About cystinuria

What is cystinuria?

Cystinuria facts

  • Cystinuria is a relatively common inherited disorder.
  • The disorder is due to a defect in the transport of amino acids including one called cystine.
  • Cystinuria features too much cystine in the urine.
  • Cystine is highly insoluble, precipitates out of solution and forms stones in the urine.
  • All the signs and symptoms of cystinuria are due to the stones.
  • The stones cause blood in the urine, pain, and obstruction and infection of the urinary tract.
  • The foremost aim of treatment is to prevent the formation of cystine stones.
  • Cystine stones can often be dissolved and new ones prevented by a high fluid intake.
  • People with cystinuria should understand that "for them, water is a necessary drug."

What is cystinuria?

Cystinuria is an inherited (genetic) disorder of the transport of an amino acid (a building block of protein) called cystine resulting in cystinuria (an excess of cystine in the urine) and the formation of cystine stones.

What are the symptoms for cystinuria?

Although cystinuria is a lifelong condition, symptoms typically first occur in young adults, according to a study in the European Journal of Urology. There have been rare cases in infants and adolescents. The symptoms may include:

  • blood in the urine
  • severe Pain in the side or the back, almost always on one side
  • Nausea and vomiting
  • Pain near the groin, pelvis, or abdomen

Cystinuria is asymptomatic, meaning it causes no symptoms, when there are no stones. However, the symptoms will recur each time stones form in the kidneys. The stones commonly occur more than once.

What are the causes for cystinuria?

Defects, also called mutations, in the genes SLC3A1 and SLC7A9 cause cystinuria. These genes provide the instructions for your body to make a certain transporter protein found in the kidneys. This protein normally controls the reabsorption of certain amino acids.

Amino acids are formed when the body digests and breaks down proteins. They’re used to perform a wide variety of bodily functions, so they’re important to your body and aren’t considered waste. Therefore, when these amino acids enter the kidneys, they’re normally absorbed back into the bloodstream. In people with cystinuria, the genetic defect interferes with the transporter protein’s ability to reabsorb the amino acids.

One of the amino acids — cystine — isn’t very soluble in urine. If it isn’t reabsorbed, it will accumulate inside the kidney and form crystals, or cystine stones. The rock-hard stones then get stuck in the kidneys, bladder, and ureters. This can be very painful.

What are the treatments for cystinuria?

The foremost aim of treatment is to prevent the formation of cystine stones. This goal is attained mainly by increasing the volume of urine. The reason for the increased urine volume is simple. By increasing the volume of urine, the concentration of cystine in the urine is reduced which prevents cystine from precipitating from the urine and forming stones.

Cystine stones in many patients can be dissolved and new ones prevented by a high fluid intake. What high fluid intake means in this context is an absolute minimum of 4 liters (roughly 4 quarts) per day. An intake of 5 to 7 liters a day is ideal. The fluids must be spaced out, including through the night. It has been said that people with cystinuria must realize that "for them, water is a necessary drug."

Alkalizing the urine: Another strategy that has been attempted to treat cystinuria is alkalization of the urine. The rationale is that in an alkaline (nonacidic) liquid, cystine tends to stay in solution and there it does no harm. To make the urine alkaline, sodium bicarbonate (and similar substances) have been used. This treatment is not without hazard because it can, while preventing cystine stones, lead to the formation of other types of kidney stones.

Penicillamine: For people with cystinuria in whom a consistent, conscientious high fluid intake does not succeed in halting the formation of stones, another option available is regular treatment with a drug called penicillamine. Penicillamine (Cuprimine, Depen) acts to form a complex with cystine that is 50 times more soluble than cystine itself. The side effects of penicillamine are rarely severe enough to prevent its use.

Percutaneous nephrolithotripsy (PNL): The stones in cystinuria are too dense to be broken up by shock waves produced outside the body (extracorporeal shock wave lithotripsy) as can be done with some other types of common kidney stones. Instead, a technique designed for removing dense (and very large) stones is utilized: percutaneousnephrolithotripsy (PNL).

PNL is performed via a port created by puncturing the kidney through the skin and enlarging the access port to 1 cm (about 3/8 inch) in diameter. There is no surgical incision. PNL is done under real-time live x-ray control (fluoroscopy). Because x-rays are involved, a super-specialist in radiology (an interventional radiologist) may perform this part of the procedure. The endourologist (another subspecialist) then inserts instruments via this port into the kidney to break up the stone and remove most of the debris from the stone.

What are the risk factors for cystinuria?

You’re at risk of getting cystinuria only if your parents have the specific defect in their gene that causes the disease. As well, you only get the disease if you inherit the defect from both of your parents. Cystinuria occurs in about 1 in every 10,000 people around the world, so it’s fairly rare.

Is there a cure/medications for cystinuria?

The major goal of cystinuria treatment is to lower the cystine concentration in the urine. Consuming big amounts of liquids both during the day and at night keeps the urine volume high and lowers the cystine content in the urine. Turning the urine more alkaline allows cystine to break down more easily and may help avoid the formation of stones.
1. Medication
Potassium citrate and acetazolamide are two medications that may be administered to make urine more alkaline. This treatment includes a salt and animal protein limitation. Cystinuria can now be treated with the orphan medicine alpha-mercaptopropionyl glycine, also referred as tiopronin (Thiola). This medication has been discovered to render cystine more soluble in cystinuria patients, lowering the likelihood of crystal and stone development.
The administration of d-penicillamine is another strategy to the treatment of cystinuria, albeit there are certain concerns of adverse effects with this medicine. D-penicillamine stimulates cystine production in a distinct chemical form (mixed disulfide), that is more volatile in urine and eliminated. Since tiopronin is at least as efficient and has fewer adverse effects, this medicine is rarely used anymore. Captopril is another medication that is occasionally used.
2. Surgery
Kidney/bladder surgery is sometimes required, however stones frequently recur. Small stones might escape on their own with plenty of fluids and, if necessary, pain relievers. If spontaneous stone transit fails, stones can be removed using a particular method. The stones are visible to the surgeon via a lighted optic tool placed into the urethra and passed up into the upper urinary system. The stones are then removed using specialized tools (endoscopic basket extraction). Laser treatments are also utilized to dissolve cystinuria stones in the bladder and/or kidneys. Although ultrasound waves have been employed to break up stones, they are ineffective for cystine stones.
3. Genetic Counseling
Patients and their families are advised to seek genetic counseling. Other forms of treatment include symptomatic and supportive.
Sharp pain in the lower back or side of the abdomen (renal colic),Other symptoms may include blood in the urine (hematuria), obstruction of the urinary tract, and/or infections of the urinary tract,Frequent recurrences ultimately may lead to kidney damage
Excessive amounts of undissolved cystine in the urine, as well as three chemically similar amino acids: arginine, lysine, and ornithine
Alpha-mercaptopropionyl glycine, also known as tiopronin (Thiola),D-penicillamine,Kidney and/or bladder surgery

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