• Definition: an inherited genetic disorder characterized by the accumulation of cystine in the kidneys and bladder due to a disruption of amino acid transporter function in the proximal convoluted tubule and intestine.
• Pathophysiology:
  • Normally, proteins and large molecules like amino acids cannot pass the glomerular filtration barrier because the glomerular capillaries are highly selective. However, small molecules like dibasic amino acids can pass through the glomerular barrier because they are small enough (molecular weight < 10 kDa) and are not repelled by the negative charge of the basement membrane. They are almost entirely reabsorbed in the PCT.
  • Impaired renal reabsorption of dibasic amino acids (cystine, ornithine, arginine, lysine) → accumulation of cystine in the urine → frequent formation of hexagonal cystine stones

Mnemonic

Cystine, Ornithine, Lysine, and Arginine (COLA) share a common transporter in kidney and intestine.

• Clinical features: recurrent nephrolithiasis > Cystine stones, starting as early as childhood
• Diagnostics
  • Urine microscopy: hexagonal cystine stones
  • Urinary cyanide nitroprusside test: positive
• Treatment: increase cystine solubility to counter the formation of renal stones
  • Adequate hydration
  • Urinary alkalinization: acetazolamide, potassium citrate
  • Chelating agents: penicillamine