ACUTE-RENAL-FAILURE AND SEPSIS - THERAPEUTIC APPROACHES

Previous studies of experimental sepsis suggested that excessive syste mic vasodilatation might be the stimulus to renal hypofiltration and f luid retention in sepsis. Successful therapy for this syndrome require s agents that either act to improve systemic haemodynamics without adv erse renal effects, or that act directly on the kidney without impairi ng circulatory homeostasis. The plasma kallikrein-kinin system is a po tent vasodilator pathway, activated by endotoxin. We studied the effec t of aprotinin (Trasylol), which inhibits plasma kallikrein, in an ovi ne model of surgically-induced intra-abdominal sepsis. Given either as an early or late intervention, aprotinin was associated with increase d mean arterial pressure and systemic vascular resistance, improved gl omerular filtration rate, and increased urinary sodium excretion. In f urther studies, treatment with the thromboxane synthetase inhibitor, U 63,557A (Upjohn), either before or after the surgical induction of per itonitis, was associated with increased glomerular filtration rate and sodium excretion, without any effect on systemic haemodynamics. Logic al use of specific antagonists, based on an understanding of the patho physiology of the septic ARF syndrome, is a desirable strategy.