Nephronophthisis

Nephronophthisis = autosomal recessive tubulointerstitial kidney disease that is a leading genetic cause of end-stage renal failure in children/teens.

Concept

• Primary disease of the tubules + interstitium, not the glomeruli.
• Progressive *tubular atrophy, basement membrane disruption, interstitial fibrosis → chronic kidney failure.
• Often a ciliopathy (genes encoding primary cilia proteins), so can be syndromic (retinal dystrophy, cerebellar anomalies, liver fibrosis, etc).

Clinical picture

• Inheritance: autosomal recessive.
• Main forms: infantile, juvenile (most common), adolescent.
• Kids/teens with:
  • Polyuria, polydipsia (concentrating defect, like nephrogenic DI-ish)
  • Growth retardation, anaemia, fatigue
  • Salt wasting, mild or absent oedema
• Urine: usually bland or only mild proteinuria/haematuria – doesn’t look like classic glomerulonephritis.
• Progresses to ESRD before adulthood in most classic cases.

Imaging

• US:
  • Kidneys small or normal size, increased echogenicity, poor corticomedullary differentiation
  • ± small cysts at the corticomedullary junction (but cysts may be subtle or late).
• CT/MR not usually first-line; mainly show small kidneys ± corticomedullary cysts.

Associations

• When combined with retinal dystrophy → Senior–Løken syndrome.
• Other overlaps with Joubert spectrum and other ciliopathies.