Effect of Demeclocycline on Renal Function and Urinary Prostaglandin E2 and Kallikrein in Hyponatremic Cirrhotics

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Abstract
Eight cirrhotics with hyponatremia were given demeclocycline (DMC) 900 mg/day to investigate its effect on renal function, plasma renin activity, aldosterone and urinary excretion of prostaglandin E2 and kallikrein. In 7 patients DMC induced an increase of free water clearance (from -0.36 .+-. 0.06 to 0.13 .+-. 0.06 ml/min) and serum Na concentration (from 125.4 .+-. 0.09 to 131.1 .+-. 1.0 meq/l, mmol/l). In 5 of these patients DMC also induced a marked reduction of glomerular filtration rate (from 72.2 .+-. 6.2 to 31,2 .+-. 4.7 ml/min) and renal plasma flow (from 468 .+-. 98 to 195 .+-. 55 ml/min) which could not be explained on the basis of hypovolemia. In each case this renal impairment was not associated with changes in urinary concentration of .beta.2-microglobulin, urinary cast excretion, fresh urine sediment or urine protein content and disappeared after discontinuation of the drug. DMC induced a marked increase in the urinary excretion of prostaglandin E2 (from 0.82 .+-. 0.27 to 6.16 .+-. 1.91 ng/min) in 6 out of the 7 patients who responded to DMC and a marked reduction in urinary kallikrein (from 16.1 .+-. 4.4 to 4.2 .+-. 1.6 pkat/min) in the 5 patients who developed renal insufficiency. The serum DMC concentration was > 5 .mu.g/ml in all patients who responded to DMC, > 8 .mu.g/ml in all cases who developed renal insufficiency and of 3 .mu.g/ml in the case not responding to DMC. DMC is an effective therapy for water retention and dilutional hyponatremia in cirrhosis but it produces renal insufficiency associated with an impairment of renal perfusion and with a reduced urinary kallikrein activity in a high proportion of patients. The inhibitory effect of DMC on water reabsorption in these patients may be due, at least in part, to an increased renal synthesis of prostaglandin E2 induced by the drug. A close relationship exists between the renal effects and the serum levels of DMC in cirrhosis.