We investigated the role of complement activation on the resolution of acute ischemic
renal failure in the rat.
Acute renal failure was induced by clamping of the renal arteries of Sprague-Dawley rats for 45 minutes (Day 0). On subsequent days, groups of rats with
acute renal failure were exposed to daily
zymosan infusion (an activator of the
complement system), or to blood incubated with
cuprophane (CUP) or
polyacrylonitrile (PAN) dialysis membranes. We serially measured the change in BUN daily, glomerular filtration rate and 24-hour
proteinuria on Day 3 and Day 5 following
ischemia. On Day 6, the animals were sacrificed and their kidneys examined histologically.
Zymosan and
cuprophane exposed rats had a significant delay in the recovery of
renal failure, reduced glomerular filtration rate, and histologically had more neutrophil infiltration than control or PAN exposed animals. To investigate the potential pathophysiology of these observations, we assessed the response of
zymosan-exposed rats to infusion of
deferoxamine (DFO), a potent inhibitor of
hydroxyl radical formation (
OH.). Infusion of DFO prior to
zymosan significantly improved recovery of renal function. We also measured urinary
thromboxane B2 levels in these groups of rats. While the groups of rats exposed to
zymosan had the highest levels of
thromboxane B2, these levels were not different between the groups exposed to
zymosan alone, or to
zymosan and DFO. These observations suggest a role for
hydroxyl radicals in the prolongation of
renal failure in this model. Taken together, these findings may have implications for the dialytic intervention in patients with
acute renal failure.