Potassium Citrate vs Thiazides for Empiric Stone Prevention: A Propensity-Matched Analysis.

OBJECTIVE: To compare the risk of stone surgery among patients with nephrolithiasis empirically initiated on potassium citrate versus thiazide diuretics. METHODS: We performed a retrospective cohort study using TriNetX, a federated database containing de-identified EHR and claims data from over 100 million patients. Adults (≥18 years) diagnosed with urolithiasis initiated on potassium citrate or a thiazide diuretic within 3 months of diagnosis were identified. Patients with documented metabolic abnormalities favoring targeted therapy (urine pH ≤6, 24-hour urine calcium ≥250mg, or 24-hour urine citrate ≤320mg), prior stone surgery, or prior exposure to either medication were excluded to approximate an empiric treatment cohort. One-to-one propensity score matching was performed. The primary outcome was 3-year incidence of stone surgery, defined as extracorporeal shock wave lithotripsy, ureteroscopy, or percutaneous nephrolithotomy. Sensitivity analyses excluded treatment crossover and stratified by hypertension and stone recurrence status. RESULTS: After matching, 16,759 patients were included in each cohort. At 3 years, patients initiated on potassium citrate had a higher risk of stone surgery than thiazide-treated patients (5.6% vs. 3.5%, absolute risk difference 2.11%, 95% CI 1.66-2.55, hazard ratio 1.57, 95% CI 1.42-1.74, p<0.0001). This association persisted after excluding treatment crossover (5.2% vs. 3.0%; HR 1.69) and across all subgroups (HR 1.22-1.73). CONCLUSIONS: Among patients without documented metabolic abnormalities empirically treated for nephrolithiasis, potassium citrate initiation was associated with a higher risk of subsequent stone surgery compared to thiazide diuretics. These findings suggest thiazide diuretics may be associated with more consistent protection against clinically significant recurrence, though prospective confirmation is needed.