(See also Introduction to Congenital Kidney Tubular Disorders and Kidney Stones.)
Cystinuria is caused by an inherited defect of the kidney tubules. The defect causes people to excrete excessive amounts of the amino acid cystine into the urine (amino acids are the building blocks for proteins). The excess cystine causes cystine kidney stones to form in the kidneys, bladder, renal pelvis (the area where urine collects and flows out of the kidney), or ureters (the long, narrow tubes that carry urine from the kidneys to the bladder). Occasionally, kidney failure develops.
There are two gene abnormalities that cause most cystinuria. The genes are recessive, so people with the disorder must have inherited two abnormal genes, one from each parent (see Figure: Non–X-Linked (Autosomal) Recessive Disorders).
Sometimes, a person who has only one abnormal gene (a carrier), such as a parent of a person who has cystinuria, may excrete larger than normal amounts of cystine into the urine but seldom enough to form cystine stones.
Boys are generally affected more than girls.
Although symptoms of cystinuria may occur in infants, they usually start between the ages of 10 years and 30 years. Often, the first symptom is intense pain caused by a spasm of the ureter where a stone becomes lodged. The stone may also become a site where bacteria collect and cause a urinary tract infection or, uncommonly, kidney failure.
A doctor tests for cystinuria when a person has recurring kidney stones. Stones that have been collected are analyzed.
Cystine crystals may be seen during a microscopic examination of the urine (urinalysis), and high cystine levels are found in the urine.
Treatment of cystinuria consists of preventing cystine stones from forming by keeping the concentration of cystine in the urine low. To keep the cystine concentration low, a person must drink enough fluids to produce at least 6 to 8½ pints (3 to 4 liters) of urine each day. During the night, however, when the person is not drinking, less urine is produced and stone formation is more likely. This risk is reduced by drinking fluids before going to bed.
Another treatment approach involves taking potassium citrate or potassium bicarbonate and sometimes acetazolamide to make the urine more alkaline (that is, less acidic) because cystine dissolves more easily in alkaline urine than in acidic urine. Efforts to increase intake of water and make the urine more alkaline can lead to abdominal bloating, making the treatment difficult for some people to tolerate. Consuming less salt and protein may help reduce the concentration of cystine in the urine.
If stones continue to form despite these measures, drugs such as penicillamine, tiopronin, or captopril may be tried. These drugs react with cystine to keep it dissolved. Penicillamine is effective in keeping the concentration of cystine in the urine low but it is toxic, so doctors give vitamin B6 (pyridoxine) supplements to people taking penicillamine. Tiopronin can be used instead of penicillamine to treat some children because it has a lower frequency of side effects. Captopril is slightly less effective than penicillamine but is less toxic. Although the treatments are usually effective, there is a fairly high risk that stones will continue to form.