Hyperuricemia
Background
Hyperuricemia is an excess of serum uric acid, typically defined as a serum urate level > 6.8 mg/dL (the approximate saturation point of urate under physiological conditions), or clinically as ≥7.0 mg/dL in males and ≥6.0 mg/dL in females.[1]
While often asymptomatic, in the Emergency Department it is most commonly encountered as the underlying etiology for Gout, Nephrolithiasis (Uric Acid stones), or as a component of Tumor Lysis Syndrome.[2]
Pathophysiology
Uric acid is the end product of purine metabolism in humans. Unlike other mammals, humans lack the enzyme uricase (urate oxidase), leading to poor solubility of urate. Hyperuricemia results from one of two mechanisms (or a combination):[3]
- Underexcretion (90% of cases): Renal handling defects involving urate transporters (e.g., URAT1, OAT4).[4]
- Overproduction (10% of cases): Increased purine breakdown.
When levels exceed saturation (>6.8 mg/dL), monosodium urate (MSU) crystals may precipitate in joints (gout) or the renal collecting system (stones/nephropathy).
Etiology
The causes are often multifactorial, involving diet, genetics, and comorbidities.
Decreased Renal Excretion
- Chronic Kidney Disease
- Medications: Thiazide diuretics, Loop diuretics, Aspirin (low dose), Cyclosporine.
- Metabolic/Endocrine: Diabetic ketoacidosis, Lactic acidosis (organic acids compete for secretion), Hypothyroidism.[1]
- Toxins: Lead poisoning ("Saturnine gout"), Alcohol (ethanol increases production and decreases excretion).
Increased Production
- Cell Turnover/Lysis:
- Tumor Lysis Syndrome (TLS): Post-chemotherapy for leukemia/lymphoma.
- Hemolysis.
- Rhabdomyolysis.
- Dietary: High purine intake (red meat, shellfish), high fructose intake.
- Genetic: Lesch-Nyhan syndrome.
Clinical Presentation
Hyperuricemia itself is distinct from the clinical syndromes it causes.
Asymptomatic Hyperuricemia
- Most common presentation.
- Patient has elevated serum urate but no history of gout or stones.
- Generally not treated in the ED, though lifestyle modifications may be suggested.[1]
Symptomatic Presentations
- Acute Gouty Arthritis: Monoarticular, intensely painful, erythematous joint (classic: 1st MTP/Podagra).
- Uric Acid Nephrolithiasis: Renal colic, hematuria.
- Acute Uric Acid Nephropathy: Oliguric acute renal failure (AKI) caused by massive crystal precipitation in tubules (seen in Tumor Lysis Syndrome).
Diagnostic Workup
Laboratory
- Serum Uric Acid:
- > 6.8 - 7.0 mg/dL confirms hyperuricemia.[3]
- Clinical Pearl: Serum uric acid levels may be normal or low during an acute gout flare due to inflammatory cytokines increasing renal excretion. Do not rule out gout based on a normal prophylactic level during an attack.
- Basic Metabolic Panel (BMP): Assess Creatinine (AKI) and Electrolytes (Hyperkalemia/Hyperphosphatemia in TLS).
- Urinalysis: Look for hematuria or acidic urine (pH < 5.5 favors uric acid stones).
Imaging
- Joint X-ray: Usually normal in early gout; "rat-bite" erosions in chronic tophaceous gout.
- Renal Ultrasound/CT: To evaluate for hydronephrosis or stones.
- Note: Pure uric acid stones are radiolucent on plain X-rays but visible on CT.
ED Management
Tumor Lysis Syndrome (TLS)
- This is a true hyperuricemic emergency.
- IV Fluids: Aggressive hydration to maintain high urine output.
- Hypouricemic Agents:
- Allopurinol: Prevents formation of new uric acid.
- Rasburicase: Recombinant urate oxidase. Converts existing uric acid into allantoin (soluble). Indicated for high-risk leukemia/lymphoma with severe hyperuricemia.
Asymptomatic Hyperuricemia
- No acute treatment indicated in the ED.
- Pharmacologic treatment (e.g., Allopurinol) carries risks of hypersensitivity (SJS/TEN) and is not cost-effective for asymptomatic patients without comorbid indications.[5]
- Discharge Advice: Hydration, weight loss, reduction of alcohol (especially beer) and high-purine foods.
Acute Gout Flare
- Goal: Treat the inflammation, not the number.
- Do NOT start Urate-Lowering Therapy (ULT) (like Allopurinol) during an acute attack, as it may precipitate worsening inflammation due to crystal mobilization. However, if the patient is already on ULT, do not stop it.[1]
- Therapy: typically NSAIDs (Indomethacin, Naproxen), Colchicine, or Corticosteroids.
Uric Acid Stones
- Standard renal colic management (analgesia, fluids, tamsulosin).
Disposition
- Discharge: Asymptomatic hyperuricemia, uncomplicated gout, small <5mm stones.
- Admit:
- Tumor Lysis Syndrome (requires electrolytes monitoring).
- Acute Uric Acid Nephropathy (AKI).
- Intractable pain or infection associated with stones.
See Also
References
- ↑ 1.0 1.1 1.2 1.3 George C, Leslie SW, Minter DA. Hyperuricemia. [Updated 2023 Oct 14]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459218/
- ↑ Leung YY, et al. Physiology of Hyperuricemia and Urate-Lowering Treatments. Front Med (Lausanne). 2018;5:160. Published 2018 May 31. doi:10.3389/fmed.2018.00160
- ↑ 3.0 3.1 Zhang, Y., et al. Hyperuricemia and its related diseases: mechanisms and advances in therapy. Sig Transduct Target Ther 9, 222 (2024). https://doi.org/10.1038/s41392-024-01916-y
- ↑ Bobulescu IA, Moe OW. Renal transport of uric acid: evolving concepts and uncertainties. Adv Chronic Kidney Dis. 2012 Nov;19(6):358-71. doi: 10.1053/j.ackd.2012.07.009. PMID: 23089270
- ↑ Chen C, Lü JM, Yao Q. Hyperuricemia-Related Diseases and Xanthine Oxidoreductase (XOR) Inhibitors: An Overview. Med Sci Monit. 2016;22:2501-2512. Published 2016 Jul 17. doi:10.12659/msm.899852