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Autosomal Recessive (Infantile) Polycystic Kidney Disease
62
PART 3 Retroperitoneum • SECTION ONE Kidney
16
Autosomal Recessive (Infantile) Polycystic Kidney Disease APRIL T. BLEICH | JODI S. DASHE
Introduction Autosomal recessive polycystic kidney disease (ARPKD) is a chronic, progressive condition that affects the kidneys and liver, causing cystic dilatation of the renal collecting ducts and congenital hepatic fibrosis (CHF), or Caroli disease.1 ARPKD is also called infantile polycystic kidney disease and ARPKD/CHF. ARPKD is
caused by mutations of a large, complex gene, PKHD1, and it has an unusually wide spectrum of phenotypic variability. Diagnosis is made prenatally or soon after birth in approximately 30% of patients,2–4 and neonatal mortality from pulmonary hypoplasia occurs in approximately 15% of cases—up to half of cases with prenatal diagnosis.3,5,6 Among children who survive infancy, morbidity is determined by the degree of renal
16 Autosomal Recessive (Infantile) Polycystic Kidney Disease
insufficiency, with current 5-year and 10-year survival rates between 80% and 90%.3,6 Some individuals do not come to medical attention until later in childhood or adulthood and have both renal and hepatic manifestations, including earlyonset hypertension, renal failure, portal hypertension, and recurrent cholangitis.4 The varying phenotypic manifestations of ARPKD can pose unique challenges from the standpoint of prenatal diagnosis, particularly in absence of an informative family history.
Disorder DEFINITION Infantile polycystic kidney disease is an autosomal recessive disease that causes cystic dilatation of the renal collecting ducts and CHF. PREVALENCE AND EPIDEMIOLOGY The prevalence of ARPKD is estimated to be 1 : 20,000 births.7 Inheritance is autosomal recessive, with complete penetrance but variable expressivity even within a family.6 Carrier frequency of a disease-causing PKHD1 mutation is estimated to be 1 : 70 in the general population.7 Family members of affected individuals should be counseled about inheritance patterns and recurrence risk. ETIOLOGY AND PATHOPHYSIOLOGY Historically, ARPKD was divided into four subtypes, based on timing of presentation and degree of renal and hepatic involvement: perinatal, neonatal, infantile, and juvenile.8 It is now viewed as a spectrum of disease. Renal involvement is characterized by dilatation and elongation of the cortical collecting ducts, resulting in a uniform distribution of radially arranged fusiform cysts.8 The outer renal cortex is spared because it contains no tubules.9 In the liver, proliferation and dilatation of portal bile ducts are responsible for development of periportal fibrosis.8 ARPKD is caused by mutations of the PKHD1 gene, which is located on the short arm of chromosome 6. PKHD1 is one of the largest human genes, possessing a complex splicing pattern that results in multiple transcripts, the largest of which is fibrocystin/polyductin. This gene product is expressed in the kidney and, to a lesser extent, in the liver, and it is believed to play a role in regulation of cell proliferation, adhesion, and repulsion.10–12 Molecular genetic testing is available for affected families. PKHD1 mutation screening using denaturing high-performance liquid chromatography has identified mutations in more than 75% of cases, including 85% of patients with perinatal or neonatal demise.6,13 However, because most affected children are compound heterozygotes (inheriting a different mutation from each parent) and because most mutations are unique to individual families, genotype-phenotype correlations pose a challenge.13,14 In general, inheritance of two truncating mutations is more strongly associated with perinatal mortality, whereas those with missense mutations tend to display a milder phenotype.6 Prenatal diagnosis is available using single gene molecular genetic analysis, as is preimplantation genetic diagnosis. Indirect, haplotype-based linkage analysis is no longer the preferred method because of the possibility of misdiagnosis.14
63
MANIFESTATIONS OF DISEASE Clinical Presentation The clinical presentation is highly variable. Diagnosis may be made in affected individuals before birth, in the neonatal period, in childhood, or in young adulthood. Manifestations may include pulmonary hypoplasia, early-onset hypertension, renal insufficiency, portal hypertension, esophageal varices, and recurrent cholangitis. Approximately 50% of patients require dialysis by age 20.6 Prenatally, the diagnosis is suspected based on ultrasound (US) findings and may be confirmed in an informative family by the identification of disease-causing mutations. Imaging Technique and Findings Ultrasound. The characteristic US finding is massive, symmetrically enlarged, echogenic kidneys, which fill and distend the fetal abdomen, measuring between 4 and 15 standard deviations above the mean for gestational age.9 Normal corticomedullary differentiation is not visible. In some cases, these findings may be apparent in the first trimester (Fig. 16.1).15 When ARPKD manifests early in gestation, amniotic fluid volume is usually severely decreased, with no urine visible in the bladder (Fig. 16.2). As with other causes of severe, prolonged oligohydramnios, there is significant risk for pulmonary hypoplasia secondary to Potter sequence (see Chapter 10). With advancing gestation, the appearance of the kidney becomes more inhomogeneous, and tiny cysts may be visible (Fig. 16.3). In many cases, the diagnosis of ARPKD is not so straightforward. Another presentation involves kidneys that are echogenic but only mildly enlarged, measuring between 2 and 4 standard deviations above the mean, with preserved amniotic fluid volume (Fig. 16.4). The kidneys may not appear noticeably abnormal until after midgestation.9 In the absence of an informative family history, counseling for such cases is problematic.16,17 Although the differential diagnosis includes ARPKD, it also includes genetic syndromes such as Bardet-Biedl syndrome and glutaric aciduria type II, aneuploidy such as trisomy 13 (Fig. 16.5), and especially, normal kidneys.9,18,19 A careful family history, diligent search for other anomalies, and consideration of amniocentesis are important.
Fig. 16.1 Coronal image of a fetus with autosomal recessive polycystic kidney disease (ARPKD) at 14 weeks’ gestation. The kidneys (arrows) appear massively enlarged and echogenic, and there is no visible amniotic fluid.
64
PART 3 Retroperitoneum • SECTION ONE Kidney
When the fetal kidneys are mildly enlarged and echogenic, and amniotic fluid volume is normal, the differential diagnosis also includes autosomal dominant polycystic kidney disease (ADPKD) (Fig. 16.6). ADPKD usually has no prenatal manifestations; patients typically present in the fourth decade of life. However, ADPKD is much more common than ARPKD, occurring in 1 : 800 births rather than 1 : 20,000. In the absence of a family history or other fetal abnormalities, consideration may be given to US evaluation of the parents’ kidneys (Fig. 16.7).
Although rare, there have been case reports of fetal hepatic fibrosis secondary to ARPKD manifesting with cystic dilatation of intrahepatic bile ducts in the setting of echogenic kidneys in the third trimester.20 Also, because of variable expressivity, normal-appearing kidneys do not preclude a diagnosis of ARPKD in an at-risk pregnancy. Renal manifestations may not be visible until childhood or even later.
CLASSIC SIGNS Bilaterally enlarged echogenic kidneys without corticomedullary differentiation, often associated with oligohydramnios.
Differential Diagnosis From Imaging Findings 1. Normal variant (provided amniotic fluid volume is normal beyond 18 weeks) 2. ADPKD 3. Trisomy 13 (see Chapter 149) 4. Multicystic dysplastic kidneys (see Chapter 15) 5. Meckel-Gruber syndrome (autosomal recessive) (see Chapter 133) 6. Bardet-Biedl syndrome (autosomal recessive) 7. Glutaric aciduria type II (autosomal recessive) 8. Perlman syndrome (autosomal recessive) 9. Beckwith-Wiedemann syndrome (see Chapter 109)
Fig. 16.2 Transverse image at the level of the bladder in a fetus with autosomal recessive polycystic kidney disease (ARPKD) at 24 weeks’ gestation. No urine is visible.
B
A
C
D
Fig. 16.3 Coronal images of a fetus with severe autosomal recessive polycystic kidney disease (ARPKD) at 18 weeks (A) and at 20 weeks (B), showing enlarged, echogenic, and inhomogeneous kidneys. There is no measurable pocket of amniotic fluid. By 26 weeks, sagittal (C) and coronal (D) images demonstrate diffuse tiny cysts within kidneys that are globular, echogenic, and fill the abdomen and pelvis.
A
B
C
D
Fig. 16.4 At 21 weeks, transverse (A) and coronal (B) images demonstrate kidneys that are echogenic, mildly enlarged, and slightly globular in appearance. Images (C) and (D) are transverse and sagittal views of the same fetus at 25 weeks. The amniotic fluid volume is normal. The differential diagnosis is broad in this situation.
D 50.5 mm
A
B
Fig. 16.5 Coronal (A) and sagittal (B) images of enlarged, echogenic kidneys in a fetus with trisomy 13. The kidneys measured 5 cm in length at 28 weeks’ gestation.
D 131.4 mm
Liver
*
Fig. 16.6 Transverse image of echogenic, mildly enlarged kidneys in a fetus with autosomal dominant polycystic kidney disease. Cysts are not visible prenatally.
Kidney
*
*
* *
Fig. 16.7 Maternal right kidney, showing autosomal dominant polycystic kidney disease. Cysts are indicated by asterisks.
Synopsis of Treatment Options
KEY POINTS
POSTNATAL
• ARPKD affects 1 : 20,000 pregnancies and has a wide spectrum of phenotypic variability. • Approximately 30% of cases are diagnosed prenatally or soon after birth; some prenatal cases have lethal pulmonary hypoplasia. • US findings include echogenic kidneys that are variably enlarged, with early oligohydramnios in the most severe cases. • For patients who survive infancy, 10-year survival is greater than 80%, but morbidity is significant, with hypertension, ascending cholangitis, portal hypertension, and renal insufficiency. Approximately 50% require dialysis by age 20.
When the amniotic fluid volume is severely decreased before 20 weeks, the prognosis is so poor that (if the pregnancy is continued) many families plan comfort care. In the absence of lethal pulmonary hypoplasia, initial postnatal management consists of evaluation of pulmonary and renal function. The growth and development of the infant are followed closely, with surveillance for hypertension, hyponatremia, renal insufficiency, cholangitis, and portal hypertension.
SUGGESTED READING
WHAT THE REFERRING PHYSICIAN NEEDS TO KNOW ARPKD, which is caused by mutations in the PKHD1 gene, is characterized by progressive renal failure and hepatic fibrosis. Cases that manifest prenatally show varying degrees of renal enlargement. Massively enlarged, echogenic kidneys, together with severely decreased amniotic fluid before midgestation, confer significant risk for pulmonary hypoplasia. However, in other cases, the kidneys are enlarged to a lesser degree, and amniotic fluid is preserved; these findings are not specific for ARPKD and may occur in ADPKD, trisomy 13, other syndromes, and normal pregnancy. Molecular genetic testing may be helpful in affected families.
Avni FE, Garel L, Cassart M, et al. Perinatal assessment of hereditary cystic renal diseases: the contribution of sonography. Pediatr Radiol. 2006;36:405-414. Guay-Woodford L, Bissler J, Braun M, et al. Consensus expert recommendations for the diagnosis and management of autosomal recessive polycystic kidney disease: report of an international conference. J Pediatr. 2014;165:611-617. Guay-Woodford LM, Desmond RA. Autosomal recessive polycystic kidney disease: the clinical experience in North America. Pediatrics. 2003;111:1072-1080. Gunay-Aygun M, Avner ED, Ballacao 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;149:159-164. Turkbey B, Ocak I, Daryanani K, et al. Autosomal recessive polycystic kidney disease and congenital hepatic fibrosis (ARPKD/CHF). Pediatr Radiol. 2009;39:100-111.
All references are available online at www.expertconsult.com.
16 Autosomal Recessive (Infantile) Polycystic Kidney Disease 66.e1
REFERENCES 1. Turkbey B, Ocak I, Daryanani K, et al. Autosomal recessive polycystic kidney disease and congenital hepatic fibrosis (ARPKD/CHF). Pediatr Radiol. 2009;39:100-111. 2. Zerres K, Rudnik-Schoneborn S, Deget F, et al. Clinical course of 115 children with autosomal recessive polycystic kidney disease. Acta Pediatr. 1996;85:437-445. 3. Guay-Woodford LM, Desmond RA. Autosomal recessive polycystic kidney disease: the clinical experience in North America. Pediatrics. 2003;111: 1072-1080. 4. Gunay-Aygun M, Avner ED, Ballacao 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;149:159-164. 5. Roy S, Dillon MJ, Trompeter RS, et al. Autosomal recessive polycystic kidney disease: long-term outcome of neonatal survivors. Pediatr Nephrol. 1997;11:302-306. 6. Bergmann C, Senderek J, Windelen E, et al. Clinical consequences of PKHD1 mutations in 164 patients with autosomal-recessive polycystic kidney disease (ARPKD). Kidney Int. 2005;67:829-848. 7. Zerres K, Mücher G, Becker J, et al. Prenatal diagnosis of autosomal recessive polycystic kidney disease (ARPKD): molecular genetics, clinical experience, and fetal morphology. Am J Med Genet. 1998;6:137-144. 8. Blyth H, Ockenden BH. Polycystic disease of kidneys and liver presenting in childhood. J Med Genet. 1971;8:257-284. 9. Avni FE, Garel L, Cassart M, et al. Perinatal assessment of hereditary cystic renal diseases: the contribution of sonography. Pediatr Radiol. 2006;36:405-414. 10. Al-Bhalal L, Akhtar M. Molecular basis of autosomal recessive polycystic kidney disease (ARPKD). Adv Anat Pathol. 2008;15:54-58.
11. Deltas C. Papagregoriou G. Cystic diseases of the kidney. Arch Pathol Lab Med. 2010;134:569-582. 12. Zerres K, Senderek J, Rudnik-Schöneborn S, et al. New options for prenatal diagnosis in autosomal recessive polycystic kidney disease by mutation analysis of the PKHD1 gene. Clin Genet. 2004;66:53-57. 13. Bergmann C, Senderek J, Kupper F, et al. PKHD1 mutations in autosomal recessive polycystic kidney disease (ARPKD). Hum Mutat. 2004;23: 453-463. 14. Guay-Woodford L, Bissler J, Braun M, et al. Consensus expert recommendations for the diagnosis and management of autosomal recessive polycystic kidney disease: report of an international conference. J Pediatr. 2014;165: 611-617. 15. Bronshtein M, Kushnir O, Ben-Rafael Z, et al. Transvaginal sonographic measurement of fetal kidneys in the first trimester of pregnancy. J Clin Ultrasound. 1990;18:299-301. 16. Lilford RJ, Irving HC, Allibone EB. A tale of two prior probabilities—avoiding the false positive antenatal diagnosis of autosomal recessive polycystic kidney disease. Br J Obstet Gynaecol. 1992;99:216-219. 17. Mashiach R, Davidovits M, Eisenstein B. Fetal hyperechogenic kidney with normal amniotic fluid volume: a diagnostic dilemma. Prenat Diagn. 2005;25:553-558. 18. Whitfield J, Hurst D, Bennett MJ, et al. Fetal polycystic kidney disease associated with glutaric aciduria type II: an inborn error of energy metabolism. Am J Perinat. 1996;13:131-134. 19. Kjaergaard S, Graem N, Larsen T, et al. Recurrent fetal polycystic kidneys associated with glutaric aciduria type II. APMIS. 1998;106:1188-1193. 20. Sgro M, Rossetti S, Barozzino T. Caroli’s disease: prenatal diagnosis, postnatal outcome and genetic analysis. Ultrasound Obstet Gynecol. 2004;23:73-76.
PART 3 Retroperitoneum • SECTION ONE Kidney
16
Autosomal Recessive (Infantile) Polycystic Kidney Disease APRIL T. BLEICH | JODI S. DASHE
Introduction Autosomal recessive polycystic kidney disease (ARPKD) is a chronic, progressive condition that affects the kidneys and liver, causing cystic dilatation of the renal collecting ducts and congenital hepatic fibrosis (CHF), or Caroli disease.1 ARPKD is also called infantile polycystic kidney disease and ARPKD/CHF. ARPKD is
caused by mutations of a large, complex gene, PKHD1, and it has an unusually wide spectrum of phenotypic variability. Diagnosis is made prenatally or soon after birth in approximately 30% of patients,2–4 and neonatal mortality from pulmonary hypoplasia occurs in approximately 15% of cases—up to half of cases with prenatal diagnosis.3,5,6 Among children who survive infancy, morbidity is determined by the degree of renal
16 Autosomal Recessive (Infantile) Polycystic Kidney Disease
insufficiency, with current 5-year and 10-year survival rates between 80% and 90%.3,6 Some individuals do not come to medical attention until later in childhood or adulthood and have both renal and hepatic manifestations, including earlyonset hypertension, renal failure, portal hypertension, and recurrent cholangitis.4 The varying phenotypic manifestations of ARPKD can pose unique challenges from the standpoint of prenatal diagnosis, particularly in absence of an informative family history.
Disorder DEFINITION Infantile polycystic kidney disease is an autosomal recessive disease that causes cystic dilatation of the renal collecting ducts and CHF. PREVALENCE AND EPIDEMIOLOGY The prevalence of ARPKD is estimated to be 1 : 20,000 births.7 Inheritance is autosomal recessive, with complete penetrance but variable expressivity even within a family.6 Carrier frequency of a disease-causing PKHD1 mutation is estimated to be 1 : 70 in the general population.7 Family members of affected individuals should be counseled about inheritance patterns and recurrence risk. ETIOLOGY AND PATHOPHYSIOLOGY Historically, ARPKD was divided into four subtypes, based on timing of presentation and degree of renal and hepatic involvement: perinatal, neonatal, infantile, and juvenile.8 It is now viewed as a spectrum of disease. Renal involvement is characterized by dilatation and elongation of the cortical collecting ducts, resulting in a uniform distribution of radially arranged fusiform cysts.8 The outer renal cortex is spared because it contains no tubules.9 In the liver, proliferation and dilatation of portal bile ducts are responsible for development of periportal fibrosis.8 ARPKD is caused by mutations of the PKHD1 gene, which is located on the short arm of chromosome 6. PKHD1 is one of the largest human genes, possessing a complex splicing pattern that results in multiple transcripts, the largest of which is fibrocystin/polyductin. This gene product is expressed in the kidney and, to a lesser extent, in the liver, and it is believed to play a role in regulation of cell proliferation, adhesion, and repulsion.10–12 Molecular genetic testing is available for affected families. PKHD1 mutation screening using denaturing high-performance liquid chromatography has identified mutations in more than 75% of cases, including 85% of patients with perinatal or neonatal demise.6,13 However, because most affected children are compound heterozygotes (inheriting a different mutation from each parent) and because most mutations are unique to individual families, genotype-phenotype correlations pose a challenge.13,14 In general, inheritance of two truncating mutations is more strongly associated with perinatal mortality, whereas those with missense mutations tend to display a milder phenotype.6 Prenatal diagnosis is available using single gene molecular genetic analysis, as is preimplantation genetic diagnosis. Indirect, haplotype-based linkage analysis is no longer the preferred method because of the possibility of misdiagnosis.14
63
MANIFESTATIONS OF DISEASE Clinical Presentation The clinical presentation is highly variable. Diagnosis may be made in affected individuals before birth, in the neonatal period, in childhood, or in young adulthood. Manifestations may include pulmonary hypoplasia, early-onset hypertension, renal insufficiency, portal hypertension, esophageal varices, and recurrent cholangitis. Approximately 50% of patients require dialysis by age 20.6 Prenatally, the diagnosis is suspected based on ultrasound (US) findings and may be confirmed in an informative family by the identification of disease-causing mutations. Imaging Technique and Findings Ultrasound. The characteristic US finding is massive, symmetrically enlarged, echogenic kidneys, which fill and distend the fetal abdomen, measuring between 4 and 15 standard deviations above the mean for gestational age.9 Normal corticomedullary differentiation is not visible. In some cases, these findings may be apparent in the first trimester (Fig. 16.1).15 When ARPKD manifests early in gestation, amniotic fluid volume is usually severely decreased, with no urine visible in the bladder (Fig. 16.2). As with other causes of severe, prolonged oligohydramnios, there is significant risk for pulmonary hypoplasia secondary to Potter sequence (see Chapter 10). With advancing gestation, the appearance of the kidney becomes more inhomogeneous, and tiny cysts may be visible (Fig. 16.3). In many cases, the diagnosis of ARPKD is not so straightforward. Another presentation involves kidneys that are echogenic but only mildly enlarged, measuring between 2 and 4 standard deviations above the mean, with preserved amniotic fluid volume (Fig. 16.4). The kidneys may not appear noticeably abnormal until after midgestation.9 In the absence of an informative family history, counseling for such cases is problematic.16,17 Although the differential diagnosis includes ARPKD, it also includes genetic syndromes such as Bardet-Biedl syndrome and glutaric aciduria type II, aneuploidy such as trisomy 13 (Fig. 16.5), and especially, normal kidneys.9,18,19 A careful family history, diligent search for other anomalies, and consideration of amniocentesis are important.
Fig. 16.1 Coronal image of a fetus with autosomal recessive polycystic kidney disease (ARPKD) at 14 weeks’ gestation. The kidneys (arrows) appear massively enlarged and echogenic, and there is no visible amniotic fluid.
64
PART 3 Retroperitoneum • SECTION ONE Kidney
When the fetal kidneys are mildly enlarged and echogenic, and amniotic fluid volume is normal, the differential diagnosis also includes autosomal dominant polycystic kidney disease (ADPKD) (Fig. 16.6). ADPKD usually has no prenatal manifestations; patients typically present in the fourth decade of life. However, ADPKD is much more common than ARPKD, occurring in 1 : 800 births rather than 1 : 20,000. In the absence of a family history or other fetal abnormalities, consideration may be given to US evaluation of the parents’ kidneys (Fig. 16.7).
Although rare, there have been case reports of fetal hepatic fibrosis secondary to ARPKD manifesting with cystic dilatation of intrahepatic bile ducts in the setting of echogenic kidneys in the third trimester.20 Also, because of variable expressivity, normal-appearing kidneys do not preclude a diagnosis of ARPKD in an at-risk pregnancy. Renal manifestations may not be visible until childhood or even later.
CLASSIC SIGNS Bilaterally enlarged echogenic kidneys without corticomedullary differentiation, often associated with oligohydramnios.
Differential Diagnosis From Imaging Findings 1. Normal variant (provided amniotic fluid volume is normal beyond 18 weeks) 2. ADPKD 3. Trisomy 13 (see Chapter 149) 4. Multicystic dysplastic kidneys (see Chapter 15) 5. Meckel-Gruber syndrome (autosomal recessive) (see Chapter 133) 6. Bardet-Biedl syndrome (autosomal recessive) 7. Glutaric aciduria type II (autosomal recessive) 8. Perlman syndrome (autosomal recessive) 9. Beckwith-Wiedemann syndrome (see Chapter 109)
Fig. 16.2 Transverse image at the level of the bladder in a fetus with autosomal recessive polycystic kidney disease (ARPKD) at 24 weeks’ gestation. No urine is visible.
B
A
C
D
Fig. 16.3 Coronal images of a fetus with severe autosomal recessive polycystic kidney disease (ARPKD) at 18 weeks (A) and at 20 weeks (B), showing enlarged, echogenic, and inhomogeneous kidneys. There is no measurable pocket of amniotic fluid. By 26 weeks, sagittal (C) and coronal (D) images demonstrate diffuse tiny cysts within kidneys that are globular, echogenic, and fill the abdomen and pelvis.
A
B
C
D
Fig. 16.4 At 21 weeks, transverse (A) and coronal (B) images demonstrate kidneys that are echogenic, mildly enlarged, and slightly globular in appearance. Images (C) and (D) are transverse and sagittal views of the same fetus at 25 weeks. The amniotic fluid volume is normal. The differential diagnosis is broad in this situation.
D 50.5 mm
A
B
Fig. 16.5 Coronal (A) and sagittal (B) images of enlarged, echogenic kidneys in a fetus with trisomy 13. The kidneys measured 5 cm in length at 28 weeks’ gestation.
D 131.4 mm
Liver
*
Fig. 16.6 Transverse image of echogenic, mildly enlarged kidneys in a fetus with autosomal dominant polycystic kidney disease. Cysts are not visible prenatally.
Kidney
*
*
* *
Fig. 16.7 Maternal right kidney, showing autosomal dominant polycystic kidney disease. Cysts are indicated by asterisks.
Synopsis of Treatment Options
KEY POINTS
POSTNATAL
• ARPKD affects 1 : 20,000 pregnancies and has a wide spectrum of phenotypic variability. • Approximately 30% of cases are diagnosed prenatally or soon after birth; some prenatal cases have lethal pulmonary hypoplasia. • US findings include echogenic kidneys that are variably enlarged, with early oligohydramnios in the most severe cases. • For patients who survive infancy, 10-year survival is greater than 80%, but morbidity is significant, with hypertension, ascending cholangitis, portal hypertension, and renal insufficiency. Approximately 50% require dialysis by age 20.
When the amniotic fluid volume is severely decreased before 20 weeks, the prognosis is so poor that (if the pregnancy is continued) many families plan comfort care. In the absence of lethal pulmonary hypoplasia, initial postnatal management consists of evaluation of pulmonary and renal function. The growth and development of the infant are followed closely, with surveillance for hypertension, hyponatremia, renal insufficiency, cholangitis, and portal hypertension.
SUGGESTED READING
WHAT THE REFERRING PHYSICIAN NEEDS TO KNOW ARPKD, which is caused by mutations in the PKHD1 gene, is characterized by progressive renal failure and hepatic fibrosis. Cases that manifest prenatally show varying degrees of renal enlargement. Massively enlarged, echogenic kidneys, together with severely decreased amniotic fluid before midgestation, confer significant risk for pulmonary hypoplasia. However, in other cases, the kidneys are enlarged to a lesser degree, and amniotic fluid is preserved; these findings are not specific for ARPKD and may occur in ADPKD, trisomy 13, other syndromes, and normal pregnancy. Molecular genetic testing may be helpful in affected families.
Avni FE, Garel L, Cassart M, et al. Perinatal assessment of hereditary cystic renal diseases: the contribution of sonography. Pediatr Radiol. 2006;36:405-414. Guay-Woodford L, Bissler J, Braun M, et al. Consensus expert recommendations for the diagnosis and management of autosomal recessive polycystic kidney disease: report of an international conference. J Pediatr. 2014;165:611-617. Guay-Woodford LM, Desmond RA. Autosomal recessive polycystic kidney disease: the clinical experience in North America. Pediatrics. 2003;111:1072-1080. Gunay-Aygun M, Avner ED, Ballacao 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;149:159-164. Turkbey B, Ocak I, Daryanani K, et al. Autosomal recessive polycystic kidney disease and congenital hepatic fibrosis (ARPKD/CHF). Pediatr Radiol. 2009;39:100-111.
All references are available online at www.expertconsult.com.
16 Autosomal Recessive (Infantile) Polycystic Kidney Disease 66.e1
REFERENCES 1. Turkbey B, Ocak I, Daryanani K, et al. Autosomal recessive polycystic kidney disease and congenital hepatic fibrosis (ARPKD/CHF). Pediatr Radiol. 2009;39:100-111. 2. Zerres K, Rudnik-Schoneborn S, Deget F, et al. Clinical course of 115 children with autosomal recessive polycystic kidney disease. Acta Pediatr. 1996;85:437-445. 3. Guay-Woodford LM, Desmond RA. Autosomal recessive polycystic kidney disease: the clinical experience in North America. Pediatrics. 2003;111: 1072-1080. 4. Gunay-Aygun M, Avner ED, Ballacao 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;149:159-164. 5. Roy S, Dillon MJ, Trompeter RS, et al. Autosomal recessive polycystic kidney disease: long-term outcome of neonatal survivors. Pediatr Nephrol. 1997;11:302-306. 6. Bergmann C, Senderek J, Windelen E, et al. Clinical consequences of PKHD1 mutations in 164 patients with autosomal-recessive polycystic kidney disease (ARPKD). Kidney Int. 2005;67:829-848. 7. Zerres K, Mücher G, Becker J, et al. Prenatal diagnosis of autosomal recessive polycystic kidney disease (ARPKD): molecular genetics, clinical experience, and fetal morphology. Am J Med Genet. 1998;6:137-144. 8. Blyth H, Ockenden BH. Polycystic disease of kidneys and liver presenting in childhood. J Med Genet. 1971;8:257-284. 9. Avni FE, Garel L, Cassart M, et al. Perinatal assessment of hereditary cystic renal diseases: the contribution of sonography. Pediatr Radiol. 2006;36:405-414. 10. Al-Bhalal L, Akhtar M. Molecular basis of autosomal recessive polycystic kidney disease (ARPKD). Adv Anat Pathol. 2008;15:54-58.
11. Deltas C. Papagregoriou G. Cystic diseases of the kidney. Arch Pathol Lab Med. 2010;134:569-582. 12. Zerres K, Senderek J, Rudnik-Schöneborn S, et al. New options for prenatal diagnosis in autosomal recessive polycystic kidney disease by mutation analysis of the PKHD1 gene. Clin Genet. 2004;66:53-57. 13. Bergmann C, Senderek J, Kupper F, et al. PKHD1 mutations in autosomal recessive polycystic kidney disease (ARPKD). Hum Mutat. 2004;23: 453-463. 14. Guay-Woodford L, Bissler J, Braun M, et al. Consensus expert recommendations for the diagnosis and management of autosomal recessive polycystic kidney disease: report of an international conference. J Pediatr. 2014;165: 611-617. 15. Bronshtein M, Kushnir O, Ben-Rafael Z, et al. Transvaginal sonographic measurement of fetal kidneys in the first trimester of pregnancy. J Clin Ultrasound. 1990;18:299-301. 16. Lilford RJ, Irving HC, Allibone EB. A tale of two prior probabilities—avoiding the false positive antenatal diagnosis of autosomal recessive polycystic kidney disease. Br J Obstet Gynaecol. 1992;99:216-219. 17. Mashiach R, Davidovits M, Eisenstein B. Fetal hyperechogenic kidney with normal amniotic fluid volume: a diagnostic dilemma. Prenat Diagn. 2005;25:553-558. 18. Whitfield J, Hurst D, Bennett MJ, et al. Fetal polycystic kidney disease associated with glutaric aciduria type II: an inborn error of energy metabolism. Am J Perinat. 1996;13:131-134. 19. Kjaergaard S, Graem N, Larsen T, et al. Recurrent fetal polycystic kidneys associated with glutaric aciduria type II. APMIS. 1998;106:1188-1193. 20. Sgro M, Rossetti S, Barozzino T. Caroli’s disease: prenatal diagnosis, postnatal outcome and genetic analysis. Ultrasound Obstet Gynecol. 2004;23:73-76.