Renal Kallikrein Excretion in Alcoholic Cirrhosis

Severe liver disease is often associated with renal hemodynamic changes, and these changes may involve vasoactive hormones. The vasodilatory renal kallikrein-kinin system has received little previous study in these patients. We measured urinary kallikrein in nine patients with alcoholic cirrhosis under rigid metabolic conditions and simultaneously evaluated renin, aldosterone and urinary prostaglandins. Plasma renin und aldosterone were generally increased as expected but urinary kallikrein was surprisingly diminished (13.3 ± 3.7 vs. 38.8 ± 11.1 SE, E.U./day. P < 0.05). despite adequate creatinine clearance (81 ± 9 ml./min.). Administration of prostaglandin inhibitors reduced urinary prostaglandin E by 72% and creatinine clearance by 56% but did not alter urinary kallikrein. Mineralocor-ticoid inhibition by spironolactone induced a natriuresis in four patients with ascites (from 1.4–140 mEq. Na⁺/day) but also failed to alter kallikrein. Thus, kallikrein excretion is paradoxically reduced and seemingly unresponsive to alterations in the prostaglandin and renin-aldosterone systems. If urinary kallikrein quantitatively reflects intrarenal kallikrein-kinin activity, the impairment in this vasodilatory system may mediate the altered renal hemodynamics of severe liver disease.