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An amino acid measured in urine that reveals whether your kidneys are allowing too much cystine to pass through, driving the formation of a rare type of kidney stone.
If you or a family member has been diagnosed with cystine kidney stones, this test tells you something no other test can: exactly how much cystine your kidneys are spilling into your urine over a full day. Urinary cystine (the amino acid cystine, collected over 24 hours) is the single most important number for diagnosing cystinuria, gauging your stone risk, and knowing whether your treatment is actually working.
Cystine is an amino acid, one of the building blocks your body assembles from dietary protein. Normally, your kidneys filter cystine out of the blood and then reabsorb almost all of it back, so very little ends up in your urine. In cystinuria, a genetic defect in the kidney's reabsorption channels (encoded by two genes called SLC3A1 and SLC7A9) lets large amounts of cystine pass straight through into the urine.
The problem is that cystine does not dissolve well. Once its concentration in urine crosses a threshold, it crystallizes and forms stones. These stones tend to be large, recurrent, and difficult to treat. A 24-hour urine collection lets you measure the total cystine your kidneys excrete and, just as importantly, calculate the concentration of cystine in your urine to see whether you are above or below the point where crystals form.
A healthy person typically excretes less than 30 mg of cystine per day. People who carry one copy of a cystinuria gene variant (called heterozygous carriers) fall into two broad groups. Type I carriers excrete normal amounts and almost never form stones. Type II and III carriers excrete intermediate amounts and may occasionally form stones.
If you have two copies of the gene variant (homozygous cystinuria), your excretion is typically 250 mg per gram of creatinine or higher, and you are at significant risk of forming stones. Excretion above 750 mg per day (greater than 3 mmol per day) generally signals severe cystinuria that requires medication beyond fluids and diet alone.
But total daily excretion is only half the picture. What matters most for stone formation is the concentration of cystine in your urine at any given moment. Cystine begins to crystallize at roughly 250 mg per liter (about 1 mmol per liter) at a urine pH of 7 or above. If your 24-hour collection shows a concentration below that threshold, your risk of new stones drops substantially.
| Category | Urinary Cystine Excretion | What It Means for You |
|---|---|---|
| Normal | Less than 30 mg/day | No stone risk from cystine |
| Type I carrier (one gene copy) | Normal values | You carry the gene but are very unlikely to form cystine stones |
| Type II/III carrier (one gene copy) | Elevated (intermediate) | Modest increase; stones are uncommon but possible |
| Homozygous cystinuria | 250 mg/g creatinine or higher | Active stone-forming risk; treatment is needed |
| Severe cystinuria | Greater than 750 mg/day | High stone burden; medication typically required |
Sources: Milliner 1990; Spasiano, Halbritter & Ferraro (GeneReviews, 2025); Joly et al. 1999.
What this means for you: if your result puts you in the homozygous or severe range, the immediate goal is to bring your urinary cystine concentration below 250 mg/L through a combination of high fluid intake, urine alkalinization, dietary changes, and, when necessary, medication. If your result is in the carrier range, periodic monitoring can help you catch any upward trend before stones form.
Your clinician will use several numbers from your 24-hour collection to judge whether your treatment plan is working. The most important target is keeping urinary cystine concentration below 250 mg/L, the approximate solubility limit. A more aggressive goal, sometimes used for people trying to dissolve existing stones, is a supersaturation level of 0.6 mmol/L or lower.
If you are taking a cystine-binding thiol drug (tiopronin or D-penicillamine), an additional target applies. These medications work by binding to cystine and converting it into a more soluble compound. To accurately measure how much free cystine remains, your lab should use a method called liquid chromatography-tandem mass spectrometry (LC-MS/MS), which can separate free cystine from the drug-cystine complexes that older methods may confuse.
Urine pH is also tracked alongside cystine. Cystine dissolves more readily as urine becomes more alkaline. A target pH of 7.5 to 8.0 maximizes solubility. And because dilution is one of the simplest ways to lower concentration, adults are generally advised to produce more than 3 liters of urine per day.
An alternative measurement called cystine capacity gauges how much additional cystine your urine could dissolve before crystallization begins. A cystine capacity of 90 mg/L or higher appears to be a clinically meaningful target. This value correlates strongly and inversely with cystine supersaturation (r = -0.88), meaning that higher capacity reliably predicts lower crystal-forming risk.
If you are monitoring your own progress between clinic visits, keeping a log of your daily fluid intake and urine output alongside your lab results can help you and your clinician spot patterns, especially if stones recur despite numbers that look acceptable on a single collection.
Because cystinuria is genetic, you cannot eliminate cystine excretion entirely. But you can control the concentration of cystine in your urine, which is the variable that determines whether crystals form. Three categories of intervention have documented effects.
Fluid intake: Drinking enough to produce more than 3 liters of urine per day dilutes cystine and is the foundation of every treatment plan. This is a straightforward dilution effect. It requires sustained effort, including waking at night to drink, but it is the single most effective non-drug intervention.
Diet: Dietary protein is the main dietary driver, because the amino acid methionine (abundant in animal protein) is metabolized into cystine. Reducing protein intake lowers the substrate available for cystine production. High sodium intake also modestly increases cystine excretion by affecting how the kidney tubules handle amino acids. Limiting salt is a simple, low-risk dietary step. Urine alkalinization through potassium citrate supplements or citrate-rich foods raises urine pH toward the 7.5 to 8.0 range where cystine is more soluble.
Cystine-binding thiol drugs: Tiopronin and D-penicillamine are prescription medications that bind to cystine in the urine and form a compound (a mixed disulfide) that is far more soluble than cystine itself. These drugs are typically added when fluid and dietary measures are not enough to keep cystine concentration below the solubility limit, particularly when excretion exceeds 750 mg per day. Doses above 1 g per day have not shown further reduction in urinary free cystine concentration, so dose escalation beyond that point is generally not beneficial.
How often you repeat a 24-hour urine collection depends on where you are in your treatment journey.
One important nuance: some people form stones even when their average 24-hour cystine concentration appears safe. This can happen because cystine excretion varies throughout the day. Overnight, when fluid intake drops and urine becomes more concentrated, cystine levels can spike above the solubility threshold even if the 24-hour average looks fine. If you are forming stones despite good average numbers, your clinician may suggest assessing diurnal variation or focusing on nighttime fluid intake.
Certain lab methods can affect accuracy. If you are on tiopronin or D-penicillamine, make sure your lab uses LC-MS/MS rather than traditional ion exchange chromatography. Older methods can overestimate or underestimate free cystine because they do not cleanly separate it from drug-cystine complexes.