthy individuals carrying defective genes will also have higher prevalence of offspring with the disease.
BRA is also more common when a parent has a distinct kidney malformation, especially unilateral renal agenesis. Research has demonstrated that unilateral renal agenesis and bilateral renal agenesis are genetically related. For this reason, when bilateral renal agenesis is detected in an infant, an ultrasound is performed on the kidneys of parents and siblings. Approximately 9% of first-degree relatives of infants with bilateral renal agenesis have some type of asymptomatic renal malformation.
As of 2005, the exact genetic causes of both unilateral and bilateral renal agenesis are unknown. It is speculated that both conditions are caused by mutations in the genes involved in fetal kidney development. Normal fetal kidney development involves an essential interaction between the forming kidney buds (ureteric bud) and a tissue known as the metanephric mesenchyme. The interaction of the ureteric bud with the metanephric mesenchyme is necessary for kidney formation. The interaction is controlled by a combination of genes, cellular-signaling molecules that control gene expression (transcription factors), and cellular-signaling molecules that control cell growth (growth factors). Animal studies have identified several of the factors that can be mutated to cause renal agenesis. Research is ongoing to determine the cause in humans.
As of 2005, the cutting edge of renal agenesis research is at the Potter syndrome tissue bank where scientists are running experiments on tissue donations from parents of children born with bilateral renal agenesis. Researchers are collecting tissue samples from the neonates and blood samples from family members in an effort to discover the gene mutations responsible for the condition. The Potter syndrome tissue bank is the only one of its kind in the world.
Demographics
Unilateral kidney agenesis is fairly common, occurring in approximately one per 1,000 live births in the United States. Bilateral renal agenesis occurs in one per 3,000 live births. There is no association of renal agenesis with race. Males have a higher rate of developing Potter syndrome than females. Individuals with bilateral renal agenesis present with the condition as neonates, whereas individuals with unilateral renal agenesis may not be aware of their condition even as adults. Unilateral renal agenesis is usually discovered in an adult undergoing tests for some other condition.
Prognosis
In the absence of kidney injury or disease, the prognosis for unilateral renal agenesis is excellent. Individuals with unilateral renal agenesis usually lead normal, healthy lives. Avoidance of injury and basic health practices are important to maintain this quality of life.
Bilateral renal agenesis has a very poor prognosis. It is usually fatal in the first few days of life. The usual cause of death is respiratory failure and acute renal failure during the neonatal period. If survival progresses to early childhood, patients may have chronic lung disease or chronic renal failure. If the lungs have sufficient development, a kidney transplant is necessary for survival. After a kidney transplant, the prognosis is improved.
BOOKS
Moore, Keith L., and T. V. N. Persaud. The Developing Human, Clinically Oriented Embryology, Seventh Edition. St. Louis, MO: Elsevier Science, 2003.
National Kidney and Urologic Diseases Information Clearinghouse. 3 Information Way, Bethesda, MD 20892-3580. (800) 891-5390. E-mail: nkudic@info.niddk.nih.gov. (April 22, 2005.) <http://kidney.niddk.nih.gov/about/index.htm>.
Potter's Syndrome Support Group Main Forum. (April 22, 2005.) <http://forums.delphiforums.com/n/main.asp?webtag=potterssyndrome&nav=start&prettyurl=%2Fpotterssyndrome%2Fstart>.
