Organs Damaged by Gout
The joints are the most commonly damaged organs in gout, but the kidneys are the most significant non-articular organ affected by gout, manifesting as urolithiasis and chronic interstitial nephropathy. 1
Primary Target Organs in Gout
- Joints: The primary sites of damage in gout are the joints, where monosodium urate monohydrate crystals deposit in the extracellular fluid, causing acute and chronic inflammation 1
- Periarticular tissues: Tophi (pathognomonic features of gout) commonly form in articular, periarticular, bursal, bone, auricular, and cutaneous tissues 1
- Kidneys: Renal manifestations include urolithiasis (kidney stones) and chronic interstitial nephropathy due to monosodium urate crystal deposition in the renal medulla 1, 2
Renal Manifestations of Gout
- Urolithiasis (kidney stones) typically occurs with acidic urine pH in gout patients 1
- Chronic interstitial nephropathy is mediated by monosodium urate crystal deposition in the renal medulla, though currently considered an uncommon clinical manifestation 1
- Hyperuricemia promotes chronic kidney disease (CKD) development by:
- Damaging endothelial cells
- Activating the renin-angiotensin system
- Promoting inflammatory responses 2
Pathophysiology of Organ Damage
- Tissue deposition of monosodium urate monohydrate crystals in supersaturated extracellular fluids mediates most clinical and pathologic features of gout 1
- Urate crystals trigger immune system recognition as a "red flag," stimulating macrophage activation and NLRP3 inflammasome activation 2
- This leads to production of pro-inflammatory cytokines (IL-1β and IL-18) that mediate inflammation, apoptosis, and necroinflammation 2
- In the kidneys, uric acid can induce glomerular hypertension, arteriolosclerosis, glomerular injury, and tubulointerstitial fibrosis 3
Clinical Importance
- While joint damage is the most common and recognizable manifestation of gout, the kidney damage can significantly impact long-term morbidity and mortality 1, 3
- Historically, before effective urate-lowering therapies, end-stage renal disease was common in gouty patients 3
- Recent evidence suggests that elevated serum uric acid independently predicts the development of chronic kidney disease 3
- Pilot studies indicate that lowering plasma uric acid concentrations may slow the progression of renal disease in subjects with CKD 3
Monitoring and Prevention
- Serum urate monitoring is essential for preventing both joint and kidney damage in gout patients 1
- Treatment targets should focus on normalizing serum urate levels to prevent crystal formation and deposition in both joints and kidneys 1
- Urate-lowering therapy is indicated for patients with chronic kidney disease, two or more flare-ups per year, urolithiasis, tophi, chronic gouty arthritis, or joint damage 4