Low-Dose Indapamide vs. Hydrochlorothiazide in Idiopathic Hypercalciuria: A Randomized Prospective Trial

Background: Idiopathic hypercalciuria (IH) is the most common genetic metabolic disorder in patients with urinary stones and is usually treated with thiazide-type diuretics. However, direct evidence comparing low-dose indapamide and hydrochlorothiazide is scarce. This study aimed to compare their safety, efficacy and adherence in patients with IH. Methods: In this randomized prospective trial, a total of 101 patients with IH were recruited at Son Espases University Hospital (2020-2023), assigned to receive indapamide 1.5 mg/day (n = 53) or hydrochlorothiazide 25 mg/day (n = 48), and followed for 18 months. Adverse events, biochemical parameters and therapeutic adherence were evaluated. Results: A total of 90.24% patients on indapamide and 85.71% on hydrochlorothiazide showed normal calciuria (p = 0.53). Both treatments increased serum urate (p = 0.62). Indapamide significantly reduced β-crosslaps (p < 0.05), suggesting bone protection. No significant differences were found in citraturia, uricosuria, phosphaturia, magnesiuria, magnesemia, natremia, or kalemia. Indapamide caused more mild adverse events, lowering adherence, while hydrochlorothiazide caused the only severe adverse effect-moderate hypokalemia. No differences in kidney stone recurrence were observed (p = 0.82). Conclusions: This is the first paper elucidating low-dose indapamide and hydrochlorothiazide efficacy and safety for the treatment of IH. No significant differences were observed between the two drugs in terms of adverse events or treatment adherence. A longer follow-up is needed to assess kidney stone recurrence.