Cystinuria - Causes, Symptoms, Diagnosis, Treatment, and Complications

Introduction:

Cystinuria is a rare hereditary condition in which stones are present within the organs of the urinary system. The principal constituent of these stones is cysteine which is an amino acid. These stones result in the blockage of the urinary tract, ultimately causing difficulty in the passage of urine. This condition results from a gene defect, so it is passed on from the parents to the children. There are treatment options available to prevent the formation of stones and control pain.

What Is Cystinuria?

Cystinuria denotes the presence of stones in the urinary system formed due to the accumulation of the amino acid cystine. Cystine is an amino acid essential for forming proteins in the body. It is produced in the body and forms an essential constituent of nails, skin, and hair. Cystine usually gets filtered out and reabsorbed by the kidneys. Still, in this condition, excessive cysteine is present in the urine leading to the build-up of stones in the urinary system. Since this is a genetic defect, it is present only when the defective genes are inherited from both parents. The patient usually presents with pain and difficulty urinating symptoms if these stones block the passage of urine.

What Are Amino Acids?

Amino acids are the molecules that join together to form proteins, the building blocks of life. Proteins carry out a variety of functions, and some of them are listed below:

1. They are required by the body to carry out various activities like digestion, muscular contraction, and blood clotting.

2. Proteins are the source of energy for the cells present in the body as they break down proteins into amino acids and use them to carry out their daily activities.

3. Some of the hormones present within the body are made of proteins, allowing the cells and tissues to communicate.

4. Proteins form an integral part of the various body structures like nails (keratin protein), bones (collagen), and the uterus (elastin) and allow them to return to their original state after contraction.

5. They aid in forming antibodies to help the body fight infection and diseases and allow the body to heal itself after an injury.

Amino acids are released when the body cells break down the proteins to carry out the functions mentioned above. Three types of amino acids have been listed below:

What Happens to Amino Acids Under Normal Conditions?

The human body comprises an amino acid transport system that works to transport the amino acids to different body organs to carry out their functions. After they are used by body cells, they are sent to the kidneys, the organs that decide the fate of the substances coming in and going out of the body. Usually, the amino acids are filtered and reabsorbed within the internal units of the kidneys to maintain an equilibrium of the amino acid levels within the body. This equilibrium gets disturbed in conditions like cystinuria, where the amino acid cysteine accumulates within the urine and forms stones. Two molecules of amino acid cysteine join together to form cystine, the culprit behind the condition, cystinuria.

What Are the Causes of Cystinuria?

Cystinuria occurs due to defects (mutations) in the genes SLC3A1 and SLC7A9. The causes of cystinuria are described below:

• These genes command the body to develop a protein for the reabsorption of amino acids. After the body has used up the amino acids, the remaining ones enter the kidneys, but they are not considered waste products by the kidneys.

• It is because the body requires them for various functions and biochemical reactions that are going on in the body.

• So these amino acids are sent back to the blood by the kidneys. In the case of cystinuria, the amino acid cysteine does not get reabsorbed from the kidneys and starts forming crystals giving rise to stones.

• Under normal conditions, cystine is filtered by the kidneys and returned to the bloodstream.

• Still, in cystinuria, the gene responsible for this function is defective and unable to transport it back to the body resulting in the clustering up of cystine in the urine.

• This genetic defect affects the transport of other amino acids also, but cystine is of primary concern because it is the one that can form stones and is the least soluble in urine.

• Also, no mechanism present could work to prevent the formation of these cystine stones.

• Typically, less than 18 milligrams of cystine are expelled from the body each day.

• Still, in the case of cystinuria, the level rises to 300 to 500 milligrams per day, making the urine saturated with cystine.

What Are Some of the Major Signs and Symptoms of Cystinuria?

Cystinuria is a type of condition that affects the individual throughout life. The presence of stones within the urinary system makes the passage of urine difficult resulting in the following symptoms:

1. Presence of Flank Pain: It refers to the pain felt in the back or side region and is of severe intensity. It usually occurs on one side, rarely affects both sides, and causes a lot of discomfort to the patient while urinating. Pain is seldom accompanied by uneasiness and vomiting and spreads to other regions like the thigh, abdomen, and area between the stomach and thigh (groin).

2. Hematuria: It is the condition in which blood is present in the urine. It can be microscopic (the presence of blood in urine can only be detected under the microscope) or gross (the patient can see the presence of blood in the urine). Hematuria is seen to occur frequently among patients.

3. Urinary Tract Infections (UTIs): Stones obstruct urine flow, leading to urinary retention. This urine becomes a potential source of infection and provides a medium for the bacteria to grow, thereby increasing the risk of urinary tract infections.

How to Diagnose Cystinuria?

The methods used to diagnose cystinuria are divided into two categories, and they are listed below:

1. Laboratory Tests: Following tests are performed to check the urine.

• Urinalysis: It is a test of urine that is done to detect changes in the appearance and content of urine and if any disorders are present related to the urinary system. The doctor asks the patient to collect urine in a container, usually in the morning. The following changes will be noted in the urine of cystinuria patients:

  • The urine smells like rotten eggs.

  • On microscopic examination, hexagonal crystals are seen, suggestive of the presence of cystine in the urine.

  • Sodium Cyanide - Nitroprusside Test: In this method, sodium nitroprusside is added to the urine sample, and it is observed that within five to ten minutes, urine turns purple suggestive of cystinuria.

• 24-Hour Urine Test: In this method, urine is collected for an entire day (24 hours), and the report of this test after analysis is sent to the doctor. This test aims to measure cystine levels. If the cysteine levels are 250 milligrams per liter (mg/L) or above, the patient is at risk of developing a stone.

2. Imaging Tests: Following imaging tests are done to make a definite diagnosis:

• Ultrasound is an imaging test to detect the presence of stones, usually in children and pregnant females. Stones larger than 4 millimeters are generally noticed on the ultrasound, but it cannot be said explicitly that they are cystine stones. It is because the ultrasound does not give any idea about the composition of stones.

• Computed Tomography (CT Scans): In this test, X-ray images of the internal organs of the body are obtained to get an idea about the presence of stones within the kidneys. It is the "gold standard" for the diagnosis of stones.

• Intravenous Pyelogram: It is an imaging test in which a particular type of material is injected into the veins. As a result, X-ray images of the kidney, ureter, and urinary bladder are obtained, giving the doctor an idea if any blood is present in the urine or any other abnormality.

What Are the Treatment Options for Cystinuria?

Treatment depends upon how severe the condition is, and it is not necessary for the patient to undergo surgery in all cases; lifestyle changes and medications also provide relief. Some of the treatment options are listed below:

1. Changes in the Diet: The following changes are required in the diet if the patient is diagnosed with cystinuria:

• Limiting the salt intake to less than 2 grams per day provides excellent help and does not allow the formation of stones.

• Animal food like chicken, beef, fish, and milk contains proteins in large amounts, leading to the crystallization of stones and making the urine acidic. Therefore, it is important to reduce the consumption of these food items.

• It is highly recommended that the patient drinks a sufficient quantity of water to increase urine concentration and prevent the formation of stones.

• Orange juice and lemon water should be consumed as much as possible as they contain citrates, which inhibit the formation of stones.

1. The pH of urine: It is vital to maintain a pH of urine above seven (alkaline) because, at alkaline pH, cystine gets dissolved in the urine rapidly instead of getting collected in the form of stones. Drugs like Acetazolamide and Potassium citrate work to increase the pH of urine.

2. Medicines: Certain medications like D-Penicillamine and Alpha-mercapto propionyl glycine work to dissolve the stones within the urine by combining them, thereby allowing urine flow.

3. Surgical Methods: If the pain is unbearable and the stones are large enough to block the urinary flow, the following surgical procedures need to be followed:

• Extracorporeal Shock Wave Lithotripsy (ESWL): In this procedure, stones are broken down into smaller pieces with the help of shock waves sent to the body so that they quickly pass through the urine.

• Percutaneous Nephrolithotomy: If the stone has become very large and the pain is unbearable, an incision is made in the back region to remove the stones, which are usually greater than 2 centimeters. A tube is passed through the incision with a telescope to remove the stone directly or break it down into smaller fragments for removal.

What Are the Complications of Cystinuria?

The presence of stones can cause permanent damage to the kidneys and urinary bladder because they obstruct the flow of urine from the body, thereby interfering with the kidneys and bladder functions. The presence of urine within the body for a prolonged period increases the risk of urinary tract infection. In addition, if present within the ureter (tubes that carry the urine from the kidneys to the bladder), the stones cause their blockage, increasing pressure on the kidneys. This results in swelling of the kidneys.

Conclusion:

Cystinuria is an inherited condition and is present in the individual throughout his life, but it does not cause any damage to other organs of the body. It is commonly seen at a young age. The patient need not be worried about the condition as it is not a life-threatening disease and rarely causes permanent damage to the kidneys. However, it is important to consult the doctor if any pain or urinary obstruction symptoms are noted to manage the condition effectively. The patient lives a healthy life ahead if the condition is treated on time.