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Unless high blood levels of uric acid are determined in a clinical laboratory, hyperuricemia may not cause noticeable symptoms in most people. [5] Development of gout – which is a painful, short-term disorder – is the most common consequence of hyperuricemia, which causes deposition of uric acid crystals usually in joints of the extremities, but may also induce formation of kidney stones ...
Lesinurad is used in combination with a xanthine oxidase inhibitor, such as allopurinol or febuxostat, for treating hyperuricemia (high levels of uric acid in the blood serum) associated with gout. It is approved only for patients who have not achieved target uric acid levels with a xanthine oxidase inhibitor alone. [2]
Notable direct causes of hyperuricosuria are dissolution of uric acid crystals in the kidneys or urinary bladder, and hyperuricemia. Notable indirect causes include uricosuric drugs, rapid breakdown of bodily tissues containing large quantities of DNA and RNA , and a diet high in purine .
Underexcretion of uric acid by the kidney is the primary cause of hyperuricemia in about 90% of cases, while overproduction is the cause in less than 10%. [5] About 10% of people with hyperuricemia develop gout at some point in their lifetimes. [19] The risk, however, varies depending on the degree of hyperuricemia.
The febuxostat drug labels already carry a warning and precaution about cardiovascular events because the clinical trials conducted before approval showed a higher rate of heart-related problems in patients treated with febuxostat compared to allopurinol. These problems included heart attacks, strokes, and heart-related deaths.
Loop diuretics usually have a ceiling effect whereby doses greater than a certain maximum amount will not increase the clinical effect of the drug. Also, there is a threshold minimum concentration of loop diuretics that needs to be achieved at the thick ascending limb to enable the onset of abrupt diuresis.
The NSAID diclofenac has an antiuricosuric action, which may be partly responsible for the extraordinary toxicity of this drug in vultures. [6] Pyrazinamide, a drug indicated only for treatment of tuberculosis, is a potent antiuricosuric [7] and, as a consequence, has an off-label use in the diagnosis of causes of abnormal uric acid clearance. [8]
Adults, especially the elderly, may show a more complicated presentation. [2] [6] Complications may include neurological problems and heart failure. [1] Most cases occur after infectious diarrhea due to a specific type of E. coli called O157:H7. [2] Other causes include S. pneumoniae, Shigella, Salmonella, and certain medications.