Hereditary form of tubulointerstitial disease characterized by formation of corticomedullary cysts.
Secondary to mutations in ciliary proteins.
Divided into NPHP types I (juvenile), II (infantile), III (adolescent) by onset of ESRD.
Mutations in NPHP1 accounts for ~85% of NPHP type 1 which maps in chr 2q13; NPHP2 encodes for inversin responsible for NPHP type II and maps to chr 9p22-31; and NPHP3 encodes for nephrocystin-3 responsible for NPHP type III.
MCKD type 1 progress to ESRD at 6th decade whereas type II progress to ESRD at 3rd decade.
MCKD1 maps to chr 1q21 and MCKD2 encodes uromodulin which maps to chr 16p12; both MCKD have autosomal dominant inheritance.
NPHP1 and II patients present with polyuria and polydipsia due to salt wasting; concentration defect; anemia disproportionate to the level of renal insufficiency, and growth retardation; hyperuricemia and gout.
NPHP II manifests with oligohydramnios, hypertension, VSD.
MCKD I and II manifest with polyuria and polydipsia due to salt wasting; concentration defect; hyperuricemia and gout.
Kidneys are small at presentation due to cortical atrophy.
Cysts congregate at the corticomedullary junction and range up to 1 cm in diameter (image A) and (image B).
Cyst formation does not appear to progress as the disease progresses.
Cysts lined by flattened to cuboidal epithelium.
Chronic tubulointerstitial inflammation with tubular atrophy, interstitial fibrosis, and glomerulosclerosis.
Interstitium fibrosis and prominent lymphoid infiltrate that may worsen with time.