top of page
Search

Cystinura: Causes, Symptoms, Treatments



Eye-level view of a vibrant community gathering with women sharing stories
Image from Prevent Cystine Stones

Cystinuria is a rare genetic condition first discovered by William Hyde Wollaston in 1810, originally named “cystic oxide” (Eisner, 2020). An individual with cystinuria has an abnormally high concentration of the amino acid cystine in their urine, which crystallizes into a type of kidney stones, due to defective renal tubular absorption. Around 1 in 10,000 people worldwide have the condition and cystine stones make up only 1-2% of kidney stones overall (Cleveland Clinic, 2024). 

The kidney stones produced by cystinuria mostly affect the urinary system, which filters blood to remove toxins, urea, water, and other substances. The by-product of this system is urine. The waste passes through several organs–two kidneys, two ureters, a bladder, and a urethra–and problems in any of those parts can result in issues urinating. Through arteries, blood first enters the kidneys which filter waste while nutrients will go back into the bloodstream, a process called renal tubular reabsorption. The waste and excess water move through ureters into the bladder, where the urine is stored until urination, when it will leave from the urethra (Cleveland Clinic, 2023).

Many cells are involved in the urinary system, but the main types include podocytes, tubular epithelial cells, and macula densa cells. Podocytes are a part of the glomerulus, which is composed of many small capillaries that filter blood (Cusabio, n.d.; Murray, 2023). Podocytes monitor filtration rates and help respond to injury. Tubular epithelial cells make up the outer layer of tubules in the kidney. They reabsorb glucose, amino acids, and other nutrients while releasing waste into the urine. These cells release inflammatory mediators as the main site of inflammation and disease in the kidney. Macula densa cells act as sensors in identifying changes in tubular fluid and sending signals to other parts of the kidney. These cells also help to regulate blood flow and the filtration rate of urine in the kidneys (Cusabio, n.d.).

Cystinuria is caused by a mutation in the SLC3A1 and/or SLC7A9 genes (Cleveland Clinic, 2024). The condition can be categorized into three classifications: A, B, and AB. Type A is a mutation of the SLC3A1 gene, Type B is a mutation of the SLC7A9 gene, and the least common Type AB is a mutation in both. There is said to be no drastic difference in severity between types A and B, however type AB has been noted to be less severe than other types (Sadiq, 2022). The SLC3A1 and SLC7A9 genes code for subunits of a protein complex in the kidneys. This protein regulates renal tubular reabsorption by transporting certain amino acids like cystine back into the bloodstream after the blood has been filtered. With the cystinuria mutation, the pathology of the condition is that these protein complexes are unable to properly facilitate reabsorption. This results in buildup of amino acids like cystine in urine (Medline Plus, n.d.). Cystine easily crystallizes when the concentration is too high due to its low solubility in acidic urine (LaRosa, 2024). A buildup of cystine specifically results in the precipitation of crystals in cystinuria form, also known as kidney stones (Medline Plus, n.d.). The stones will obstruct urine flow, causing swelling of the kidney and spasming in the ureters. (Mayo Clinic, 2025). Individuals with cystinuria experience symptoms such as blood in urine, severe back or side pain, vomiting, and pain in groin or abdominal areas (Mayo Clinic, 2025; Medline Plus, n.d.).

However, because cystinuria is caused by a genetic mutation, the condition is hereditary. The condition is only caused by inheriting two autosomal recessive genes. This means that a child will only receive this gene if both parents carry the mutation (Cleveland Clinic, 2024). Some risk factors for more intense cases of cystinuria are gender, age, and lifestyle, but mainly genetics. Men typically are affected more by cystinuria because they form more stones, and most cystine stones develop at age 22 but can begin as early as childhood (Care Hospitals, n.d.).

A primary care physician will be able to diagnose an individual based on symptoms and medical records, specifically family history. They can order a series of tests including ultrasounds, CT scans, urine tests, and stone tests. A stone that has already been passed can be tested to determine what chemical it is made of and in the case of this condition, cystine (Cleveland Clinic, 2024).

Cystinuria is a lifelong condition and has no cure because it is caused by a genetic mutation. Treatment for cystinuria mainly includes preventing the formation of stones but in extreme cases cystine stones may have to be removed surgically (Cleveland Clinic, 2023). A healthcare provider can prescribe over the counter medicines for pain management, or medications that prevent stones by binding to the cystine and making them more soluble (Cleveland Clinic, 2023; Care Hospitals, n.d.). Furthermore, it is extremely important for individuals with cystinuria to maintain a balanced urinary pH because cystine is less soluble in high concentrations of acid. Urinary alkalinization prevents cystine buildup and aids in dissolving existing stones. This can be done through supplementation of citric juices, mineral water, and potassium citrate (Leslie, 2023). Along with that, diet is also an important factor in preventing the development of kidney stones. Fruits and vegetables can help to balance urine pH, however individuals with cystinuria should avoid eating meat, as it will increase acidity (National Kidney Foundation, n.d.). Water is especially important in flushing out or passing kidney stones as well as preventing them. An increased water intake will reduce the high concentrations of uric acid and cystine in urine (Cleveland Clinic, 2024).

There are currently many ongoing research trials in efforts to find a cure or lessen the effects of cystinuria. Other medications such as Dapagliflozin, which typically inhibits the SGLT-2 protein, are being tested for effectiveness in preventing the formation of cystine stones. As cystinuria is a genetic condition, it is continued to be studied as a target for gene therapy. In the future, using CRISPR-Cas9 technology, the SLC3A1 and SLC7A9 genes could potentially be modified and used as a method to cure cystinuria (Goldfarb, 2024). Additionally, scientists have utilized this technology to create models of cystinuria Type A in mice for further research and testing, hoping to develop a cure (Beckermann, 2020). Cystinuria is a painful and chronic disease but can be manageable with a treatment plan, and hopefully cures will be developed with future testing.


Bibliography

Beckermann, T. M., Welch, R. C., Williams, F. M., Mortlock, D. P., Sha, F., Ikizler, T. A., Woodard, L. E., & Wilson, M. H. (2020, February 20). CRISPR/Cas9 engineering of albino cystinuria Type A mice. Wiley Online Library. Retrieved May 29, 2025, from https://onlinelibrary.wiley.com/doi/abs/10.1002/dvg.23357#:~:text=In%20conclusion%2C%20we%20have%20successfully,targeting%20the%20underlying%20genetic%20disease

Cystine Stones. (2025, July 24). Cleveland Clinic. Retrieved May 29, 2025, from https://my.clevelandclinic.org/health/diseases/17794-cystine-stones

Eisner, B. H., Goldfarb, D. S., Baum, M. A., Langman, C. B., Curhan, G. C., Preminger, G. M., Lieske, J. C., Pareek, G., Thomas, K., Zisman, A. L., Papagiannopoulos, D., & Sur, R. L. (2020, November 10). Evaluation and Medical Management of Patients with Cystine Nephrolithiasis: A Consensus Statement. National Library of Medicine. Retrieved May 29, 2025, from https://pmc.ncbi.nlm.nih.gov/articles/PMC7869875/#:~:text=Cystinuria%20was%20first%20described%20in,it%20in%20the%20early%201900s

Goldfarb, D. S., & Patel, A. A. (2024, October 16). Current Management Strategies for Cystinuria. AUA News. Retrieved May 29, 2025, from https://auanews.net/issues/articles/2024/october-extra-2024/current-management-strategies-for-cystinuria

International Cystinuria Foundation. (n.d.). Micro Essential Laboratory. Retrieved May 29, 2025, from https://www.microessentiallab.com/custom.aspx?id=33#:~:text=Urine%20pH%2C%20the%20measure%20of,likely%20to%20form%20and%20grow

LaRosa, C. J. (2024, October). Cystinuria. MSD Manual. Retrieved May 29, 2025, from https://www.msdmanuals.com/professional/pediatrics/congenital-renal-transport-abnormalities/cystinuria

Leslie, S. W., Sajjad, H., & Nazzal, L. (2023, May 30). Cystinuria. National Library of Medicine. Retrieved May 29, 2025, from https://www.ncbi.nlm.nih.gov/books/NBK470527/

Murray, I. V., & Paolini, M. A. (2023, April 17). Histology, Kidney and Glomerulus. National Library of Medicine. Retrieved May 29, 2025, from https://www.ncbi.nlm.nih.gov/books/NBK554544/

Sadiq, S., & Cil, O. (2022, July 1). Cystinuria: An Overview of Diagnosis and Medical Management. National Library of Medicine. Retrieved May 29, 2025, from https://pmc.ncbi.nlm.nih.gov/articles/PMC9317473/

Urinary System. (2023, June 13). Cleveland Clinic. Retrieved May 29, 2025, from https://my.clevelandclinic.org/health/body/21197-urinary-system

 
 
 

Comments

bottom of page