From the Guidelines
There is a limited correlation between increased serum uric acid levels and the presence of calcium oxalate crystals in urine microscopy, and management should focus on treating both conditions separately if they coexist, with allopurinol being a potential treatment option for patients with recurrent calcium oxalate stones and hyperuricosuria, as recommended by the AUA guideline 1.
Key Points
- Elevated serum uric acid (hyperuricemia) primarily leads to uric acid crystal formation rather than calcium oxalate crystals.
- Indirect relationships exist between hyperuricemia and calcium oxalate crystal formation, including acidic urine and shared risk factors like dehydration and high-purine diets.
- Uric acid crystals can act as nucleation sites for calcium oxalate crystal growth through a process called heterogeneous nucleation.
- Management of hyperuricemia may involve medications like allopurinol (starting at 100mg daily, increasing as needed) or febuxostat (40-80mg daily), while calcium oxalate crystals typically require increased fluid intake, dietary oxalate restriction, and sometimes potassium citrate (10-15 mEq twice daily) to alkalize urine.
Treatment Recommendations
- For patients with recurrent calcium oxalate stones and hyperuricosuria, allopurinol may be offered as a treatment option, as recommended by the AUA guideline 1.
- Comprehensive metabolic evaluation is necessary to identify underlying causes and prevent kidney stone formation in patients with both hyperuricemia and calcium oxalate crystals.
Evidence Summary
- The AUA guideline recommends allopurinol for patients with recurrent calcium oxalate stones and hyperuricosuria, based on a prospective randomized controlled trial that demonstrated a reduced risk of recurrent calcium oxalate stones in this setting 1.
- The American College of Physicians (ACP) guideline recommends management with increased fluid intake and pharmacologic monotherapy with a thiazide diuretic, citrate, or allopurinol to prevent recurrent nephrolithiasis, although the evidence is graded as weak and of low to moderate quality 1.
From the Research
Correlation between Hyperuricemia and Calcium Oxalate Crystals
- Hyperuricemia, or elevated serum uric acid, has been linked to the formation of calcium oxalate stones, as disturbances in purine metabolism with hyperuricaemia and/or hyperuricosuria are a risk factor in uric acid and Ca oxalate stone formation 2.
- The formation of Ca oxalate stones depends on the state of urinary supersaturation with respect to Ca and oxalate and the action of urinary inhibitors of crystal nucleation, aggregation, and growth 3.
- Higher urinary uric acid excretion is a suspected risk factor for calcium oxalate stone formation, and reducing urinary uric acid excretion can help prevent stone growth or new stone formation 4.
Mechanisms and Risk Factors
- Hyperoxaluria is a major predisposing factor in calcium oxalate urolithiasis, and dietary risk factors such as low calcium intake and high ascorbate intake can contribute to hyperoxaluria 5.
- Hyperoxaluria can result from either inherited disorders of glyoxylate metabolism or increased intestinal oxalate absorption, leading to urinary supersaturation of calcium oxalate and crystal formation 6.
- Reducing urinary supersaturation of Ca oxalate by increasing urine volume, reducing urine Ca, and maintaining dietary Ca intake can help prevent stone recurrence 3.
Treatment and Management
- Xanthine oxidase inhibitors such as allopurinol and febuxostat can reduce uric acid levels in serum and urine, and may be effective in preventing stone recurrence 2, 4.
- Management of hyperoxaluria and oxalate nephropathy includes high fluid intake, use of calcium supplements, and management of underlying causes 6.