Does the management of underexcretors or overproducers of uric acid differ?

From the Guidelines

The management of under excretors and over producers of uric acid differs significantly in gout treatment, with under excretors typically treated with uricosuric agents and over producers treated with xanthine oxidase inhibitors. According to the 2012 American College of Rheumatology guidelines for management of gout, part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia 1, under excretors are treated with uricosuric agents like probenecid, which increase renal excretion of uric acid. On the other hand, over producers are preferentially treated with xanthine oxidase inhibitors such as allopurinol or febuxostat, which reduce uric acid production.

The distinction between under excretors and over producers is crucial, as uricosuric agents may increase the risk of kidney stones in over producers by increasing urinary uric acid concentration 1. Testing for 24-hour urinary uric acid excretion can help differentiate between these two mechanisms, with values >800mg in men or >750mg in women suggesting overproduction. The 2014 multinational evidence-based recommendations for the diagnosis and management of gout also support the use of allopurinol as the first line urate-lowering therapy, with alternatives including uricosurics and febuxostat 1.

Key considerations in the management of gout include:

• Maintaining adequate hydration, particularly in patients on uricosuric therapy
• Targeting a serum uric acid level below 6mg/dL for effective gout management
• Monitoring serum uric acid levels, frequency of gout attacks, and tophi size
• Using prophylaxis to prevent flare when introducing urate-lowering therapy, with options including colchicine, NSAIDs, or low-dose glucocorticoids 1.

Overall, the management of under excretors and over producers of uric acid requires a tailored approach, taking into account the individual patient's needs and characteristics, and prioritizing the reduction of serum uric acid levels to prevent gout attacks and tophi formation.

From the FDA Drug Label

The etiology of this hyperuricemia is the overproduction of uric acid in relation to the patient's ability to excrete it Allopurinol tablets reduce both the serum and urinary uric acid levels by inhibiting the formation of uric acid The action of allopurinol tablets differs from that of uricosuric agents, which lower the serum uric acid level by increasing urinary excretion of uric acid.

The management of under excretors or over producers of uric acid differs.

• Over producers of uric acid are managed with allopurinol which reduces uric acid production.
• Under excretors of uric acid are managed with uricosuric agents such as probenecid which increase uric acid excretion 2, 2, 3.

From the Research

Management of Underexcretors or Overproducers of Uric Acid

• The management of underexcretors or overproducers of uric acid differs in terms of the treatment approach and the medications used 4, 5, 6, 7, 8.
• Underexcretors of uric acid, who have primary gout, show lower uric acid clearance, fractional excretion of uric acid, and urinary uric acid to creatinine ratio than controls, indicating renal underexcretion as the main mechanism for the development of primary hyperuricemia in gout 6.
• Overproducers of uric acid, on the other hand, have increased production of uric acid, which can be due to various biochemical defects associated with primary overproduction gout 7.
• The treatment of underexcretors and overproducers of uric acid involves the use of urate-lowering therapies (ULTs) such as febuxostat, allopurinol, and lesinurad, which have been shown to be effective in achieving the target serum urate level at month 6 compared with placebo in hyperuricemic patients with gout 4.
• Febuxostat 80/120/240 mg/day has been shown to be superior to allopurinol and well tolerated for urate reduction, while lesinurad in combination with febuxostat or allopurinol is effective in urate lowering, especially for patients with inadequate response to xanthine oxidase inhibitor monotherapy 4.
• However, the choice of treatment depends on various factors, including the patient's renal function, liver function, and history of adverse reactions, and the treatment should be individualized to achieve the best therapeutic effect while minimizing the risk of adverse events 8.

Treatment Options

• Xanthine oxidase inhibitors, such as allopurinol and febuxostat, are the safest and most effective uric acid lowering drugs for the management of chronic hyperuricemia 5.
• Uricosuric agents, such as lesinurad, can be used in combination with xanthine oxidase inhibitors to achieve better urate lowering, especially in patients with inadequate response to monotherapy 4, 5.
• Benzbromarone is another uricosuric agent that can be used to treat gout patients, especially those with renal impairment 8.
• Peglotidase is an emerging drug that has been shown to be effective in the acute management of refractory hyperuricemia, but its use is supported by a relatively small number of clinical trials, and further research is needed to deepen its efficacy and safety profile 5.