Urine alkalinization to a pH of 7.0 to 7.2 optimized uric acid stone dissolution in an in vitro study published in European Urology Open Science, supporting current European Association of Urology (EAU) guidance for oral chemolysis.
The researchers evaluated dissolution kinetics of intact and ground natural uric acid stones in artificial urine at 37°C. They tested dissolution across pH levels from 6.0 to 7.4 and separately assessed dissolution at varying uric acid saturation levels across pH 5.5, 6.0, 6.5, 7.0, and 7.2. Uric acid concentrations were measured using ultraviolet-visible spectrophotometry, and precipitates were analyzed with X-ray diffraction.
Current guideline recommendations differ regarding alkalinization targets for uric acid stone dissolution. The American Urological Association recommends urine pH above 6 without specifying a dissolution target range, whereas the EAU recommends a target pH of 6.5 to 7.2 for dissolution therapy. The findings in the current study aligned more closely with the EAU recommendation.
Dissolution rates increased sharply as pH rose above 6.5. Among intact stones, average dissolution rates increased from 0.13 μg/dL/min at pH 6.0 to 5.98 μg/dL/min at pH 7.2 before falling to 0.12 μg/dL/min at pH 7.4. Average dissolution rates were fourfold higher in the pH 6.5 to 7.0 range compared with pH 6.0 to 6.5, and nearly ninefold higher in the pH 7.0 to 7.2 range compared with pH 6.5 to 7.0.
At pH 7.4, dissolution rates declined substantially and small urate and hydroxyapatite nanoparticles were detected after prolonged incubation. The researchers noted that the experiment used supraphysiologic phosphate concentrations and incubation times exceeding typical in vivo urine transit time, which may have contributed to hydroxyapatite crystallization.
The investigators also addressed a common clinical concern regarding calcium phosphate stone formation at higher urine pH. They noted that potassium citrate alkalinization appears less likely than sodium-based alkalinizing agents to promote calcium phosphate crystallization and may reduce urinary calcium excretion. Prior studies using sodium bicarbonate or sodium-based buffers demonstrated sodium urate shell formation at higher pH levels, potentially impairing dissolution.
Stone surface area strongly influenced dissolution kinetics. Ground stones demonstrated dissolution rates approximately tenfold higher than intact stones of identical weight across all pH levels tested. At pH 7.2, average dissolution rates were 69 μg/dL/min for ground stones compared with 5.98 μg/dL/min for intact stones.
Lowering uric acid saturation had minimal effect at pH 5.5 and 6.0, where dissolution remained limited. However, at pH 6.5 and higher, dissolution increased significantly after uric acid saturation was reduced by more than 55% from baseline levels, with the strongest effect observed at pH 7.2.
The researchers concluded that these findings support alkalinization as the primary determinant of uric acid stone dissolution and help explain why allopurinol is generally reserved for patients with hyperuricosuria or incomplete dissolution despite adequate alkalinization.
The researchers also suggested that increasing stone surface area through fragmentation may have a potential adjunctive role in patients with incomplete chemolysis, particularly those who are poor candidates for complete surgical stone removal.
The study was limited by its in vitro design. The artificial urine model could not fully replicate the in vivo urinary environment, including urinary macromolecules, electrolyte variability, and urine transit time. The researchers emphasized that clinical studies are needed to confirm the findings.
The researchers reported no conflicts of interest or external funding.
Source: European Urology Open Science
