CYSTINURIA

Cystinuria is a genetic disorder with both autosomal recessive and incompletely autosomal dominant inheritance with variable expressivity. The disorder interferes with the transport of cystine and other dibasic amino acids in the proximal tubules of the kidney, resulting in recurrent kidney stone formation. Confirmation of stone composition either by review of outside medical records or stone analysis is essential for the diagnosis. Cystine stones account for about 1% of all stones in adults and about 6% to 10% of stones in children.

Cystinuria results from mutations in the genes SLC3A1 and SLC7A9, which code for the two subunits of a transporter and mediate nearly complete reabsorption of cysteine and other dibasic amino acids (ornihine, lysine, and arginine) in the proximal tubule and intestine.

Amino acids are the building blocks of proteins. The defect causes excessive amounts of these amino acid in. two cysteines attached with disulphide bond makes cystine. Excessive cysteine in urine can lead to recurrent precipitation of hexagonal cystine stones because of the low solubility of cystine at normal urinary pH. Apart from the formation of cystine stones, there are no other clinical manifestations associated with the excessive loss of the others three amino acids in the urine.

1. Stone composition determined by X-ray crystallography or infrared spectroscopy.

2. Microscopy of spot urine demonstrating hexagonal crystals in the sediment.

3. Cyanide–nitroprusside qualitative test.

► When urine cystine excretion is greater than 75 mg/L, this spot test will turn the urine purple.

4. Quantitative testing of cystine in urine

► 24-hour urine cystine measurement or random spot urinary cystine, ornithine, arginine, and lysine excretion normalized by creatinine excretion.

5. Genetic testing, if possible, however therapy does not depend on the underlying genotype.

Increased water intake dissolve small stones and reduces further precipitation. a daily fluid intake to maintain a minimum urine output of 3.0 L/day/1.73 m2 spread throughout the day and evening to decrease urine cystine concentration and cystine crystallization is recommended.

Sodium restriction has been shown to decrease urinary cystine excretion.

Restriction of animal protein intake may reduce the net acid load requiring less urinary acid excretion. Potential benefits include a higher urine pH, greater cystine solubility, and reduction of the dose of alkali needed to achieve an increased urine pH. ► However, excessive dietary protein restriction is not recommended for children due to the requirement of protein intake for optimal growth.

Potassium citrate or potassium bicarbonate is generally recommended as a first-line therapy for urinary alkalinization in patients with cystinuria due to its effect of raising the urinary pH without increasing cystine excretion, which can prevent cystine stones from formin. Cystine solubility is pH dependent and optimal urine pH in these patients is 7.0 to 7.5.

Cystine-binding thiol drugs (CBTDs)- Medications like tiopronin or D-penicillamine can help bind to cystine and reduce its concentration in the urine and are recommended to patients with frequent, recurrent cystine stones who have failed therapy with fluids, diet, and alkalinization.

The two most commonly used and studied CBTDs are alphamercaptopropionyl glycine (tiopronin) and D-penicillamine. This class of drugs, each containing a thiol group, accomplishes disulfide exchange with cystine. The result is the formation of a soluble drug–cystine complex. Both medications reduce free urinary cystine levels and decrease the risk of recurrence of cystine stones.

In severe cases, when stones are large or causing blockages, surgical procedures may be necessary to remove or break them.