You or a loved one may have been recently diagnosed with a condition called “cystinuria” (pronounced “si-stih-nu-ree-uh”) or “cystine stones,” and have many questions about what it is, what causes it, treatment options, and what to expect. While your healthcare provider is the best source of information about your personal health, the information presented here is intended as a starting point, so you can have more productive discussions with your healthcare team.
Cystinuria is a rare genetic (inherited) condition that affects about 1 in 7,000 people in the United States.1 It occurs when high levels of an amino acid called “cysteine” are found in the urine. When two molecules of cysteine (note the different spelling) are bound together, it is called “cystine.”2 Cystine is a basic building block of proteins that are used throughout the body. It is normally broken down and reabsorbed (recycled) in the body by the kidneys. However, in people with cystinuria, the cystine cannot be reabsorbed into the bloodstream, and it builds up in the urine. As the levels of cystine increase, the excess cystine forms crystals. These crystals can gradually become larger, producing jagged stones that get stuck in the urinary tract (kidneys, bladder, and the ureters, which join the kidneys and bladder) resulting in severe pain and infections.3,4
Cystinuria only causes symptoms after stones have been formed and the stones are present in the urinary tract. The symptoms of cystine stones may include a sharp, stabbing pain in the side or back, or pain near the groin, pelvis, genitals or abdomen. Pain is usually felt on one side. Some people have blood in their urine, nausea or vomiting, and pain during urination.5 A urinary tract infection can occur when a cystine stone is lodged somewhere in the urinary tract, allowing bacteria to grow.3,4
Cystinuria is a lifelong disorder without a cure. This means that people with this condition can have many episodes of cystine stones over their lifetime. In addition to pain, over time these stones can cause urinary tract infections, bladder or kidney damage due to a stone, chronic kidney disease, and blockage of the ureter that requires surgery. If not properly managed, the risk of some degree of kidney injury or failure is high, and a small percentage (less than 5%) of patients may get serious end-stage kidney disease.1 Although cystinuria cannot be prevented, there are medications that can help prevent cystine stones from forming, and this is an important part of managing the condition and its complications.4
Cystine stones are a type of kidney stone that are formed when the amino acid cystine builds up in the urine.4 Cystine comes mainly from your diet and is formed when high-protein foods such as meat, eggs, dairy products and legumes are broken down.6,11 Normally, the body processes cystine effectively, and it dissolves and goes back into the bloodstream after entering the kidneys. In people with cystinuria, there is a genetic mutation (change) in one of two genes (either the SCLC3A1 or SLC7A9 gene) that disrupts this process. Cystine is not absorbed back into the bloodstream and builds up in the urine.3
Normal excretion (elimination from the body) of cystine is less than 30 mg per day. People with cystinuria can excrete more than 300 mg per day, or ten times this amount.7 As the levels of cystine increase in the urine, they form crystals that can eventually become stones. Cystine stones tend to be large compared to the passageways in our urinary tract, and can get stuck in the kidneys, ureters or bladder, causing pain, infection and/or damage, if not removed.5,8
If your healthcare provider suspects that you have cystine stones, you may be referred to a urologist or nephrologist (kidney doctor), specialists who can diagnose and help you manage cystine stones.9
Cystinuria is usually diagnosed by looking at drops of the patient’s urine under a microscope.3,7 Hexagonal (6-sided) cystine crystals in the urine strongly suggest a diagnosis of cystinuria. A definite diagnosis of cystinuria can be made based on a 24-hour urine test to look at levels of cystine in the urine. The urine from the 24-hour collection is also tested for pH, or how acidic (low pH) or alkaline (high pH) the urine is.7 Cystine does not dissolve well in acidic urine and clumps together to form crystals and eventually a stone.2,10 Any stones that are passed can also be analyzed at a laboratory to look at the chemical makeup of these stones.3
Because cystinuria is a life-long condition, it requires ongoing management.11 The goals of treatment are to relieve symptoms due to presence of a stone, help the stone to pass, and to prevent future stone formation by reducing the levels of cystine in urine.2,10 If you are having symptoms of a cystine stone, you should contact your healthcare provider. If they think that the stone will pass on its own, they may recommend that you drink plenty of fluids, especially water around the clock, to produce large amounts of urine. They may also suggest medication to reduce the pain and spasms. If you are unable to pass the stones, there are a number of surgical options that can be used to remove the stones.5,10
Long-term management of cystinuria requires a multifaceted approach to keep stones from forming. This includes drinking more fluids (especially water), reducing salt intake, and making changes to your diet. If these steps are not enough, medication can be added to reduce urine acidity and/or to bind to cystine to help it dissolve more easily.1
Hydration: increasing your water intake helps to dilute cystine in the urine to make it more difficult for stones to form in your urine. This usually means drinking more than 3 liters (13 8-ounce glasses) of fluid per day, including before bedtime, so that you produce at least 2.5 liters of urine daily.12 However, the exact amount depends on the person’s body weight and other factors, so ask your doctor how much you should drink each day.
Changes to your diet: eating meat causes your body to produce more acidic urine. Because cystine stones form more easily in acidic urine, reducing your intake of animal proteins (meat) and eating more fruits and vegetables can make your urine less acidic.11
Reducing your sodium (salt intake): doing things to reduce sodium like eating less salt and eliminating processed or canned foods can help prevent cystine stones from forming by reducing urinary cystine excretion.11
Hydration and diet changes may not be sufficient. More than half of patients continue forming stones if they are using these methods alone, and need to add medication(s) to keep stones from forming.13
Some medications work by changing the pH balance (how acidic or alkaline a substance is) of your urine. These are called “alkalinizing agents,” and they increase the pH of your urine to a pH goal range of 7.5 to 8 (slightly alkaline) so that the excess cystine dissolves and does not form into crystals.7,10 Various combinations of over-the-counter and prescription alkalinizing medications such as potassium citrate, sodium citrate, citric acid, sodium bicarbonate, and magnesium citrate may be recommended to reduce the acidity of your urine.1 You should talk to your doctor before taking any kind of supplement.
Cystine-binding medications such as tiopronin and D-penicillamine may be prescribed if you continue to have frequent stones despite other measures such as increased fluid intake, diet modification, and alkalinizing treatments. The most commonly prescribed cystine-binding drug in the United States is tiopronin. Tiopronin works by chemically binding to cystine in the urine and making it dissolve more easily so that stones become less likely to form.7,10 Tiopronin should be used in combination with other measures such as drinking more water, watching your diet, and alkalinizing treatment.14 Ask your healthcare provider about which of these cystine-binding medications may be right for you. Your healthcare provider can also adjust the dosage to help dissolve cystine in the urine and to manage side effects.
Although cystinuria is a lifelong condition, you can partner with your healthcare team to manage it with diet, lifestyle changes, and medication(s). You will play an important role in the management of cystinuria and there are a number of things you can do to help manage your condition:
Build a healthcare team: Find a doctor you can communicate with and who supports your care goals. Be your own advocate and ask questions until you understand everything. It’s important to work with your healthcare provider to set treatment goals and an action plan, including a plan for setbacks. Your provider will also help you find a treatment plan that works for you, monitor your treatment, and teach you how to detect stones early on.
Gather information about your disorder: Your care team is a good source of accurate information. Avoid unreliable sources of information.
Keep a record of symptoms: Use an app to record important information such as symptoms of a stone when they occur, and side effects of medication. There are many apps available to help keep all your medical information in one place.
Shared decision-making with your doctor: Discuss what is working and what is not. Your doctor will be able to help you adjust your dose of medication to optimize benefits and reduce side effects.
Compliance with your treatment plan: It is important to take your medication as prescribed, and to continue lifestyle changes that can reduce stone formation. Work with your doctor to choose a medication plan that works best for you, your lifestyle, and your health goals.
Self-monitoring: All cystinuria patients should monitor their urine pH regularly with dipsticks, pH paper, or electronic meters. These can be purchased at your local pharmacy or medical supply store. A target pH goal for your alkalinizing therapy is generally recommended to be 7.5-8.0.10 Also, look for signs of cystine build-up such as small stones that look like sand or gravel in your urine. If you have symptoms of stone formation, call your doctor immediately to set up an appointment.
Urine testing: Your healthcare provider may ask you to do a 24-hour urine collection to check your cystine levels. Cystine stones can form when your cystine level in your urine is above a certain level (generally >250 mg/L) so that it cannot dissolve.1 This is called the “solubility limit”. Your doctor will work with you to optimize your treatment plan to lower cystine levels and prevent cystine stones from forming.
Prepare for your visit: Prior to each doctor’s visit, come prepared with a list of questions about optimizing management of your condition, such as: What is my cystine level? Is it above 250 mg/L? Is my urine pH in the right range? Do I need to drink more water or change my dose of medication? What else do I need to do to minimize the risk of more stones forming?
The good news is that the prognosis for cystinuria can be positive with lifestyle changes, medication, treatment compliance, and monitoring. Work with your healthcare provider to set up an individualized management plan to reduce cystine buildup and remove excess cystine from your body.
References
Proudly manufactured in the USA
This material is intended to provide basic information and is not medical advice. All medical advice, diagnosis, and treatment should be obtained from your physician. The product information provided in this site is intended for residents of the United States.
Copyright © 2025 BioComp Pharma, Inc. All rights reserved.
Proudly manufactured in the USA
This material is intended to provide basic information and is not medical advice. All medical advice, diagnosis, and treatment should be obtained from your physician. The product information provided in this site is intended for residents of the United States.
Copyright © 2025 BioComp Pharma, Inc. All rights reserved.
What are Tiopronin Delayed-Release Tablets?
Tiopronin Delayed-Release Tablets are a prescription medication. It is used in combination with high fluid intake, alkali (low acid), and dietary changes to help prevent the formation of one type (cystine) of kidney stones in certain adult and pediatric patients that weigh at least 44 pounds (20 kg) and who do not respond to these measures alone.
Who should not take Tiopronin Delayed-Release Tablets?
Tiopronin Delayed-Release Tablets should not be taken if you:
What should I tell my doctor before taking Tiopronin Delayed-Release Tablets?
Tiopronin Delayed-Release Tablets may not be right for you. Before taking Tiopronin Delayed-Release Tablets, tell your doctor about:
What should I avoid while taking Tiopronin Delayed-Release Tablets?
You should avoid drinking alcohol 2 hours before and 3 hours after taking Tiopronin Delayed-Release Tablets.
What are possible side effects of Tiopronin Delayed-Release Tablets?
Serious Side Effects: Tiopronin Delayed-Release Tablets can cause proteinuria (high amounts of protein in urine), including serious kidney problems, and hypersensitivity reactions (including fever, rash, joint pain and enlarged or swollen lymph nodes).
Most Common Side Effects: Nausea, diarrhea or soft stools, sores in the mouth, rash, fatigue, fever, muscle or joint pain, high amounts of protein in urine, vomiting.
These are not all the possible side effects of Tiopronin Delayed-Release Tablets. Call your doctor for medical advice about side effects.
You may report negative side effects to BioComp Pharma, Inc. at 1-866-762-2365, or to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Please click here for full Prescribing Information including additional Important Safety Information.