Cystinuria

Definition

Cystinuria is an inborn error of amino acid transport that results in the defective absorption by the kidneys of the amino acid called cystine. The name means "cystine in the urine."

Description

Cystine is an amino acid. Amino acids are organic compounds needed by the body to make proteins and for many normal functions. When the kidneys don't absorb cystine, this compound builds up in the urine. When the amount of cystine in the urine exceeds its solubility (the greatest amount that can be dissolved), crystals form. As the amount of cystine continues to increase in the urine, the number of crystals also increases. When very large numbers of cystine crystals form, they clump together into what is called a stone.

Causes & symptoms

Cystinuria is a rare disease that occurs when people inherit an abnormal gene from their parents. This disease occurs in differing degrees of severity in people who have inherited either one or two abnormal genes. Humans have two copies of each gene. When both are abnormal, the condition is called homozygous for the disease. When one copy is normal and the other is abnormal, the condition is called heterozygous for the disease. Persons with one abnormal gene can have a milder form of cystinuria that rarely results in the formation of stones.

Severe cystinuria occurs when people are homozygous for the disease. For these individuals, the kidneys may excrete as much as 30 times the normal amount of cystine. Research has shown that this condition is caused by mutations on chromosome number two (humans have 23 pairs of chromosomes).

A person who has inherited cystinuria may have other abnormal bodily functions. In addition to excess levels of the amino acid cystine, high amounts of the amino acids lysine, arginine, and ornithine are found in the urine. This condition indicates that these amino acids are not being reabsorbed by the body.

When excess cystine crystals clump together to form a stone, the stone can block portions of the interior of the kidney or the tube (the ureter) that connects the kidney to the urinary bladder. These cystine stones can be painful, and depending upon where the stone becomes trapped, the pain can be felt in the lower back or the abdomen. Nausea and vomiting can also occur, and patients may sometimes feel the need to urinate often. Cystine stones can also cause blood in the urine. When the urinary tract is blocked by a stone, urinary tract infections or kidney failure may result.

Diagnosis

Small stones (called "silent") often do not cause any symptoms, although they can be detected by an x ray. Large stones are often painful and easily noticed by the patient. Blood in the urine can also mean that a stone has formed.

When the urine contains extremely high amounts of cystine, yellow-brown hexagonal crystals are visible when a sample is examined under the microscope. Urine samples can also be mixed with chemicals that change color when high levels of cystine are present. When the compound nitroprusside is added to urine that has been made alkaline by the addition of ammonia, the urine specimen turns red if it contains excess cystine.

Treatment

No treatment can decrease cystine excretion. The best treatment for cystinuria is to prevent stones from forming. Stones can be prevented by drinking enough liquid each day (about 5-7 qts) to produce at least 8 pts of urine, thus keeping the concentration of cystine in the urine low. Because a person doesn't drink throughout the night, less urine is produced and the likelihood of stone formation increases. This risk can be minimized by drinking water or other liquids just before going to bed.

Drug treatments

In addition to drinking large amounts of fluids, it is helpful to make the urine more alkaline. Cystine dissolves more easily in alkaline urine. To increase urine alkalinity, a person may take sodium bicarbonate and acetazolamide. Penicillamine, a drug that increases the solubility of cystine, may be prescribed for patients who do not respond well to other therapies. This drug must be used with caution, however, because it can cause serious side effects or allergic reactions. For those unable to take penicillamine, another drug, alpha-mercaptopropionylglycine (Thiola), may be prescribed.

Surgical treatments

Most stones can be removed from the body by normal urination, helped by drinking large amounts of water. Large stones that cannot be passed this way must be removed by surgical procedures.

Large stones can be surgically removed by having a device called a uretoscope placed into the urethra, up through the bladder and into the ureter, where the trapped stone can be seen and removed. Another method involves using sound-wave energy aimed from outside the body to break the large stone into small pieces that can be passed by urination. This external technique is called extracorporeal shock-wave lithotripsy (ESWL).

For large stones in the kidney, a procedure called percutaneous nephrolithomy may be used. In this procedure, the surgeon makes a small incision in the back over the kidney. An instrument called a nephroscope is inserted through the incision into the kidney. The surgeon uses the nephroscope to locate and remove the stone. If the stone is very large, it may be broken up into smaller pieces by an ultrasonic or other kind of probe before removal.

Prognosis

As many as 50% of patients who have had surgical treatment for a kidney stone will have another stone within five years if no medicines are used to treat this condition.

Prevention

Cystinuria is a genetic disorder that currently cannot be prevented.

Key Terms

Alkaline

A solution is considered alkaline if it contains fewer hydrogen atoms than pure water.

Amino acid

An organic compound made of an amino group (containing nitrogen and hydrogen) and a carbolic acid group. Amino acids are an essential part of protein molecules.

Nephroscope

An instrument made of a light source in a tube. The tube is inserted into the kidney through an incision in the back and used to locate kidney stones. The stones are broken up with high frequency sound waves and removed by suction through the scope.

Nitroprusside

A compound that is used in laboratory tests to identify large amounts of cystine in urine samples.

Uretoscope

A tube-shaped device inserted into the body through the urinary system that allows objects to be both seen and grasped for removal.

Further Reading

For Your Information

Books

• Elsas, Louis S., Nicola Longo, and Leon E. Rosenberg. "Inherited Defects of Membrane Transport." In Harrison's Principles of Internal Medicine, edited by Anthony S. Fauci, et al. New York: McGraw-Hill, 1998.
• "Kidney Stones in Adults." In Kidney and Urinary Tract Diseases and Disorders Sourcebook, edited by Linda M. Ross. Detroit: Omnigraphics, 1997.
• Presti, Joseph C., Jr., Marshall L. Stoller, and Peter R. Carroll. "Urology." In Current Medical Diagnosis and Treatment, edited by Lawrence M. Tierney, Jr., et al. Stamford: Appleton and Lange, 1996.

  Organizations

• Cystinuria Support Network. 21001 NE 36th Street, Redmond, WA 98053. (206) 868-2996.
• National Kidney Foundation. 30 East 33rd Street, New York, NY 10016. (800) 622-9010.

Gale Encyclopedia of Medicine. Gale Research, 1999.