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New approaches to delay the progression of chronic renal failure
Saulo Klahr1, Jeremiah Morrissey, Keith Hruska
1of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110-1092, USA. sklahr@im.wustl.edu
Background:
The molecular cloning of many bone morphogenetic proteins (BMP)-encoding genes and their identification as transforming growth factor-beta (TGF-beta) relatives enhanced the interest in these molecules and allowed expression and functional studies to be performed.
Methods:
Rats with ureteral obstruction were distributed into four groups. Group 1 received vehicle, group 2 received enalapril 12.5 mg/kg body wt/day, group 3 received 50 or 300 microg/kg body wt BMP-7, and group 4 received both enalapril and the high dose of BMP-7. We also studied the effects of BMP-7 administration in a model streptozocin-induced diabetes.
Results:
Treatment with BMP-7 in rats with ureteral obstruction of 3 days duration and subsequent release indicated that this compound decreases interstitial volume and accelerates the return of renal function. After 16 weeks of diabetes, the rats were treated with BMP-7. The administration of BMP-7 partially reversed renal hypertrophy, restored GFR to normal, and decreased proteinuria.
Conclusions:
These studies indicate that administration of BMP-7 maintains and restores renal function and structure in animals with ureteral obstruction and diabetic nephropathy.