INCREASED SUSCEPTIBILITY TO THIAZIDE-INDUCED HYPONATREMIA IN THE ELDERLY

Hyponatremia is a common cause of morbidity in the elderly, and thiazi de diuretics are often implicated. Eleven healthy young volunteers, ei ght healthy old volunteers, and five elderly patients with a history o f thiazide-induced hyponatremia were studied to determine susceptibili ty to thiazide-induced hypoosmolality in age. Each of the healthy subj ects ingested a water load (20 mL/kg) after 3 days of hydrochlorothiaz ide (HCTZ) (100 mg/day) or placebo. Although there were no differences in minimum Uosm between young and old, the healthy old had lower hour ly free water clearances (CH2O) as compared with the young and a great er 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 ol d (P < 0.005, placebo versus HCTZ), but the impairment in the latter t wo parameters was greater in the healthy elderly (P < 0.05, young vers us old). Vasopressin levels were not different between healthy young a nd old (1.9 +/- 0.3 versus 2.0 +/- 1.0 pm with placebo; 3.0 +/- 0.7 ve rsus 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 signific antly 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. Five elderly subjects with a prior history of thiazide-induced hyponatremia were a lso challenged with a water load. Compared with the healthy elderly su bjects, these patients had an impairment in the ability to dilute the urine maximally as well as an impairment in free water excretion and a greater reduction in serum osmolality (P < 0.05). Vasopressin levels were not elevated in these patients. In summary, HCTZ produces defects in water excretion after a water load (a decrease in CH2O and a decli ne in serum osmolality) that are greater in healthy elderly than young subjects and that are unrelated to differences in vasopressin or mini mum Uosm. Prostaglandin inhibition in young subjects together with thi azide further decreased CH2O and compromised the recovery of serum osm olality in a manner similar to that observed in the elderly. The elder ly patients with a history of thiazide-induced hyponatremia had defect s in urinary dilution and an even greater susceptibility to hyponatrem ia. In conclusion, alterations in the distal tubular delivery of water , possibly related to lower prostaglandin production, may contribute t o susceptibility to thiazide-induced hyponatremia in the elderly. Elde rly subjects with unsuspected underlying defects in urinary dilution m ay present with clinically significant hyponatremia in the setting of thiazide use and water ingestion.