Cystinuria
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
