Sonographic pattern of recessive polycystic kidney disease in young adults. Differences from the dominant form

Carlos Nicolau1,, Roser Torra2, Celia Badenas3, Laureano Pérez2, Jesús A Oliver4, Alejandro Darnell2 and Concepció Brú1

1 Imaging Diagnosis Center (Ultrasound Unit), 2 Departments of Nephrology and 3 Genetics, Hospital Clínic, IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), University of Barcelona and 4 Department of Nephrology, Hospital Juan XXIII, Tarragona, Spain



   Abstract
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
Background. To study the sonographic pattern of autosomal recessive polycystic kidney disease (ARPKD) in early adulthood in order to identify imaging criteria to diagnose this disease and to distinguish between recessive and autosomal dominant polycystic kidney disease (ADPKD) in that age group.

Methods. An abdominal ultrasound was performed on four ARPKD subjects (with a mean age of 20.2) and on 33 ADPKD subjects in early adulthood (29 without renal failure with a mean age of 20.5, and four with renal failure with a mean age of 26.5). Linkage studies with ADPKD and ARPKD markers were compatible with the clinical diagnosis in all cases.

Results. The renal sonographic features in ARPKD subjects included multiple small cysts in a normal-sized kidney, increased cortical echogenicity and loss of corticomedullary differentiation. In ADPKD subjects without renal failure, sonographic features included few or multiple cysts of different sizes, in normal-sized kidneys in 22 out of 29 patients (75.8%), normal cortical echogenicity and conserved corticomedullary differentiation, except in patients with nephromegaly. All ADPKD subjects with renal failure had nephromegaly and loss of corticomedullary differentiation. The hepatic sonographic features in ARPKD patients included portal fibrosis and in some cases Caroli's disease, while in ADPKD patients a normal hepatic echostructure was detected in all but one case, in addition to simple hepatic cysts in a few cases.

Conclusions. The evaluation of the sonographic features of the kidneys and those of the liver may help in the differential diagnosis between ARPKD and ADPKD in early adulthood.

Keywords: ADPKD; ARPKD; Caroli's disease; hepatic fibrosis; sonography; ultrasound



   Introduction
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
Autosomal recessive polycystic kidney disease (ARPKD) is a hereditary disorder that affects the kidney and the liver. Its occurrence ranges from 1 in 10 000 to 1 in 40 000 births [1,2]. As a recessive disorder both parents of an affected child carry one copy of the defective gene but are not clinically affected. The disease is caused by mutation in a gene located in chromosome 6 which has yet to be identified. The main characteristic in the kidneys is the presence of multiple cysts resulting from the dilatation of collecting ducts [24]. In the liver, the disease is diffuse and presents as portal fibrosis, dilatation of the bile ducts (Caroli's disease), or a combination of both [2,3]. This disease shows a wide clinical variability ranging from perinatal death to diagnosis in adolescence or in adulthood, in progressively milder forms [46]. In the latter cases, ARPKD can be clinically indistinguishable from autosomal dominant polycystic kidney disease (ADPKD) because there is an overlap in the clinical presentation. Therefore, it may be difficult to establish a differential diagnosis between them [4]. It is particularly difficult when there is no definitive family history of these diseases, the possibility of illegitimate paternity or spontaneous mutation of ADPKD [2]. Moreover, in these cases the genetic linkage analysis is useless as well as being expensive, and unavailable in most hospitals. Thus, in these rare cases, the diagnosis is based on imaging of the involved organs (kidney and liver) or eventually kidney and/or liver biopsy. Sonography is the most useful non-invasive imaging technique in the evaluation of patients with polycystic kidney disease. In this article we present ultrasonographic renal and hepatic findings of ARPKD in early adulthood and compare them with ultrasonographic findings of ADPKD in the same age group and/or same clinical presentation in order to characterize these conditions and to assist in differentiating them.



   Subjects and methods
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
Subjects
The sonographic findings of 37 young adults with polycystic kidney disease were retrospectively evaluated. We classified patients into three groups, using linkage analysis, age, and presence of renal failure. The first group consisted of four patients with ARPKD (one man, three women; age range 19–22 years, mean age 20.2). The second group consisted of all the ADPKD patients who visited our department during the last 3 years who were in the same age group as the patients with ARPKD (29 patients, 15 men, 14 women; age range 18–23 years, mean age 20.5). None of these 29 subjects had renal failure. The third group consisted of all the ADPKD young adults (younger than 30 years) who visited our department during the last 3 years, with renal failure (four patients, three men, one woman; age range 24–29 years, mean age 26.5).

Methods
A complete medical history, physical examination, measurement of arterial blood pressure and serum creatinine and a complete abdominal ultrasound study were performed on these patients. Using ultrasound, the kidneys (kidney size, number of cysts per kidney (<6, 6–15, >15), cysts size, cortical echogenicity, corticomedullary differentiation), liver (echostructure, signs of hepatic fibrosis, presence of cysts) and biliary tree (dilatation) were specifically studied. All studies were performed and evaluated by a single consultant radiologist, with a Toshiba SSA 140 (Toshiba, Japan) equipped with a 3.7 MHz transducer. The diagnosis of ARPKD and ADPKD was confirmed by linkage genetic studies in each case. Linkage analysis was performed by using microsatellite markers flanking the PKHD1 (D6S269, 272, 436, 427, 465, 423, 466, 295, 294, 257), PKD1 (AC2.5-D16S291, KG8-PKD1 and CW2-D16S663) and PKD2 (D4S423, D4S1534 and D4S1542) genes as previously described [7,8]. We obtained informed consent from all subjects who participated in the study. The study was approved by the Ethical Committee of the Hospital.

Clinical data
Group 1. ARPKD patients All subjects were products of non-consanguineous marriages.

Case 1. A 20-year-old man was admitted to our hospital because of biochemical features of advanced renal failure. His medical history included palpable masses in both flanks and hepatomegaly at birth. At that time, an exploratory laparotomy had showed enlarged kidneys with multiple cysts. His growth and development were apparently normal. There was no family history of renal disease. The patient had been apparently well until 3 months earlier, when he began to experience fatigue, anorexia, weight loss, and muscle cramps. On admission he presented with end-stage renal disease (ESRD) and non palpable kidneys, and he underwent haemodialysis. Due to the sonographic findings and the presence of pancytopenia, an endoscopy was indicated. Endoscopy excluded oesophageal varices, and the patient refused a haemodynamic study to evaluate portal hypertension. The patient underwent a liver biopsy that showed periportal fibrosis. After the procedure the patient presented with severe hepatic bleeding that required surgery. Results from abdominal ultrasound examinations in both parents and two sisters were normal.

Case 2. A 19-year-old woman underwent a blood test due to asthenia and amenorrhoea during the previous 3 months. The blood analysis showed clear signs of ESRD and the patient underwent haemodialysis. There were no clinical signs of portal hypertension. The patient's younger brother had died at 2 months of age from ARPKD. Results of abdominal ultrasound examinations of both parents and another brother were normal.

Case 3. This 20-year-old woman had been diagnosed of ARPKD at birth. She was known to have severe portal hypertension and renal failure in her teens. At 18 years of age she had gone to the emergency room because of upper digestive bleeding due the rupture of oesophageal varices. The intensity of haemorrhage precluded treatment with sclerosis, so she underwent a portocaval shunt that prevented any subsequent variceal bleeding. The patient's renal function is severely impaired (serum creatinine of 6 mg/dl) but she still does not need renal replacement therapy. Results of abdominal ultrasound examinations of both parents, two sisters, and one brother were strictly normal.

Case 4. A 22-year-old woman was diagnosed of ARPKD at birth. At 5 years of age she had upper digestive bleeding caused by rupture of oesophageal varices. After various bleeding episodes she underwent a splenorenal shunt. On admission, her renal function was impaired and serum creatinine levels were of 2.8 mg/dl. Her brother and parents showed normal abdominal sonography scans.

Group 2. ADPKD young adults None of the 29 ADPKD patients in this group had renal failure. Five of them had hypertension. None of them had a history of haematuria or renal calculi. They were initially examined in our department because of family history of ADPKD.

Group 3. ADPKD patients <30 years old with renal failure All four of these patients had hypertension. Two of them entered ESRD at 28 and 26 years of age. The other two, who were 24 and 25 years old, had serum creatinine levels of 6 and 4 mg/dl respectively.



   Results
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 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
Comparison of ultrasonographic findings of ARPKD and ADPKD subjects are shown in Table 1Go.


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Table 1. Ultrasonographic findings in young adults with ARPKD or ADPKD

 
Group 1. ARPKD patients
Linkage analysis of the four ARPKD families was consistent with ARPKD linked to the PKHD1 locus. Renal sonography revealed multiple (more than 15) small cysts (smaller than 1.5 cm) in a normal-sized kidney, and loss of corticomedullary differentiation in all patients with ARPKD (Figure 1Go). In case 2 there were also two cysts bigger than 1.5 cm in each kidney. Increase of the cortical echogenicity was studied and demonstrated in cases 2 and 4. The other two cases had both kidneys massively full of cysts, preventing the examination of cortical echogenicity. In all cases there were signs of hepatic fibrosis (confirmed by liver biopsy in case 1). In case 1 hepatosplenomegaly and diffuse heterogeneous liver echostructure were present. No duct ectasia were seen. In cases 2 and 4 there were multiple diffuse echogenic areas scattered throughout the liver and compatible with hepatic periportal thickening (Figure 2Go). In case 3, hepatosplenomegaly was present with increase of the hepatic echogenicity and multiple intrahepatic duct ectasia showing a characteristic echogenic central dot corresponding to fibrovascular bundles containing a portal vein radicle and an accompanying branch of the hepatic artery (confirmed by Doppler ultrasound) compatible with Caroli's disease (Figure 3Go). In case 4, there were also intrahepatic duct ectasia. No simple hepatic cysts were observed in any patient.



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Fig. 1. A longitudinal ultrasound scan of the right kidney in a 20-year-old man with ARPKD shows a normal-sized kidney with multiple small cysts, and loss of corticomedullary differentiation.

 


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Fig. 2. An ultrasound scan of the right lobe of the liver in a 19-year-old woman with ARPKD shows multiple echogenic areas scattered throughout the liver. These areas represent the thickened fibrosed portal tracts that are characteristics of hepatic fibrosis.

 


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Fig. 3. An ultrasound scan of the right lobe of the liver in a 20-year-old woman with ARPKD shows a typical case of Caroli's disease with saccular dilatations of the bile ducts containing intraluminal bulbar protrusions and cross-bridges. Arterial flow inside a bulbar protrusion of a ductal ectasia was detected using Doppler ultrasound.

 

Group 2. ADPKD patients without renal failure
Linkage analysis of all the families was consistent with ADPKD linked to the PKD1 gene. Nephromegaly was only seen in seven patients (24.1%) while kidney size was normal in 22 (75.9%) (Figure 4Go). Loss of corticomedullary differentiation was detected in only five patients (all of them having nephromegaly). No increase of cortical echogenicity was detected in any patient in whom it was possible to evaluate this (not evaluated in seven patients because the kidneys were almost completely full of cysts). Simple hepatic cysts were found in six subjects (20.6%) (Figure 5Go). No signs of hepatic fibrosis, portal hypertension or bile ducts ectasia were seen in any patient.



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Fig. 4. Longitudinal ultrasound scan of the left hepatic lobe and of the right kidney in a 19-year-old man with ADPKD shows a branch of the left portal vein in a normal liver with homogeneous echostructure and a normal-sized kidney with multiple cortical cysts of different sizes. The renal corticomedullary differentiation and cortical echogenicity remain conserved.

 


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Fig. 5. Simple hepatic cysts in a 20-year-old woman with ADPKD. Ultrasound scan of the liver showed two simple cysts in a liver with normal echostructure.

 

Group 3. ADPKD patients with renal failure
Linkage analysis was consistent with ADPKD linked to the PKD1 gene in each patient. Moderate or severe nephromegaly (at least >15 cm) was seen in all subjects. The parenchyma was almost completely replaced by innumerable cysts of different sizes, distributed throughout all the renal parenchyma with loss of corticomedullary differentiation, not allowing the examination of the cortical echogenicity. There were simple hepatic cysts in all cases. In one case we also detected multiple intrahepatic duct ectasia compatible with Caroli's syndrome as well as signs of hepatic fibrosis, with cavernous transformation of the portal vein.



   Discussion
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 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
ARPKD is characterized by cystic dilatation of the renal collecting ducts and hepatic biliary dysgenesis with periportal fibrosis [2,3,9]. For those patients who survive the perinatal period, the chance of being alive at 15 years of age is considered to be from 50 to 80% [10]. In one of the most representative prognostic analyses reported, 55 ARPKD patients were retrospectively reviewed; 23 patients (42%) presented within the first month of life, and 12 of them (about 50%) survived beyond 2 years of age; of this selected study group survival rates revealed that 46% survived to at least 15 years of age [11]. In a retrospective study that included 14 patients in whom the diagnosis of ARPKD was made before 2 weeks of life, nine children (64%) were still alive at the moment of the report: five of them remained with normal serum creatinine (aged between 8 months and 7 years), while four presented with renal insufficiency (aged between 7 and 14 years) [12]. Additionally, there are some case reports of late-onset symptoms in ARPKD patients who survived into adulthood [7,13].

The differentiation of ARPKD from ADPKD is important for genetic counseling and prognosis. A patient with ARPKD is not going to pass the disease to the following generation while the children of an ADPKD patient have a 50% chance of suffering from the disease. A positive family history is the most important information in establishing the diagnosis of ADPKD, and in most cases, ultrasonography of both parents is a reliable way to distinguish between ADPKD and ARPKD. However, when paternity is in doubt, or in cases of spontaneous mutations (accounting for up to 10% of ADPKD cases) parental sonograms are irrelevant. The linkage technique is also useful in diagnosing both entities. However, it is an expensive technique not available in most hospitals, not useful in sporadic cases, and frequently not informative in small families. When mutational detection in the PKD genes becomes available the differential diagnosis of these diseases will become easier. Until then, in these rare cases, a classification problem arises, and the diagnosis must be performed using radiological methods or biopsy of the involved organs [13,14]. Computed tomography (CT) and magnetic resonance imaging (MRI) have been used with success in the evaluation of ARPKD patients [1416], especially in older children who are able to co-operate during the performance of the test. These techniques can delineate fine details of the renal architecture and may add useful information to the ultrasound data. However, the intravenous contrast used in CT scans can be dangerous for patients with renal failure. Thus, for these patients, ultrasound is the most useful non-invasive diagnostic tool.

The sonographic findings in children with ARPKD are well known. Sonography reveals diffusely increased cortical echogenicity when compared with the hepatic parenchyma as well as loss of the corticomedullary differentiation [17]. Kidney size in ARPKD patients peaks at 1–2 years of age, gradually becoming smaller and stabilizing by 4–5 years of age, while echogenicity tends to normalize over time [17]. Furthermore, secondary cortical cyst formation can be found in older children and young adults with ARPKD, producing a pattern that has been described as being similar to that seen in sonograms of ADPKD patients [9,17]. Nevertheless, our study suggests that these sonographic findings may be different enough in comparison with those found in ADPKD patients to allow a correct diagnosis.

The loss of the corticomedullary differentiation, increase of cortical echogenicity, and presence of multiple cyst smaller than 1.5 cm throughout the normal-sized kidney are common findings in young adults with ARPKD. The basic pathological lesion in ARPKD is at the level of the collecting ducts. The increased echogenicity is due to the interfaces produced by the walls of ectatic tubules that are too small to be resolved by sonography [18]. Jain et al. [19] explained that the peripheral layer of cortex remains free of cysts because the peripheral cortex does not have any collecting or connecting ducts. Nevertheless our study does not corroborate this finding in any ARPKD patient because the peripheral cortex also had cysts, probably due to secondary cortical cyst formation in older children and young adults.

In ADPKD patients multiple or discrete cysts of varying sizes may be seen scattered throughout the cortex, including the subcapsular location, because cysts in ADPKD can arise from anywhere in the nephron or collecting system. The natural history of ADPKD kidneys is well established, with a correlation between the sonographic findings (number and size of cysts and size of the kidney) and the age and/or severity of the disease [20]. As the diseases progresses, the size and number of cysts and the renal volume increases. Nevertheless, we have found a high incidence of normal-sized kidneys (75.9%) in young adults with ADPKD (without the marked increase in kidney size described in other reports) [17,18] and less than 15 cysts per kidney (65.4%), probably because they were asymptomatic subjects. In this age group, the renal cortex is almost always conserved, unlike with ARPKD, except in patients with more advanced forms of ADPKD in which there is moderate or severe nephromegaly and the cortex is barely visible. Detecting nephromegaly can help in differentiating ADPKD from ARPKD, as in the four ADPKD subjects with renal failure in our study. Moreover, in general, ADPKD patients with renal failure present with larger cysts than those in ARPKD patients.

Our results also indicate that the sonographic evaluation of the liver is very useful in differentiating between ADPKD and ARPKD. In patients with ARPKD whose disease becomes manifest in later childhood, hepatic disease is more severe than in early onset [5,18,19]. ARPKD is always associated with hepatic fibrosis and may occasionally be associated with Caroli's disease. Liver histopathology reveals biliary dysgenesis or ‘ductal plate malformation’, characterized by the fibrous enlargement of the portal tracts or by portal–portal bands of fibrous tissue containing abnormal bile ducts. In addition, various segments of the intrahepatic bile ducts may be dilated, producing bile stasis and cholangitis. The sonographic findings observed in the four patients with ARPKD in our study represent the spectrum of hepatic involvement of the disease. The sonographic appearance of hepatic fibrosis can show increase of the echogenicity and diffuse heterogeneous structure, but the visualization of multiple diffuse echogenic areas that represent the thickened fibrosed portal tracts encompassing portal tributaries is characteristic. This finding is non-specific because it has been described in other diseases such as schistosomiasis, hepatitis, etc. [21]. In ARPKD patients thickened fibrosed portal tracts reveal abnormal development of the biliary tree. The sonographic appearance of Caroli's disease is characteristic: saccular dilatations of bile ducts, which may contain intraluminal bulbar protrusions and cross-bridges, as the result of an encasement of portal radicles by areas of ductal ectasia [22]. Colour Doppler discloses hepatic arterial and portal venous flow within the fibrovascular projections in the bile ducts [23]. Demonstration of communication between sacculi and bile ducts is important in distinguishing Caroli's disease from polycystic liver disease [24]. Our results indicate that the presence of a polycystic kidney in a young adult with hepatic fibrosis or Caroli's disease is highly suggestive of ARPKD. In rare cases without any clear clinical signs of hepatic fibrosis, or without typical findings in the ultrasound study, a liver biopsy can be useful [13] in demonstrating congenital fibrosis. Only one of the patients presented in this study underwent a liver biopsy. We did not perform this procedure in the other patients, because liver biopsy is an invasive procedure with a risk of complications (two patients had multiple and large intrahepatic duct ectasia), and linkage analysis was consistent with ARPKD in all cases. However, ADPKD cannot be completely excluded in patients with polycystic kidneys and hepatic fibrosis because this association has been reported in ADPKD patients [25,26]. Of the 400 ADPKD subjects studied in our department in the last 3 years, we have found this association in only one case (a subject of the group of ADPKD with renal failure), thus confirming that it is a rare association. On the other hand, the presence of a normal liver or simple hepatic cysts in a young adult with polycystic kidneys is highly suggestive of ADPKD [3]. Simple hepatic cysts are a common feature in ADPKD adults and in 20% of ADPKD patients younger than 30, but are extremely rare in ARPKD patients.

In conclusion, the evaluation of the sonographic features of the kidneys and those of the liver may help in the differential diagnosis between ARPKD and ADPKD in early adulthood.



   Notes
 
Correspondence and offprint requests to: Dr Carlos Nicolau, Department of Radiology, Hospital Clinic, Villarroel 170, 08036 Barcelona, Spain. E-mail: cnicolau{at}clinic.ub.es Back



   References
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 

  1. Bosniak MA, Ambos MA. Polycystic kidney disease. Semin Roentgenol1975; 10: 133–143[ISI][Medline]
  2. Zerres K, Rudnik-Schoneborn S, Steinkamm C, Mucher G. Autosomal recessive polycystic kidney disease. Nephrol Dial Transplant1996; 11 [Suppl 6]: 29–33
  3. Gang DL, Herrin JT. Infantile polycystic kidney disease of the liver and kidneys. Clin Nephrol1986; 25: 28–36[ISI][Medline]
  4. Welling LW, Grantham JJ. Cystic and developmental diseases of the kidney. In. Brenner BM (ed.). The Kidney, 5th edn. Saunders, Philadelphia, 1996; 1839–1842
  5. Blyth H, Ockenden BG. Polycystic disease of kidneys and liver presenting in childhood. J Med Genet1971; 8: 257–284[ISI][Medline]
  6. Potter EL. Normal and Abnormal Development of the Kidney. Year Book Medical Publishers, Chicago 1972
  7. Perez L, Torra R, Badenas C et al. Autosomal recessive polycystic kidney disease presenting in adulthood. Molecular diagnosis of the family. Nephrol Dial Transplant1998; 13: 1273–1276[Free Full Text]
  8. Torra R, Badenas C, Darnell A et al. Linkage, clinical features and prognosis of autosomal dominant polycystic kidney disease types 1 and 2. J Am Soc Nephrol1996; 7: 2142–2151[Abstract]
  9. Guay-Woodford L, Galliani CA, Musulman-Mroczek E, Spear GS, Guillot AP, Bernstein J. Diffuse renal cystic disease in children: morphologic and genetic correlations. Pediatr Nephrol1998; 12: 173–182[ISI][Medline]
  10. Gagnadoux MF, Habib R, Levy M et al. Cystic renal disease in children. Adv Nephrol1989; 18: 33
  11. Kaplan BS, Fay J, Shah V. Autosomal recessive polycystic kidney disease. Pediatr Nephrol1989; 3: 43–49[ISI][Medline]
  12. Deget F, Rudnik Schöneborn S, Zerres K. Course of autosomal recessive polycystic kidney disease in siblings: a clinical comparison of 20 sibships. Clin Genet1995; 47: 248–253[ISI][Medline]
  13. Neumann HPH, Zerres K, Fischer CL et al. Late manifestation of autosomal-recessive polycystic kidney disease in two sisters. Am J Nephrol1988; 8: 194–197[ISI][Medline]
  14. Kern S, Zimmerhackl LB, Hildebrandt F, Uhl M. Rare-MR-urography a new diagnostic method in autosomal recessive polycystic kidney disease. Acta Radiol1999; 40: 543–544[ISI][Medline]
  15. Howie JL, Nicholson RL. CT evaluation of infantile polycystic disease. J Can Assoc Radiol1980; 31: 202–203[ISI][Medline]
  16. Berger PE, Munschauer RW, Kuhn JP. Computed tomography and ultrasound of renal and perirenal diseases in infants and children. Relationship to excretory urography in renal cystic disease, trauma and neoplasm. Pediatr Radiol1980; 9: 91–99[ISI][Medline]
  17. Blickman JG, Bramson RT, Herrin JT. Autosomal recessive polycystic kidney disease: Long-term sonographic findings in patients surviving the neonatal period. Am J Roentgenol1995; 164: 1247–1250[Abstract]
  18. Grossman H, Rosenberg ER, Bowie JD, Ram P, Merten DF. Sonographic diagnosis of renal cystic diseases. Am J Roentgenol1983; 140: 81–85[ISI][Medline]
  19. Jain M, Le Quesne GW, Bourne AJ, Henning P. High-resolution ultrasonography in the differential diagnosis of cystic diseases of the kidney in infancy and childhood: preliminary experience. J Ultrasound Med1997; 16: 235–240[Abstract]
  20. Gabow PA. Autosomal dominant polycystic kidney disease—More than a renal disease. Am J Kidney Dis1990; 5: 403–413
  21. Medhat A, Nafeh M, Swifee Y et al. Ultrasound-detected hepatic periportal thickening in patients with prolonged pyrexia. Am J Trop Med Hyg1998; 59: 45–48[Abstract/Free Full Text]
  22. Marchal GJ, Desmet VJ, Proesmans WC et al. Caroli disease: high-frequency US and pathologic findings. Radiology1986; 158: 507–511[Abstract]
  23. Gorka W, Lewall DB. Sonography in the assessment of patients with Caroli's disease. J Clin Ultrasound1998; 26: 283–287[ISI][Medline]
  24. Miller WJ, Sechtin AG, Campbell WL, Pieters PC. Imaging findings in Caroli's disease. Am J Roentgenol1995; 165: 333–337[Abstract]
  25. Torra R, Badenas C, Darnell A, Bru C, Escorsell A, Estivill X. Autosomal dominant polycystic kidney disease with anticipation and Caroli's disease associated with a PKD1 mutation. Kidney Int1997; 52: 33–38[ISI][Medline]
  26. Cobben J, Breuninng M, Kate CSL, Zerres K. Congenital hepatic fibrosis in autosomal dominant polycystic kidney disease. Kidney Int1990; 38: 880–885[ISI][Medline]
Received for publication: 26. 6.99
Revision received 31. 3.00.