Studies in Acute Renal Failure

Abstract

In a previously documented experimental model of acute renal failure in the rat (intravenous methemoglobin-ferrocyanide) 1 ml doses of 25% mannitol (1.21–1.54 g/kg) intravenously prevented both functional and histologic renal injury within –1 h and +30 min of attempted induction. When varying mannitol doses were given 15 min following attempted induction, a sigmoid log-log relationship of plasma urea nitrogen (PUN) concentration to mannitol dose was demonstrated. Mannitol doses above 300 mg/kg (at + 15 min) are estimated to be fully protective in the model. Similarly at 15 min following attempted induction, isosmolal 1 ml doses of aqueous mannitol, mannose, sucrose, sodium sulfate, sodium chloride, THAM [tris(hydroxymethyl)aminomethane] and thriceisosmolal urea prevented acute renal failure, but isosmolal urea and dextrose, isotonic saline and 6% human serum albumin did not. Both 6% dextran (av. mol. wt. 75,000) and 10% dextran (av. mol. wt. 40,000) intensified the lesions, possibly a unique reaction in the rat. Effective agents induced higher rates of urinary flow in anesthetized, normal rats than ineffective ones. The results indicate that, in this model, (a) several osmotic diuretic agents are capable of preventing acute renal failure; (b) preventive effectiveness correlates with the ability of an agent to induce prompt, brisk diuresis; (c) the preventive therapy must be timely to be effective; and (d) the probable protective mechanism is that the agent augments the pathogenetically-significant, reduced renal tubular fluid flow. The results also imply that the protective mechanism does not depend upon extracellular or plasma volume expansion, relief of renal ischemia, osmotic loading per se, or a specific chemical or pharmacological characteristic of any single agent.

Renin and Acute Renal Failure: Studies in Man

“…Susceptible states in which renin is known to be increased (see Brown et al, 1966a) include pregnancy, depletion of sodium or plasma volume, Addison's disease, cirrhosis with ascites, and terminal cardiac failure (Black and Williams, 1962; Shear et al, 1965;Thiel et al, 1967;Papper and Vaamonde, 1968;Kinsey Smith et al, 1968;Domenet and Evans, 1969). Conversely, sodium loading reduces plasma renin concentration (Brown et al, 1963(Brown et al, , 1964b and protects against acute renal failure (Teschan and Lawson, 1966;Wilson et al, 1967;Henry et al, 1968). Moreover, denervation of the kidney reduces its renin content (Ueda et al, 1967), and there is evidence that it may also protect the kidney against acute renal ilure-Brown et al (Powers et al, 1957).…”

Mitigation of amphotericin B nephrotoxicity by mannitol.

“…Though no direct measurements of renal blood flow were made they presumed that mannitol prevented the reduction of renal blood flow secondary to the renal vasoconstriction which occurs with amphotericin B (Butler et al, 1964 b). Mannitol protects against the development of acute renal failure (Teschan et al, 1966), and the demonstration of the prevention of mannitol of endothelial cell swelling that follows renal arterial pedicle clamping in the dog (Flores et al, 1972) lends further support to this concept.…”