Nephronophthisis

Nephronophthisis 

Updated: 09/30/2021

© Jun Wang, MD, PhD

General features
  • Heterogeneous group
  • Autosomal recessive
  • Most common genetic cause of pediatric end stage kidney disease
  • Characterized by corticomedullary cysts, atrophy and interstitial fibrosis
  • Diagnosis based on clinical findings and confirmed by genetic testing
Key pathogenesis
  • Cilia/basal body abnormality
  • Abnormal renal tubular development and function
Clinical presentations
  • Infantile
Most severe form
Bilateral disease
Median age for renal failure: 1 year of age
Extrarenal presentations common: retinitis pigmentosa, hepatic fibrosis, skeletal / CNS malformations, situs inversus, etc
  • Juvenile form
Most common
Polyuria/polydipsia due to cortical and tubulointerstitial damage
Progresses to chronic renal failure in 5-10 years
Anemia and growth retardation
May be associated with retinitis pigmentosa
  • Adolescent form: Similar to juvenile with later presentation (median age renal failure, 19 years)
  • Extraneral manifestations
Bone: Mainzer-Saldino syndrome (cone-shaped epiphyses, retinal degeneration and cerebellar ataxia); RHYNS syndrome (retinitis pigmentosa, hypopituitarism, NPHP, skeletal dysplasia), etc
Liver:  Hepatosplenomegaly and portal fibrosis with NO or only mild bile duct proliferation
Situs inversus: Arrangement of the internal organs as mirror image of normal anatomy; infantile NPHP and mutation in the NPHP2 gene
Septal cardiac defects if NPHP2 and NPHP3 mutations
Pathological findings
  • Normal or small sized kidneys
  • Cysts at corticomedullary junction
  • Severe tubular atrophy with thick basement membranes, interstitial fibrosis and chronic inflammation
Genetic abnormalities
  • Mutation of NPHP1 (Nephronophthisis 1): Encode nephrocystin-1
  • Mutation of NPHP2 (inversin) mutation
  • Others
Features suggestive of NPHP
  • Infantile or young child (<5): End-stage renal disease (ESRD), severe hypertension, and extrarenal anomalies
  • Older children and adolescents
    • Polyuria and polydipsia
    • Progressive chronic kidney disease (CKD) with normal blood pressure
    • Absence of proteinuria or mild tubular proteinuria
    • Absence of hematuria and cellular elements
    • Normal or slightly decreased-in-size kidneys with increased echogenicity, reduced corticomedullary differentiation, and renal cysts on ultrasound examination
Diagnosis
  • Clinical: Child with renal and extrarenal manifestations, including retina, ocular movement abnormalities, cardiac malformations, etc
  • Radiologic studies: Small kidneys with poor corticomedullary differentiation
  • Genetic testing: NPHP mutation
  • Renal biopsy if genetic testing negative or unavailable
Differential diagnosis


 
Treatment
  • Correction of water and electrolyte imbalances
  • Renal transplantation
  • Erythropoietin and iron if anemic
  • Vitamin D and phosphate binder if secondary hyperparathyroidism



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