Genetic nephrolithiasis

Including: Cystinuria; hyperoxaluria; Dent’s disease

 

Cystinuria

  • Autosomal recessive
  • Pathology
    • Encodes a family of solute carrying tubular proteins
    • Defective uptake of cystine from urine leads to hyper-saturation in filtrate and stone formation
  • Presentation
    • Nephrolithiasis
  • Investigations
    • Urine microscopy shows hexagonal crystals, raised cystine on 24 hour urine collection, radio-opaque stones on imaging
  • Treatment
    • Increase fluid intake, can add in penicillamine or others to increase solubility in urine

 

Hyperoxaluria

  • Autosomal recessive
  • Pathology
    • Defective proteins associated with alanineglyoxylate aminotransferase.
    • Normally Glyoxalate converted to glycine
    • In hyperoxaluria compensatory pathway leads glyoxalate to be converted to oxalate
    • Systemic hyperoxalaemia and hyperoxaluria
  • Presentation
    • Calcium oxalate nephrolithiasis
    • Systemic oxalate deposition affecting joints, heart and blood vessels
  • Investigations
    • Raised urinary oxalate excretion, calcium oxalate renal stones
  • Treatment
    • Liver-kidney transplant (the oxalate metabolic pathway occurs in the liver)
    • Pyridoxine (vitamin B-6) is a cofactor in this chemical pathway and be given as a holding measure

 

Dent’s disease

  • X-linked recessive
  • Pathology
    • Defect in CLCN5, renal chloride channel
    • Failure of transport of proximal tubule proteins from urine to blood
  • Presentation
    • Nephrolithiasis
    • Nephrocalcinosis
    • Fanconi’s syndrome
  • Treatment
    • Renal transplant once end-stage renal failure sets in

 

 

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