American Urological Association - Medullary Cystic Disease/Nephronophthisis
Medullary Cystic Disease/Nephronophthisis
- 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.
- 10-15% retinitis pigmentosa (Senior-Loken syndrome).
- 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.