What are the implications of hyperuricemia (elevated uric acid)?

From the Guidelines

Elevated uric acid levels, or hyperuricemia, should be addressed through both lifestyle modifications and medication if symptomatic or persistently high, with the goal of reducing morbidity, mortality, and improving quality of life.

Lifestyle Modifications

To manage hyperuricemia, start by reducing purine-rich foods like red meat, seafood, and alcohol (especially beer) 1. Increase water intake to at least 2-3 liters daily to help flush uric acid through the kidneys. Weight loss if overweight, limiting high-fructose corn syrup, and managing conditions like diabetes and hypertension are also important.

Medication

For medication, allopurinol is typically the first-line treatment, starting at 100mg daily and gradually increasing to 300-600mg daily as needed to reach target uric acid levels below 6 mg/dL 1. Febuxostat (40-80mg daily) is an alternative for those who cannot tolerate allopurinol. During initial treatment, colchicine (0.6mg once or twice daily) may be prescribed to prevent gout flares. For acute gout attacks, NSAIDs like naproxen or indomethacin, colchicine, or corticosteroids can provide relief.

Monitoring and Long-term Management

Uric acid-lowering therapy should be continued long-term, as stopping treatment typically results in the return of elevated levels and potential gout attacks. Regular monitoring of uric acid levels and kidney function is necessary to ensure treatment effectiveness and safety.

Some key points to consider:

• The 2012 American College of Rheumatology guidelines recommend that serum urate should be lowered in gout patients to achieve, at a minimum, a serum urate below 6 mg/dL 1.
• Allopurinol dosing should be adjusted in patients with renal impairment, and rapid, PCR-based HLA-B5801 screening should be considered as a risk management component in sub-populations where both HLA-B5801 allele frequency is elevated and the HLA-B*5801 positive subjects have a very high hazard ratio for severe allopurinol hypersensitivity reaction 1.
• Uricosuric therapy, such as probenecid, can be a valuable component of comprehensive urate-lowering strategies, but its use should be carefully considered due to potential risks and limitations 1.

From the FDA Drug Label

Hyperuricemia may be primary, as in gout, or secondary to diseases such as acute and chronic leukemia, polycythemia vera, multiple myeloma, and psoriasis It may occur with the use of diuretic agents, during renal dialysis, in the presence of renal damage, during starvation or reducing diets, and in the treatment of neoplastic disease where rapid resolution of tissue masses may occur. Gout is a metabolic disorder which is characterized by hyperuricemia and resultant deposition of monosodium urate in the tissues, particularly the joints and kidneys. The etiology of this hyperuricemia is the overproduction of uric acid in relation to the patient's ability to excrete it If progressive deposition of urates is to be arrested or reversed, it is necessary to reduce the serum uric acid level below the saturation point to suppress urate precipitation.

The implications of hyperuricemia (elevated uric acid) are:

• Gout: a metabolic disorder characterized by hyperuricemia and deposition of monosodium urate in tissues, particularly joints and kidneys
• Deposition of urates: in tissues, which can lead to joint and kidney damage if not treated
• Increased risk: of diseases such as acute and chronic leukemia, polycythemia vera, multiple myeloma, and psoriasis
• Kidney damage: hyperuricemia can occur in the presence of renal damage, and reducing serum uric acid levels is necessary to prevent further damage
• Nephrolithiasis: although not directly mentioned as a common problem, the increased xanthine and hypoxanthine in the urine have not been accompanied by problems of nephrolithiasis, except in rare cases of xanthine crystalluria 2
• Gout flares: may occur after initiation of treatment, due to changing serum uric acid levels resulting in mobilization of urate from tissue deposits 3

Key points:

• Hyperuricemia can lead to gout and deposition of urates in tissues
• Reducing serum uric acid levels is necessary to prevent further damage
• Hyperuricemia can occur in various diseases and conditions, including kidney damage and neoplastic diseases
• Treatment of hyperuricemia should be carefully managed to prevent gout flares and other complications 2, 3

From the Research

Implications of Hyperuricemia

The implications of hyperuricemia, or elevated uric acid levels, are significant and can have a major impact on various aspects of health. Some of the key implications include:

• Increased risk of chronic kidney disease (CKD) progression 4, 5, 6
• Rapid progression of renal function in patients with CKD 7
• Increased risk of cardiovascular disease 8
• Potential for kidney damage, although the exact cutoff uric acid value associated with this risk is not clear 4

Treatment and Management

Treatment and management of hyperuricemia are crucial to mitigate its implications. Some of the key points to consider include:

• Lifestyle interventions such as exercise, weight reduction, low consumption of purine-rich meat, and avoiding high fructose intake are recommended for all hyperuricemic patients 4
• Urate-lowering therapy (ULT) may be effective in slowing down the progression of CKD, although more research is needed to confirm this 5, 6, 8
• Febuxostat may be a more effective and safer alternative to allopurinol for patients with hyperuricemia and CKD 5, 8, 7
• Routine measurement of serum urate levels is recommended for patients with CKD, and ULT may be considered for those with hyperuricemia and evidence of deteriorating renal function 6

Renoprotective Effects

The renoprotective effects of different treatments for hyperuricemia are also an important consideration. Some of the key points to consider include:

• Febuxostat may have renoprotective effects compared to allopurinol, although more research is needed to confirm this 5, 7
• Febuxostat may be more effective in reducing serum uric acid levels and slowing down the progression of renal disease compared to allopurinol 5, 7
• The changes in estimated glomerular filtration rate (eGFR) and albuminuria levels may be significant between febuxostat and allopurinol groups 7