Cystinuria Symptoms and Treatment

Cystinuria is an autosomal recessive disorder. The pathology of cystinuria is defective transport of amino acids lysine, arginine, ornithine, and cystine in the renal tubule and small intestine. There is impaired re-absorption and excess excretion of these amino acids (lysine, arginine, ornithine, and cystine). Of all these amino acids cystine is poorly soluble and as a result of excess excretion of cystine there may be stone formation in the kidneys (cystine nephrolithiasis), ureters and urinary bladder. Most of the signs and symptoms of cystinuria are due to presence of stone in kidneys, ureters or urinary bladder.

There are two types (variants) of cystinuria, homozygotes and heterozygotes (type-I and non type-I). In homozygotes there excess urinary excretion of all four amino acids cystine, lysine, arginine, and ornithine, but in type-I heterozygotes there is normal urinary excretion of four amino acids, whereas in non type-I heterozygotes there is moderate eise in urinary excretion of cystine, lysine, arginine, and ornithine.

What are the symptoms of cystinuria?

The symptoms of cystinuria are due to presence of stones in the urinary tract (may be in kidney, ureters or bladder), such as blood in urine, renal colic, pain in the flanks, infection and uropathy due to obstruction of urine flow. Presence of stone for long duration may lead to renal insufficiency. Stones generally appear in the second or third decades of life, but can be as early as during first year of life.

Patient with cystinuria (especially homozygotes variants) may excrete 600-1800 mg cystine daily. Normal urine in physiological pH (4.5–7.0) can dissolve maximum of 300 mg per liter and due to excretion of huge quantity of cystine daily (600-1800 mg), a person may need 3-7 liters of urine production daily to prevent cystine stone formation by dissolving the huge cystine that is excreted.

Treatment of cystinuria:

Treatment of cystinuria is aimed at preventing formation of cystine stones by increasing urine output/volume and by increasing pH of urine or making it alkaline, because cystine is more soluble at alkaline pH. The daily urine output should be targeted at 5-7 liters per day and for this intake of more than 4 liters of fluid is essential. The intake of liquid should be evenly spaced over 24 hours and 1/3rd should be during bedtime to 3 A.M. in the morning. The urinary cystine concentration of less than 250 mg per liter should be aimed.

Solubility of cystine increases when urine pH is more than 7.5 and urine alkalinization with bicarbonate or potassium citrate can be done. Penicillamine (1–3 gram/day) and tiopronin (800–1200 mg/day in four divided doses) can be used as they undergo sulfhydryl-disulfide exchange with cystine to form mixed disulfides which are more soluble. But penicillamine is highly toxic and should be used only for high risk (single kidney, renal insufficiency) cases and who do not respond to hydration therapy.

If medical management fails, surgical approaches such as shock wave lithotripsy, ureteroscopy, and percutaneous nephrolithotomy are effective. Open surgery option should be exercised in case of complex stones such as stag-horn calculus.

How common is cystinuria?

The global incidence of cystinuria is reported to be 1 in 10,000 to 1 in 15,000. Cystine stones are not common urinary tract stones (accounts for only 1-2%), but they are the commonest stones among children.

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