An additive effect of anti-PAI-1 antibody to ACE inhibitor on slowing the progression of diabetic kidney disease.

An additive effect of anti-PAI-1 antibody to ACE inhibitor on slowing the progression of diabetic kidney disease. Am J Physiol Renal Physiol. 2016 Nov 1;311(5):F852-F863 Authors: Gu C, Zhang J, Noble NA, Peng XR, Huang Y Abstract While angiotensin II blockade slows the progression of diabetic nephropathy, current data suggest that it alone cannot stop the disease process. New therapies or drug combinations will be required to further slow or halt disease progression. Inhibition of plasminogen activator inhibitor type 1 (PAI-1) aimed at enhancing ECM degradation has shown therapeutic potential in diabetic nephropathy. Here, using a mouse model of type diabetes, the maximally therapeutic dose of the PAI-1-neutralizing mouse monoclonal antibody (MEDI-579) was determined and compared with the maximally effective dose of enalapril. We then examined whether addition of MEDI-579 to enalapril would enhance the efficacy in slowing the progression of diabetic nephropathy. Untreated uninephrectomized diabetic db/db mice developed progressive albuminuria and glomerulosclerosis associated with increased expression of transforming growth factor (TGF)-β1, PAI-1, type IV collagen, and fibronectin from weeks 18 to 22, which were reduced by MEDI-579 at 3 mg/kg body wt, similar to enalapril given alone from weeks 12 to 22 Adding MEDI-579 to enalapril from weeks 18 to 22 resulted in further reduction in albuminuria and markers of renal fibrosis. Renal ...
Source: American Journal of Physiology. Renal Physiology - Category: Physiology Authors: Tags: Am J Physiol Renal Physiol Source Type: research