engleski

Recombinant human OP-1 prevents rapid loss of glomerular function and improves mortality associated with chronic renal failure

We have shown that OP-1/BMP-7, a member of the TGF-B superfamily of proteins, is expressed predominantly in both developing and adult kidney and is capable of inducing metanephric mesenchyme differentiation during kidney development. These findings are further supported by the gene knock-out studies that show OP-1/BMP-7 null mutation mice die shortly after birth due to renal failure. In the present study, we examined the effect of systemically administered OP-1 to delay or halt progression of end stage renal failure in the 5/6 nephrectomy rat model. Recombinant human OP-1 at doses of 1, 10 and 100 ug per kg bw were administered three times per week intravenously through the tail vein beginning three weeks after surgery and continued 10 to 24 weeks. The protective action of OP-1 was monitored by serum blood urea nitrogen (BUN) and creatinine, glomerular filtration rate (GFR) and mortality. Kidneys were subjected to histopathology at the end of the study. The results show that 10 or 100 ug OP-1 per kg bw treated groups significantly decreases the elevated serum BUN and creatinine values from two weeks after the initiation of OP-1 therapy (five weeks post 5/6 nephrectomy) compared to control nephrectomy (Nx) group. The GFR was improved significatly in OP-1 treated group compared to vehicle treated Nx group. The mortality monitored during the course of the study also showed a statistically significant improvement in OP-1 treated groups as compared to vehicle treated Nx group. Histological evaluation of kidney tissue sections showed cytoprotection against glomerular sclerosis and there was also evidence of preservation of proximal and distal tubular structures. Our findings provide data to suggest that OP-1 may play a role in cell survival and tissue morphogenesis and, as such, may provide a basis for the treatment of chronic renal disease.

OP-1; chronic renal failure

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