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| Cystinuria | |
|---|---|
| Other names | Cystinuria-lysinuria[1] |
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| These cystine crystals were found in the urine sediment of a male dog who presented to the veterinary hospital with a history of chronic stranguria (straining to urinate) and pollakiuria (abnormally increased frequency of urination). A cystotomy was performed and numerous cystoliths (bladder stones) were removed. 5μm scale bar; 1,000x magnification; focus-stacked image consisting of 12 exposures; courtesy of Lance Wheeler. | |
| Specialty | Endocrinology  |
Cystinuria is an inheritedautosomal recessive disease[1] characterized by highconcentrations of the amino acidcystine in theurine, leading to the formation of cystinestones in thekidneys,ureters, andbladder. It is a type ofaminoaciduria. "Cystine", not "cysteine," is implicated in this disease; the former is adimer of the latter.
Cystinuria is a cause of recurrent kidney stones. It is a disease involving the defective transepithelial transport of cystine and dibasic amino acids in the kidney and intestine and is one of many causes of kidney stones. If not treated properly, the disease could cause serious damage to the kidneys and surrounding organs, and in some rare cases death. The stones may be identified by a positivenitroprusside cyanide test. The crystals are usually hexagonal, translucent, and white. Upon removal, the stones may be pink or yellow, but later they turn greenish due to exposure to air. Cystinuria is usually asymptomatic when no stone is formed. However, once a stone is formed, signs and symptoms can occur:[1]
People with cystinuria pass stones monthly, weekly, or daily, and need ongoing care. Cystinurics have an increased risk forchronic kidney disease[2][3] and since kidney damage or poor function is often present in people with cystinuria,nonsteroidal anti-inflammatory drugs (NSAIDs) or over the counter (OTC) medications should be used with caution.
Cystine stones are often difficult to detect using plain X-rays.Computed tomography orultrasound may be used instead for imaging.[4]
Urine odor in cystinuria smells of rotten eggs due to the increase in cystine.[5]
Cystinuria is an autosomal recessive disease,[1] which means that the defective gene responsible for the disease is located on anautosome, and two copies of the defective gene (one inherited from each parent) are required to be born with the disease. The parents of an individual with an autosomal recessive disease bothcarry one copy of the defective gene, but usually do not experience any signs or symptoms of the disease. Although signs and symptoms are rare, there are some directly and indirectly associated with cystinuria. These signs and symptoms consist of 1) hematuria- blood in the urine, 2) flank pain – pain in the side due to kidney pain, 3) renal colic – intense, cramping pain due to stones in the urinary tract, 4) obstructive uropathy- urinary tract disease due to obstruction, and 5) urinary tract infections.[citation needed]
Cystinuria is caused by mutations in theSLC3A1 andSLC7A9 genes. These defects prevent proper reabsorption of basic, or positively charged, amino acids:cystine,lysine,ornithine,arginine.[6] Under normal circumstances, this protein allows certain amino acids, including cystine, to be reabsorbed into the blood from the filtered fluid that will become urine. Mutations in either of these genes disrupt the ability of this transporter protein to reabsorb these amino acids, allowing them to become concentrated in the urine. As the levels of cystine in the urine increase, it formscystine crystals, resulting in kidney stones. Cystine crystals form hexagonal-shaped crystals that can be viewed upon microscopic analysis of the urine. The other amino acids that are not reabsorbed do not create crystals in urine.[citation needed]
The overallprevalence of cystinuria is approximately 1 in 7,000 neonates (from 1 in 2,500 neonates inLibyanJews to 1 in 100,000 amongSwedes).[7]
Cystinuria is characterized by the inadequate reabsorption of cystine in the proximal convoluted tubules after the filtering of the amino acids by the kidney's glomeruli, thus resulting in an excessive concentration of thisamino acid in the urine. Cystine mayprecipitate out of theurine, if the urine isneutral or acidic, and formcrystals or stones in the kidneys, ureters, or bladder. It is one of severalinborn errors of metabolism included in theGarrod's tetrad. The disease is attributed to a deficiency in the transport and metabolism of amino acids.[citation needed]
Regular X-rays often fail to show the cystine stones, however, they can be visualized in the diagnostic procedure that is calledintravenous pyelogram (IVP). Stones may show up on XR with a fuzzy gray appearance. They are radioopaque due to sulfur content, though more difficult to visualize than calcium oxalate stones.[citation needed]
Initial treatment is with adequate hydration, alkalization of the urine with citrate supplementation or acetazolamide, and dietary modification to reduce salt and protein intake (especiallymethionine). If this fails then patients are usually started onchelation therapy with an agent such aspenicillamine.[8][9]Tiopronin is another agent.Once renal stones have formed, however, the first-line treatment is endoscopic laser lithotripsy. ESWL (Extracorporeal shock wave lithotripsy) is often not effective because of the hardness of the stones that do not fragment easily. Conventional open-abdominal surgery is rarely used but has proven to be an effective treatment modality for patients with more advanced forms of the disease. Adequate hydration is the foremost aim of treatment to prevent cystine stones. The goal is to increase the urine volume because the concentration of cystine in the urine is reduced which prevents cystine from precipitating from the urine and forming stones. People with cystine stones should consume 5 to 7 liters a day. The rationale behind alkalizing the urine is that cystine tends to stay in solution and causes no harm. To alkalinize the urine, sodium bicarbonate has been used. One must be careful in alkalizing their urine because it could lead to other forms of stones in the process of preventing cystine stones. Penicillamine is a drug that acts to form a complex with cystine that is 50 times more soluble than cystine itself. Percutaneous nephrolithotripsy (PNL) is performed via a port created by puncturing the kidney through the skin and enlarging the access port to 1 cm in diameter. Most of the time, cystine stones are too dense to be broken up by shock (ESWL) so PNL is needed.[citation needed]
Videos of surgery are available on various websites that show stone removal by percutaneous nephrolithotomy.[citation needed]
In February 2017, an article was published inNature Medicine entitled "Alpha lipoic acid treatment prevents cystine urolithiasis in a mouse model of cystinuria", suggesting that a high dose of the readily available antioxidant, alpha-lipoic acid at 2,700 mg/67 kg body weight daily reduced the incidence of stones. The effects were dose dependent.[10] The results are unprecedented for cystinuria.[11] A clinical trial is underway based on this mouse model.[11]
This disease is known to occur in at least fourmammalian species:humans, domesticcanines, domestic ferrets, and a wild canid, themaned wolf ofSouth America.Cystine uroliths have been demonstrated, usually in male dogs, from approximately 70 breeds including the Australian cattle dog, Australian shepherd, Basenji, Basset, Bullmastiff, Chihuahua, Scottish deerhound, Scottish terrier, Staffordshire terrier, Welsh corgi, andNewfoundland dogs.[12]