What is Cystinuria?

Cystinuria is a type of inherited autosomal recessive metabolic disorder [1] characterized by the formation and buildup of cystine stones or crystals in the kidneys, bladder and ureter.


Cystinuria Epidemiology

It affects one in every 29,000 individuals and has a greater prevalence in white people. Almost one out of every 2500 Libyan Jews is affected by it. Men are more prone to develop this disorder. It is more severe in males and has an early age of onset. Although no age predilection is associated with this condition, it is mostly observed in the 2nd or 3rd decade of life.

Cystinuria Causes

Cystinuria occurs due to genetic abnormalities, or mutations in the SLC7A9 and SLC3A1 genes [2]which encode two portions of a transporter protein that is primarily manufactured in the kidneys. Defects in these genes prevent adequate reabsorption of the basic or the positively charged amino acids, such as:

  • Ornithine
  • Lysine
  • Arginine

This protein usually promotes reabsorption of certain amino acids, such as cystine, into the bloodstream from filtered fluids that will turn to urine. Mutations in these genes disturb the ability of this protein to reabsorb the amino acids, thereby allowing them to accumulate in the urine. With increasing levels of cystine (amino acid) in the urine, the stones or crystals associated with cystinuria are formed and get accumulated in the kidney.

The parents of cystinuria patients are heterozygotes, with one normal and another defective gene. Children of parents, one having the disease and another only acting as a carrier, have a 50% risk of suffering from cystinuria. The risk of being a carrier is also 50%.

Cystinuria Symptoms

Cystinuria is a major factor responsible for persistent kidney stones. If left untreated, serious harm can occur to the kidneys as well as the surrounding organs and death may occur. It is normally asymptomatic in the absence of stones. If the stone formation gets to a critical stage, it can be manifested with certain symptoms like:

  • Nausea
  • Vomiting
  • Renal colic
  • Hematuria
  • Depression
  • Chronic pain
  • Ureteric colic
  • Blood in urine
  • Bilateral calculi
  • Tiredness and fatigue
  • Dull ache or a “colicky” pain
  • Infective syndromes such as Pyelonephritis
  • Obstructive syndromes such as Hydronephrosis
  • Flank pain or severe painful sensations felt in the back or side, pelvis, genitals, groin, or between back and upper abdomen

Patients may also experience:

  • Acute chronic pain in either or both kidneys, due to scars left by the jagged or rough edges of the stones
  • Severe, constant pain caused by damage due to various stone removal surgeries, calling for medical intervention
  • Intense pain, caused by passing of stones, demanding emergency medical assistance

Cystinuria Diagnosis

Diagnostic tests include:

  • Urinalysis
  • 24-hour urine collection
  • Nitroprusside cyanide test
  • Intravenous pyelogram (IVP)
  • Amino acid chromatography
  • Abdominal MRIs, CT scans, or ultrasounds
  • Genetic analysis for determining the mutation responsible for the disease
  • Blood tests; routine hemogram evaluation along with urea, blood sugar and creatinine

Cystine stones often go undetected on most ultrasounds, CT scans and X rays and need a trained eye to be spotted.

Cystinuria Differential Diagnosis

The symptoms of cystinuria should be told apart from those of other disorders, such as:

  • Hyperoxaluria
  • Wilson Disease
  • 2p21 deletion syndrome
  • Hartnup disease, involving absorption of neutral amino acids
  • Hypotonia-cystinuria syndrome (HCS)
  • Atypical Hypotonia-cystinuria syndrome

Cystinuria Treatment

Treatment mainly aims to relieve the symptoms of this disease and prevent the formation of more stones. Patients with severe symptoms should be hospitalized.

Initial treatment involves adequate hydration. At least 6 to 8 glasses of water per day should be the norm during treatment. In some instances, intravenous fluids might be required.

Later-stage treatment may include:

  • Painkillers
  • Alkalization of urine, using acetazolamide or citrate supplementation
  • Dietary modification, to reduce stone formation
  • Chelation therapy, involving curative agents like Penicillamin

The smaller stones generally pass through urine but the larger stones might need additional treatments.

Other possible medications include:

  • Potassium citrate
  • Sodium bicarbonate
  • Potassium bicarbonate
  • Angiotensin-converting enzyme (ACE) inhibitors (Captopril)
  • Reducing agents (Alpha-mercaptopropionylglycine)

Once the formation of renal stones has been confirmed, the following measures might be taken to remove them:

  • Open surgery
  • Multimodal therapy
  • Extracorporeal shock wave lithotripsy (ESWL)
  • Retrograde endoscopic lithotripsy and extraction
  • Percutaneous nephrostomy for chemical dissolution
  • Percutaneous nephrolithotomy or nephrostolithotomy
  • Ureteroscopy; this is mostly used for the stones formed in lower urinary tract

Both conventional open-abdominal surgery and endoscopic surgery have proven effective in treating patients with more progressed forms of the disease. If a patient receives the organ from a donor not having the disorder during a kidney transplant, he or she would have a normally functioning kidney.  Unfortunately, transplantation has long-term risks and is hence opted for only in acute cases.

Women suffering from cystinuria, and planning to have children, should talk with genetic counselors to manage the condition before pregnancy.

Cystinuria Diet

As Cystine is created during metabolism of methionine, patients should stick to a low- methionine diet. Dietary methionine should be kept at 1 g/d. As many patients do not easily accept a full vegetarian diet, dieticians usually prescribe a well-balanced, mixed and low-protein diet (0.8 g protein/kg body weight/d) for proper nutrition.

The following dietary recommendations should be followed:

  • Avoidance of processed foods rich in NaCl (sodium chloride).
  • Minimum intake of protein-rich foods like fish, meat, sausages, cheese, eggs and soybeans.
  • Enough consumption of low-protein eatables like vegetables, fruits, salads and cereals
  • Very limited intake of canned foods, pickled foods, smoked foods and additional dietary salt.
  • Increase in dietary fiber intake.

Cystinuria Complications

Severe or progressed cases of the disease can cause the following complications:

  • Hypertension
  • Nephrectomy
  • Kidney infections
  • Renal impairment
  • Ureteral obstruction
  • Urinary tract infection
  • End-stage renal failure
  • Chronic pyelonephritis
  • Chronic kidney disease
  • Kidney injuries from stones
  • Bladder injuries from stones
  • Mental retardation and mental illnesses

Cystinuria Prognosis

This is a chronic (lifelong) condition. The stones commonly recur after a period of time. Although appropriate treatment can ensure survival in most cases, acute renal failure or other kidney-related problems might cause death of some sufferers. Fortunately, kidney failure is highly uncommon in patients.

Cystinuria Prevention

Stone-formation can be prevented by various medications, which should be taken after proper medical consultation. Those with a history of renal or urinary stones should drink adequate amounts of water to facilitate high urine production. Regular urination can remove and prevent accumulation and enlargement of crystals and stones in the body.

Cystinuria and Cystinosis

Both cystinuria and cystinosis are recessive genetic conditions and can be confused for one another. However, the disorders are slightly different in the sense that the kidney is the initial, but not the only organ of target, in cystinosis.

Hypotonia-Cystinuria Syndrome (HCS)

It is a rare disease that involves the following health issues:

  • Cystinuria Type 1
  • Failure to thrive
  • Infantile hypotonia
  • Minor facial dysmorphism
  • Neonatal hypotonia
  • Nephrolithiasis
  • Growth retardation, caused by growth hormone deficiency

International Cystinuria Foundation

The International Cystinuria Foundation (ICF) is a non-profit organization based in Colorado which provides patients of the disease with related educational resources.

Mailing address:

International Cystinuria Foundation

PO Box: 271004

Fort Collins, CO 80527-1004

E-mail: (Matthew Lewis, President)

Cystinuria ICD-9 Code

The ICD-9 Code for cystinuria is 270.0[4].

Cystinuria in Animals

Apart from humans, cystinuria can also occur in domestic dogs (Mastiffs, Newfoundland dogs) and in South America’s maned wolf.

  1. Cystinuria (emedicine.medscape)
  2. Cystinuria (
  3. Cystinuria (Wikipedia)
  4. Image source molekuul

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