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Adverse metabolic side effects of thiazides: implications for patients with calcium nephrolithiasis
Sarah C Huen1, David S Goldfarb
1Department of Medicine, New York University School of Medicine, New York, New York 10010, USA.
Insights
Thiazide diuretics may cause metabolic side effects like low potassium and high uric acid in patients with kidney stones. More research is needed to understand these risks in non-hypertensive individuals.
Area of Science:
- Nephrology
- Endocrinology
- Pharmacology
Background:
- Thiazide diuretics are established treatments for preventing recurrent calcium nephrolithiasis.
- Concerns exist regarding thiazide-induced metabolic adverse effects, such as hyperglycemia, hyperuricemia, hypokalemia, and dyslipidemia, particularly in hypertensive patients.
- The clinical significance of these metabolic effects in non-hypertensive patients with kidney stones is not well-defined.
Purpose of the Study:
- To review the literature for randomized controlled trials (RCTs) investigating the metabolic effects of thiazide use in patients with calcium nephrolithiasis.
- To assess the incidence and clinical significance of hyperglycemia, hyperuricemia, hypokalemia, and dyslipidemia in this patient population.
Main Methods:
- A systematic literature review was conducted, focusing on RCTs of thiazide treatment for calcium nephrolithiasis.
- Data on metabolic parameters including glucose, lipids, potassium, and uric acid levels were extracted and analyzed.
Main Results:
- Nine RCTs met the inclusion criteria, with a mean patient age of 42 years and follow-up of 2.6 years.
- Limited data were available; only two studies reported glucose and lipid levels, showing no significant changes.
- Three studies reported serum potassium, with two showing a significant decrease.
- Three studies reported serum uric acid, all indicating an increase.
- None of the included trials assessed the development of diabetes mellitus or cardiovascular disease.
Conclusions:
- There is a significant lack of data regarding the metabolic effects of thiazides in patients treated for recurrent calcium nephrolithiasis.
- It remains unclear whether thiazide-induced metabolic changes pose a clinically significant risk for cardiovascular disease in otherwise healthy individuals with recurrent kidney stones.
- Further research is essential to explore alternative treatments for recurrent nephrolithiasis and fully understand thiazide's metabolic impact.
Purpose:
Thiazide use to prevent recurrent calcium nephrolithiasis is supported by randomized, controlled trials. Concerns regarding adverse metabolic effects of thiazides, which are also used to treat hypertension, have reemerged with analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. The risks posed by thiazide induced hyperglycemia, hyperuricemia, hypokalemia and dyslipidemia may decrease the expected cardiovascular benefit of lowering blood pressure in hypertensive patients. Whether these side effects occur and are clinically significant in nonhypertensive patients with kidney stones treated with thiazides is unclear.
Materials And Methods:
A review of the literature was performed for randomized, controlled trials with thiazides for calcium nephrolithiasis. We sought data regarding metabolic effects in this population, including hyperglycemia, hyperuricemia, hypokalemia and dyslipidemia.
Results:
Nine randomized, controlled trials of thiazide treatment for kidney stones were included. Mean patient age was 42 years and followup was 2.6 years. Only 2 of the 9 studies measured glucose and lipid levels, which did not significantly change with treatment. Three studies measured serum potassium and 2 showed a significant decrease. Three of the 9 studies measured serum uric acid levels, which increased in all 3. None of the trials studied the development of diabetes mellitus or cardiovascular disease.
Conclusions:
There is a lack of data on the metabolic effects of thiazides used to prevent recurrent calcium nephrolithiasis. It remains unclear if metabolic effects occur and increase the risk of cardiovascular disease in otherwise healthy patients with recurrent nephrolithiasis on thiazide prophylaxis. Further research is needed to elucidate other alternatives for the treatment of recurrent nephrolithiasis.
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