Hyperuricemia

Hyperuricemia is an elevated concentration of uric acid in the blood. It is commonly defined as a serum urate level exceeding 6.8 mg/dL (404 μmol/L) at physiologic temperature. Uric acid is the end product of purine metabolism; in humans, uricase is inactive, allowing urate to accumulate. Most cases are asymptomatic, but sustained hyperuricemia can lead to monosodium urate crystal deposition in joints and soft tissues, causing gout, and to uric acid stones in the kidney or nephropathy.

Etiology is divided into overproduction and underexcretion of uric acid. Underexcretion by the kidneys accounts for many cases; overproduction can occur with high purine intake, increased cell turnover, or certain genetic disorders. Risk factors include male sex, older age, obesity, metabolic syndrome, hypertension, diabetes, kidney disease, alcohol use, and certain medications (diuretics, low-dose aspirin, niacin, cyclosporine).

Diagnosis relies on measuring serum urate, ideally fasting. Urate levels can be influenced by recent purine intake and renal function. In gout or urate nephrolithiasis, crystal deposition may be confirmed by examination of synovial fluid showing negatively birefringent crystals. Imaging such as ultrasound or dual-energy CT may assist in detecting tophi or urate deposits in chronic disease.

Management depends on presentation. Asymptomatic hyperuricemia generally requires no specific treatment. Treatment is indicated for gout or uric acid stones, and aims to lower serum urate to below about 6 mg/dL (360 μmol/L). First-line pharmacotherapy includes xanthine oxidase inhibitors (allopurinol, febuxostat). Uricosurics (probenecid) may be used in those with good renal function. Severe or refractory cases may require pegloticase. Lifestyle modifications, such as weight management, reduced alcohol intake, and moderation of purine-rich foods, may support management.