Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Pediatric Polycystic Kidney Disease Workup

  • Author: Priya Verghese, MD, MPH; Chief Editor: Craig B Langman, MD  more...
 
Updated: Nov 11, 2014
 

Approach Considerations

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 deoxyribonucleic acid (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.

Blood and urine studies are useful in evaluating patients with both types of polycystic kidney disease, 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.

Blood urea nitrogen (BUN) levels in plasma are also increased in renal dysfunction. However, this is not as reliable a test as the serum creatinine level test, because BUN levels are also elevated in cases of intravascular depletion, increased protein intake, catabolism, and GI hemorrhage and may be reduced in chronic liver disease.

Liver function is usually normal. However, liver function test findings are often abnormal in the later stages of the disease, particularly in autosomal recessive polycystic kidney disease.

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

Urine analysis findings can be normal. Microhematuria or macrohematuria may be present. Macrohematuria is more common in autosomal dominant polycystic kidney disease. Gross hematuria often develops after minor trauma to the flank. Proteinuria, pyuria, and, sometimes, evidence of urinary concentrating defects, such as prerenal azotemia, may be present. Metabolic acidosis may be present.

Maternal alpha fetoprotein (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 the diagnosis of autosomal recessive polycystic kidney disease.

Brain imaging is used in the diagnosis of autosomal dominant polycystic kidney disease. Left ventricular hypertrophy and early ramifications are revealed using echocardiography; diastolic dysfunction is present, even in normotensive patients. Renal biopsy in polycystic kidney disease is not usually indicated, particularly when the family history is positive.

Next

Electrolytes

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 hypocalcemia. Tubular dysfunction can also cause electrolyte abnormalities.

Previous
Next

Radiography

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.

Autosomal dominant polycystic kidney disease

Radiographic findings in autosomal dominant polycystic kidney disease include the following (see also the images below):

  • Grossly enlarged kidneys with lobular appearance
  • Distorted calyces secondary to nonopacified cysts with smooth or irregular indentations
  • Numerous bilateral cysts of various sizes
  • Intravenous pyelogram findings - May be normal or show abnormalities in 1 or both kidneys
    Frontal excretory urogram of autosomal dominant po 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 po 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.
Previous
Next

Ultrasonography

Autosomal recessive polycystic kidney disease

Prenatal findings include the following:

  • 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 include the following:

  • 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 ultrasonographic findings. In older children who present late, renal ultrasonography findings may be less reliable. Hepatic features are often the prominent presenting feature.

Enlarged kidneys in older children with autosomal recessive polycystic kidney disease differ from enlarged kidneys in younger children with the disease in that the hyperechogenicity is mainly in the medulla because of focal tubular cysts.

Renal macrocysts are more common in older children. Also in this age group, the liver is often enlarged, with heterogeneously or homogenously increased echogenicity, macrocysts in the liver and pancreas are often visualized, and splenomegaly is observed. Macroscopic liver cysts are uncommon in older children, although choledochal cysts have been reported. When present, biliary duct dilatation is indistinguishable from Caroli disease.

The reversal of hepatic venous blood flow in older children, revealed by Doppler ultrasonography, suggests portal hypertension.

Adult ultrasonographic findings include the following:

  • Multiple small cysts, typically in normal-sized kidney
  • Increased cortical echogenicity
  • Loss of corticomedullary differentiation

Autosomal dominant polycystic kidney disease

Ultrasonography should be the first line of imaging in patients who are at risk for autosomal dominant polycystic kidney disease, especially in patients older than 30 years. In patients younger than 30 years, ultrasonography may not reveal manifestations, and linkage analysis may be more sensitive. It is limited in the differentiation of hemorrhage of the cyst and infection, as both the conditions show internal echoes, fluid debris levels, and thickened walls. (See the images below.)

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

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 ultrasonographic screening that demonstrates even 1 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.

Ovarian cysts may be present in patients with autosomal dominant polycystic kidney disease. Pancreatic cysts are found exclusively in patients with PKD1 and are usually asymptomatic.

Multicystic kidney disease differs from polycystic kidney disease in that it is unilateral, with multiple noncommunicating macrocysts of varying size.

Previous
Next

Cross-Sectional Imaging - CT Scanning and MRI

CT scanning

Computed tomography (CT) can be helpful for distinguishing between cystic wall calcifications and calculi.

Combining enhanced and unenhanced CT scanning, cystic walls can be evaluated for signs of infection, bleeding, or malignancy. CT scanning also helps in the evaluation of perinephric extension of a bleeding or infected cyst..

In autosomal recessive polycystic kidney disease, noncontrast CT scanning reveals smooth, enlarged kidneys.

With intravenous contrast, kidneys have a striated appearance due to the accumulation of contrast in dilated tubules. Depending on the degree of renal insufficiency, a proportionate delay in the arrival of contrast to the kidneys is observed. Macrocysts may appear as well-circumscribed, lucent defects. The bladder may be opacified. See the image below.

CT shows bilaterally smooth enlarged kidneys. Thes CT shows bilaterally smooth enlarged kidneys. These findings are compatible with a diagnosis of autosomal recessive polycystic kidney disease (ARPKD).

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 and this can be measured by CT scanning.

If a cyst hemorrhage is present, it can be observed as a high-density cyst on nonenhanced images, with sharp contours and interface and no contrast enhancement.

If it is an infected cyst, the density is close to water or has mildly increased attenuation, presenting ticked walls and enhancement.

CT scanning also allows detection of complications such as emphysematous pyelonephritis, which is highly sensitive by the presence of intracystic air. See the image below.

CT shows bilateral renal and liver cysts with enla CT shows bilateral renal and liver cysts with enlarged kidneys and remaining renal cortex enhancement compatible with a diagnosis of autosomal dominant polycystic kidney disease (ADPKD).

MRI

MRI is the best imaging tool in polycystic kidney disease to determinate renal/cyst size and volume and to help in the evaluation of cystic bleeding and infection. Even though the association with renal cell carcinomas is controversial, its incidence is higher in these patients, in whom MRI can play a role showing restricted diffusion and morphological changes.

MRI findings in autosomal recessive polycystic kidney disease include the following (see image below):

  • Enlarged kidneys with T2-weighted imaging that show increased signal intensity
  • A characteristic hyperintense, linear, radial pattern in the cortex and medulla
    T2-weighted MRI shows bilateral smooth enlarged ki T2-weighted MRI shows bilateral smooth enlarged kidneys with a hyperintense, linear, radial pattern in the cortex and medulla, compatible with autosomal recessive kidney disease.

Findings in autosomal dominant polycystic kidney disease include the following:

  • The presence of a single cyst in childhood can lead to the diagnosis, as simple cysts are extremely rare in this age group
  • Enlarged kidneys with low T1-weighted and high T2-weighted signal cysts
  • Morphological changes and restricted diffusion in high cellularity areas help in the diagnosis of associated renal cell carcinomas and sarcomas, which are not associated but occur more frequently in these patients
  • Signal changes on hemorrhagic cysts usually present hyperintense on T1-weighted images, with varied signals in all sequences, depending on the age of the hemorrhage, and they often show fluid hematic or iron levels
  • Infected cysts commonly present hypointense on T1-weighted images and hyperintense on T2-weighted images, with marked mural thickening

Note the images below.

T1- and T2-weighted MRIs demonstrating a superior T1- and T2-weighted MRIs demonstrating a superior left kidney cyst with high T1 and intermediary T2 signal compatible with a bleeding cyst in autosomal dominant polycystic kidney disease (ADPKD).
T1- and T2-weighted MRIs demonstrating bilateral r T1- and T2-weighted MRIs demonstrating bilateral renal and liver cysts compatible with autosomal dominant polycystic kidney disease (ADPKD).
Previous
Next

Genetic Testing

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 1 established index case of the 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 living, related potential 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, as well as 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.

Previous
Next

Ethical Diagnostic Considerations

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 the choice to know or not know; psychological, educational, and career implications; insurability issues) outweigh the benefits.

Previous
 
 
Contributor Information and Disclosures
Author

Priya Verghese, MD, MPH Fellow in Pediatric Nephrology, Seattle Children's Hospital, University of Washington School of Medicine

Priya Verghese, MD, MPH is a member of the following medical societies: American Society of Pediatric Nephrology

Disclosure: Nothing to disclose.

Coauthor(s)

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

Disclosure: Nothing to disclose.

Jordan M Symons, MD Associate Professor of Pediatrics, University of Washington School of Medicine; Director of the Acute Dialysis Program, Seattle Children's Hospital

Jordan M Symons, MD is a member of the following medical societies: American Society of Nephrology, American Society of Pediatric Nephrology, Renal Physicians Association

Disclosure: Nothing to disclose.

José Luiz de Oliveira Schiavon, MD Associate Professor, Department of Pediatric Radiology, Instituto de Oncologia Pediatrica, Universidade Federal De Sao Paulo, Brazil

José Luiz de Oliveira Schiavon, MD is a member of the following medical societies: Radiological Society of North America

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Luther Travis, MD Professor Emeritus, Departments of Pediatrics, Nephrology and Diabetes, University of Texas Medical Branch School of Medicine

Luther Travis, MD is a member of the following medical societies: Alpha Omega Alpha, American Federation for Medical Research, International Society of Nephrology, Texas Pediatric Society

Disclosure: Nothing to disclose.

Chief Editor

Craig B Langman, MD The Isaac A Abt, MD, Professor of Kidney Diseases, Northwestern University, The Feinberg School of Medicine; Division Head of Kidney Diseases, The Ann and Robert H Lurie Children's Hospital of Chicago

Craig B Langman, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Nephrology, International Society of Nephrology

Disclosure: Received income in an amount equal to or greater than $250 from: Alexion Pharmaceuticals; Raptor Pharmaceuticals; Eli Lilly and Company; Dicerna<br/>Received grant/research funds from NIH for none; Received grant/research funds from Raptor Pharmaceuticals, Inc for none; Received grant/research funds from Alexion Pharmaceuticals, Inc. for none; Received consulting fee from DiCerna Pharmaceutical Inc. for none.

Additional Contributors

Richard Neiberger, MD, PhD Director of Pediatric Renal Stone Disease Clinic, Associate Professor, Department of Pediatrics, Division of Nephrology, University of Florida College of Medicine and Shands Hospital

Richard Neiberger, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Federation for Medical Research, American Medical Association, American Society of Nephrology, American Society of Pediatric Nephrology, Christian Medical and Dental Associations, Florida Medical Association, International Society for Peritoneal Dialysis, International Society of Nephrology, National Kidney Foundation, New York Academy of Sciences, Shock Society, Sigma Xi, Southern Medical Association, Southern Society for Pediatric Research, Southwest Pediatric Nephrology Study Group

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors H Jorge Baluarte, MD, and Peter J Hurh, MD,to the development and writing of the source article.

References
  1. OSATHANONDH V, POTTER EL. PATHOGENESIS OF POLYCYSTIC KIDNEYS. TYPE 1 DUE TO HYPERPLASIA OF INTERSTITIAL PORTIONS OF COLLECTING TUBULES. Arch Pathol. 1964 May. 77:466-73. [Medline].

  2. OSATHANONDH V, POTTER EL. PATHOGENESIS OF POLYCYSTIC KIDNEYS. HISTORICAL SURVEY. Arch Pathol. 1964 May. 77:459-65. [Medline].

  3. Grantham JJ, Torres VE, Chapman AB, et al. Volume progression in polycystic kidney disease. N Engl J Med. 2006 May 18. 354(20):2122-30. [Medline].

  4. Yoder BK, Mulroy S, Eustace H, Boucher C, Sandford R. Molecular pathogenesis of autosomal dominant polycystic kidney disease. Expert Rev Mol Med. 2006 Jan 17. 8(2):1-22. [Medline].

  5. Sweeney WE Jr, Avner ED. Molecular and cellular pathophysiology of autosomal recessive polycystic kidney disease (ARPKD). Cell Tissue Res. 2006 Dec. 326(3):671-85. [Medline].

  6. Zerres K, Mücher G, Bachner L, et al. Mapping of the gene for autosomal recessive polycystic kidney disease (ARPKD) to chromosome 6p21-cen. Nat Genet. 1994 Jul. 7(3):429-32. [Medline].

  7. Sharp AM, Messiaen LM, Page G, et al. Comprehensive genomic analysis of PKHD1 mutations in ARPKD cohorts. J Med Genet. 2005 Apr. 42(4):336-49. [Medline]. [Full Text].

  8. Gunay-Aygun M, Avner ED, Bacallao RL, et al. Autosomal recessive polycystic kidney disease and congenital hepatic fibrosis: summary statement of a first National Institutes of Health/Office of Rare Diseases conference. J Pediatr. 2006 Aug. 149(2):159-64. [Medline]. [Full Text].

  9. O'Brien K, Font-Montgomery E, Lukose L, et al. Congenital hepatic fibrosis and portal hypertension in autosomal dominant polycystic kidney disease. J Pediatr Gastroenterol Nutr. 2012 Jan. 54(1):83-9. [Medline].

  10. Gunay-Aygun M, Font-Montgomery E, Lukose L, Tuchman Gerstein M, Piwnica-Worms K, Choyke P, et al. Characteristics of congenital hepatic fibrosis in a large cohort of patients with autosomal recessive polycystic kidney disease. Gastroenterology. 2013 Jan. 144(1):112-121.e2. [Medline]. [Full Text].

  11. Boyer O, Gagnadoux MF, Guest G, et al. Prognosis of autosomal dominant polycystic kidney disease diagnosed in utero or at birth. Pediatr Nephrol. 2007 Mar. 22(3):380-8. [Medline].

  12. Bajwa ZH, Sial KA, Malik AB, Steinman TI. Pain patterns in patients with polycystic kidney disease. Kidney Int. 2004 Oct. 66(4):1561-9. [Medline]. [Full Text].

  13. Chapman AB. Approaches to testing new treatments in autosomal dominant polycystic kidney disease: insights from the CRISP and HALT-PKD studies. Clin J Am Soc Nephrol. 2008 Jul. 3(4):1197-204. [Medline].

  14. Sweeney WE, Chen Y, Nakanishi K, et al. Treatment of polycystic kidney disease with a novel tyrosine kinase inhibitor. Kidney Int. 2000 Jan. 57(1):33-40. [Medline].

 
Previous
Next
 
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 kidneys. These findings are compatible with a diagnosis of autosomal dominant polycystic kidney disease (ADPKD).
Sonogram shows cysts with bilaterally enlarged kidneys. These findings are compatible with a diagnosis of autosomal dominant polycystic kidney disease (ADPKD).
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 polycystic kidney disease (ADPKD) shows a spider-legs configuration of the collecting system secondary to compression due to cysts.
Pathologic specimen of end-stage autosomal dominant polycystic kidney disease (ADPKD) with deformed lobulated kidneys.
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 changes caused by a mild form of autosomal recessive polycystic kidney disease (ARPKD).
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 (spongelike) contrast pattern in autosomal recessive polycystic kidney disease (ARPKD).
Excretory urogram shows the typical mottled (spongelike) contrast pattern in autosomal recessive polycystic kidney disease (ARPKD).
Excretory urogram shows the typical mottled (spongelike) contrast enhancement pattern in autosomal recessive polycystic kidney disease (ARPKD).
CT shows bilaterally smooth enlarged kidneys. These findings are compatible with a diagnosis of autosomal recessive polycystic kidney disease (ARPKD).
CT shows bilateral renal and liver cysts with enlarged kidneys and remaining renal cortex enhancement compatible with a diagnosis of autosomal dominant polycystic kidney disease (ADPKD).
T2-weighted MRI shows bilateral smooth enlarged kidneys with a hyperintense, linear, radial pattern in the cortex and medulla, compatible with autosomal recessive kidney disease.
T1- and T2-weighted MRIs demonstrating a superior left kidney cyst with high T1 and intermediary T2 signal compatible with a bleeding cyst in autosomal dominant polycystic kidney disease (ADPKD).
T1- and T2-weighted MRIs demonstrating bilateral renal and liver cysts compatible with autosomal dominant polycystic kidney disease (ADPKD).
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.