From the Guidelines
Elevated uric acid levels are primarily caused by a combination of dietary factors, medical conditions, and certain medications, with chronic kidney disease, overweight, and excess alcohol consumption being key risk factors, as identified in the 2018 updated European League Against Rheumatism evidence-based recommendations for the diagnosis of gout 1. The main reasons for uric acid elevation can be broken down into several categories:
- Dietary factors: consumption of excess alcohol, non-diet sodas, meat, and shellfish, which are high in purines, can lead to increased uric acid production 1.
- Medical conditions: chronic kidney disease (CKD) impairs the excretion of uric acid, while overweight and obesity can increase uric acid production 1.
- Medications: diuretics, low-dose aspirin, cyclosporine, and tacrolimus can raise uric acid levels by reducing its excretion or increasing its production 1. It is essential to identify and address these modifiable risk factors, as they can contribute to the development of gout and other cardiovascular comorbidities, and managing them can help reduce uric acid levels and prevent related complications 1. Key considerations for managing hyperuricemia include:
- Gradual weight loss in obese patients to lower serum uric acid (SUA) levels and reduce the likelihood of gout flare 1.
- Lifestyle modifications, such as increased fluid intake, dietary changes, and reduced alcohol consumption, to prevent cardiovascular disease and kidney disease 1.
- Medications like allopurinol or febuxostat may be necessary to reduce uric acid production or enhance excretion, depending on the underlying cause of hyperuricemia.
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. The reason for uric acid elevation can be:
- Primary hyperuricemia, as in gout
- Secondary hyperuricemia due to diseases such as:
- Acute and chronic leukemia
- Polycythemia vera
- Multiple myeloma
- Psoriasis
- Use of diuretic agents
- Renal dialysis
- Renal damage
- Starvation or reducing diets
- Treatment of neoplastic disease with rapid resolution of tissue masses 2
From the Research
Uric Acid Elevation
The elevation of uric acid levels can be caused by various factors, including:
- Renal reabsorption and the loss of uricase activity, which leads to a higher physiological level of uric acid in humans than in other mammals 3
- Abnormal elevation of uric acid levels, which has been linked to certain diseases such as gout 3
- Deposition of monosodium urate crystals, which is the central cause of gout 4
Pathological Involvement of Hyperuricemia
Hyperuricemia, or elevated uric acid levels, has been linked to various pathological conditions, including:
- Gout, a common inflammatory arthritis caused by the deposition of monosodium urate crystals 5, 6, 7, 4
- Kidney disease, as uric acid levels can be affected by renal function 7
- Cardiovascular disease, as febuxostat, a urate-lowering therapy, has received a U.S. FDA black box warning for cardiovascular safety 6
Physiological Functions of Uric Acid
Uric acid has various physiological functions, including:
- Providing a survival advantage during evolution by maintaining a higher physiological level in humans than in other mammals 3
- Having protective potential in aging and some diseases, although the role of uric acid as a double-edged sword in humans is determined by its physiological or non-physiological levels 3