Hydrochlorothiazide and Prevention of Kidney-Stone Recurrence

Dhayat, Nasser; Bonny, Olivier; Roth, Beat; Christe, Andreas; Ritter, Alexander; Mohebbi, Nilufar; Faller, Nicolas; Pellegrini, Lisa; Bedino, Giulia; Venzin, Reto; Grosse, Philipp; Hüsler, Carina; Koneth, Irene; Bucher, Christian; Giorno, Rosaria Del; Gabutti, Luca; Mayr, Michael; Odermatt, Urs; Buchkremer, Florian; Ernandez, Thomas; Stoermann-Chopard, C.; Teta, Daniel; Vogt, Bruno; Roumet, Marie; Tamò, Luca; Cereghetti, Grazia M; Trelle, Sven; Fuster, Daniel

doi:10.1056/nejmoa2209275

Cited by 60 publications

(35 citation statements)

References 24 publications

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“…Furthermore, a recent clinical trial of thiazide therapy also failed to show significant reduction in recurrence, either based on a composite outcome or symptomatic recurrence alone. 19 Overall, our findings are compatible with ongoing uncertainty about the efficacy of thiazides or uric acid-lowering medications to reduce symptomatic recurrence but do support a beneficial effect for alkali therapy in the context of hypocitraturia.…”

Section: Discussionsupporting

confidence: 82%

Preventive Pharmacological Therapy and Risk of Recurrent Urinary Stone Disease

Arivoli,

Valicevic,

Oerline

et al. 2024

CJASN

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Background: Urinary stone disease is a prevalent condition associated with a high recurrence risk. Preventive pharmacological therapy has been proposed to reduce recurrent stone episodes. However, limited evidence exists regarding its effectiveness, contributing to its underutilization by physicians. This study aimed to evaluate the association between preventive pharmacological therapy (thiazide diuretics, alkali therapy, and uric acid lowering medications) and clinically significant urinary stone disease recurrence. Methods: Using data from the Veterans Health Administration, adults with an index episode of urinary stone disease from 2012 through 2019 and at least one urinary abnormality (hypercalciuria, hypocitraturia, or hyperuricosuria) on 24-hour urine collection were included. The primary outcome was a composite variable representing recurrent stone events that resulted in emergency department visits, hospitalizations, or surgery for urinary stone disease. Cox proportional hazards regression was performed to estimate the association between preventive pharmacological therapy use and recurrent urinary stone disease while adjusting for relevant baseline patient characteristics. Results: Among the cohort of patients with urinary abnormalities (n=5,637), treatment with PPT was associated with a significant 19% lower risk of recurrent urinary stone disease during the 12–36-month period following the initial urine collection (hazard ratio [HR] 0.81; 95% confidence interval [CI] 0.65-1.00, p = 0.0496. However, the effectiveness of preventive pharmacological therapy diminished over longer follow-up periods (12-48 months and 12-60 months following the urine collection) and did not reach statistical significance. When examining specific urinary abnormalities, only alkali therapy for hypocitraturia was associated with a significant 26% lower recurrence risk within the 12–36-month timeframe (HR 0.74, 95%CI 0.56-0.97, p=0.03). Conclusions: When considering all urinary abnormalities together, this study demonstrates that use of preventive pharmacological therapy is associated with a lower risk of clinically significant recurrent episodes of urinary stone disease in the 12-36 month timeframe following urine collection, though only the association with use of alkali therapy for hypocitraturia was significant when individual abnormalities were examined.

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Section: Discussionsupporting

confidence: 82%

Preventive Pharmacological Therapy and Risk of Recurrent Urinary Stone Disease

Arivoli,

Valicevic,

Oerline

et al. 2024

CJASN

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“…[5][6][7] However, the largest trial-the NOSTONE trial (Efficacy of Standard and Low Dose Hydrochlorothiazide Treatment in the Prevention of Recurrent Nephrolithiasis)-did not show a difference in composite symptomatic and radiographic stone recurrence among 416 patients with recurrent calcium-containing stones receiving various hydrochlorothiazide doses compared with placebo. 8,9 The study's ability to detect stone events may have been limited due to its short duration of follow-up. Additionally, the NOSTONE trial reported less reduction in urinary calcium than previous successful trials, suggesting that inadequate drug dosage or poor medication adherence may have contributed to its null treatment effect.…”

Section: Introductionmentioning

confidence: 99%

“…These recommendations are based on multiple clinical trials and meta-analyses, in which thiazides demonstrated a significant reduction in stone recurrence rates . However, the largest trial—the NOSTONE trial (Efficacy of Standard and Low Dose Hydrochlorothiazide Treatment in the Prevention of Recurrent Nephrolithiasis)—did not show a difference in composite symptomatic and radiographic stone recurrence among 416 patients with recurrent calcium-containing stones receiving various hydrochlorothiazide doses compared with placebo . The study’s ability to detect stone events may have been limited due to its short duration of follow-up.…”

Section: Introductionmentioning

confidence: 99%

Mendelian Randomization Analysis of Genetic Proxies of Thiazide Diuretics and the Reduction of Kidney Stone Risk

Triozzi,

Hsi,

Wang

et al. 2023

JAMA Netw Open

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ImportanceClinical trial data have called into question the efficacy of thiazide diuretics for the prevention of kidney stones.ObjectiveTo identify whether there is an association between genetic proxies of thiazide diuretics and the risk of kidney stones.Design, Setting, and ParticipantsThis genetic association study undertook a mendelian randomization analysis of derived exposures and outcomes from genome-wide association study summary statistics. Genetic proxies of thiazide diuretics were derived from the International Consortium for Blood Pressure. Kidney stone cases and controls were derived from the Million Veteran Program, UK Biobank, and the FinnGen study. These cross-sectional designs do not report a duration of follow-up. Data analysis was performed in May 2023.ExposureGenetic proxies of thiazide diuretics were genetic variants in the thiazide-sensitive sodium chloride cotransporter gene associated with systolic blood pressure. Genetic proxies of β-blockers and systolic blood pressure served as negative controls.Main Outcomes and MeasuresThe main outcome was the odds of kidney stones. The secondary outcomes were serum laboratory values relevant to the treatment of kidney stones.ResultsThe main analysis included up to 1 079 657 individuals, including 50 832 kidney stone cases and 1 028 825 controls. In a meta-analysis of all cohorts, genetic proxies of thiazide diuretics were associated with a lower odds of kidney stones (OR, 0.85; 95% CI, 0.81-0.89; P &lt; .001). Genetic proxies of β-blockers (OR, 1.02; 95% CI, 0.96-1.07; P = .52) and systolic blood pressure (OR, 1.00; 95% CI, 1.00-1.01; P = .49) were not associated with kidney stones. Genetic proxies of thiazide diuretics were associated with higher serum calcium (β [SE], 0.051 [0.0092]; P &lt; .001) and total cholesterol (β [SE], 0.065 [0.015]; P &lt; .001), but lower serum potassium (β [SE], −0.073 [0.022]; P &lt; .001).Conclusions and RelevanceIn this genetic association study, genetic proxies of thiazide diuretics were associated with reduced kidney stone risk. This finding reflects a drug effect over the course of a lifetime, unconstrained by the limited follow-up period of clinical trials.

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“…Furthermore, the studied population consisted mainly of normocalciurics who disclosed only a modest hypocalciuric effect of thiazide. 1 ] allopurinol) (for sake of simplicity kidney stone prophylaxis hereinafter) should last in kidney stone formers is frequently answered as long as the conditions causing stones persist. However, our opinion is that this answer is biased because it is dictated by the typically narrow perception of the problem (i.e., the prevention of stone recurrence and/or growth).…”

mentioning

confidence: 99%

The Optimal Length of Pharmacological Prophylaxis in Calcium Kidney Stone Formers

2023

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c Cystine stones c Struvite stones c One kidney patient c Distal renal tubular acidosis (complete) c Primary hyperoxaluria c Secondary hyperoxaluria c Bariatric surgery, inflammatory bowel disease, bowel resection, and malabsorptive syndromes c Other forms of nephrocalcinosis c Anatomic abnormalities of the kidney and urinary tracts c Horseshoe kidney, ureterocele, vesicoureteral reflux, etc. c Neurological bladder c Patients with CKD c Patients with previous major surgeries for stones c Patients with previous major stone complications Adapted from EAU guidelines. 21

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Hydrochlorothiazide and Prevention of Kidney-Stone Recurrence

Cited by 60 publications

References 24 publications

Preventive Pharmacological Therapy and Risk of Recurrent Urinary Stone Disease

Preventive Pharmacological Therapy and Risk of Recurrent Urinary Stone Disease

Mendelian Randomization Analysis of Genetic Proxies of Thiazide Diuretics and the Reduction of Kidney Stone Risk

The Optimal Length of Pharmacological Prophylaxis in Calcium Kidney Stone Formers

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