Makindo Medical Notes

Cystinuria is an inherited cause of kidney stones due to defective reabsorption of dibasic amino acids in the renal tubules. 💡 Remember with the mnemonic COAL: Cystine, Ornithine, Arginine, Lysine. Only cystine forms stones because it is poorly soluble in acidic urine.

🧬 About

• Autosomal recessive disorder (incidence ~1 in 2,500).
• Accounts for <3% of all kidney stones, but a major cause of stones in children and young adults.
• Recurrent and difficult-to-treat, often causing staghorn calculi.

🧪 Genetics

• Caused by mutations in SLC3A1 or SLC7A9 genes.
• These encode transporters for dibasic amino acids in renal tubules and intestine.
• Failure of reabsorption → ↑ urinary cystine, ornithine, arginine, lysine.
• Only cystine precipitates → forms crystals/stones.

⚙️ Pathophysiology

• Defective transport → excess urinary cystine.
• Cystine is insoluble at acidic pH → crystallises → stones.
• Other amino acids (OAL) remain soluble and don’t form stones.
• Leads to recurrent nephrolithiasis, obstruction, and renal damage.

🩺 Clinical Features

• Renal colic: Severe flank pain radiating to groin.
• Obstruction/Anuria: If large stone blocks outflow → risk of AKI.
• Haematuria: Microscopic or macroscopic.
• Recurrent UTIs: From irritation/obstruction.
• Staghorn calculi: May form if untreated, filling renal pelvis.

🔎 Investigations

• Urine microscopy: Characteristic hexagonal cystine crystals.
• Cyanide–nitroprusside test: Screening test for urinary cystine.
• 24h urine collection: Quantifies cystine excretion.
• Genetic testing: Identifies mutations (for family counselling).
• Imaging: Non-contrast CT or ultrasound to assess size and site of stones.

💊 Management

• Hydration: 3–4 L/day → dilute urine, ↓ risk of stone formation.
• Urine alkalinisation: Potassium citrate or sodium bicarbonate → raises pH > 7.0, ↑ solubility of cystine.
• Thiol drugs: Tiopronin or penicillamine bind cystine → form soluble complexes. Used in refractory cases.
• Stone removal options:
  • ESWL – less effective for cystine (hard stones).
  • Ureteroscopy – for smaller stones in ureter.
  • PCNL – for large/staghorn stones.
• Dietary advice: ↓ sodium intake (as sodium ↑ cystine excretion). ↓ methionine-rich foods may help.

📌 Key Clinical Pearls

• Suspect in recurrent kidney stones in children/young adults.
• Look for hexagonal crystals on microscopy → pathognomonic.
• Cystine stones are relatively radiodense (visible on X-ray, unlike uric acid stones).
• Unlike calcium stones, cystine stones are often resistant to shockwave lithotripsy.

📚 References

• Cystinuria: From a genetic disorder to a clinical condition
• UpToDate – Cystinuria: Clinical manifestations, diagnosis, and management