What is Cystinuria?

What is Cystinuria?

Cystinuria is an autosomal-recessive disorder that alters how the kidneys reabsorbs with amino acids. The resultant improper reabsorption causes a loss of large amounts of amino acids into the urine, allowing the urine to become concentrated with amino acids. Cystine, in large concentrations, start to form the crystals that clump to form the kidney stones, a prominent characteristic of Cystinuria. As one of the most common genetic disorders in amino acid transport, approximately 1 in 10,000 people are affected by cystinuria with most of those symptomatic for the kidney stones being under the age of 40.

Genetics

Being autosomal recessive, the faulty gene that causes cystinuria is always inherited from both parents, which implies that both the parents must be carrying the faulty gene. Due to it being recessive, the parents could appear either as symptomatic for cystinuria or asymptomatic carriers. Likewise, affected individuals will pass down the faulty gene to their children.

Symptoms and diagnostic tests

Cystinurics would often experience symptoms such as:

• Hematuria (a.k.a. Bloody urine)
• Nausea
• Vomiting
• Chronic pain
• Pain in abdomen/back

Serious complications like kidney infection, uretal obstruction or even kidney failure can occur if cystinuria is left untreated. Tests such as an abdominal CT scan, MRI, Intravenous pyelogram (IVP) or a 24-hour urine collection can be done to detect kidney stones for early treatment.

Biochemistry behind Cystinuria

Cystinuria is caused by the mutations in the SLC3A1 and SLC7A9 genes. The SLC3A1 and SLC7A9 genes code for two different subunits that associate with each other to form the active transporter for cystine. The mutation then causes the disruption of the transporter protein from reabsorbing the amino acid from the filtered fluid in the proximal renal tubules of the kidneys. Cystine in large concentrations then forms crystals which clump to form the kidney stones.

Cures/Prevention

While there are no direct ways of curing cystinuria due to its genetic origin, there is still treatment to prevent the formation of kidney stones as much possible in a variety of ways.

Hydration is one of the oldest and most effective way to prevent cystine crystal formation. This works as it tries to dilute the urine as much as possible to lower the overall concentrations of cystine in the urine which directly prevents the formation of the cystine crystal. Suggested intake volumes are around 4 to about 4.5 litres of alkalizing beverages that are rich in bicarbonate and low in sodium like mineral water or citric juices. Lowering sodium intake of the patient's diet also has a similar effect.

Alkalinization of the urine can also help prevent the precipitation of the cystine crystals and can also help dissolve existing cystine crystals due to the fact that the solubility of cystine crystals greatly increases at higher pH levels. A typical way of doing this is by prescribing Potassium citrate to the patient at a dose that would maintain a urine pH of about 7.5. However, constant monitoring of urinary pH is required with any form of alkalinization therapy.

Chelating agents such as Penicillamine or Alpha-mercaptopropionylglycine are able to dissociate the cystine molecules into products that are more soluble, preventing formation of crystals and dissolving crystals to a certain extent. Despite its effectiveness, the chelating agents are used only if alkalinization and hydration fails due to the adverse side effects like gastrointestinal intolerance, arthralgia or rash that can occur due to intake of the chelating agents.

If renal stones that are too large to be dissolved feasibly are detected via the various diagnostic tests, a non-invasive procedure known as an extracorporeal shock wave lithotripsy (ESWL) can be performed. This technique uses focused, high-intensity acoustic pulses to crush stones up to 1.5 cm in diameter in the kidney into smaller fragments that can then be passed out through the urine, preventing further obstruction.

However due to uncontrolled growth, some stones are able to grow to the point at which they are unlikely to dissolve or break and pose a more serious risk. In this case, its is normally suggested to remove the kidney stones from the patient through invasive surgery.

Percutaneous nephrolithotomy (PCNL) is the standard invasive surgical procedure for the removal of cystine calculi that are larger than 1 cm in diameter. This procedure is normally used upon failure of fragmenting the stones via ESWL due to the fact that complications may arise by doing this procedure such as, injury to the colon, renal blood vessels or sepsis. If even percutaneous nephrolithotomy fails, open surgery to remove the stones via laser or electrohydraulic lithotripsy can be done.