A one month old female is brought to her pediatrician with a chief complaint of an abdominal mass. Her mother noticed the mass earlier in the week and immediately made an appointment to see the pediatrician. The mother also notes that the infant has been frequently wetting her diapers, although there is no history of fever, vomiting or diarrhea. The infant's perinatal and birth history are unremarkable (spontaneous vaginal delivery at term with a birth weight of 2750 grams). There is a family history of cystic kidneys in the infant's 14 year old brother. The infant's four other brothers and sisters do not have any renal disease and both parents do not have a history of renal disease.
Exam: VS T 37.5, P 110, R 26, BP 115/85, Weight 3.32 kg (10th percentile). She is alert and active, in no distress. Her physical exam is unremarkable except for a nontender 7 cm by 8 cm left-sided abdominal mass.
Urinalysis reveals cloudy urine, positive for leukocyte esterase and nitrites. A renal ultrasound is ordered and reveals bilateral enlargement of her kidneys with diffuse echogenicity and microcysts. A hepatic ultrasound reveals periportal fibrosis. The infant is diagnosed with autosomal-recessive polycystic kidney disease and a possible urinary tract infection. She is hospitalized for antibiotic treatment and further evaluation. She improves and is discharged from the hospital. Her renal function is sufficient, but it is anticipated that it will worsen as she grows.
Cystic kidneys in children and adolescents present in various forms and can range from a single cyst to multiple bilateral cysts. In this chapter, a few of the more common disease conditions will be discussed: multicystic dysplastic kidneys, autosomal recessive polycystic kidney disease and autosomal dominant polycystic kidney disease. Other cystic kidney diseases that will not be discussed include nephronophthisis (a common genetic cause of chronic renal insufficiency in children which presents with polyuria and polydipsia, anemia and growth retardation), medullary cystic disease (autosomal dominant disease in which young adults develop renal failure), medullary sponge kidney (dilated intrapapillary collecting ducts and multiple small cysts that usually presents in adulthood), glomerulocystic kidney disease (seen in a variety of inherited syndromes), simple renal cysts (incidental findings that generally do not impair renal function), multilocular cysts (unilateral benign tumor), acquired cystic kidney disease (occurs in patients with renal failure), and syndromes with cystic kidneys (such as tuberous sclerosis, Meckel syndrome, and von Hippel-Lindau disease).
Multicystic dysplastic kidney (MCDK) is usually a benign unilateral disorder of small to large renal cysts separated by dysplastic parenchyma. The shape of the kidney is irregular and normal renal architecture is lost. There are two types of MCDK: the classic type and the hydronephrotic type (1). The classic type contains multiple cysts of various size, with an abnormal renal shape and an atretic proximal ureter. The hydronephrotic type is rarer and consists of peripheral cysts that communicate with a large central cyst with a dilated pelvis and calyces (1).
MCDK is the most common type of renal cystic disease, comprising 10% of fetal uropathies (1). The most recent studies estimate that the incidence is 1 in 2400 livebirths, and it is more common in males (1,2). The disease usually occurs unilaterally, but can be seen bilaterally in as many as 20% of cases (2). MCDK is generally considered to be nonhereditary and sporadic, although rare cases have shown an autosomal dominant inheritance (2,3). Two theories stand out as the most probable causes of MCDK. The first proposes that abnormal induction of the metanephric blastema leads to dysplasia of the renal parenchyma that is non-uniform, resulting in cysts that increase in size and eventually compress normal renal tissue (1). The second theory suggests that MCDK is due to obstruction of the ureter that results in cyst formation (1,3). This theory was exhibited in Beck's experiments of fetal lamb ureter ligations, which resulted in cyst formation in the lambs (1). Urine is usually present in the cysts and causes the cysts to enlarge. In unilateral cases, there is a compensatory hypertrophy in the contralateral kidney.
The most common presentation of MCDK is on prenatal ultrasonography (71% of cases), viewed as early as 16 weeks gestation (1). MCDK usually presents in newborns as a unilateral flank mass, but can occasionally cause vomiting, anorexia and failure to thrive secondary to compressive effects (2). Other possible but rare presentations include urinary tract infection, abdominal pain, hematuria, hypertension, and compromised respiratory function (1,2). MCDK is associated with other anomalies of the urinary tract in half of cases and 15-28% show vesicoureteral reflux in the contralateral kidney (1). There is also an association with contralateral ureteropelvic junction obstruction (1). Other major anomalies can be seen in the cardiac, respiratory and gastrointestinal systems (1). Bilateral cystic kidneys are usually not compatible with life due to oligohydramnios and result in either stillborn babies or newborns requiring dialysis at birth (2). MCDK is diagnosed with ultrasonography but also requires radionuclide imaging to determine functioning of the kidney after 1 month of age (1).
The differential diagnosis for MCDK includes hydronephrosis as well as the other cystic kidney diseases, and may be distinguishable by ultrasound. Hydronephrosis usually retains a reniform shape and shows apparent renal parenchyma around a central cyst (1). Hydronephrosis also retains communication of the cysts with the collecting systems (2). A radionuclide study may need to be performed when distinguishing hydronephrosis from the hydronephrotic type of MCDK. Autosomal dominant polycystic kidneys are usually bilaterally enlarged while autosomal recessive polycystic kidneys are generally small with a hyperechoic pattern.
The management of MCDK is controversial because it is not clear that nephrectomy results in a better outcome. It is recommended to obtain sonography and perform a voiding cystourethrogram within the first 48 hours of life. Radionuclide studies are also performed after 1 month of age to determine renal functioning. Since most cases are asymptomatic, nephrectomy is not always performed and instead close follow-up is maintained. Ultrasound is performed every 3 months up to 1 year of age and then every 6 months up to 5 years of age. Blood pressure is also monitored. Nephrectomy is usually performed only if the child is symptomatic or the parents choose surgery after understanding the benefits and risks.
Unilateral MCDK has an excellent prognosis, especially if there is an absence of other anomalies. In 73% of cases, the cysts decrease in size, with a 40% complete resolution rate (1). However, in 13% of cases, the cysts increase in size and may cause symptoms (1). Uncommonly, children may have pain, infection, or hypertension and even rarer is the possibility of malignant degeneration into a Wilms tumor (1). In the 5% to 17% of cases that are bilateral, newborns generally do not survive and if they do, they require dialysis immediately (1).
Autosomal-recessive polycystic kidney disease (ARPKD) is a recessively inherited disorder that results in bilateral cystic dilation of renal collecting ducts and hepatic fibrosis. The kidneys are enlarged, while retaining their normal shape and have a spongy appearance. The incidence of ARPKD is believed to be 1 in 6000 to 1 in 55,000 livebirths (4). A single defective gene on chromosome 6p causes ARPKD and is inherited as a typical autosomal recessive disorder (5). Heterozygotes are unaffected. There is a 25% chance of recurrence with subsequent pregnancies. Males and females are equally affected.
Three factors have been shown to contribute to the formation of renal cysts and their subsequent enlargement. The first factor is that tubular hyperplasia is present in all cystic diseases and contributes to cystic expansion (5). Second, secretion of tubular fluid leads to the accumulation of intratubular fluid and progressive enlargement (5). Third, abnormalities in extracellular matrix interactions appear to have an effect on cell growth and can lead to abnormal epithelial hyperplasia and secretion (5).
ARPKD may present with various features but is usually seen within the first year of life (4). Many cases are seen prenatally on ultrasound with oligohydramnios and large renal masses (5). Other presentations include enlarging abdominal masses, respiratory problems due to limited diaphragm mobility (or pulmonary hypoplasia), failure to thrive due to enlarged kidneys, proteinuria, pyuria, hypertension due to fluid overload, and urinary tract infections due to vesicoureteral reflux (4). Children eventually develop chronic renal failure and end-stage renal disease with associated electrolyte imbalances of hyperkalemia and hyperphosphatemia (4). Liver abnormalities may present as signs of portal hypertension such as esophageal varies, hepatomegaly, and spider nevi.
The diagnosis of ARPKD is suspected in children with bilaterally enlarged kidneys and is highly suspected if siblings also have a history of ARPKD. Ultrasound is the diagnostic test of choice, although an intravenous pyelogram will also show enlarged kidneys (4). On renal ultrasound, there is increased echogenicity with a possible hypoechoic rim (4). It is important to rule out autosomal-dominant polycystic kidney disease (ADPKD), nephroblastomatosis and bilateral Wilms' tumor (4). ADPKD usually does not have associated liver abnormalities and the inheritance pattern is dominant instead of recessive (4).
Management of ARPKD involves ventilatory support for respiratory problems due to pulmonary hypoplasia and diaphragmatic compression. Hypertension should be treated with medications, although it may be difficult to control. Urinary tract infections should be properly diagnosed and treated with antibiotics. Chronic renal failure and end-stage renal disease are treated by managing electrolyte abnormalities, anemia, and renal osteodystrophy, with eventual dialysis and transplantation (4). Nephrectomy may be an option if there are respiratory problems and/or feeding problems due to compression (4).
Improvements in technology continue to increase the survival rates of ARPKD. Studies show that about 46% are alive at 15 years of age and those that survive through the first year of life have an even higher survival rate (79% alive at 15 years) (5). Renal failure is the most common cause of death and ARPKD continues to have significant long-term morbidity (4).
Autosomal-dominant polycystic kidney disease (ADPKD) rarely presents in children but occasionally exhibits a severe course in childhood. It is characterized by renal cysts in various locations and extrarenal manifestations in the gastrointestinal and cardiovascular systems. As the disease progresses, renal fibrosis and glomerulosclerosis increase (4). ADPKD is the most common inherited renal disease, occurring between 1 in 500 to 1 in 1000 livebirths (4). Mutations in any one of three genetic loci (PKD1, PKD2, PKD3) result in ADPKD. PKD1 is located on chromosome 16p and encodes the protein polycystin, a transmembrane protein (4). PKD2 is found on chromosome 4q and encodes for polycystin-2, another transmembrane protein that interacts with polycystin (4). There is not much known about PKD3 (4). The variability in cyst formation and disease severity depends on the locus affected and how much protein is being made.
The clinical presentation of ADPKD depends on the age of presentation. Most often, children are asymptomatic and are only diagnosed because of a positive family history and subsequent CT or sonogram. Symptomatic children typically present in late childhood or adolescence with any of the following: hematuria, hypertension, abdominal or flank pain, abdominal mass, urinary tract infection, or proteinuria (4). Symptoms in childhood usually correlate with greater than 10 cysts present (4). The third pediatric presentation is severe neonatal disease that is frequently fatal. These neonates usually die from respiratory failure but they may also die of renal failure during the first year of life (4). Extrarenal manifestations are not common in children but are common in adults. These extrarenal problems include mitral valve prolapse, hypertension, extrarenal cysts, aortic aneurysms, intracranial aneurysms, hernias, colonic diverticula, cholangiocarcinoma, and congenital hepatic fibrosis (4). Intracranial aneurysms are a significant cause of mortality when they rupture (4).
ADPKD is diagnosed with sonogram or CT scan as macroscopic renal cysts. As children age, the number and size of cysts increases and therefore, the sensitivity and specificity of diagnosis by ultrasound increases as children become older (4). ADPKD can often be distinguished from other cystic kidney diseases through family history. Ultrasound can also be used to distinguish ARPKD from ADPKD. ARPKD shows bilaterally enlarged kidneys with microcysts as well as hepatic periportal fibrosis, while ADPKD will show enlarged kidneys with macrocysts as well as extrarenal cysts (4,5).
Management of ADPKD includes physical examination, urinalysis and blood pressure monitoring every 6-12 months (4). Ultrasound should also be performed every 2-3 years (4). Presenting problems of ADPKD should be treated with standard therapy. Chronic renal insufficiency is monitored carefully, especially with respect to its effects on nutrition and growth (4). Hypertension is treated with antihypertensives and urinary tract infections are treated appropriately. Screening for intracranial aneurysms should be performed in teenagers with a family history of intracranial aneurysms due to the serious consequences of rupture (4,5).
Since most children with ADPKD are asymptomatic, the prognosis throughout childhood is generally good. One study showed that 80% of children diagnosed maintained normal renal function throughout childhood (5). As adults, disease progression is variable and unpredictable.
Potter syndrome is variably defined as including congenital renal failure or cystic kidneys associated with oligohydramnios, abnormal facies and hypoplastic lungs. If the fetal kidneys are non-functional or minimally functional, oligohydramnios results since the source of amniotic fluid is fetal urine. Oligohydramnios results in the abnormal facies due to the compression of the developing face against the inner uterine wall. Pulmonary hypoplasia results from large kidneys (due to one of the cystic kidney conditions) compressing the diaphragms, preventing fetal lung development. Congenital bilateral renal agenesis is also included in Potter syndrome. Potter syndrome is generally incompatible with life due to congenital renal failure and pulmonary hypoplasia.
1. Which renal cystic diseases are inherited? What is the most common inherited renal disease?
2. How can you differentiate between ARPKD and ADPKD?
3. Compare the outcomes of MCDK and ARPKD?
4. What abnormalities besides renal manifestations should a clinician look for on physical examination of a patient with ARPKD?
5. Do extrarenal manifestations of ADPKD usually present in children?
1. Wiener JS. Chapter 21 - Multicystic dysplastic kidney. In: Belman AB, King LR, Kramer SA (eds). Clinical Pediatric Urology, fourth edition. 2002, London: Martin Dunitz, pp. 633-645.
2. Watkins SL, McDonald RA, Avner ED. Chapter 24 - Renal Dysplasia, Hypoplasia, and Miscellaneous Cystic Disorders. In: Barratt TM, Avner ED, Harmon WE (eds). Pediatric Nephrology, fourth edition. 1999, Baltimore: Lippincott, Williams & Wilkins, pp. 415-424.
3. Hildebrandt F. Renal cystic disease. Curr Opin Pediatr 1999;11(2):141-151.
4. Greenbaum LA. Chapter 22 - Cystic kidney disease. In: Belman AB, King LR, Kramer SA (eds). Clinical Pediatric Urology, fourth edition. 2002, London: Martin Dunitz, pp. 647-676.
5. McDonald RA, Watkins SL, Avner ED. Chapter 27 - Polycystic Kidney Disease. In: Barratt TM, Avner ED, Harmon WE (eds). Pediatric Nephrology, fourth edition. 1999, Baltimore: Lippincott, Williams & Wilkins, pp. 459-473.
Answers to questions
1. ARPKD and ADPKD are inherited. MCDK is usually non-heritable. ADPKD is the most common inherited renal disease.
2. ARPKD: bilateral enlargement and microcysts on ultrasound. Hepatic fibrosis is also present in ARPKD. ADPKD: macrocysts and usually involve extrarenal cysts in the liver, pancreas, ovary, and/or spleen. ADPKD will also have a positive family history in a parent and the aunts/uncles on the affected parent's side of the family.
3. Unilateral MCDK has an excellent prognosis with most cases decreasing in size. ARPKD, since it is bilateral, eventually leads to end-stage renal disease.
4. Signs of portal hypertension: spider nevi, esophageal varices, hepatomegaly. There can also be signs of respiratory distress or abnormal feeding due to the compressive effects of enlarged kidneys.
5. No, extrarenal manifestations of ADPKD such as intracranial aneurysms and extrarenal cysts usually present in adulthood.