About Cystinuria
Cystinuria, an autosomal recessive disorder, is marked by impaired reabsorption and excessive urinary excretion of cystine along with the three other dibasic amino acids (lysine, ornithine, arginine). The poor urinary solubility of cystine leads to the formation of renal, uteral, and bladder stones. The prevalence of cystinuria is 1 per 10,000 to 15,000 in the general population.1
Clinical manifestations and diagnostic considerations
Signs and symptoms of cystinuria include hematuria, flank pain, renal colic, obstructive uropathy, and infection. Typically, stone formation first occurs in the teens or twenties. Quantitative urine amino acid analysis confirms the diagnosis by showing selective over-excretion of the four dibasic amino acids.1Early diagnosis is important for long-term management.2
The goal of medical management
Cystine stone prevention involves hydration therapy to reduce urinary cystine concentration below 250 mg/L, with fluid ingestion of 4L/day essential.1 It also requires maintaining an alkaline urinary pH. Ideally, a pH between 7.0 and 7.5 should be maintained for optimal stone prevention.2 If these measures fail to prevent cystine stone recurrence, Cuprimine® (penicillamine), a chelating agent, may be used as additional therapy.
Important Safety Information
CUPRIMINE® (Penicillamine) is a chelating agent used in the treatment of Wilson's disease. It is also used to reduce cystine excretion in cystinuria and to treat patients with severe active rheumatoid arthritis unresponsive to conventional therapy. Physicians planning to use penicillamine should thoroughly familiarize themselves with its toxicity, special dosage considerations and therapeutic benefits. Penicillamine should never be used casually. Each patient should remain constantly under the close supervision of the physician. Patients should be warned to report promptly any symptoms suggesting toxicity. Penicillamine can cause fetal harm when administered to a pregnant woman, therefore except for the treatment of Wilson's disease or certain patients with cystinuria, use of penicillamine during pregnancy is contraindicated. Mothers on therapy with penicillamine should not nurse their infants. Patients with a history of penicillamine-related aplastic anemia or agranulocytosis should not be restarted on penicillamine. Because of its potential for causing renal damage, penicillamine should not be administered to rheumatoid arthritis patients with a history or other evidence of renal insufficiency. The use of penicillamine has been associated with fatalities due to certain diseases such as aplastic anemia, agranulocytosis, thrombocytopenia, Goodpasture's syndrome, and myasthenia gravis. Leucopenia and thrombocytopenia have been reported to occur up to five percent of patients during penicillamine therapy. Proteinuria and/or hematuria may develop during therapy and may be warning signs of membranous glomerulopathy which can progress to t nephritic syndrome. Intrahepatic cholestasis, toxic hepatitis and obliterative bronchiolitis have been reported. Onset of new neurological symptoms has been reported, or existing neurological symptoms have worsened. Most of the various forms of pemphigus have occurred during treatment with penicillamine. Some patients may experience a drug fever sometimes accompanied with a macular cutaneous eruption. Early and late rashes have occurred. Certain patients may develop a positive antinuclear antibody (ANA) test and some of these may show a lupus erythematosus-like syndrome. Some patients may develop oral ulcerations. Hypogeusia has been reported in some patients. Penicillamine should not be used in patients who are receiving concurrently gold therapy, antimalarial or cytotoxic drugs, oxyphenbutazone or phenylbutazone.
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Reference: 1. Brewer GJ. Wilson's disease. In: Kasper DL, Fauci AS, Longo DL, eds. Harrison's Principles of Internal Medicine. New York. 16th ed. McGraw-Hill. 2005: 2313-15. 2. Biyani CS, Cartledge JJ. Cystinuria – diagnosis and management. European Urology. 2006; 175-183.
