by the Cochrane Collaboration specifically recommended that low-dose thiazides be used as the initial pharmacological therapy for high blood pressure. Low-dose thiazides are more effective at treating hypertension than beta blockers and are similar to angiotensin-converting enzyme (ACE) inhibitors. Thiazides are a recommended treatment for hypertension in Europe (ESC/ESH). However, the UK National Institute for Health and Clinical Excellence recommends ACE inhibitor and calcium channel blockers for first-line treatment of hypertension in adults (CG127). Thiazides should be considered as initial treatment if the patient has a high risk of developing heart failure. Thiazides have also been replaced by ACE inhibitors in Australia due to the association between thaizide use and increased risk of developing diabetes mellitus type 2. Diabetes insipidus Thiazides can be used to paradoxically decrease urine flow in people with nephrogenic diabetes insipidus. Thiazides may also be useful in treating hyponatremia (low blood sodium) in infants with central diabetes insipidus. Calcium balance Urinary stones Thiazides are useful in treating kidney stones and bladder stones that result from hypercalciuria (high urine calcium levels). Thiazides increase the uptake of calcium in the distal tubules, to moderately reduce urinary calcium. Thiazides combined with potassium citrate, increased water intake and decreased dietary oxalate and sodium can slow or even reverse the formation of calcium-containing kidney stones. High-dose therapy with the thiazide-like diuretic indapamide can be used to treat idiopathic hypercalcinuria (high urine calcium with unknown cause). Dent's disease Thiazides may be used to treat the symptoms of Dent's disease, an X-linked genetic condition that results in electrolyte imbalance with repeated episodes of kidney stones. A case study of two brothers with the condition, two years of treatment with hydrochlorothiazide reduced the incidence of kidney stones and improved kidney function. The thiazide-like diuretic chlortalidone reduced urine calcium oxalate in seven of the eight males with inactivated CLCN5 gene that participated in the study. Inactivation of the CLCN5 gene causes Dent's disease Type 1. The rare nature of Dent's disease makes it difficult to coordinate large controlled studies, so most evidence for thiazide use is with too few patients to make broad recommendations possible. Long-term thiazide use may not be advisable due to the risk of significant adverse side effects. Osteoporosis Hypocalcemia (low blood calcium) can be caused by a variety of conditions that reduce dietary calcium absorption, increase calcium excretion or both. Positive calcium balance occurs when calcium excretion is decreased and intake