Adherence to Potassium Citrate, Changes in 24-Hour Stone Risk Parameters, and Recurrent Kidney Stone Events

KEY POINTS: Pharmacy claims-based adherence (percentage of days covered) and urine-based adherence (change in urinary potassium excretion divided by dose) showed discordant associations with physiologic response and recurrence. Although change in urinary potassium excretion divided by dose was more strongly associated with changes in urinary citrate and pH, only percentage of days covered was significantly associated with recurrent stone events. BACKGROUND: Patient adherence limits the effectiveness of preventive pharmacologic therapy (PPT) for urinary stone disease, highlighting the need for accurate adherence monitoring. We assessed associations between potassium citrate adherence measures, changes in 24-hour urine parameters, and the risk of recurrent stone events. METHODS: In this retrospective cohort study, we identified adult patients enrolled in Medicare with urinary stone disease, a baseline 24-hour urine collection (2010-2019), hypocitraturia or low urine pH, a prescription for potassium citrate monotherapy, and a follow-up urine collection. We defined two adherence measures: ( 1 ) percentage of days covered (PDC) using pharmacy claims and ( 2 ) change in urinary potassium between baseline and follow-up divided by medication dose (change in urinary potassium excretion divided by dose [ΔK/dose]). We assessed the association of these measures with changes in urinary citrate and pH using analysis of covariance, and the association between adherence and recurrent stone events using Cox models. RESULTS: Among 793 patients meeting the study criteria, 504 (63.6%) patients were adherent on the basis of pharmacy claims (PDC ≥80%) and 389 (49.1%) patients on the basis of ΔK/dose ≥0.5. Compared with PDC ≥80%, ΔK/dose ≥0.5 had a stronger association with change in urinary citrate ( P < 0.001) and pH ( P < 0.001). Compared with PDC ≥80%, patients with PDC <80% had a higher risk of recurrent stone events (hazard ratio, 1.431; 95% confidence interval, 1.049 to 1.952), whereas ΔK/dose was not statistically significantly associated with recurrent stone events (hazard ratio, 1.032; 95% confidence interval, 0.740 to 1.439). CONCLUSIONS: There are clinically meaningful differences in potassium citrate adherence measures. ΔK/dose was more strongly associated with the change in urinary citrate and pH. However, only PDC was significantly associated with recurrent stone events.