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Renal kallikrein excretion in alcoholic cirrhosis. Relationship to other vasoactive systems
Insights
Patients with severe liver disease show reduced urinary kallikrein, a key component of the vasodilatory kallikrein-kinin system. This impairment appears independent of prostaglandin and renin-aldosterone systems, potentially explaining altered kidney function in liver disease.
Area of Science:
- Nephrology
- Hepatology
- Endocrinology
Background:
- Severe liver disease frequently causes renal hemodynamic alterations.
- Vasoactive hormones are implicated in these renal changes.
- The role of the renal kallikrein-kinin system in liver disease is understudied.
Purpose of the Study:
- To investigate urinary kallikrein excretion in patients with alcoholic cirrhosis.
- To evaluate the relationship between kallikrein, renin, aldosterone, and prostaglandins in these patients.
Main Methods:
- Measurement of urinary kallikrein, renin, aldosterone, and prostaglandins in nine patients with alcoholic cirrhosis under controlled metabolic conditions.
- Assessment of creatinine clearance.
- Evaluation of the effects of prostaglandin inhibitors and spironolactone (mineralocorticoid inhibition).
Main Results:
- Urinary kallikrein was significantly diminished in patients with alcoholic cirrhosis compared to controls (P < 0.05).
- Plasma renin and aldosterone levels were generally elevated, as expected.
- Prostaglandin inhibition reduced urinary prostaglandin E and creatinine clearance but did not affect urinary kallikrein.
- Spironolactone administration induced natriuresis but did not alter kallikrein excretion.
Conclusions:
- Kallikrein excretion is paradoxically reduced in severe liver disease.
- This reduction appears unresponsive to changes in prostaglandin and renin-aldosterone systems.
- Impaired intrarenal kallikrein-kinin system activity may contribute to altered renal hemodynamics in liver disease.
Abstract:
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 and 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 less than 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. Mineralocorticoid 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.