Hyperuricemia: Clinical Understanding, Risks, and the Need for Early Awareness

Hyperuricemia is defined as a persistent elevation of serum uric acid above normal physiological limits and represents a biochemical state with significant long-term implications. Although many patients remain asymptomatic for years, sustained high uric acid levels can eventually lead to gout, nephrolithiasis, and contribute to broader metabolic and cardiovascular disturbances.

Uric acid is the end product of purine metabolism, and its balance depends on the interplay between production and renal excretion. In clinical practice, reduced renal excretion accounts for the majority of hyperuricemia cases, while overproduction is less frequent but clinically important.

Reduced excretion occurs in chronic kidney disease, dehydration, metabolic acidosis, and in patients on medications such as diuretics, cyclosporine, tacrolimus, and low-dose aspirin. Overproduction is encountered in conditions with high cell turnover (psoriasis, hematologic malignancies), excessive purine intake, and hereditary enzymatic abnormalities. Alcohol—particularly beer and spirits—contributes by generating lactate, which competes with urate for excretion.

While elevated uric acid alone may not produce symptoms, its downstream effects are well established:

Monosodium urate crystal deposition within synovial fluid induces acute inflammatory arthritis characterized by sudden, severe pain, swelling, and erythema—classically affecting the first metatarsophalangeal joint. Chronic, uncontrolled disease leads to tophaceous deposits and joint deformities.

Uric acid stones occur preferentially in acidic urine and may present with flank pain, hematuria, or recurrent urinary tract symptoms. Chronic urate nephropathy develops from prolonged crystal deposition within the renal interstitium and may contribute to progressive renal impairment.

Current evidence links hyperuricemia with hypertension, insulin resistance, and an increased cardiometabolic burden. Though causality continues to be explored, the association underscores the importance of early intervention.

Assessment includes fasting serum uric acid levels, renal function evaluation, urine pH, and imaging when nephrolithiasis is suspected. In the setting of acute arthritis, synovial fluid analysis demonstrating needle-shaped, negatively birefringent crystals confirms gout.

These remain foundational in both prevention and treatment:

Adequate hydration.

Weight reduction and improving metabolic health.

Avoiding high-fructose beverages.

Indicated for recurrent gout attacks, tophi, uric acid stones, CKD, or markedly elevated urate levels.

Xanthine Oxidase Inhibitors: Allopurinol and febuxostat reduce uric acid synthesis and remain first-line.

Uricosurics: Probenecid enhances renal urate excretion and is suitable for under-excretors with preserved renal function.

Biologic Therapy: Pegloticase is reserved for refractory, severe disease.

The therapeutic goal is a target serum uric acid level below 6 mg/dL, and below 5 mg/dL for tophaceous disease.

Hyperuricemia often produces no symptoms but carries significant long-term risks.

Early monitoring is essential, particularly in patients with CKD, metabolic syndrome, hypertension, or those on chronic diuretics.

Diet and hydration are powerful modifiers of serum uric acid levels.

Untreated high uric acid can lead to gout, kidney stones, and chronic renal damage.

Prompt evaluation of joint pain or swelling can prevent complications.

Long-term control requires adherence to lifestyle measures and, when indicated, urate-lowering therapy.