insipidus. Nephrogenic diabetes insipidus occurs when the kidney is unable to produce concentrated urine because it has an inadequate response to vasopressin-dependent removal of free water from the renal tubular filtrate. By blocking sodium ion resorption in the distal convoluted tubule, chlortalidone induces an increase in excretion of sodium ion in urine (natriuresis). Giving chlortalidone while simultaneously restricting dietary sodium intake causes mild hypovolemia (low intravascular volume), which induces isotonic reabsorption of solute from the proximal renal tubule, reducing solute delivery in the renal collecting tubule and renal medullary collecting duct. This reduced delivery of solute to the collecting tubule and medullary collecting duct allows increased water resorption and higher concentration of urine, which leads to reversal of nephrogenic diabetes insipidus by a means that is independent of vasopressin. Adverse effects Some reviews have found a similar risk as hydrochlorothiazide, while other reviews found a higher risk of side effects. Hypokalemia (low blood potassium) occurs occasionally; the risk of hypokalemia is higher in persons who are magnesium deficient Hypomagnesemia (low blood magnesium) a review of four clinical trials found that low blood magnesium occurred in 20% of persons within a few weeks of beginning treatment with 50 mg of chlortalidone daily. The risk of chlortalidone-associated hypomagnesemia is higher in persons with diabetes mellitus who have low dietary magnesium intake. Hyponatremia (low blood sodium) occurred in 4.1% of subjects randomized to chlortalidone in the Systolic Hypertension in the Elderly Trial, compared to 1.3% of control subjects. The risk of hyponatremia varies from 5 per 100,000 person-years for those younger than 40 years of age to 730 per 100,000 person-years in those older than 80 years of age. Hyponatremia is more likely in persons with certain genetic variants of the prostaglandin transporter SLCO2A1 associated with elevated urinary PGE2 and inappropriately low plasma ADH levels in the setting of low plasma osmolality. Thiazide-associated hyponatremia is often more severe than loop diuretic-associated hyponatremia because the predominant action of thiazides occurs late in the tubular flow, reducing opportunity to apply additional corrective action further along the tubule. Hypercalcemia (high blood calcium level) can occur in normal persons exposed to chlortalidone but is more likely to occur when persons with sub-clinical hyperparathyroidism are exposed to chlortalidone. Hyperuricemia, high levels of uric acid in the blood Hyperglycemia, high blood sugar is more common in persons who are magnesium deficient Hyperlipidemia, high cholesterol and triglycerides Headache Nausea/vomiting Photosensitivity