Contemporary concepts and imaging findings in paediatric cystic kidney disease, p. 65-79 HR VOLUME 3 | ISSUE 2 J Urogenital Imaging Review Contemporary concepts and imaging findings in paediatric cystic kidney disease Vasiliki Dermentzoglou, Virginia Grigoraki, Maria Zarifi Department of Radiology, Agia Sophia Children's Hospital, Athens, Greece Submission: 31/1/2018 | Acceptance: 27/5/2018 Abstract The purpose of this article is to review the renal cyst- cystic tumours. Imaging plays an important role, as ic diseases in children with regard to classification, it helps to detect and characterise many of the cyst- genetic background, antenatal and postnatal ultra- ic diseases based primarily on detailed sonographic sonographic appearances and evolution of findings analysis. Diagnosis can be achieved in many condi- in childhood. Numerous classifications exist, even tions during foetal life with ultrasound (US) and in though the prevailing one divides cystic diseases in selected cases with foetal magnetic resonance imag- hereditary and non-hereditary. Contemporary data ing (MRI). After birth, combined use of conventional are continuously published for most of the sub-cat- and high-resolution US allows detailed definition of egories. Genetic mutations at the level of primary the extent and evolution of kidney manifestations. cilia are considered a causative factor for many re- Appropriate monitoring with US seems crucial for nal cystic diseases which are now included in the patients’ management. In selected cases (e.g. hepa- spectrum of ciliopathies. Genetic mapping has doc- tobiliary disease, cystic tumours) primarily MRI and umented gene mutations in cystic diseases that are occasionally computed tomography (CT) are valua- generally considered non-hereditary, as well as in ble diagnostic tools. paediatric cystic kidney disease; ciliopathy; phacomatosis; Key words hereditary cystic kidney disease; non-hereditary cystic kidney disease Corresponding Corresponding author: Vasiliki Dermentzoglou, MD Department of Radiology, Agia Sophia Children's Hospital, 1 Thivon & Papadiaman- Author, topoulou Str., Athens 11527, Greece Guarantor Email: [email protected] Guarantor: Maria Zarifi, MD, PhD Department of Radiology, Agia Sophia Children's Hospital, 1 Thivon & Papadiaman- topoulou Str., Athens 11527, Greece Email: [email protected] 65 HR Contemporary concepts and imaging findings in paediatric cystic kidney disease, p. 65-79 J VOLUME 3 | ISSUE 2 Introduction er, pancreas, retina, central nervous system and skel- “Cystic degeneration” of the kidneys was first de- etal system. The unifying molecular pathogenesis of scribed pathologically in 1841 and “polycystic kid- this emerging class of disorders explains the overlap neys” as a clinical syndrome in 1888. The heritable of abnormalities in different organ systems and links nature in some families was noted in 1899. Since then a diseases of widely varied phaenotypes. It is important great progress has taken place in the field of research for radiologists to be able to recognise the multisys- and acquiring knowledge. The classification of renal tem manifestations of these syndromes, as imaging cystic diseases in children in this review is based on play an important role in the diagnosis and follow-up the genetic or non-genetic origin [1]. Classification is of affected patients [3-7]. currently reappraised, based on greater understand- ing of the developmental and genetic pathobiology of 1. Autosomal Recessive Polycystic Kidney Disease paediatric cystic kidney disease. A large group of he- (ARPKD) reditary renal cystic diseases are ciliopathies, that are ARPKD is an inherited disease with an estimated fre- genetic diseases with mutations affecting the forma- quency of 1:20.000 live births, caused by mutations tion and function of the cilia. This group includes clas- in the PKHD1 (Polycystic Kidney Hepatic Disease 1) sic diseases such as autosomal recessive and dominant gene which is located on chromosome 6p12. Fibro- polycystic kidney diseases and more recently recog- cystin is the protein encoded by this gene, function- nised diseases, such as nephronophthisis-medullary ing on the primary cilia of renal and biliary epitheli- cystic disease complex associated with ciliopathies al cells. Cilia’s dysfunction affects both kidneys and and glomerulocystic kidney disease. Phakomatoses liver, promoting formation of ectatic renal collecting represent a distinct group of hereditary multisystem and biliary ducts, leading to renal and hepatic fibro- disorders whose pathobiology is related to mutations sis. However, the relative severity of organ involve- in genes that regulate tumour suppressor pathways ment is quite variable and the clinical manifestations and may have abdominal manifestations, including re- of ARPKD differ considerably, with renal impairment nal cystic lesions [2]. Among the non-hereditary cyst- representing the most common clinical feature [2, ic diseases are multicystic dysplastic kidney disease, 8-10]. In severe cases, extensive involvement of the medullary sponge kidney, simple renal cysts and sec- kidneys leads to oligohydramnios and pulmonary hy- ondary or acquired renal cysts. Cystic renal tumours poplasia during the fetal period. The disease may be are included, though new data focus on their associa- diagnosed in utero or during the perinatal period and tion with gene mutations (DICER1 gene) [2]. (Table 1). the patients may die rapidly after birth due to severe respiratory distress [11, 12]. Other forms, with milder Hereditary Diseases organ involvement, present during the first months The Ciliopathies of life with renal failure and portal hypertension and Ciliopathies are a group of clinically and genetical- the patients may survive and progress satisfactorily ly overlapping disorders whose aetiologies lie in de- through childhood as a consequence of better nephro- fective cilia. Cilia are antenna-like sensory organelles logical management. There is also a juvenile form that that are present on the surface of nearly every cell in presents later in childhood with complications relat- the body. They sense the extracellular environment ed primarily to liver disease (congenital hepatic fibro- and transduce signal back to the cells to facilitate their sis, CHF) [8, 10, 13]. response. In this way they play essential roles affect- In line with the variable clinical spectrum, the radi- ing organ development and organ maintenance and ologic manifestations of ARPKD can also be variable. repair. Defects in the structure and function of the pri- In neonates and infants with moderate to severe re- mary cilia of renal tubular epithelial cells have been nal disease the kidneys are diffusely affected and ap- associated with the development of cysts in different pear markedly enlarged, even on foetal imaging or ab- forms of polycystic kidney disease. Ciliary disorders dominal x-rays during the neonatal period. At US the are caused by mutations of genes encoding ciliary pro- kidneys are bulky and diffusely echogenic, with loss of teins and affect multiple organs, including kidney, liv- corticomedullary differentiation because of the many 66 HR VOLUME 3 | ISSUE 2 J Contemporary conceptsandimagingfindingsinpaediatriccystickidneydisease,p.65-79 Table 1. Paediatric Cystic Kidney Diseases and discriminating features Echogenicity Cyst size Corticomedullary Renal Size of parenchyma Position of cysts Genes and shape differentiation (related to liver) HEREDITARY DISEASES The ciliopathies Multiple bilateral Medullary and cortical Markedly microscopic cysts, cysts, sparing of 1. ARPKD enlarged Diffusely increased Lost PKHD1 in some cases non subcapsular area in some discernible cases Unilateral or bilateral Initially normal, Medullary and cortical 2. ADPKD PKD1, PKD2 cysts, increasing number progressively Normal Normal cysts and size with time may enlarge 3. Nephronophthisis, Initially normal NPHP genes/ Bilateral small Medullary and corticomed- MCKD, nephronoph- and gradually MCKD genes/ discrete cysts Increased Poor ullary cysts thisis associated decreasing genes related to ciliopathies syndromes PKD1,PKD2/ 4. Glomerulocystic Bilateral Cortical and subcapsular TCF2, genes Increased Increased Lost kidney Disease small cysts cysts related to syndromes The phacomatoses Multiple bilateral cysts of varying size and 1. Tuberous sclerosis Medullary and cortical number, sometimes Normal Normal Normal TSC1, TSC2 cysts in combination with angiomyolipomas 2. Von Hippel- Medullary and cortical Simple or complex cysts Normal Normal Normal VHL Lindau Syndrome cysts 67 HR J VOLUME 3 | ISSUE 2 68 Table 1. Paediatric Cystic Kidney Diseases and discriminating features Echogenicity Cyst size Corticomedullary Position Renal Size of parenchyma Genes and shape differentiation of cysts (related to liver) NON HEREDITARY DISEASES No recognisa- ble pattern of distribution/ Unilateral cysts of Become gradu- EYA1, Contemporary conceptsandimagingfindingsinpaediatriccystickidneydisease,p.65-79 Absent or dys- hydronephrot- variable sizes and ally smaller and SIX1, 1. Multicystic dysplastic kidney plastic echogenic Absent ic form with a shapes in the area in some cases PAX2 parenchyma of the kidney disappear large central cyst and small peripheral cysts Medullar Normal cortex, Normal cortex, distribution Non discernible hyperechoic medul- hyperechoic GPNF 2. Medullary sponge kidney Normal because cysts la, nephrolithiasis medulla in some cases of dilated collecting ducts More often solitary small or - 3. Simple renal