Cystinuria is a rare, inherited disorder where the kidneys fail to properly reabsorb certain amino acids, including cystine, ornithine, lysine, and arginine. This malfunction leads to a high concentration of cystine in the urine. Because cystine is poorly soluble, it can form crystals that aggregate into stones within the kidneys, ureters, and bladder.
The Genetic Basis of Cystinuria
Cystinuria follows an autosomal recessive inheritance pattern, meaning an individual must inherit a defective gene from each parent to develop the disorder. People with only one copy of the mutated gene are carriers who do not show symptoms but can pass the gene to their children.
The two genes implicated in the condition are SLC3A1 and SLC7A9. These genes provide instructions for a protein complex that transports amino acids in the kidneys.
This transporter is responsible for reabsorbing cystine from filtered fluid back into the blood. When mutations occur in these genes, the transporter is defective, impairing reabsorption and causing cystine to accumulate in the urine.
Symptoms and Diagnosis
The defining characteristic of cystinuria is the recurrent formation of kidney stones, with symptoms appearing between the ages of 10 and 30. The presence of these stones leads to severe pain, known as renal colic, which is felt in the flank or lower back and can radiate toward the groin. It often comes in intense waves as the stone moves through the urinary tract.
Other common signs include:
- Blood in the urine (hematuria)
- Nausea and vomiting
- An increased frequency of urination
- A higher susceptibility to urinary tract infections (UTIs)
Diagnosing cystinuria involves laboratory tests and imaging. A urinalysis may reveal distinctive, six-sided hexagonal crystals, and a 24-hour urine collection is performed to measure the amount of cystine being excreted. Levels above 400 mg per day indicate the condition. Imaging studies like CT scans and renal ultrasounds are used to detect the location and size of existing stones, while stone analysis or genetic testing can also confirm the diagnosis.
Treatment and Management Strategies
The goal of managing cystinuria is to prevent new stones from forming and to manage existing ones.
Lifestyle Changes
Aggressive hydration is the first step in management. Patients are advised to drink enough fluid, often 3 to 4 liters per day, to produce a high volume of dilute urine. This helps keep the concentration of cystine low and reduces the chance of crystallization.
A low-sodium diet is also advised, as high sodium intake can increase the amount of cystine excreted in the urine. Reducing the intake of animal protein is beneficial because these proteins are high in methionine, an amino acid the body metabolizes into cystine.
Medications
When lifestyle changes are not enough, medication is introduced. Urinary alkalinizing agents, such as potassium citrate, increase the pH of the urine. Cystine is more soluble in alkaline urine, which helps prevent crystals from forming.
For patients with more severe or recurrent stone formation, chelating agents like tiopronin may be prescribed. These drugs bind to cystine in the urine, forming a new, more soluble compound that is easily excreted.
Medical Procedures
For stones that are too large to pass on their own, procedural intervention is necessary. Ureteroscopy involves passing a thin scope through the bladder to locate the stone, which can then be broken up with a laser and removed. Another option is shock wave lithotripsy (SWL), which uses sound waves to break stones into smaller pieces, though its effectiveness on hard cystine stones can be limited.
Living with a Chronic Condition
Managing cystinuria is a lifelong commitment that requires continuous monitoring to prevent stone recurrence and preserve long-term kidney function. Patients need regular follow-up appointments with a nephrologist to track their progress. This care includes periodic 24-hour urine collections to ensure cystine levels are controlled and imaging tests to check for new stone development.
The long-term objective is to avoid complications from repeated stone formation, such as urinary tract infections and kidney damage. Although rare, occurring in less than 5% of patients, recurrent stones and subsequent infections can lead to chronic kidney disease over time. Consistent adherence to treatment plans is important for maintaining kidney health.
Living with a condition marked by unpredictable and painful episodes can have a psychological impact. The awareness of a potential stone event can be a source of stress and anxiety. Support from healthcare providers, family, and patient groups is valuable for navigating the challenges of this condition and maintaining the best possible quality of life.