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Pediatric Polycystic Kidney Disease

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

Background

Polycystic kidney disease, a disorder that can be diagnosed in adult and pediatric patients, is an inherited disease that involves bilateral renal cysts without dysplasia. The condition is broadly divided into 2 forms: autosomal recessive polycystic kidney disease, previously known as infantile polycystic kidney disease, and autosomal dominant polycystic kidney disease, previously known as adult polycystic kidney disease. The nomenclature of infantile versus adult is no longer used because it is not an accurate description. (See the image 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).

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 radiologic manifestations of both types of polycystic kidney disease have considerable overlap. (See Clinical and Workup.)

Autosomal recessive polycystic kidney disease

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. (See the image below.) (See Etiology.)

Sonogram shows enlargement of both kidneys, diffus 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).

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

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 (see the image below), with variable extrarenal manifestations in the gastrointestinal (GI) tract, cardiovascular system, reproductive organs, and brain.[3] (See Etiology.)

Pathologic specimen of end-stage autosomal dominan Pathologic specimen of end-stage autosomal dominant polycystic kidney disease (ADPKD) with deformed lobulated kidneys.

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, similar to autosomal recessive polycystic kidney disease, it may present with severe neonatal manifestations. (See Clinical and Workup.)

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Etiology

The 3 basic processes involved in renal cyst formation and progressive enlargement are as follows[4, 5] :

  • Tubular cell hyperplasia
  • Tubular fluid secretion
  • Abnormalities in tubular extracellular matrix and/or function

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 2.

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.[6] 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.[7]

Autosomal recessive polycystic kidney disease is characterized by nonobstructive, bilateral, symmetrical 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. (See the images below.)

Excretory urogram shows minimal bilateral tubular 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 bila 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 (spong Excretory urogram shows the typical mottled (spongelike) contrast pattern in autosomal recessive polycystic kidney disease (ARPKD).
Excretory urogram shows the typical mottled (spong Excretory urogram shows the typical mottled (spongelike) contrast pattern in autosomal recessive polycystic kidney disease (ARPKD).
Excretory urogram shows the typical mottled (spong Excretory urogram shows the typical mottled (spongelike) contrast enhancement pattern in autosomal recessive polycystic kidney disease (ARPKD).

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 a 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.[8]

The results from one study noted that characteristics of CHF are similar in both autosomal dominant and autosomal recessive polycystic kidney diseases.[9]

In a study designed to better understand the complications of autosomal recessive polycystic kidney disease, researchers at the NIH analyzed clinical, molecular and imaging data from 73 patients (ages 1-56 years old, average 12.7) with mutations in PKHD1 and kidney and liver involvement. The findings identified platelet count as the best predictor of the severity of portal hypertension, which has early onset but is underdiagnosed in patients with autosomal recessive polycystic kidney disease.[10]

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 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 containing 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. It has been hypothesized that patients with an associated marked epithelial hyperplasia may have a higher rate of malignant transformation than does the general population.

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Epidemiology

Occurrence in the United States

The exact incidence of autosomal recessive polycystic kidney disease 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.

The estimated prevalence of autosomal dominant polycystic kidney disease is 1 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 occurrence

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

Race- and sex -related demographics

Both forms of polycystic kidney disease affect all racial and ethnic groups and both equally affect males and females.

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Prognosis

Determining the prognosis of polycystic kidney disease 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.

Autosomal recessive polycystic kidney disease

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

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 age 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.[11]

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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

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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].

 
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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).
 
 
 
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