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eMedicine Specialties > Pediatrics: General Medicine > Nephrology

Polycystic Kidney Disease

Priya Verghese, MD, Fellow in Pediatric Nephrology, Seattle Children's Hospital, University of Washington
Jordan M Symons, MD, Associate Professor of Pediatrics, University of Washington School of Medicine; Dialysis Medical Director, Department of Nephrology, Children's Hospital and Regional Medical Center; Henrique M Lederman, MD, PhD, Consulting Staff, Department of Radiology, LeBonheur Children's Medical Center and St Jude Children's Research Hospital; Professor of Radiology and Pediatric Radiology, Chief, Division of Diagnostic Imaging in Pediatrics, Federal University of Sao Paulo, Brazil; Peter J Hurh, Research Fellow, Department of Radiology, The Children's Hospital of Philadelphia; H Jorge Baluarte, MD, Medical Director, Renal Transplant Program, Division of Nephrology, Department of Pediatrics, The Children's Hospital of Philadelphia; Professor of Pediatrics, University of Pennsylvania

Updated: Aug 13, 2008

Introduction

Background

Polycystic kidney disease (PKD) is an inherited disorder that involves bilateral renal cysts without dysplasia.Polycystic kidney disease is broadly divided into 2 forms: autosomal recessive polycystic kidney disease (ARPKD), previously known as infantile polycystic kidney disease, and autosomal dominant polycystic kidney disease (ADPKD), previously known as adult polycystic kidney disease. The nomenclature of infantile versus adult is no longer used because it is not an accurate description.

Both autosomal recessive polycystic kidney disease and autosomal dominant polycystic kidney disease can involve the presence of renal cysts at any time during an affected person's life, from the prenatal period to adolescence or older. The clinical and radiological manifestations of both types of polycystic kidney disease have considerable overlap.

Autosomal recessive polycystic kidney disease is characterized by cystic dilatation of renal collecting ducts associated with hepatic abnormalities of varying degrees, including biliary dysgenesis and periportal fibrosis. Autosomal recessive polycystic kidney disease was first recognized in 1902; however, the histology was not reported until 1947. In 1964, Osathanondh and Potter classified autosomal recessive polycystic kidney disease as type 1 cystic kidney disease.[1,2 ]Eventually, because neither parent had the disease and no sex predilection was observed, this disease was concluded to have an autosomal recessive mode of inheritance. Autosomal recessive polycystic kidney disease was originally described as 4 separate clinical entities based on age of presentation. This classification is no longer considered valid because of the large degree of overlap among the different groups and the wide range of possible presentations, regardless of age.

Autosomal dominant polycystic kidney disease is the most common inherited kidney disease in humans. It is a multisystem disorder characterized by progressive cystic dilatation of both kidneys with variable extrarenal manifestations in the GI tract, cardiovascular system, reproductive organs, and brain. Hepatic cysts are possible in autosomal dominant polycystic kidney disease, although they are less common than in autosomal recessive polycystic kidney disease. Autosomal dominant polycystic kidney disease has a wide clinical spectrum. It may present asymptomatically as an incidental finding or may present with severe neonatal manifestations similar to autosomal recessive polycystic kidney disease.

Pathophysiology

The 3 basic processes involved in renal cyst formation and progressive enlargement are as follows:

  • Tubular cell hyperplasia: This may be mediated by factors that control cell proliferation (eg, epidermal growth factor, transforming growth factor-α), dysregulation of apoptosis, or the balance between the two.
  • Tubular fluid secretion: The solid tumor cell nests produced by the cell hyperplasia described above are transformed into fluid-filled cysts by the secretion of fluid by the tubular cells associated with efferent tubular obstruction or slow or absent afferent flow. This accounts for the fluid within the cysts of kidneys in patients with autosomal dominant polycystic kidney disease, 70% of which have no afferent or efferent tubular connections.
  • Abnormalities in tubular extracellular matrix and/or function: These are thought to be responsible for amplifying tubular cell hyperplasia and tubular fluid secretion. Interstitial inflammation and fibrosis are responsible for progression in all forms of polycystic kidney disease.

Autosomal recessive polycystic kidney disease

In 1994, the autosomal recessive polycystic kidney disease gene (PKDHD1) was localized to the short arm of chromosome 6.[3 ]Fibrocystin/polyductin, a protein encoded by PKDHD1, is expressed on the cilia of renal and bile duct epithelial cells and is thought to be crucial in maintaining the normal tubular architecture of renal tubules and bile ducts. However, the precise function of this protein has yet to be completely studied or understood. The protein strengthens the theory that the primary defect in autosomal recessive polycystic kidney disease is linked to ciliary dysfunction.

Autosomal recessive polycystic kidney disease is characterized by nonobstructive, bilateral, symmetric dilatation and elongation of 10-90% of the renal collecting ducts, focally accounting for a wide variability of renal dysfunction. As the number of ducts involved increases, the kidneys enlarge. However, at autopsy, the reniform shape is maintained because the abnormality is in the collecting ducts and the cysts are usually minute (<3 mm). In older patients, cysts as large as 1 cm may be seen. At autopsy, gross examination of a kidney in patients with autosomal recessive polycystic kidney disease reveals multiple minute cystic spaces throughout the capsular surfaces. Cut sections of the kidney show that these cystic structures are subcapsular extensions of radially oriented cylindrical or fusiform ectatic spaces, with poor corticomedullary differentiation due to the extension of the elongated and dilated collecting ducts from the medulla to the cortex.

All patients with autosomal recessive polycystic kidney disease have congenital hepatic fibrosis (CHF), which may have more severe clinical manifestation than the renal disease. The CHF results from malformation of the developing ductal plate. The liver biopsy findings reveal enlarged, fibrotic portal tracts and hyperplastic, dilated, and dysgenetic biliary ducts with normal hepatocytes. The ductules can show true cystic changes, and, when the changes are macroscopic, autosomal recessive polycystic kidney disease can be indistinguishable from Caroli disease. The portal hypertension secondary to the CHF can be clinically debilitating, with splenomegaly, varices, and GI hemorrhage.

Autosomal dominant polycystic kidney disease

The genes responsible for autosomal dominant polycystic kidney disease were localized to the short arm of chromosome 16 (PKD1) in 85% of cases and the long arm of chromosome 4 (PKD2) in most of the remaining cases. The proteins encoded by PKD1 and PKD2 are polycystin 1 and polycystin 2, respectively. These proteins are expressed in the developing kidney, and their functions overlap considerably. The dysfunction of these proteins is thought to be pathogenetically responsible for the manifestations of autosomal dominant polycystic kidney disease, primarily by renal ciliary dysfunction. Whether a third gene accounts for a small number of unlinked families is uncertain. Homozygous or compound heterozygous genotypes have been thought to be lethal in utero. Individuals heterozygous for both PKD1 and PKD2 mutations usually survive to adulthood but have more severe renal disease.

Autosomal dominant polycystic kidney disease differs from autosomal recessive polycystic kidney disease in that cysts associated with autosomal dominant polycystic kidney disease develop anywhere along the nephron. Upon clinical presentation, kidneys are usually enlarged, with numerous, large, round nodules on the external surface of the kidney, causing the loss of its original reniform shape, which is different from kidneys in patients with autosomal recessive polycystic kidney disease. Cysts of varying sizes, which contain pale fluid or blood, are randomly distributed throughout the parenchyma and involve any segment along the nephron. The cysts have thickened basement membranes with pericystic interstitial fibrosis, and their epithelium maintains active secretion and reabsorption. Some have hypothesized that patients with an associated marked epithelial hyperplasia may have a higher rate of malignant transformation than the general population.

Frequency

United States

  • Autosomal recessive polycystic kidney disease: The exact incidence is unknown because of varying reports in patient autopsies versus survivors, as well as the possibility of affected children who die perinatally without a definitive diagnosis. The frequency of autosomal recessive polycystic kidney disease has been reported as one case per 10,000-40,000 births, although the frequency of the gene in the general population is estimated to be 1 case per 70 population. Because of the recessive inheritance of autosomal recessive polycystic kidney disease, both parents are unaffected. The recurrence risk in subsequent pregnancies is 25%. Unaffected siblings have a 66% chance of being carriers. Carriers or heterozygotes are asymptomatic.
  • Autosomal dominant polycystic kidney disease: The estimated prevalence of autosomal dominant polycystic kidney disease is one case per 200-1000 population. Autosomal dominant polycystic kidney disease is responsible for 6-10% of cases of end-stage renal disease in North America. Because of the autosomal dominant inheritance, one parent is usually affected, and each offspring has a 50% chance of inheriting the gene, with a penetrance of almost 100%.
  • With education, better quality of prenatal ultrasonography, awareness, and gene testing, more accurate reports regarding the incidence and prevalence of autosomal recessive polycystic kidney disease and autosomal dominant polycystic kidney disease will hopefully be available soon.

International

Autosomal dominant polycystic kidney disease is responsible for 6-10% of cases of end-stage renal disease in Europe.

Mortality/Morbidity

The clinical manifestations of autosomal recessive polycystic kidney disease vary depending on the number of collecting ducts involved, as well as the degree of interstitial fibrosis. Fetuses with severe impairment of renal function and reduced fetal urinary output present with oligohydramnios, which may result in pulmonary hypoplasia. Most of these infants die from pulmonary complications after birth. Babies with less severe renal manifestations who survive the neonatal period may still develop chronic kidney disease, which occurs at varying ages depending on the degree of renal involvement. Pulmonary insufficiency with respiratory distress due to oligohydramnios that is worsened by large renal masses is a major cause of morbidity and mortality in neonates.

In patients who survive the neonatal period, renal prognosis has improved over time because of renal transplantation. CHF still causes considerable morbidity, even in patients who have received transplants; some die from GI hemorrhage secondary to portal hypertension. Oliguric acute renal failure (ARF) often improves as the pulmonary function improves.

Autosomal dominant polycystic kidney disease can also present prenatally but usually does not involve the severe renal impairment seen in autosomal recessive polycystic kidney disease. In adults, it more commonly causes chronic kidney disease that progresses to further cystic development of the renal cortex, often with transition into end-stage renal disease. Thus, the chance of end-stage renal disease is 2% in patients younger than 40 years and increases to 50% by the seventh decade of life.

Autosomal dominant polycystic kidney disease is a multisystem disorder, and some patients develop associated intracranial aneurysms, which can cause stroke and intracranial hemorrhage. Much of the morbidity of autosomal dominant polycystic kidney disease is due to chronic hypertension. Autosomal dominant polycystic kidney disease can manifest in utero with the Potter phenotype, with death from pulmonary hypoplasia.

Race

Both forms of polycystic kidney disease affect all racial and ethnic groups.

Sex

Autosomal recessive polycystic kidney disease and autosomal dominant polycystic kidney disease equally affect males and females.

Age

Because it is a genetic disease, polycystic kidney disease begins at conception. In both autosomal recessive polycystic kidney disease and autosomal dominant polycystic kidney disease, the renal manifestations may occur prenatally or later in life. Autosomal recessive polycystic kidney disease usually presents in the neonatal period or in childhood. Rare reports have described initial presentations in late adolescence and even in early adulthood. Autosomal dominant polycystic kidney disease most often initially presents in adults aged 20-40 years.

Clinical

History

  • Autosomal recessive polycystic kidney disease (ARPKD)
    • Presentation at birth
      • Babies may present with large palpable flank masses that may cause difficulty in delivery.
      • These babies may have classic Potter facies and abnormal extremities.
    • Presentation in infancy
      • Parents or pediatricians may discover abdominal masses in older infants.
      • Older infants may have abdominal distension secondary to renal masses or hepatosplenomegaly.
    • Presentation in all patients: Urinary concentrating defects include polyuria and polydipsia.
  • Autosomal dominant polycystic kidney disease (ADPKD)
    • The initial presentation in older children includes the following:
      • Abdominal pain
      • Urinary tract infections: These may manifest as pain, perinephric abscess, hemorrhage, chronic pyelonephritis, sepsis, and death.
      • Abdominal or inguinal hernias
      • Renal insufficiency (rarely occurs in childhood)
      • Concentrating defects that cause polydipsia and polyuria (more common in autosomal recessive polycystic kidney disease)
      • Extrarenal manifestations of autosomal dominant polycystic kidney disease (more common in adults but can occur in children as young as age 1 y)

Physical

  • Autosomal recessive polycystic kidney disease
    • Presents prenatally with massively enlarged kidneys and oligohydramnios
    • In infants, Potter facies with low set flattened ears, short snubbed nose, deep eye creases, and micrognathia, all secondary to oligohydramnios
    • Clubfoot commonly secondary to oligohydramnios because of pressure effect in utero
    • Abdominal mass: This may manifest after the newborn period because of renal masses or hepatosplenomegaly.
    • Hypertension: This may be severe and may be a presenting feature, even in patients with normal renal function. The pathophysiology is unknown because renin levels are within the reference range.
    • Cardiac hypertrophy and congestive heart failure (may develop in patients with poorly managed hypertension)
    • Evidence of portal hypertension
    • Hepatic involvement: This is present in all children with autosomal recessive polycystic kidney disease but may not manifest in neonates (50-60%).
    • Impaired renal function (present in 70-80% of infants)
    • Renal cysts in children (may be an incidental finding)
  • Autosomal dominant polycystic kidney disease
    • Commonly presents as abdominal pain with or without abdominal pain
    • Hematuria
    • The pathophysiology of hypertension, which can present in patients of all age groups (even in patients with normal renal function), is as follows:
      • Increased activation of renin-angiotensin system
      • Reduced renal blood flow
      • Sodium retention
    • May have signs of portal hypertension and CHF (rare compared with autosomal recessive polycystic kidney disease)
    • Manifestations of stroke secondary to cerebral hemorrhage of ruptured aneurysms
    • Renal involvement (often asymmetric but usually bilateral)
    • Renal masses
    • Hepatic cysts (These are usually asymptomatic in children unlike in adults, in whom pain, infection, and hepatomegaly are present.)
    • Cerebral vessel aneurysms
    • Cardiovascular system manifestations
      • Mitral valve prolapse
      • Endocardial fibroelastosis in children as well as adults
    • Increased left ventricular mass with diastolic dysfunction, even in normotensive children
    • Coronary aneurysms, exclusively in adults

Causes

Polycystic kidney diseases are genetically transmitted multisystem diseases found in 2 forms (see Background). In 1994, Zerres et al localized the autosomal recessive polycystic kidney disease gene (PKDHD1) to the short arm of chromosome 6;[3 ] PKDHD1 is responsible for the expression of the ciliary protein fibrocystin. In autosomal recessive polycystic kidney disease, the mutant fibrocystin is found to be completely destabilized and rapidly degraded, leading to ciliary dysfunction and the features of autosomal recessive polycystic kidney disease.

The genes responsible for autosomal dominant polycystic kidney disease are found at the tip of the short arm of chromosome 16 (PKD1) in 85% of the cases and the long arm of chromosome 4 (PKD2) in most of the remaining cases. The PKD1 gene encodes for a protein called polycystin-1, and the PKD2 gene encodes for a protein called polycystin-2, both of which are widely expressed in the kidney and are thought to play an important role in tubular architecture. The loss of these proteins may cause altered differentiation in affected cells, with dysfunction of the renal primary cilium that leads to clinical manifestations of autosomal dominant polycystic kidney disease. Some families have no linkage to PKD1 or PKD2, suggesting that other loci for this disease may be implicated.

Differential Diagnoses

Caroli Disease
Congenital Hepatic Fibrosis
Multicystic Renal Dysplasia
Neonatal Hypertension
Polycystic Kidney Disease
Ureteropelvic Junction Obstruction

Other Problems to Be Considered

Glomerulocystic kidney disease

Workup

Laboratory Studies

  • Blood and urine studies are useful in evaluating patients with both types of polycystic kidney disease (PKD), although none are diagnostic. Based on the patient's clinical presentation, these studies are performed at diagnosis and are repeated as appropriate during the disease course.
  • The glomerular filtration rate (GFR) is measured with various tests. The most common is the serum creatinine level test. Creatinine is a product of creatine and phosphate metabolism in the muscle and is therefore produced in quantities directly proportional to muscle mass. Normal values of creatinine depend on the patient's muscle mass and, therefore, age and build of the children. Acute or gradual loss of renal function causes an increase in the serum creatinine concentration.
  • BUN levels in plasma are also increased in renal dysfunction. However, this is not as reliable as the serum creatinine level test because BUN levels are also elevated in cases of intravascular depletion, increased protein intake, catabolism, and gastrointestinal hemorrhage and may be reduced in chronic liver disease.
  • Serum electrolyte levels may reveal further evidence of glomerular and tubular dysfunction in polycystic kidney disease. Reduced glomerular filtration results in intravascular fluid overload, which can cause hyponatremia. Hyponatremia related to fluid overload in patients with oliguria resolves with time. It can also be associated with hyperkalemia, hyperphosphatemia, and metabolic acidosis. Reduced renal function causes abnormalities in the conversion of vitamin D into its active form, leading to hypocalcemia. Alkaline phosphatase levels may be normal or can be elevated secondary to the hyperparathyroidism triggered by this hypocalcemia. Tubular dysfunction can also cause electrolyte abnormalities.
  • Liver function is usually normal.
  • Metabolic acidosis may be present.
  • Gross or microscopic hematuria may be present. Gross hematuria often develops after minor trauma to the flank.
  • Serum albumin levels may be low (<3.5 g/dL) because of a number of factors, including the following:
    • Urinary protein losses
    • Malnutrition (often due to poor appetite in patients with renal insufficiency)
    • Liver dysfunction (can cause protein malabsorption)
    • Decreased hepatic synthesis in patients with advanced liver disease
  • Liver function test findings are often abnormal in the later stages of the disease, particularly in autosomal recessive polycystic kidney disease.
  • Urine analysis findings can be normal. Microhematuria or macrohematuria may be present. Macrohematuria is more common in autosomal dominant polycystic kidney disease. Proteinuria, pyuria, and, sometimes, evidence of urinary concentrating defects such as prerenal azotemia may be present.

Imaging Studies

  • Ultrasonography findings in autosomal recessive polycystic kidney disease (ARPKD)
    • Prenatal findings
      • Bilaterally enlarged echogenic kidneys
      • Small or nonvisualized bladder with absence of urine
      • Large renal masses
      • Oligohydramnios, usually not observed before 30 weeks' gestation
    • Neonatal findings
      • Bilaterally smooth, enlarged kidneys, which are diffusely echogenic with poor corticomedullary differentiation
      • Microcysts that are difficult to visualize and account for the diffuse echogenicity
      • Hypoechoic macrocysts, which may be visualized in worsening disease
      • Hepatic parenchymal echogenicity (may be diffusely increased with fibrous tissue that causes poor depiction of peripheral portal veins)
    • Patients are most commonly diagnosed based on prenatal ultrasonography findings. In older children who present late, renal ultrasonography findings may be less reliable. Hepatic features are often the prominent presenting feature. Findings in older children include the following:
      • Enlarged kidneys in older children with autosomal recessive polycystic kidney disease differ from enlarged kidneys in younger children with autosomal recessive polycystic kidney disease in that the hyperechogenicity is mainly in the medulla because of focal tubular cysts.
      • Renal macrocysts are more common in this age group.
      • The Liver is often enlarged with heterogeneously or homogenously increased echogenicity.
      • Macrocysts in the liver and pancreas are often visualized.
      • Splenomegaly is also observed.
      • The reversal of hepatic venous blood flow revealed by Doppler ultrasonography suggests portal hypertension.
      • Macroscopic liver cysts are uncommon, although choledochal cysts have been reported.
      • When present, biliary duct dilatation is indistinguishable from Caroli disease.
    • Adult findings
      • Multiple small cysts, typically in normal-sized kidney
      • Increased cortical echogenicity
      • Loss of corticomedullary differentiation
  • Ultrasonography findings in autosomal dominant polycystic kidney disease (ADPKD)
    • Ultrasonography should be first line of imaging in patients who are at risk for autosomal dominant polycystic kidney disease, especially patients older than 30 years. In patients younger than 30 years, ultrasonography may not reveal manifestations, and linkage analysis may be more sensitive.
    • Ultrasonography findings in patients with autosomal dominant polycystic kidney disease include the following:
      • Occasionally, prenatal ultrasonography reveals renal cysts. Multiple, bilateral macrocysts smaller than 2 cm may be present. Renal cysts combined with positive family history findings suggest autosomal dominant polycystic kidney disease. In families with known autosomal dominant polycystic kidney disease, routine screening ultrasonography often reveals cysts in asymptomatic children.
      • Kidneys are usually normal in size with normal echogenicity. Infants may have large hyperechoic kidneys, with or without macrocysts, with varying degrees of renal insufficiency.
      • In patients with renal insufficiency, nephromegaly and loss of corticomedullary differentiation has been observed.
      • Less commonly, prenatal ultrasonography findings and ultrasonography findings in infants may be indistinguishable from findings in patients with autosomal recessive polycystic kidney disease.
      • Routine ultrasonography screening that demonstrates even one cyst is highly predictive of the development of symptomatic autosomal dominant polycystic kidney disease later in life in a child with a family history of autosomal dominant polycystic kidney disease.
      • Multicystic kidney disease differs from polycystic kidney disease in that it is unilateral with multiple noncommunicating macrocysts of varying size.
      • Pancreatic cysts are found exclusively in patients with PKD1 and are usually asymptomatic.
      • Ovarian cysts may be present.
  • MRI findings in autosomal recessive polycystic kidney disease
    • Enlarged kidneys with T2-weighted imaging that shows increased signal intensity
    • Characteristic hyperintense, linear, radial pattern in cortex and medulla
    • MRI is not routinely performed in patients with autosomal dominant polycystic kidney disease.
  • CT scanning is not a diagnostic procedure of choice in either form of polycystic kidney disease.
    • In autosomal recessive polycystic kidney disease, noncontrast CT scanning reveals smooth, enlarged kidneys. With intravenous contrast, kidneys have a striated appearance due to accumulation of contrast in dilated tubules. Depending on degree of renal insufficiency, a proportionate delay in arrival of contrast to kidneys is observed. Macrocysts may appear as well-circumscribed lucent defects. The bladder may be opacified.
    • In autosomal dominant polycystic kidney disease, well-delineated cysts that do not enhance following intravenous contrast administration may be present in both kidneys. Over time, kidneys and cysts often grow as revealed by CT scanning. If a cyst hemorrhage is present, it can be observed as a high-density cyst.
  • Radiographic findings in autosomal recessive polycystic kidney disease
    • Abdominal radiography may reveal enlarged neonatal kidneys, abdominal distension, and centrally deviated gas-filled bowel loops.
    • Chest radiography reveals pulmonary hypoplasia, which manifests as a small thorax.
    • Pneumothorax can occur in infants after birth.
  • Radiographic findings in autosomal dominant polycystic kidney disease
    • Intravenous pyelogram findings may be normal or have abnormalities of one or both kidneys
    • Grossly enlarged kidneys with lobular appearance
    • Distorted calyces secondary to non-opacified cysts with smooth or irregular indentations
    • Numerous bilateral cysts of various sizes

Other Tests

  • Maternal alpha feto-protein (AFP) is increased, and amniotic fluid trehalase activities are potential markers for autosomal recessive polycystic kidney disease in utero.
  • Liver hydroxyiminodiacetic acid (HIDA) imaging and transient liver elastography may aid in diagnosis of autosomal recessive polycystic kidney disease.
  • Genetic testing may be performed.
    • Genetic testing in autosomal recessive polycystic kidney disease has improved because of haplotype-based molecular analysis. It is performed only if the patient's family has at least one established index case of autosomal recessive polycystic kidney disease.
    • Genetic testing can be used when the imaging results are equivocal or when a definite diagnosis is required in a younger individual, such as a potential living-related kidney donor. 
    • Genetic testing can be done by linkage or sequence analysis. In linkage analysis, polymorphic markers are used to flank the location of the known disease gene and to track the disease. Linkage analysis uses highly informative microsatellite markers flanking PKD1 and PKD2 and requires accurate diagnosis, and willingness of sufficient affected family members to be tested. Therefore, linkage analysis is suitable in fewer than 50% of families. It can reveal disease and carrier status in the fetus or newborn.
    • The large size and complexity of PKD1 and marked allelic heterogeneity are obstacles to molecular testing by direct DNA analysis.
    • Mutation scanning by methods such as denaturing high-performance liquid chromatography (DHPLC) in research settings has yielded mutation detection rates of around 65–70% for PKD1 and PKD2. Higher rates of around 85% are now possible by direct sequencing. However, because most mutations are unique and as many as one third of PKD1 changes are missense, the pathogenicity of some changes is difficult to prove.
  • Brain imaging is used in the diagnosis of autosomal dominant polycystic kidney disease.
  • Prenatal diagnosis in autosomal dominant polycystic kidney disease represents an ethical dilemma because symptoms may not present until well into adulthood. Making such an early diagnosis is a potential cause of "vulnerable child" syndrome. The parents view the child as prematurely "sick," and this thought process is transferred to the child, leading to behavioral and psychological changes. Until effective treatments become available, the adverse effects from presymptomatic diagnosis in children (removal of choice to know or not know, psychological, educational, and career implications, and insurability issues) outweigh the benefits.
  • Left ventricular hypertrophy and early ramifications mentioned above are revealed using echocardiography. Diastolic dysfunction is present, even in normotensive patients.

Histologic Findings

Renal biopsy is not usually indicated, particularly when the family history is positive.

Treatment

Medical Care

  • Medical care in autosomal recessive polycystic kidney disease (ARPKD)
    • Survival of neonates depends on neonatal artificial ventilation and intensive care, as well as the degree of pulmonary hypoplasia.
    • In order to optimize ventilation, fluid overload can be managed with diuretics, continuous renal replacement therapy, and nephrectomy.
    • If evidence of concentrating defects is observed in infants without significant renal insufficiency, thiazides may be useful. Bicarbonate supplements may be necessary for correction of metabolic acidosis.
    • Systemic hypertension should be aggressively treated with antihypertensive medication. ACE inhibitors are the drugs of choice. Calcium channel blockers, beta-blockers, and the judicious use of diuretics are also potential options.
    • Antibiotics are used to treat urinary tract infections.
    • Once children with autosomal recessive polycystic kidney disease develop chronic kidney disease, they require management of anemia with iron and erythropoietin; prevention of metabolic bone disease with calcium supplements, phosphate binders, and parathyroid-suppressing medication; and growth hormone to counter the growth-limiting effects of uremia.
    • Once children with autosomal recessive polycystic kidney disease are in end-stage renal disease, dialysis or transplantation is the only option.
    • With better renal care, the course of children with autosomal recessive polycystic kidney disease is further complicated by the hepatic complications listed above, which require specific therapy by specialists.
  • Medical care in autosomal dominant polycystic kidney disease is directed at reducing morbidity and mortality due to the complications of the disease and includes management of hypertension, renal insufficiency, and end-stage renal disease, similar to autosomal recessive polycystic kidney disease.

Surgical Care

  • Surgical care in autosomal recessive polycystic kidney disease
    • Because of the large size of the kidneys, unilateral or bilateral nephrectomy is often performed if respiratory compromise is present in the neonatal period or if failure to thrive is present because of the large, bilateral, space-occupying masses that prevent appropriate nourishment.
    • In patients who require dialysis, peritoneal dialysis requires surgery for the placement of peritoneal dialysis catheters, and hemodialysis requires surgery for access.
    • Renal transplantation may be necessary in a large number of patients with autosomal recessive polycystic kidney disease.
    • A large number of hepatic complications require surgical management (eg, sclerotherapy for esophageal varices or portocaval and splenorenal shunt placement).
  • Surgical care in autosomal dominant polycystic kidney disease: Renal insufficiency is less common in children with autosomal dominant polycystic kidney disease, but hemodialysis or peritoneal dialysis or transplantation may be required, as in patients with autosomal recessive polycystic kidney disease.

Diet

The medical management of autosomal recessive polycystic kidney disease is supportive. Infants and young children without significant renal insufficiency need close follow-up. Adequate nutrition (protein and energy) is essential.

  • Salt supplementation is necessary only if salt wasting occurs.
  • Alkali therapy with sodium bicarbonate or sodium citrate is required in patients with metabolic acidosis.
  • The risk of severe dehydration due to urinary concentration defects, particularly during episodes of intercurrent illnesses that can increase insensible water losses (eg, fever), that can limit free water intake (because of nausea), or that can increase extrarenal water losses (diarrhea), can be overcome with oral or parenteral intake of generous amounts of salt and water.
  • The treatment of chronic kidney disease among children with autosomal recessive polycystic kidney disease is similar to the treatment for any child with chronic kidney disease. Supplemental energy intake and nasogastric or gastrostomy tube feedings should optimize the management of nutrition. These measures must be considered to improve growth and overall health of the child.
  • The natural history of the presymptomatic child with proven autosomal dominant kidney disease remains largely unknown. Close monitoring is recommended, and the treatment of hypertension, renal insufficiency, and end-stage renal disease should be treated as in autosomal recessive polycystic kidney disease.

Medication

Drug therapy is not currently a component of the standard of care in this condition. Medications are used only to treat the complications that arise from the disease process.

Because of the availability of animal models, preclinical trials have been developed, and promising candidate drugs have been identified for clinical trials. The role of cyclic adenosine monophosphate (cAMP) in cystogenesis provided the rationale for preclinical trials of vasopressin V2 receptor antagonists. One of these drugs, OPC-31260, substantially reduced concentrations of cAMP and inhibited cyst development in models of autosomal recessive polycystic kidney disease (ARPKD) and autosomal dominant polycystic kidney disease (ADPKD) and nephronophthisis.

An antagonist with high potency and selectivity for the human VPV2R (tolvaptan) has also been shown to be an effective treatment in the rat model of autosomal recessive polycystic kidney disease and the Pkd2 mouse model of autosomal dominant polycystic kidney disease. These drugs have no effect on liver cysts. Somatostatin that acts on SST2 receptors inhibits cAMP accumulation in the kidney and in the liver. Octreotide, a synthetic metabolically stable somatostatin analogue, halts the expansion of hepatic cysts from a rat model of polycystic kidney disease in vitro and in vivo.

Other drugs shown to be effective in preclinical trials for the treatment of human polycystic kidney disease include inhibitors of epidermal growth factor receptor, Erb-B2 tyrosine kinase, and Src kinase.[4 ]

The results of Consortium for Radiologic Imaging for the Study of Polycystic Kidney Disease (CRISP) have shown that the rate of renal growth is a good predictor of functional decline and justify the use of kidney volume as a surrogate marker of disease progression in clinical trials for the disease.[5 ]

Follow-up

Further Outpatient Care

  • The primary care physician and consulting nephrologist should participate in the care of children and adults with polycystic kidney disease (PKD). Once polycystic kidney disease is diagnosed, the frequency of outpatient follow-up with the nephrologist depends on the degree of renal dysfunction and on complicating features such as a failure to thrive, nutritional and feeding difficulties, hypertension, electrolyte disturbances, urinary infections, and hepatic fibrosis (ie, portal hypertension).
  • In addition to the significant medical problems, the psychosocial stress on the patient and family can be overwhelming. A team approach in which the skills of the nephrologist are used together with those of other medical specialists (eg, gastroenterologist), specialized nurses, nutritionists, social workers, psychiatrists, and other support staff provides optimal comprehensive care.

Prognosis

  • Determining the prognosis is difficult; however, with advances in medical management and continued progress in end-stage renal disease therapy in young infants, further improvements in survival and rehabilitation can be expected.

Patient Education

  • The Polycystic Kidney Research (PKR) Foundation is devoted to determining the cause of polycystic kidney disease, improving its clinical treatment, and discovering a cure. To become members, patients, family members, friends, physicians, and allied health professionals can contact the foundation at the following: PKR Foundation
    4901 Main Street
    Suite 200
    Kansas City, MO 64112-2634
    Telephone: 1-800-PKD-CURE
    Fax: (816) 931-8655
    Email: pkdcure@pkrcure.org
  • Additional information can be obtained by contacting the National Kidney Foundation at the following: National Kidney Foundation
    30 East 33rd Street
    New York, NY 10016
  • For excellent patient education resources, visit eMedicine's Kidneys and Urinary System Center. Also, see eMedicine's patient education articles Chronic Kidney Disease and Kidney Transplant.

Miscellaneous

Medicolegal Pitfalls

  • Molecular genetic testing by direct mutation screening is clinically available; however, sometimes a relatively large number of affected family members need to be tested in order to establish which of the 2 possible genes is responsible within each family. The large size and complexity of PKD1 and PKD2 genes, as well as marked allelic heterogeneity, present obstacles to molecular testing by direct DNA analysis.
  • Because of other potential mutations of known or unknown significance that may arise as incidental findings, sequencing an entire gene carries a significant risk of medical liability. Consequently, clear family history with known allelic mutations is preferred.

Multimedia

Frontal excretory urogram of autosomal dominant p...

Media file 1: Frontal excretory urogram of autosomal dominant polycystic kidney disease (ADPKD) shows a spider-legs configuration of the collecting system secondary to compression due to cysts.

Lateral excretory urogram of autosomal dominant p...

Media file 2: Lateral excretory urogram of autosomal dominant polycystic kidney disease (ADPKD) shows a spider-legs configuration of the collecting system secondary to compression due to cysts.

Sonogram shows cysts with bilaterally enlarged ki...

Media file 3: Sonogram shows cysts with bilaterally enlarged kidneys. These findings are compatible with a diagnosis of autosomal dominant polycystic kidney disease (ADPKD).

Sonogram shows cysts with bilaterally enlarged ki...

Media file 4: Sonogram shows cysts with bilaterally enlarged kidneys. These findings are compatible with a diagnosis of autosomal dominant polycystic kidney disease (ADPKD).

Sonogram shows cysts with bilaterally enlarged ki...

Media file 5: Sonogram shows cysts with bilaterally enlarged kidneys. These findings are compatible with a diagnosis of autosomal dominant polycystic kidney disease (ADPKD).

Pathologic specimen of end-stage autosomal domina...

Media file 6: Pathologic specimen of end-stage autosomal dominant polycystic kidney disease (ADPKD) with deformed lobulated kidneys.

Sonogram shows enlargement of both kidneys, diffu...

Media file 7: Sonogram shows enlargement of both kidneys, diffuse increased echogenicity, and loss of corticomedullary differentiation. These findings are compatible with a diagnosis of autosomal recessive polycystic kidney disease (ARPKD).

Excretory urogram shows minimal bilateral tubular...

Media file 8: Excretory urogram shows minimal bilateral tubular changes caused by a mild form of autosomal recessive polycystic kidney disease (ARPKD).

Excretory urogram shows enlarged kidneys with bil...

Media file 9: Excretory urogram shows enlarged kidneys with bilateral distortion of the collecting system (spider-legs configuration). These findings are compatible with a diagnosis of autosomal recessive polycystic kidney disease (ARPKD).

Excretory urogram shows the typical mottled (spon...

Media file 10: Excretory urogram shows the typical mottled (spongelike) contrast pattern in autosomal recessive polycystic kidney disease (ARPKD).

Excretory urogram shows the typical mottled (spon...

Media file 11: Excretory urogram shows the typical mottled (spongelike) contrast pattern in autosomal recessive polycystic kidney disease (ARPKD).

Excretory urogram shows the typical mottled (spon...

Media file 12: Excretory urogram shows the typical mottled (spongelike) contrast enhancement pattern in autosomal recessive polycystic kidney disease (ARPKD).

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Keywords

polycystic kidney disease, PKD, cystic kidney disease, genetic cystic disease, autosomal dominant polycystic kidney disease, ADPKD, adult polycystic kidney disease, autosomal recessive polycystic kidney disease, ARPKD, infantile polycystic kidney disease, medullary cystic disease, obstructive cystic disease, multicystic dysplasia, cystic dysplasia, cysts associated with systemic disease, tubular cell hyperplasia, congenital hepatic fibrosis, oligohydramnios, pulmonary hypoplasia, chronic kidney disease, acute renal failure, ARF, end-stage renal disease, hepatosplenomegaly, urinary tract infection, chronic pyelonephritis, clubfoot, renal cysts, portal hypertension, mitral valve prolapse, endocardial fibroelastosis, hyperkalemia, hyperphosphatemia, metabolic acidosis

Contributor Information and Disclosures

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Priya Verghese, MD, Fellow in Pediatric Nephrology, Seattle Children's Hospital, University of Washington
Priya Verghese, MD is a member of the following medical societies: American Society of Pediatric Nephrology
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Coauthor(s)

Jordan M Symons, MD, Associate Professor of Pediatrics, University of Washington School of Medicine; Dialysis Medical Director, Department of Nephrology, Children's Hospital and Regional Medical Center
Jordan M Symons, MD is a member of the following medical societies: American Society of Nephrology, American Society of Pediatric Nephrology, and Renal Physicians Association
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Henrique M Lederman, MD, PhD, Consulting Staff, Department of Radiology, LeBonheur Children's Medical Center and St Jude Children's Research Hospital; Professor of Radiology and Pediatric Radiology, Chief, Division of Diagnostic Imaging in Pediatrics, Federal University of Sao Paulo, Brazil
Henrique M Lederman, MD, PhD is a member of the following medical societies: Society for Pediatric Radiology
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Peter J Hurh, Research Fellow, Department of Radiology, The Children's Hospital of Philadelphia
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H Jorge Baluarte, MD, Medical Director, Renal Transplant Program, Division of Nephrology, Department of Pediatrics, The Children's Hospital of Philadelphia; Professor of Pediatrics, University of Pennsylvania
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Craig B Langman, MD, The Isaac A Abt, MD, Professor of Kidney Diseases, Feinberg School of Medicine, Northwestern University; Division Head of Kidney Diseases, Children's Memorial Hospital, Chicago
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