What other damage can high uric acid levels cause besides gout?

Systemic Damage from Hyperuricemia Beyond Gout

High uric acid levels cause significant damage to the kidneys and cardiovascular system, independent of gout, and should be recognized as red flags for metabolic syndrome and cardiovascular disease. 1

Renal (Kidney) Damage

Chronic Kidney Disease Progression

• Hyperuricemia directly causes renal disease through multiple mechanisms, not merely serving as a marker of kidney dysfunction 2, 3
• Uric acid induces systemic hypertension, glomerular hypertrophy/hypertension, afferent arteriolar sclerosis, and macrophage infiltration in kidney tissue 3
• In patients with existing progressive renal disease (such as cyclosporine nephropathy or remnant kidney), elevated uric acid accelerates disease progression 3
• An increased incidence of end-stage renal disease occurs with hyperuricemia, and patients with gout show a fourfold increase in mortality due to kidney disease compared to non-gouty patients 1
• Screening for renal disease is strongly recommended based on the robust evidence of association and implications for treatment 1

Mechanisms of Renal Injury

• Uric acid causes decreased nitric oxide bioavailability, oxidative stress, and inflammasome activation in renal tissue 2
• Xanthine oxidoreductase (XOR)-mediated reactive oxygen species contribute to kidney damage 2
• Chronic interstitial nephropathy can occur from monosodium urate crystal deposition in the renal medulla, though this is currently uncommon 1

Cardiovascular Disease

Increased Cardiovascular Mortality and Morbidity

• Patients with gout have significantly increased risk of coronary heart disease-related mortality 1
• Hyperuricemia is strongly linked with cardiovascular morbidity and mortality, outcomes that are highly prevalent in kidney disease patients 4
• Multiple large epidemiologic studies demonstrate that uric acid plays an important role in initiating vascular endothelial dysfunction 5
• This endothelial dysfunction ultimately leads to stroke, coronary artery disease, and chronic kidney disease 5

Vascular Endothelial Damage

• Uric acid damages endothelial cells through multiple pathways 5
• It functions as a "pro-oxidant" once it gains entrance into cells, despite its antioxidant properties in serum 5
• The mechanisms include inflammasome activation, decreased nitric oxide bioavailability, and oxidative stress 2

Metabolic Complications

Hypertension Development

• Evidence suggests that hyperuricemia may increase the risk of developing hypertension 1
• Uric acid induces systemic hypertension through direct vascular effects 3
• Hyperuricemia and gout should be considered red flags for metabolic syndrome 1

Diabetes Risk

• Hyperuricemia may increase the risk of developing diabetes, though prospective studies specifically in gout patients are limited 1
• The association is part of the broader metabolic syndrome cluster 1

Kidney Stone Formation (Urolithiasis)

• Renal manifestations include urolithiasis, typically occurring with acidic urine pH 1
• Renal uric acid excretion should be determined in selected patients, especially those with family history of young-onset gout, onset under age 25, or with renal calculi 1

Post-Kidney Donation Considerations

• Kidney donation is associated with an increase in serum uric acid concentration, which may increase the risk for gout 1
• Donors should be informed of this modest increase and their subsequent gout risk 1

Clinical Implications

The evidence clearly establishes that hyperuricemia causes multi-organ damage beyond the classic gouty arthritis. The relationship between hyperuricemia and chronic kidney disease is bidirectional, though whether lowering serum uric acid prevents further renal deterioration remains under investigation 1. The key takeaway is that elevated uric acid should prompt comprehensive screening for renal function and cardiovascular risk factors, not just monitoring for gout attacks 1.