Acute renal failure and sepsis: therapeutic approaches.
Previous studies of experimental sepsis suggested that excessive systemic vasodilatation might be the stimulus to renal hypofiltration and fluid retention in sepsis. Successful therapy for this syndrome requires agents that either act to improve systemic haemodynamics without adverse renal effects, or that act directly on the kidney without impairing circulatory homeostasis. The plasma kallikrein-kinin system is a potent vasodilator pathway, activated by endotoxin. We studied the effect of aprotinin (Trasylol), which inhibits plasma kallikrein, in an ovine model of surgically-induced intra-abdominal sepsis. Given either as an early or late intervention, aprotinin was associated with increased mean arterial pressure and systemic vascular resistance, improved glomerular filtration rate, and increased urinary sodium excretion. In further studies, treatment with the thromboxane synthetase inhibitor, U63,557A (Upjohn), either before or after the surgical induction of peritonitis, was associated with increased glomerular filtration rate and sodium excretion, without any effect on systemic haemodynamics. Logical use of specific antagonists, based on an understanding of the pathophysiology of the septic ARF syndrome, is a desirable strategy.
Cumming
A D
AD
University Dept of Medicine, Royal Infirmary, Edinburgh, UK.
D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000209:etiology* / Q000517:prevention & control; D000818:Animals; D007611:Aprotinin / Q000494:pharmacology; D001572:Benzofurans / Q000494:pharmacology; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D016234:Kallikrein-Kinin System / Q000187:drug effects; D009318:Natriuresis / Q000187:drug effects; D010538:Peritonitis / Q000150:complications; D018805:Sepsis / Q000150:complications*; D012756:Sheep; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D001572:Benzofurans; D007611:Aprotinin; D013930:Thromboxane-A Synthase; C039936:furegrelate