There are two major types of cystic disease affecting the medulla: medullary sponge kidney, a relatively common and usually innocuous condition, occasionally associated with nephrolithiasis, which will not be discussed further, and nephronophthisis-medullary cystic disease complex, which is almost always associated with renal dysfunction.
Nephronophthisis–medullary cystic disease complex is an underappreciated cause of chronic kidney disease that usually begins in childhood. Four variants are recognized on the basis of the timing of onset: infantile, juvenile, and adolescent nephronophthisis, and medullary cystic disease developing later in adult life. The juvenile form is the most common. Approximately 15% to 20% of children with juvenile nephronophthisis have extrarenal manifestations, which most often appear as retinal abnormalities, including retinitis pigmentosa, and even early-onset blindness in the most severe form. Other abnormalities found in some individuals include oculomotor apraxia, mental retardation, cerebellar malformations, and liver fibrosis. In aggregate, the various forms of nephronophthisis are now thought to be the most common genetic cause of end-stage renal disease in children and young adults.
At least nine gene loci (NHP1 to NHP9) have been identified for the autosomal recessive forms of the nephronophthisis complex. The majority of these genes encode proteins that are components of epithelial cilia, as is the case with other types of polycystic disease. Two autosomal Table 14.5 Prevalence of Various Types of Renal Stones forms cause disease in adults; these are far less common.
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MORPHOLOGYPathologicfeaturesofmedullarycysticdiseaseincludesmall contracted kidneys. Numeroussmallcystslinedbyflattenedorcuboidalepitheliumarepresent,typicallyatthecorticomedullaryjunction.Otherpathologicchangesarenonspecific,butmostnotablyincludeachronictubulointerstitialnephritiswithtubularatrophyandthickenedtubularbasementmembranesandprogressiveinterstitialfibrosis.
The initial manifestations are usually polyuria and polydipsia, a consequence of diminished tubular function. Progression to end-stage renal disease ensues over a 5-to 10-year period. The disease is difficult to diagnose because there are no serologic markers, and the cysts may be too small to be seen with radiologic imaging. Adding to this difficulty, cysts may not be apparent on renal biopsy if the corticomedullary junction is not well sampled. A positive family history and unexplained chronic renal failure in young patients should lead to suspicion of nephronophthisis.
Adult polycystic kidney disease isadiseaseofautosomaldominantinheritancecausedbymutationsinthegenesencodingpolycystin-1orpolycystin-2.Itaccountsforabout10%ofcasesofESRD;thekidneysmaybeverylargeandcontainmanycysts.
Autosomal recessive (childhood) polycystic kidney disease iscausedbymutationsinthegeneencodingfibrocystin.Itislesscommonthantheadultformandstronglyassociatedwithliverabnormalities;thekidneyscontainnumeroussmallcysts.
Nephronophthisis–medullary cystic disease complex isbeingincreasinglyrecognizedasacauseofchronickidneydiseaseinchildrenandyoungadults.Ofautosomalrecessiveinheritance,itisassociatedwithmutationsinseveralgenesthatencodeepithelialcellproteinscallednephrocystins thatmaybeinvolvedinciliaryfunction;thekidneysarecontractedandcontainmultiplesmallcysts.