Urinary Supersaturation in a Randomized Trial among Individuals with Recurrent Nephrolithiasis comparing Empiric versus Selective Preventive Therapy: The URINE Trial.

Abstract

To compare a strategy utilizing testing to guide treatment, also known as selective therapy, to a strategy of initiating interventions without testing, termed empiric therapy, on urinary supersaturation of calcium oxalate and calcium phosphate. In this single-center trial, adult individuals with recurrent idiopathic calcium stone disease were randomized to either an empiric or selective strategy. Participants received 24-hour urine testing at baseline, 4 weeks, and 8 weeks. Treatment in the empiric arm was comprised of dietary and fluid counseling and pharmacologic treatment with indapamide and potassium citrate irrespective of 24-hour urine results. For the selective arm, diet and pharmacologic treatments, which included indapamide, potassium citrate, and/or allopurinol, were tailored based on urine testing at baseline and 4 weeks. The primary outcome was urinary supersaturation of calcium oxalate and calcium phosphate at 8 weeks. The analytic sample included 56 participants (mean [SD] age, 44.5 [13.2] years; 30 women [54%]), with 29 randomized to the empiric and 27 to the selective groups. At week 8, there were no significant differences comparing the empiric and selective arms with respect to mean [SD] urinary supersaturation of calcium oxalate (4.7 [2.9] vs 5.0 [2.9], respectively, <i>p</i> = 0.81) or calcium phosphate (1.3 [0.9] vs 1.4 [1.1], respectively, <i>p</i> = 0.58). Similarly, there were no significant differences at 8 weeks in urine volume and pH, or in excretion of calcium, oxalate, citrate, uric acid, and sodium. In this short-term trial among individuals at high-risk for stone recurrence, there was no statistically significant difference in the urinary stone risk comparing an empiric versus selective strategy for kidney stone prevention.