Journal
KIDNEY INTERNATIONAL
Volume 60, Issue 6, Pages 2205-2214Publisher
ELSEVIER SCIENCE INC
DOI: 10.1046/j.1523-1755.2001.00054.x
Keywords
leukocytes; disease models; kidney failure; delayed graft function; transplantation; cold kidney storage; renal artery clamping
Categories
Funding
- NIDDK NIH HHS [R0-1 DK54770] Funding Source: Medline
Ask authors/readers for more resources
Background. The pathophysiologic and potential therapeutic role of selectins in renal ischemia-reperfusion injury (IRI) is not fully understood, due in part to redundancy in the roles of individual selectins. We hypothesized that blockade of ligands for all three selectins using a novel small molecule (TBC-1269) would improve the course of renal IRI by overcoming redundancy issues. This was investigated in a rat model of renal IRI. Methods. Rats were treated with TBC-1269 either during or post-IRI. The effects of TBC-1269 were investigated in two models of renal IRI: moderate IRI (30 minutes bilateral renal artery clamping) and severe IRI (45 minutes clamping). The combination of anti-E- and anti-P-selectin antibodies also was investigated in rats subjected to moderate IRI. Renal function, histological injury and mortality were assessed. Results. Rats treated with TBC-1269 during moderate IRI showed significantly reduced serum creatinine (S-Cr) and tubular necrosis post-ischemia compared to control animals. By contrast, delayed treatment (post-IRI) did not show a reduction in S-Cr. In rats with severe IRI, TBC-1269 treatment during IRI significantly reduced mortality at 48 hours post-ischemia. Rats with moderate IRI and treated with the combination of anti-E- and anti-P-selectin antibodies showed significantly reduced S-Cr compared to control rats at 24 hours post-ischemia. Conclusions. Small molecule selectin ligand inhibition provides a novel and effective approach to attenuate ischemic acute renal failure. Timing of treatment is crucial to success.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available