What is Cystinuria?
Cystinuria is an inherited genetic disorder affecting the active transport of the diamino acids cystine, ornithine, lysine, and arginine across the renal tubule and small intestine, resulting in excessive urinary cystine excretion and recurrent kidney stone formation. 1, 2
Pathophysiology
The disorder results from defective function of the cystine transporter (b0,+), which is a heterodimer consisting of rBAT (encoded by SLC3A1) and b0,+AT (encoded by SLC7A9) subunits joined by a disulfide bridge. 3
The only significant clinical manifestation is urinary tract stone formation due to the poor solubility of cystine in urine. 1
Cystine stones are among the hardest stones to fragment, with structural characteristics that make them resistant to shockwave lithotripsy. 4
Clinical Presentation
Patients typically have their first stone event early in life and are prone to recurrent stones throughout their lifetime. 4
Males are generally more severely affected than females, though the reason for this gender difference is not fully understood. 3
The disorder may lead to chronic kidney disease in many patients due to repeated stone formation and removal procedures. 4, 3
Diagnosis is confirmed through 24-hour urine collection showing elevated cystine levels, with stone analysis revealing characteristic hexagonal cystine crystals. 5
Stone Characteristics
Cystine stones may be barely opaque on standard imaging or fluoroscopy, which can compromise shock-wave focusing during lithotripsy treatment. 4
Stone morphology varies—stones with rough-appearing external surfaces are more amenable to fragmentation than those with smooth contours. 4
These stones have significantly higher CT attenuation values compared to other stone types, correlating with their resistance to fragmentation. 4
Clinical Significance
Cystinuria should be considered in all people, regardless of age, who form urinary stones. 1
Early diagnosis is critical because the clinical effects can be prevented with appropriate treatment, allowing affected individuals to lead normal lives. 1
The condition requires lifelong management to prevent stone recurrence and preserve renal function. 5, 4