cystinuria

Cystinuria is a genetic disorder defined by defective renal reabsorption of the amino acids cystine and the dibasic amino acids ornithine, lysine, and arginine. As a result, elevated levels of cystine in urine lead to the formation of kidney stones, which are often recurrent. Cystine stones tend to be hard and slow to pass, causing flank pain, hematuria, and urinary tract infections. The condition is the most common inherited cause of nephrolithiasis and is usually inherited in an autosomal recessive pattern. In many patients, mutations in the genes SLC3A1 or SLC7A9—encoding components of the proximal tubule transporter for dibasic amino acids—impair reabsorption in the kidney and intestine, resulting in increased urinary cystine excretion.

Diagnosis relies on demonstrating elevated urinary cystine. The cyanide-nitroprusside test can screen for elevated cystine in spot or 24-hour urine samples; quantitative amino acid analysis confirms high dibasic amino acids. Urine microscopy may reveal hexagonal cystine crystals. Stone analysis and imaging studies (ultrasound or CT) help assess burden. Genetic testing can confirm the underlying mutation.

Treatment aims to reduce cystine concentration in urine and prevent stones. This includes high fluid intake to dilute urine, urinary alkalinization (pH maintained above 7.5, typically with potassium citrate), and dietary sodium restriction to lower cystine excretion. In patients with recurrent stones or intolerance of conservative measures, thiol drugs such as tiopronin or d-penicillamine can increase cystine solubility by forming mixed disulfides, but they require careful monitoring for adverse effects. Some patients may require endourologic or surgical intervention for stones.

With long-term management, many individuals can reduce stone recurrence and maintain kidney function.