What is Cystinuria?

Cystinuria is a rare genetic disorder that causes an accumulation of cystine, a type of amino acid, in the urine. This condition occurs due to defects in the renal tubules, which are responsible for reabsorbing amino acids in the kidneys. When the renal tubules fail to properly reabsorb cystine, excess cystine is excreted in the urine, leading to the formation of cystine crystals that can create kidney stones. Over time, these crystals can build up and cause kidney damage or complications such as kidney stones and urinary tract blockages.

Cystinuria is inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of the defective gene—one from each parent—in order to develop the condition.

What Causes Cystinuria?

Cystinuria is caused by mutations in the genes that encode for proteins responsible for the transport of amino acids in the kidneys. Specifically, the mutations affect the transport of cystine and other dibasic amino acids, leading to their accumulation in the urine.

• Genetic mutations: The condition is caused by mutations in two main genes:
  • SLC3A1: This gene provides instructions for making a protein involved in the transport of amino acids, including cystine, across kidney cells.
  • SLC7A9: This gene also encodes a protein that aids in amino acid transport in the kidneys.

When either of these genes is mutated, the ability to reabsorb cystine is impaired, resulting in excess cystine being excreted in the urine.

Types of Cystinuria

Cystinuria is categorized into three types based on the specific genetic mutations involved. The types are:

1. Type I: Caused by mutations in the SLC3A1 gene, type I is the most common form of cystinuria.
2. Type II: Caused by mutations in the SLC7A9 gene, type II is less common and can have a milder form of the condition.
3. Type III: This rare form of cystinuria is due to mutations in both the SLC3A1 and SLC7A9 genes, leading to more severe symptoms.

What Are the Symptoms of Cystinuria?

The most common symptoms of cystinuria are related to the formation of cystine stones in the kidneys, bladder, or ureters. These symptoms can vary depending on the size and location of the stones, but they typically include:

• Pain: Pain, particularly in the lower back or sides, can be a sign of kidney stones or urinary tract obstruction. The pain can be intense and may come and go.
• Hematuria: Blood in the urine (hematuria) can occur when kidney stones irritate the lining of the urinary tract or when stones pass through the ureter.
• Frequent urination: The presence of stones or blockages can lead to increased urgency and frequency of urination.
• Painful urination: Stones moving through the urinary tract can cause a sharp, burning sensation during urination.
• Urinary tract infections (UTIs): Blockages caused by cystine stones can increase the risk of UTIs.
• Nausea and vomiting: In some cases, severe pain from kidney stones may lead to nausea or vomiting.

Because cystine stones can recur over time, individuals with cystinuria may experience repeated episodes of pain and other symptoms.

How is Cystinuria Diagnosed?

Cystinuria is diagnosed through a combination of clinical evaluation, urine tests, and imaging studies. Some common diagnostic methods include:

• Urine tests: The primary diagnostic test for cystinuria is a 24-hour urine collection. This test measures the amount of cystine in the urine. A high level of cystine in the urine, along with other amino acids, can indicate cystinuria.
• Urine microscopic examination: If a patient presents with symptoms of kidney stones, a doctor may perform a urine microscopic examination to check for the presence of cystine crystals. These crystals are typically hexagonal in shape and may be visible under a microscope.
• Genetic testing: Genetic testing can be performed to confirm the presence of mutations in the SLC3A1 and SLC7A9 genes, providing a definitive diagnosis of cystinuria.
• Imaging studies: Imaging tests such as ultrasound, CT scans, or X-rays may be used to visualize cystine stones in the kidneys, bladder, or ureters.

How is Cystinuria Treated?

Treatment for cystinuria focuses on preventing the formation of cystine stones, managing symptoms, and minimizing complications. The treatment plan may involve a combination of dietary modifications, medications, and, in some cases, surgery.

1. Hydration: One of the most important aspects of managing cystinuria is ensuring adequate hydration. Drinking plenty of fluids helps dilute the concentration of cystine in the urine, reducing the likelihood of stone formation. A high fluid intake of 3-4 liters per day is generally recommended.
2. Alkalinization of urine: Cystine is less likely to form stones in an alkaline environment. As such, doctors may recommend medications that help make the urine less acidic, such as potassium citrate or sodium bicarbonate.
3. Medications: Several medications may be prescribed to help prevent cystine stones and manage symptoms:
   • Penicillamine: A medication that binds to cystine and prevents it from crystallizing in the urine. It is typically used when other treatments are ineffective.
   • Tiopronin: Another medication that can help reduce cystine crystal formation by binding to cystine and increasing its solubility in urine.
4. Dietary changes: A low-salt, low-protein diet may be recommended to reduce the strain on the kidneys. In some cases, a diet that limits methionine (an amino acid) may help prevent the buildup of cystine.
5. Stone removal: If cystine stones cause significant pain or urinary obstruction, medical intervention may be required to remove the stones. Techniques such as extracorporeal shock wave lithotripsy (ESWL), ureteroscopy, or surgery may be used to break down or remove stones.
6. Preventive measures: In individuals with recurrent cystine stones, long-term preventive treatments and regular monitoring are often necessary to reduce the risk of future stone formation.

What Are the Risks and Complications of Cystinuria?

Without proper treatment, cystinuria can lead to several complications, including:

• Chronic kidney disease: Repeated formation of cystine stones can cause long-term kidney damage, leading to impaired kidney function.
• Urinary tract infections: Blockages caused by cystine stones can increase the risk of urinary tract infections.
• Hydronephrosis: The buildup of urine in the kidneys due to a blockage from stones can lead to hydronephrosis, a condition where the kidneys swell.
• Frequent stone recurrence: Individuals with cystinuria are at risk of developing new cystine stones throughout their life, requiring ongoing management and monitoring.

How Can Cystinuria Be Prevented?

Cystinuria is a genetic condition, and there is no way to prevent its occurrence. However, with proper treatment and lifestyle changes, individuals with cystinuria can effectively manage the condition and reduce the risk of kidney stone formation. Regular follow-up appointments with a healthcare provider are essential for monitoring and adjusting treatment plans as needed.