Makindo Medical Notes

Due to inadequate reabsorption of dibasic amino acids, nephrolithiasis can occur, specifically involving cystine, ornithine, arginine, and lysine. This is easily remembered with the mnemonic COAL.

About

• Cystinuria is a rare autosomal recessive disorder causing the formation of cystine stones.
• It has an incidence of approximately 1 in 2,500 individuals and accounts for less than 3% of all renal calculi.

Genetics

• Cystinuria is caused by mutations in the SLC3A1 or SLC7A9 genes.
• These genes encode proteins involved in the transport of cystine and other dibasic amino acids across the renal tubules.
• Mutations lead to an inability to properly reabsorb cystine in the kidneys, resulting in excessive cystine excretion in the urine.
• This impaired reabsorption extends to other dibasic amino acids: cystine, ornithine, arginine, and lysine.

Pathophysiology

• Due to defective transport, there is a failure to reabsorb filtered COAL (cystine, ornithine, arginine, and lysine) dibasic amino acids.
• Cystine is relatively insoluble, especially in acidic urine, leading to the formation of crystals and stones.
• The other dibasic amino acids (ornithine, arginine, and lysine) remain soluble and do not contribute directly to stone formation.
• Cystine stones can form large, staghorn calculi or act as a nidus for other types of kidney stones.

Clinical Features

• Renal Colic: Severe pain due to the passage of stones through the urinary tract.
• Obstruction and Anuria: Blockage of the urinary flow can cause acute kidney injury (AKI).
• Haematuria: Blood in the urine, which may be visible (gross) or microscopic.
• Recurrent Urinary Tract Infections (UTIs): Due to irritation or blockage from stones.
• Frequent Urination: Irritation of the urinary tract may increase the need to urinate.

Investigations

• Urine Tests: Microscopic examination may reveal characteristic hexagonal cystine crystals. The cyanide-nitroprusside test is used to detect elevated cystine levels in the urine.
• 24-Hour Urine Collection: Measures the levels of cystine and other relevant substances to assess stone risk.
• Genetic Testing: Identifies mutations in the SLC3A1 or SLC7A9 genes for a definitive diagnosis.
• Imaging Studies: Ultrasound or CT scan is used to detect kidney stones, their size, and location.

Management

• Hydration: Aim for a fluid intake of 3-4 liters per day to dilute the urine, reducing cystine concentration and stone formation risk.
• Alkalinizing Agents: Potassium citrate or sodium bicarbonate helps raise urine pH, increasing cystine solubility.
• Thiol-Containing Drugs: Medications like tiopronin or penicillamine form complexes with cystine, making it more soluble and easier to excrete.
• Extracorporeal Shock Wave Lithotripsy (ESWL): Uses sound waves to break stones into smaller fragments that can pass through the urine.
• Ureteroscopy: A minimally invasive procedure using a scope to remove stones from the ureter or kidney.
• Percutaneous Nephrolithotomy (PCNL): Surgical removal of large or complex stones directly from the kidney.
• Dietary Modifications: Reducing sodium intake can decrease cystine excretion in urine, and a diet low in methionine (a precursor to cystine) may be beneficial.

References

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