Thiazide therapy in chronic hypoparathyroidism: effects on hypercalciuria and renal function—a systematic review and exploratory meta-analysis

Chronic hypoparathyroidism is associated with impaired renal calcium reabsorption, resulting in persistent hypercalciuria and increased risk of nephrolithiasis, nephrocalcinosis, and chronic kidney disease. Thiazide diuretics are commonly used to reduce urinary calcium excretion; however, evidence regarding their efficacy and renal safety remains limited. This study aimed to evaluate the effects of thiazide therapy on hypercalciuria and renal outcomes in patients with chronic hypoparathyroidism.

A systematic search of PubMed/MEDLINE, Embase, Scopus, and Cochrane CENTRAL was conducted from inception to January 2026. Randomized and observational studies assessing thiazide therapy in adults with chronic hypoparathyroidism were included. Meta-analysis was performed using a random-effects model, with outcomes expressed as standardized mean differences (SMDs).

Four studies involving 64 participants were included, comprising three physiological interventional studies and one randomized crossover trial. Two studies (n = 26) were eligible for quantitative synthesis. Meta-analysis showed no statistically significant reduction in urinary calcium excretion (SMD − 0.42; 95% CI − 4.64 to 3.80), with substantial imprecision. Qualitative evidence, including one randomized crossover trial, suggested reductions in urinary calcium excretion with thiazide therapy; however, pooled quantitative estimates remained inconclusive, and overall certainty of evidence was limited by small sample sizes, methodological heterogeneity, and short follow-up durations. Renal function remained stable across studies.

Current evidence suggests a possible reduction in urinary calcium excretion with thiazide therapy in chronic hypoparathyroidism; however, certainty remains low due to limited heterogeneous data and reliance on predominantly small physiological studies with only one randomized crossover trial. Quantitative pooled estimates were inconclusive, and definitive efficacy or long-term renal benefit remain unproven. Larger, well-designed prospective studies are needed to confirm efficacy and establish long-term renal safety.

PROSPERO: CRD420261323680.