Demeclocycline treatment of water retention in congestive heart failure.

Demeclocycline has been shown to induce nephrogenic diabetes insipidus in normal subjects.' It has been used successfully for treating the syndrome of inappropriate antidiuretic hormone secretion2 3 and water retention related to liver cirrhosis.4 The findings presented here show its efficacy in cardiac oedema unresponsive to classic diuretic treatment. Six patients with chronic congestive heart failure were investigated. Each patient had longstanding overt salt and water retention which had become unresponsive to low salt diet, diuretics, and digitalis treatment. Three patients had overt hyponatraemia. Except for digitalis, which was maintained at the same daily dose, all drugs were withheld throughout the study. The patients were allowed to drink water freely but dietary salt was restricted to 10-20 mmol (mEq)/day. After five days' bed rest and dietary salt restriction without any change in salt and water retention demeclocycline (1200 mg/day by mouth) was started. One patient did not respond to treatment over nine days. The figure shows the results in the other five patients. Progressive weight loss (mean 6 3 kg) occurred together with an increase in diuresis (mean 1 67 1/day) and overt salt excretion (mean increase 99 mmol/day). The mean urine osmolality of 550 mmol(mosmol)/kg H2O decreased to 198 mmol/kg H2O. Blood urea and creatinine concentrations rose moderately in all patients. Initial hypo-natraemia was easily corrected without any significant change in other serum electrolytes. All patients experienced nausea during demeclocycline administration but no other side effects were noted. No glycosuria, proteinuria, or aminoaciduria occurred. Demeclocycline administration was stopped when oedema was clinically undetectable. This was followed by a gradual decrease in diuresis and in salt excretion, and a rise in urine osmolality toward baseline values. The impairment of renal function was completely reversed within 10 days. Comment Demeclocycline is known to inhibit the antidiuretic hormone sensitive medullary adenylcyclase from the kidney,' thus inducing a reversible nephrogenic diabetes insipidus. The drug has been shown to be useful in treating hyponatraemia and water intoxication in patients with inappropriate antidiuretic hormone secretion,' suggesting inhibition of the tubular response to tumoral antidiuretic products. Demeclocycline has also been successfully used to treat chronic oedema in cirrhotic patients,' inducing substantial increases iI urinary water and sodium excretion. An identical effect occurred iI our patients with chronic oedema of cardiac origin, suggesting tha the antidiuretic hormone is at least partially responsible for th4 abnormal water metabolism in liver cirrhosis and heart decompensa tion. Demeclocycline seems to …