From the Guidelines
Hyperuricemia is primarily caused by an excess body burden of uric acid, which can be attributed to various factors, including diet, genetics, and certain medical conditions.
Key Factors Contributing to Hyperuricemia
- Diet: Consumption of foods high in purines, such as meat and seafood, as well as high-fructose foods and drinks, can increase uric acid levels 1.
- Genetics: Genetic polymorphisms of renal transporters of urate and other genes can affect uric acid excretion and contribute to hyperuricemia 1.
- Medical Conditions: Certain conditions, such as hypertension, diabetes mellitus, metabolic syndrome, and renal and cardiovascular diseases, are associated with hyperuricemia 1.
- Medications: Diuretics, such as thiazide and loop diuretics, can increase uric acid levels by reducing uric acid excretion 1.
Pathophysiology of Hyperuricemia
Hyperuricemia occurs when the body produces more uric acid than it can excrete, leading to an accumulation of uric acid in the blood. This can be due to increased production of uric acid, decreased excretion of uric acid, or a combination of both. The excess uric acid can then crystallize and deposit in joints and other tissues, leading to the formation of monosodium urate (MSU) crystals and the development of gout 1.
Clinical Implications
Hyperuricemia is a major risk factor for gout, and managing uric acid levels is crucial in preventing and treating gout attacks. The American College of Physicians recommends discussing the benefits, harms, costs, and individual preferences with patients before initiating urate-lowering therapy, including concomitant prophylaxis, in patients with recurrent gout attacks 1.
From the Research
Causes of Hyperuricemia
- Lower excretion of uric acid, which can be caused by higher waist circumference and BMI, leading to higher insulin resistance and leptin production 2
- Higher synthesis of uric acid, which can be caused by the de novo synthesis of purine, accelerating UA production 2
- Diet, including high intake of fructose-rich industrialized food and high alcohol intake (particularly beer) 2
- Renal handling of urate, including variations in renal urate handling, which can influence the risk of gout 3
- Massive urate overproduction, usually occurring acutely due to tumor lysis, rhabdomyolysis, or some other cause of rapid nucleic acid turnover or tissue destruction 4
Factors Associated with Hyperuricemia
- Metabolic syndrome, diabetes, hypertension, and kidney and cardiovascular diseases 3
- Gout, an increasingly common condition 3
- Kidney disease, with hyperuricemia predicting kidney disease onset and progression 3
- Cardiovascular disease, with chronic asymptomatic hyperuricemia associated with cardiovascular impairment over the long term 4
- Neurological diseases, with low uric acid levels associated with a higher prevalence and progression of some neurological diseases 5
Mechanisms of Hyperuricemia
- Inflammatory response, with monosodium urate (MSU) crystals inducing an inflammatory reaction, recognized by toll-like receptors (TLRs) 6
- Generation of free radicals, with soluble uric acid mediating the generation of free radicals and functioning as a pro-oxidant 6
- Antioxidant capacity, with uric acid contributing to > 50% of the antioxidant capacity of the blood 2