Late intervention with the small molecule BB3 mitigates postischemic kidney injury

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


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acute Kidney Injury / pathology
  • Acute Kidney Injury / prevention & control*
  • Animals
  • Apoptosis
  • Hepatocyte Growth Factor / metabolism
  • Kidney Tubules / pathology
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Regeneration / drug effects
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control*


  • Hepatocyte Growth Factor