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Thiazide diuretics will be more effective in lowering urine calcium excretion if taken at night as compared to the daytime. It will therefore be more effective in reducing kidney stone recurrence in nephrolithiasis patients with elevated urine calcium who are known to have increased risk of kidney stones at night time.
The study will be divided into three phases for every single patient, investigators will study 15-20 stone formers who have previously documented elevated urine calcium excretion, with a plan to measure their urine chemistries at baseline (if they currently use thiazide diuretics, they will come off of their respective thiazide for a 7-day washout period). Investigators will ask them to collect urine samples in two 12-hour intervals: on awakening, the 1st sample starts to before supper; 2nd sample begins after dinner and extends overnight with fasting after dinner, These measurements will be used as controls. Then patients will be started back on diuretics (25mg of chlorthalidone for the primary study; pending the results this may be repeated with 25mg of hydrochlorothiazide as a second substudy) which they will take in the daytime; after a 6-day acclimation period, two 12-hour urine samples will be collected as in the washout period. For the third study period, the patients will then begin taking the thiazide after dinner. After a 6-day acclimation period, the third set of urine collections will be done.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| thiazide | Experimental | Stone formers History of calcium containing kidney stones, hypercalciuria on previous urine tests, no kidney disease, not pregnant/lactating |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| chlorthalidone | Drug |
| ||
| Hydrochlorothiazide |
| Measure | Description | Time Frame |
|---|---|---|
| Change in excretion and supersaturation of urine calcium oxalate / phosphate | 1 week |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| David Goldfarb, MD | New York Harbor VA Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| VA New York Harbor Healthcare System | New York | New York | 10010 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 40194294 | Derived | Wollin DA, Fattah H, Asplin JR, Goldfarb DS. Effect of Chlorthalidone and Hydrochlorothiazide on 12-Hour vs 24-Hour Urinary Calcium Excretion. J Urol. 2025 Sep;214(3):280-288. doi: 10.1097/JU.0000000000004562. Epub 2025 Apr 7. |
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| ID | Term |
|---|---|
| D007669 | Kidney Calculi |
| D053040 | Nephrolithiasis |
| D053565 | Hypercalciuria |
| ID | Term |
|---|---|
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
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| ID | Term |
|---|---|
| D002752 | Chlorthalidone |
| D006852 | Hydrochlorothiazide |
| ID | Term |
|---|---|
| D000096926 | Benzenesulfonamides |
| D013449 | Sulfonamides |
| D000577 | Amides |
| D009930 | Organic Chemicals |
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|
| D000091642 | Urogenital Diseases |
| D052878 | Urolithiasis |
| D014545 | Urinary Calculi |
| D052801 | Male Urogenital Diseases |
| D002137 | Calculi |
| D020763 | Pathological Conditions, Anatomical |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D020924 | Urological Manifestations |
| D012816 | Signs and Symptoms |
| D001555 |
| Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D001577 | Benzophenones |
| D010797 | Phthalimides |
| D007094 | Imides |
| D007659 | Ketones |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
| D054833 | Isoindoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D002740 | Chlorothiazide |
| D001581 | Benzothiadiazines |
| D049971 | Thiazides |