Cystinuria

Cystinuria is an inherited metabolic disorder characterized by defective reabsorption of the amino acid cystine (and the dibasic amino acids ornithine, lysine, and arginine) in the proximal renal tubule and the gastrointestinal tract. This leads to excessive urinary excretion of cystine, which is poorly soluble in urine, resulting in the formation of recurrent cystine kidney stones (nephrolithiasis). Cystinuria is one of the most common inherited causes of kidney stones and is caused by pathogenic variants in the SLC3A1 gene (type A) or the SLC7A9 gene (type B). The condition primarily affects the urinary system, including the kidneys, ureters, and bladder. Patients typically present with recurrent renal colic (severe flank pain), urinary tract infections, hematuria (blood in the urine), and in some cases, obstructive uropathy that can lead to chronic kidney disease if inadequately managed. Cystine stones are often large, bilateral, and may form staghorn calculi. The age of onset is variable, but many patients experience their first stone episode in childhood or adolescence, with some presenting as early as infancy. Males tend to be more severely affected than females. Treatment focuses on reducing urinary cystine concentration and increasing cystine solubility. First-line management includes high fluid intake (to maintain dilute urine, typically exceeding 3 liters per day in adults), dietary sodium restriction, urinary alkalinization with potassium citrate to maintain urine pH above 7.0, and dietary moderation of animal protein. When conservative measures are insufficient, thiol-binding drugs such as D-penicillamine or tiopronin (alpha-mercaptopropionylglycine) are used to form more soluble cysteine-drug complexes. Captopril has also been used, though evidence for its efficacy is limited. Surgical intervention, including extracorporeal shock wave lithotripsy (ESWL), ureteroscopy, or percutaneous nephrolithotomy, may be necessary for stone removal, though cystine stones are often resistant to ESWL. Lifelong monitoring and treatment adherence are essential to prevent recurrent stone formation and preserve kidney function.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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