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Am J Physiol Renal Physiol. 2016 Aug 1;311(2):F352-61. doi: 10.1152/ajprenal.00455.2015. Epub 2016 Jun 1.

Late intervention with the small molecule BB3 mitigates postischemic kidney injury.

Author information

1
Department of Preclinical Research, Angion Biomedica Corporation, New York, New York; pnarayan@angion.com.
2
Department of Preclinical Research, Angion Biomedica Corporation, New York, New York;
3
Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, New York; and.
4
Division of Nephrology, Department of Medicine, University of Maryland Medical Center, Baltimore, Maryland.

Abstract

Ischemia-reperfusion-mediated acute kidney injury can necessitate renal replacement therapy and is a major cause of morbidity and mortality. We have identified BB3, a small molecule, which when first administered at 24 h after renal ischemia in rats, improved survival, augmented urine output, and reduced the increase in serum creatinine and blood urea nitrogen. Compared with control kidneys, the kidneys of BB3-treated animals exhibited reduced levels of kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, and reduced tubular apoptosis and acute tubular necrosis but enhanced tubular regeneration. Consistent with its hepatocyte growth factor-like mode of action, BB3 treatment promoted phosphorylation of renal cMet and Akt and upregulated renal expression of the survival protein Bcl-2. These data suggest that the kidney is amenable to pharmacotherapy even 24 h after ischemia-reperfusion and that activation of the hepatocyte growth factor signaling pathway with the small molecule BB3 confers interventional benefits late into ischemia-reperfusion injury. These data formed, in part, the basis for the use of BB3 in a clinical trial in kidney recipients presenting with delayed graft function.

KEYWORDS:

ischemia-reperfusion; kidney; small molecule; therapy

PMID:
27252491
PMCID:
PMC5008674
DOI:
10.1152/ajprenal.00455.2015
[Indexed for MEDLINE]
Free PMC Article

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