Osteogenic protein-1 (bone morphogenetic protein-7) reduces severity of injury after ischemic acute renal failure in rat

J Clin Invest. 1998 Jul 1;102(1):202-14. doi: 10.1172/JCI2237.


We have shown that osteogenic protein-1 (OP-1) (bone morphogenetic protein-7) is responsible for the induction of nephrogenic mesenchyme during embryonic kidney development. Gene knock-out studies showed that OP-1 null mutant mice die of renal failure within the first day of postnatal life. In the present study, we evaluated the effect of recombinant human OP-1 for the treatment of acute renal failure after 60 min bilateral renal artery occlusion in rats. Bioavailability studies in normal rats indicate that approximately 1.4 microg OP-1/ml is available in the circulation 1 min after intravenous administration of 250 microg/kg, which then declines steadily with a half life of 30 min. About 0.5% of the administered OP-1 dose/g tissue is targeted for OP-1 receptors in the kidney. We show that OP-1 preserves kidney function, as determined by reduced blood urea nitrogen and serum creatinine, and increased survival rate when administered 10 min before or 1 or 16 h after ischemia, and then at 24-h intervals up to 72 h after reperfusion. Histochemical and molecular analyses demonstrate that OP-1: (a) minimizes infarction and cell necrosis, and decreases the number of plugged tubules; (b) suppresses inflammation by downregulating the expression of intercellular adhesive molecule, and prevents the accumulation and activity of neutrophils; (c) maintains the expression of the vascular smooth muscle cell phenotype in pericellular capillaries; and (d) reduces programmed cell death during the recovery. Collectively, these data suggest that OP-1 prevents the loss of kidney function associated with ischemic injury and may provide a basis for the treatment of acute renal failure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / drug therapy*
  • Animals
  • Apoptosis
  • Bone Morphogenetic Protein 7
  • Bone Morphogenetic Proteins / genetics
  • Bone Morphogenetic Proteins / pharmacology*
  • Growth Substances / genetics
  • Humans
  • Intercellular Adhesion Molecule-1 / analysis
  • Ischemia / drug therapy*
  • Kidney / blood supply*
  • Kidney / drug effects
  • Male
  • RNA, Messenger / analysis
  • Rats
  • Rats, Wistar
  • Recombinant Proteins / therapeutic use
  • Transforming Growth Factor beta*


  • BMP7 protein, human
  • Bmp7 protein, rat
  • Bone Morphogenetic Protein 7
  • Bone Morphogenetic Proteins
  • Growth Substances
  • RNA, Messenger
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • Intercellular Adhesion Molecule-1