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Nephronophthisis and medullary cystic kidney disease are inherited disorders that cause cysts restricted to the renal medulla or corticomedullary border and, eventually, renal failure.

Nephronophthisis and medullary cystic kidney disease are grouped together because they share many features. Pathologically, they cause cysts restricted to the renal medulla or corticomedullary border, as well as a triad of tubular atrophy, tubular basement membrane disintegration, and interstitial fibrosis. They probably share similar mechanisms, although these are not well characterized. Both disorders cause a vasopressin Some Trade Names
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-resistant urine-concentrating defect that leads to polyuria and polydipsia; Na wasting severe enough to require supplementation; hypertension; and anemia. Growth retardation and bone disease are key features in affected children. However, in many patients, these problems develop slowly over years and are so well compensated for that they are not recognized as abnormal until significant uremic symptoms appear. Both disorders eventually cause renal failure.

Nephronophthisis: Inheritance is autosomal recessive. Nephronophthisis accounts for 10 to 20% of chronic renal failure in children and young adults (< 20 yr). There are 4 types: juvenile (types 1 and 4; median age at onset, 13 yr), infantile (type 2; median age at onset, 1 to 3 yr), and adolescent (type 3; median age at onset, 19 yr). Mutations in genes that code for tubular ciliary proteins (nephrocystin for types 1, 2, and 4; inversin for type 2) presumably cause ciliary dysfunction; the mechanism leading to cystic transformation may be similar to that in polycystic kidney disease but is unclear.

The mutation responsible for type 1 causes extrarenal manifestations, including oculomotor apraxia, retinitis pigmentosa (Senior-Loken syndrome), liver fibrosis, cone-shaped epiphyses (Mainzer-Saldino syndrome), and optic nerve coloboma with cerebellar vermis aplasia (Joubert's syndrome type B).

Diagnosis is by history and imaging, but cysts often occur only late in disease. Ultrasonography, CT, or MRI may show smooth renal outlines with normal-sized or small kidneys, loss of corticomedullary differentiation, and multiple cysts at the corticomedullary junction. PCR testing for the gene deletion causing type 1 disease is available.

In early disease, treatment involves management of hypertension, electrolyte and acid-base disorders, and anemia. Children with growth retardation may respond to nutritional supplements and growth hormone therapy. Ultimately, all patients develop renal failure and require dialysis or transplantation.

Medullary cystic kidney disease: Inheritance is autosomal dominant. The disease affects people in their 30s through 70s. There are 2 types, which differ by median age at onset (type 1, 62 yr; type 2, 32 yr) and by genetic mutation (type 1 is localized to chromosome 1; type 2, to chromosome 16). About 15% of patients have no family history, suggesting a sporadic new mutation. Hyperuricemia and gout are the only extrarenal manifestations. End-stage renal disease typically develops at age 30 to 50. Diagnosis and treatment are similar to those of nephronophthisis.

Last full review/revision November 2005

Content last modified November 2005