This disorder is a common cause of ESKD in younger individuals, and is associated with almost universal progression to ESKD. The childhood type—juvenile nephronophthisis—is an autosomal recessive disorder caused by mutations in any of 20 NPHP genes; the type appearing in adulthood—medullary cystic disease—is autosomal dominant. Both types are manifested by multiple small renal cysts at the corticomedullary junction and medulla. The cortex becomes fibrotic, and as the disease progresses, interstitial inflammation and glomerular sclerosis develop.
Patients with both forms exhibit polyuria, pallor, and lethargy. Hypertension occurs as the disease progresses. The juvenile form causes growth retardation and ESKD before age 20 years. Patients require large amounts of salt and water due to urinary salt-wasting. Ultrasound and CT scan show small, scarred kidneys.
There is no current medical therapy that will prevent progression to kidney failure. Adequate salt and water intake are essential to replenish kidney losses.