From the Radiologic Pathology Archives: Pediatric Polycystic Kidney Disease and Other Ciliopathies: Radiologic-Pathologic Correlation

Abstract

Genetic defects of cilia cause a wide range of diseases, collectively known as ciliopathies. Primary, or nonmotile, cilia function as sensory organelles involved in the regulation of cell growth, differentiation, and homeostasis. Cilia are present in nearly every cell in the body and mutations of genes encoding ciliary proteins affect multiple organs, including the kidneys, liver, pancreas, retina, central nervous system (CNS), and skeletal system. Genetic mutations causing ciliary dysfunction result in a large number of heterogeneous phenotypes that can manifest with a variety of overlapping abnormalities in multiple organ systems. Renal manifestations of ciliopathies are the most common abnormalities and include collecting duct dilatation and cyst formation in autosomal recessive polycystic kidney disease (ARPKD), cyst formation anywhere in the nephron in autosomal dominant polycystic kidney disease (ADPKD), and tubulointerstitial fibrosis in nephronophthisis, as well as in several CNS and skeletal malformation syndromes. Hepatic disease is another common manifestation of ciliopathies, ranging from duct dilatation and cyst formation in ARPKD and ADPKD to periportal fibrosis in ARPKD and several malformation syndromes. The unifying molecular pathogenesis of this emerging class of disorders explains the overlap of abnormalities in disparate organ systems and links diseases of widely varied clinical features. It is important for radiologists to be able to recognize the multisystem manifestations of these syndromes, as imaging plays an important role in diagnosis and follow-up of affected patients.

Cystic Kidney Disease: A Primer

“…The cortex is often compressed to the periphery by the dilated medullary collecting ducts, forming a hypoechoic halo. 20 Macrocysts are not routinely present at birth. Furthermore, kidney size in ARPKD stabilizes or may decrease over time and does not show progressive macrocystic enlargement as in ADPKD.…”

“…In comparison, ADPKD kidneys in utero tend to be moderately enlarged with a hyperechoic cortex and relatively hypoechoic medulla causing "increased" corticomedullary differentiation. 20 In addition, high-resolution US can detect the dilatations of branching collecting ducts that are readily distinguished from the round cysts of ADPKD. 20 Renal US evaluation of the parents may be useful.…”

“…20 In addition, high-resolution US can detect the dilatations of branching collecting ducts that are readily distinguished from the round cysts of ADPKD. 20 Renal US evaluation of the parents may be useful. Absence of cysts in the parents (particularly if they are .30 years) suggests ARPKD rather than ADPKD.…”

“…Absence of cysts in the parents (particularly if they are .30 years) suggests ARPKD rather than ADPKD. 20,21 However, it is important to note that in 5% to 10% of patients, ADPKD can result from spontaneous mutations. A number of commercial genetic testing laboratories offer gene-based testing for ARPKD.…”

Modifier loci in non-mutant, female Wistar Kyoto rats influence cellular pathogenesis of nephronophthisis in Lewis polycystic kidney rats

“…Nephronophthisis (NPHP) is one of these genetic diseases whose cellular progression is influenced by genetic loci of the background strains. Pathologically, NPHP simply means damaged nephrons; it is a form of autosomal recessive polycystic kidney disease (ARPKD) [1,2], which is a chronic interstitial nephropathy whose cellular pathogenesis involves multiple organ systems and causes cystic kidneys, which eventually deteriorate to end stage renal disease [3].…”