Increased susceptibility to thiazide-induced hyponatremia in the elderly

Hyponatremia is a common cause of morbidity in the elderly, and thiazide diuretics are often implicated. Eleven healthy young volunteers, eight healthy old volunteers, and five elderly patients with a history of thiazide-induced hyponatremia were studied to determine susceptibility to thiazide-induced hypoosmolality in age. Each of the healthy subjects ingested a water load (20 mL/kg) after 3 days of hydrochlorothiazide (HCTZ) (100 mg/day) or placebo. Although there were no differences in minimum Uosm between young and old, the healthy old had lower hourly free water clearances (CH2O) as compared with the young and a greater decline in serum osmolality in response to water loading (P < 0.05). HCTZ impaired minimum urine osmolality and CH2O and delayed recovery of serum osmolality after the water load in both healthy young and old (P < 0.005, placebo versus HCTZ), but the impairment in the latter two parameters was greater in the healthy elderly (P < 0.05, young versus old). Vasopressin levels were not different between healthy young and old (1.9 +/- 0.3 versus 2.0 +/- 1.0 pm with placebo; 3.0 +/- 0.7 versus 4.4 +/- 1.0 with HCTZ). Five of the young subjects were restudied after the addition of ibuprofen (400 mg thrice daily) to the thiazide and placebo regimens. Creatinine clearance was not changed, but free water clearance and serum osmolality after water loading were significantly reduced to a degree similar to that seen in the elderly subjects on the thiazide regimen (P < 0.05), suggesting an important role for renal prostaglandins in the defense against hyponatremia.