engleski

Osteogenic Protein-1 Reduces Severity of Injury in Nephrotoxic and Ischemic Acute Renal Failure in Rat

Osteogenic protein-1 (OP-1/BMP-7), a member of TGF-b superfamily of proteins, is required for the kidney development and OP-1/BMP-7 null mutation mice die shortly after birth due to renal failure. In the present study, we examined the ability of systemically administered recombinant human OP-1 (250 ľg/kg) to modulate the degree of injury following either ischemia and reperfusion or toxic injury in a rat model. OP-1 was administered both 10 minutes before (prophylactic mode) or 1h after the onset of injury (therapeutic mode). Blood samples were obtained at 24h intervals following injury until sacrifice. 24h urine samples for GFR determination were collected on metabolic cages. Pharmacokinetic studies of the bioavailability of OP-1, using OP-1 enzyme immunoassay, indicate that high serum levels of OP-1 were achieved after iv injection followed by steadily decline with a half-time of about 30 min. The prophylactic and therapeutic effect of OP-1 indicate significant suppression of urea and creatinine serum levels and effective increase in the survival rate in both models tested. Additional biochemical and histochemical analyses demonstrate that OP-1: 1) improves glomerular filtration rate 2) significantly reduces serum potassium and phosphorus 3) minimizes infarction and cell necrosis and 4) reduces programmed cell death during the recovery phase. These results suggest taht OP-1 prevents kidney damage against toxic and ischemic insults.

acute renal failure; BMP-7

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