Adverse Metabolic Side Effects of Thiazides: Implications for Patients With Calcium Nephrolithiasis

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Abstract
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. 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. 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. 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.