Urinary supersaturation in a Randomized trial among Individuals with Nephrolithiasis comparing Empiric versus selective therapy (URINE): design and rationale of a clinical trial

Clinical guidelines disagree on whether the identification of abnormal urine chemistries should occur before starting diet and medication interventions to prevent the recurrence of kidney stone events. We describe the rationale and design of the Urinary supersaturation in a Randomized trial among Individuals with Nephrolithiasis comparing Empiric versus selective therapy (URINE) study, a randomized trial comparing two multi-component interventions to improve urinary supersaturation. Participants are randomized (1:1 ratio) to the empiric or selective arm. The target sample size is 56 participants. Adults ≥ 18 years of age with idiopathic calcium stone disease and two symptomatic stone events within the previous 5 years. Exclusion criteria include systemic conditions predisposing to kidney stones and pharmacologic treatment for stone prevention at baseline. Participants in the empiric arm receive standard diet therapy recommendations, thiazide, and potassium citrate. Participants in the selective arm receive tailored diet and nutrient recommendations and medications based on baseline and 1-month follow-up of 24-h urine testing results. The primary endpoints are urinary supersaturations of calcium oxalate and calcium phosphate at 2 months of follow-up. Secondary endpoints include side effects, diet and medication adherence, and changes in 24-h urine volume, calcium, oxalate, citrate, and pH. Short-term changes in urinary supersaturation may not reflect changes in future risk of stone events. The URINE study will provide foundational data to compare the effectiveness of two prevention strategies for kidney stone disease.