DOI:
Pictorial essay
Cystic renal diseases: role of ultrasound. Part II, genetic cystic renal diseases
Adnan Kabaalioglu
1, Nesrin Gunduz
2, Ayse Keven
3, Emel Durmaz
3, Mine Aslan
4, Ahmet Aslan
4, Serkan Guneyli
11Department of Radiology, Koc University School of Medicine, Istanbul, Turkey, 2Department of Radiology, Istanbul Medeniyet University, School of Medicine, Istanbul, Turkey, 3Department of Radiology, Akdeniz University School of Medicine, Antalya, Turkey, 4Department of Radiology, King Hamad University Hospital, Muharraq, Bahrain
Received 26.07.2020 Accepted 29.09.2020 Med Ultrason
2022, Vol. 24, No 1, 107-113
Corresponding author: Assoc. Prof. Dr. Serkan Guneyli, M.D.
Department of Radiology, Koc University School of Medicine, Istanbul, Turkey Phone: 0090 533 6981477
Fax: 0090 212 311 3410
E-mail: [email protected]
Introduction
In this second part, eye-catching features of genetic cystic renal diseases are demonstrated. In general, cysts are probably the most frequent abnormal findings to be reported during sonography due to their high prevalenc- es. Actually, simple cysts, even if they are multiple, are considered to be almost a normal developmental varia- tion in the elderly. On the other hand, even a tiny simple cyst in a child may be the strong evidence of a genetic cystic renal disease.
Genetic cystic renal diseases include autosomal dom- inant polycystic kidney disease (ADPKD), autosomal recessive polycystic kidney disease (ARPKD), juvenile nephronophthisis / medullary cystic kidney disease com- plex, and multiorgan syndromes with pluricystic kidneys.
Genetic cystic renal diseases
Autosomal dominant polycystic kidney disease ADPKD is the most well-known and most frequent hereditary cystic disease which usually manifests in the third decade of life. However, some patients are inciden- tally discovered in their sixth or seventh decades; the genetic basis for these almost 15% of cases, have been discovered in recent years. Chromosome 4 is responsi- ble in these mild cases instead of chromosome 16. In the elderly, multiple bilateral cysts due to aging, may some- times create a suspicion of ADPKD, then kidney volume and other clues may be required for a certain diagnosis.
Abstract
Kidney cysts are quite common in adults. Though small simple renal cysts in an adult over 30-40 years of age are not too unusual, however, if the same cysts are seen in a child, and especially if there are additional findings, then several diagnostic possibilities may come to mind. The role of ultrasound, together with the help of intravenous contrast agents and Doppler mode, are very critical in describing the morphologic features and follow-up of the complex or multiple and bilateral renal cysts. These sonographic signs are occasionally specific for diagnosis, but in many cases sonographic clues should be evalu- ated together with the other genetic and clinical data to reach diagnosis.
The first part of this pictorial essay included the introduction into the subject and the classification of non-genetic cystic renal diseases. The key features for the non-genetic cystic renal diseases are illustrated. In the second part, eye-catching fea- tures of genetic cystic renal diseases are demonstrated.
Keywords: cyst; cystic; Doppler; kidney; ultrasound (US)
DOI: 10.11152/mu-2690
The high-resolution linear probes can certainly change the diagnosis in the majority of children screened by US because of a parent with known ADPKD.
Hemorrhage and infection rates of cysts in ADPKD are interestingly higher than the simple usual cysts in the normal population [1] (fig 3). Calcifications and stones are also frequent and may be difficult to find out by US alone in a big mass; Doppler US and CT may help (fig 4).
Renal cell carcinoma (RCC) incidence is not increased in patients with ADPKD; but if they start having dialysis, then the risk increases (fig 5). Rarely, biliary hamartomas may be seen; cysts in ADPKD and biliary hamartomas are thought to develop from the interrupted remodeling Fig 6. a) Multiple tiny echogenic foci in the liver of a 70-year- old male with ADPKD. The lesions had low density on CT (not shown). b) Multiple cysts were also present in the liver.
Fig 5. a) A solid mass (arrow) in a 55-year-old male with AD- PKD which was found to be a RCC after resection. b) Power Doppler US shows the vascularity of the mass.
with ADPKD.
Fig 3. a) A complex hemorrhagic cyst (arrow) in an adult with ADPKD. b) A complex hemorrhagic cyst in another adult with ADPKD.
Fig 2. a) 11-year-old boy. Only 2 cysts are seen by the convex probe. b) Linear probe shows more than 5 tiny cysts (arrows) in each kidney of the same patient with ADPKD, similar to the findings of his mother.
Fig 1. Typical ADPKD; bilateral enlarged kidneys with hun- dreds of tiny cysts compressing the parenchyma.
of the ductal plates during the late phase of embryologic development [1] (fig 6).
Autosomal recessive polycystic kidney disease ARPKD is primarily a pediatric disease that is more severe than ADPKD; almost half of the patients die either in utero or soon after birth. The liver is always involved with progression to end-stage disease [2]. The kidneys get larger, starting prenatally, and individual cysts may not be seen especially in the early phase; instead echo- genic parenchyma is noted. The echogenic medullary re- gion may be described as “nephrocalcinosis” and almost all cases show strong twinkling artifacts (fig 7, fig 8). The tiny cysts or rather dilated tubules can be seen with high- resolution probes as fusiform structures (fig 9a). Another frequent sonographic observation is the lateralization of the gallbladder due to relative atrophy of the right liver lobe and hypertrophy of the left liver lobe (fig 9b). Be- sides diffuse liver parenchymal heterogeneity, biliary dilatations and biliary cysts can be diagnosed by US as Caroli disease accompanying ARPKD (fig 10).
Differential diagnosis includes other genetic syn- dromes which may have a similar kidney appearance with extrarenal findings and unique genetic features [3].
Nephronophthisis / Medullary cystic kidney disease complex
This group of rare genetic diseases with already some controversies in classifications, have recently been split as “nephronophthisis” and “autosomal dominant tubu- lointerstitial kidney disease” (ADTKD) in a consensus statement of an international working group composed mainly of pediatric nephrologists and pediatric radiolo-
Fig 9. a) Dilated fusiform tubules (arrows) and tiny cysts in a 4-year-old boy with ARPKD. b) Heterogeneity in the liver and later- alization of the gallbladder (arrow).
Fig 8. a) Typical, big for age (130 mm) echogenic kidneys with tiny cysts and dilated tubules in a 7-month-old girl with ARPKD. b) Striking parenchymal twinkling artifacts occur by Doppler US mode.
Fig 7. a) Bilateral big and echogenic kidneys in a 6-year-old boy. b) Intense twinkling artifacts are seen.
gists [3]. ADTKD includes the previous “uremic med- ullary cystic kidney diseases” and some more genetic cystic diseases. US or other imaging methods are not so useful and specific in these diseases; the kidneys may be normal or small in size, the parenchyma may be echogen- ic, and medullary cysts may not always be seen [3]. The most important clue is the specific location of small cysts (almost always less than 2 cm), in the cortico-medullary junction (fig 11). Caroli disease and hepatic fibrosis may accompany and should be checked. Genetic analysis is mandatory for verification of diagnosis.
Multiorgan syndromes with pluricystic kidneys In addition to ADPKD and ARPKD, cystic kidney disease is a common feature of ciliopathies with extrare- nal manifestations which require careful clinical workup to identify the underlying genetic disorder, especially in children. In the recent years, our understanding of the basis of polycystic kidney disease has increased substan- tially and more than 100 genes have been discovered to be involved in these cystic kidney diseases with enor- mous complexity [2,4].
The most common disease in this diverse group is tu- berous sclerosis complex (TSC). This disorder is usually identified in infants and children based on characteristic skin lesions, seizures, and cellular overgrowth or hamar-
tomas in the heart, brain, and kidneys [5]. Although renal involvement is asymptomatic initially, more than 75%
die of renal failure. The disease can be suspected in utero by the presence of cardiac rhabdomyomas (fig 12). The most frequent renal finding is angiomyolipoma (AML) with an incidence of 40-90 % (fig 13). Fat-poor AMLs
Fig 12. The prenatal US shows a cardiac echogenic mass re- ported as probable rhabdomyoma. The child is still on follow- up with TSC diagnosis.
Fig 11. Two different cases followed up with a probable diagnosis of nephronophthisis. Bilateral echogenic small kidneys with tiny medullary cysts (arrows) are shown in a 19-year-old (a) and a 10-year-old girl (b).
Fig 10. a) Irregularly dilated bile ducts (arrows) in a 9-year-old girl with ARPKD and Caroli syndrome. Axial CT (b) and coronal MRI (c) of the same patient after liver transplantation showing the polycystic kidneys, transplanted left liver lobe, and an enlarged spleen.
are not rare and they can be confusing, since RCCs may also be rarely seen in TSC patients. In these patients, US may not be sufficient for the diagnosis, and CT or mag- netic resonance imaging (MRI) is required for the dif- ferential diagnosis. Bilateral multiple cysts are seen in 15-40 % of patients (fig 14). The cysts and the kidneys are bigger earlier in childhood in the TSC2/PKD1 CGS (Tuberous Sclerosis Complex 2/Polycystic Kidney Dis- ease 1 Contagious Gene Syndrome) form of the disease [6] (fig 15). AMLs larger than 3-4 cm should be observed and evaluated for the need of embolisation against the bleeding risk (fig 16).
Von Hippel-Lindau disease, which is a rare disorder is characterized by cysts, cystic and hypervascular vis- ceral neoplasms. Renal lesions, including renal cysts and RCC are seen in 30–75% of cases [7]. Pancreatic cysts and cystadenomas, neuroendocrine tumors and pheo- chromocytomas may be also seen (fig 17).
In Meckel-Gruber syndrome, most cases are prenatal- ly detected (90%) and die in utero or soon after birth [8].
Although many multiorgan anomalies are seen, the triad of polycystic kidneys, encephalocele, and polydactyly is the most common finding [8] (fig 18).
The diagnosis of HNF1B-associated disease can not be made with imaging alone and requires genetic con- firmation [3]. It is considered to belong to the ADTKD
Fig 16. a) Multiple AMLs (arrows) in the right kidney of a 17-year-old boy with TSC. One of them was a huge (14 cm in diameter) fat-poor AML and embolised. This lesion (arrow) is shown on US (b) and CT (c).
Fig 15. Multiple big cysts in big kidneys (16 cm) of a 4-year- old boy with Type 2 TSC.
Fig 14. Multiple, bilateral, and tiny cysts (arrows) in a 9-year- old boy with TSC.
Fig 13. a-c) Multiple, bilateral, different-sized, and highly echogenic angiomyolipomas in an 18-year-old boy with TSC.
group and is the most common cause of hyperechoic kid- neys on the prenatal US. However, usually the renal US findings are nonspecific; may mimic ARPKD, may be unilateral, may reflect dysplasia, and may be normal. As- sociated anomalies, especially female genital anomalies should be screened with US [3].
McKusick-Kaufman syndrome may have similar findings with HNF1B disease, and polydactyly may ac- company genital anomalies and renal cysts (fig 19).
Bardet-Biedl syndrome, Beckwith–Wiedemann syn- drome, glomerulocystic kidney disease, Zellweger syn- drome, Joubert syndrome, Oral-facial-digital syndrome, and Jeune syndrome are relatively well-known hereditary multiorgan syndromes with cystic renal changes. How- ever, the whole family is very large and includes multiple syndromes. Without genetic testing, diagnosis and differ- ential diagnosis is not easy. US or MRI is most often not specific and not helpful in the initial diagnostic phase, and sonography is almost always used during follow-up.
Conclusion
Cystic renal diseases are a large spectrum contain- ing many genetic and non-genetic conditions, in which sonographic signs might be very helpful in diagnosis if the meaning, sensitivity, and specificity of these US signs
are known. Doppler and CEUS features are especially important for differential diagnosis of neoplastic cystic renal masses from other non-neoplastic cysts.
Acknowledgement: The authors thank Gokce Ak- gunduz Annac for creative illustrations in fig 1 in the first part.
Conflict of interest: None.
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Fig 19. Abdominal mass measuring 8 cm in a 10-month-old girl with polydactyly of both hands and feet was diagnosed as hydromet- rocolpos due to vaginal atresia. Transverse (a) and longitudinal (b) sonograms show the huge abdominal midline cystic mass with internal echoes. c) Both kidneys are enlarged and appear polycystic (arrows).
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