Cystinuria

Did you know that some people's bodies can't process certain amino acids properly? This is the case with cystinuria, a rare genetic condition that affects how the kidneys work. Cystinuria causes too much of an amino acid called cystine to accumulate in the urine. This can result in painful kidney stones and other health issues. Understanding cystinuria is essential for those who have it and their families. This article will explore what cystinuria is and how it affects the body. We'll look at its causes, symptoms, and risk factors. We'll also discuss how doctors diagnose cystinuria disease and the treatments available. 

What is Cystinuria?

Cystinuria is a rare genetic disease that affects how the kidneys process certain amino acids. It causes an excessive amount of cystine to build up in the urine. This condition occurs in about 1 in 7,000 to 10,000 people worldwide.

In cystinuria, the body can't correctly reabsorb cystine and other amino acids from the urine back into the bloodstream. As a result, cystine levels in the urine become very high. Because cystine doesn't dissolve easily, it forms crystals and stones in the kidneys, bladder, or urinary tract. While some people with cystinuria may not form stones, others might experience frequent stone formation.

Causes of Cystinuria

Cystinuria is a genetic disorder that impacts how the kidneys process certain amino acids. Mutations in two genes cause it: SLC3A1 and SLC7A9. These genes provide instructions for making parts of a protein complex found in the kidneys. This complex typically controls the reabsorption of amino acids, including cystine, from urine into the blood.

When mutations occur in either of these genes, they disrupt the protein complex's ability to reabsorb amino acids. This leads to high levels of cystine in the urine.

Cystine is the least soluble amino acid of all essential amino acids, so it doesn't dissolve easily. As cystine levels rise in the urine, crystals form, leading to stone development.

Cystinuria is inherited in different patterns depending on the gene involved. SLC3A1 mutations follow an autosomal recessive pattern, while SLC7A9 mutations can be considered autosomal dominant with incomplete penetrance.

Cystinuria Symptoms

Cystinuria itself doesn't cause symptoms. However, when cystine stones form, they can lead to various issues, such as:

• Sharp pain in the side or back, typically on one side 
• Pain may radiate towards the groin 
• Pain near the pelvis or abdomen
• Blood in the urine
• Pain while urinating
• Nausea or vomiting

Cystine stones are generally larger than other kidney stones, which can lead to complications like urinary tract infections. These stones may appear as yellowish-brown hexagonal crystals in the urine. It's worth noting that about 80% of people with cystinuria have their first stone before they turn 20. The recurring nature of these stones can significantly affect a person's quality of life.

Risk Factors

The condition is inherited from both parents, making family history a crucial risk factor. Various factors can increase the risk of cystinuria, such as: 

• Gender: Men are generally more severely affected than women, experiencing a larger number of stones. 
• Age: The peak age for the first cystine stone is around 22 years, but about 22% of patients start forming stones in childhood. 
• Other risk factors for cystine crystallisation include low urine pH, reduced ion strength, the presence of cystine crystals, and low levels of urinary macromolecules.

Complications of Cystinuria

Cystinuria has a significant impact on a person's health and can result in serious complications if not properly managed, such as: 

• Kidney stones
• Chronic kidney disease 
• Urinary tract infections and kidney infections 
• In some cases, cystine stones can block the ureters, the tubes that carry urine from the kidneys to the bladder. This obstruction can be extremely painful and may require immediate medical attention. 
• Although rare, end-stage renal disease occurs in less than 5% of cystinuria patients.

Cystinuria Diagnosis

Diagnosing cystinuria begins with clinical suspicion, especially in children with kidney stones. Doctors may suspect cystinuria in patients with a family history or those experiencing severe stone disease, including recurrent or bilateral renal stones.

Several methods are used to confirm the diagnosis, such as: 

• Stone analysis is the gold standard diagnostic measure for cystinuria, as it can reveal the presence of cystine. 
• Microscopic examination of the first-morning urine sample may show hexagonal crystals, which are highly specific to cystinuria. 
• Renal ultrasounds to detect stones inside the kidneys 
• Routine 24-hour urine tests to measure cystine level
• The sodium-nitroprusside test serves as an initial screening tool, turning urine purple in the presence of high cystine levels. However, this test can yield false positives, so positive results require confirmation through quantitative chromatographic analysis of urine for cystine excretion.

Cystinuria Treatment

Treatment for cystinuria focuses on preventing stone formation and managing existing stones. 

• Conservative Mesures:
  • The primary approach involves increasing fluid intake to dilute urine and reduce cystine concentration. Patients are advised to drink at least 3-4 litres of water daily, including at night. 
  • Dietary modifications play a crucial role, with recommendations to limit sodium and animal protein intake. 
• pH Balancing:
  • Urinary alkalinisation is another critical strategy, aiming to raise urine pH to 7.0-7.5 using potassium citrate. 
• Medications:
  • When these conservative measures fail, doctors may prescribe thiol-based medications. These drugs bind to cystine, forming more soluble compounds. 
• Surgery:
  • Surgical interventions are considered for large or obstructing stones, with ureteroscopy and laser lithotripsy preferred over shock wave lithotripsy due to cystine stones' resistance to fragmentation.

When to See a Doctor

If you experience sharp pain in your lower back or side of the abdomen, immediately contact your doctor. These symptoms might indicate the presence of cystinuria. Other signs that warrant medical attention include: 

• Blood in the urine
• Difficulty urinating
• Frequent urinary tract infections. 
• Individuals with a family history of cystinuria or those who have had kidney stones at a young age should seek medical advice. Regular check-ups are essential for people with cystinuria to monitor stone production and kidney function. 

Preventions

While cystinuria cannot be prevented, there are ways to reduce the risk of stone formation.

• Increasing water intake is crucial, aiming for at least 3 litres of urine output daily. This helps to dilute the urine and decrease cystine concentration. 
• Limiting sodium intake to less than 2 grammes per day can also help, as high salt consumption increases cystine excretion. 
• Consumption of a diet low in animal-derived protein reduces urinary acidity. 
• Consuming alkalinising beverages like lemonade and orange juice can help raise urine pH. 
• Regular monitoring of urine-specific gravity and pH is essential. 

Conclusion

Cystinuria is a complex genetic condition that significantly impacts kidney function and overall health. This rare disorder causes an excessive buildup of cystine in the urine, resulting in the formation of painful kidney stones. Understanding the causes, symptoms, and available treatments is crucial for those affected by cystinuria and their families to manage the condition effectively.

Living with cystinuria requires ongoing care and lifestyle adjustments. By increasing fluid intake, modifying diet, and following medical advice, people with cystinuria can reduce the risk of stone formation and prevent complications. Regular check-ups and monitoring are essential to maintain kidney health and quality of life. With proper management and support, individuals with cystinuria can lead fulfilling lives even with the challenges posed by this condition.

FAQ's

1. Who is at risk for cystinuria?

Cystinuria is an inherited disorder that affects about 1 in 7,000 to 10,000 people worldwide. Those with a family history of the condition are at higher risk. Both parents must carry the defective gene for a child to develop cystinuria. Men are generally more severely affected than women, experiencing a larger number of stones.

2. What enzyme deficiency causes cystinuria?

An enzyme deficiency does not cause cystinuria. It results from mutations in the SLC3A1 and SLC7A9 genes, which affect the kidneys' reabsorption of cystine and other amino acids. This leads to excessive cystine excretion in the urine.

3. What is the test for cystinuria?

Cystinuria is typically diagnosed through stone analysis, microscopic examination of urine for hexagonal crystals, or quantitative measurement of urinary cystine levels. The sodium-nitroprusside test is helpful as an initial screening tool. Genetic testing is also available but less commonly used.

4. What age does cystinuria occur?

Cystinuria symptoms usually begin between ages 10 and 30, with a median age of onset around 16 years. However, about 22% of patients start forming stones in childhood. The peak age for the first cystine stone is around 22 years old.

5. What foods help cystinuria?

A diet low in sodium and animal-derived protein can help manage cystinuria. Increasing fluid intake is crucial to dilute urine and reduce cystine concentration. Alkalising foods like fruits and vegetables may be beneficial. Limiting high-methionine foods such as fish, poultry, meat, and eggs is recommended. 

CARE Medical Team