Prevention of diabetic nephropathy in db/db mice with glycated albumin antagonists. A novel treatment strategy.

• DOI: 10.1172/jci117926
• Publication Date: 2008-02-29T14:50:35Z
• Authors: M P Cohen; K Sharma; Y Jin; E Hud; V Y Wu; J Tomaszewski; F N Ziyadeh
• Keywords: Mesangium; Pathogenesis; Albuminuria; Serum Albumin

Accelerated protein glycation in diabetes has been mechanistically linked to the pathogenesis of diabetic nephropathy. Because glycated albumin induces abnormalities cultured mesangial cells that resemble those characterizing glomerular mesangium diabetes, and monoclonal antibodies (A717) specific for Amadori-modified prevent these abnormalities, we postulated vivo administration A717 could retard progression To test this hypothesis, db/db mice their nondiabetic db/m littermates were treated with eight consecutive weekly injections 150 micrograms (Fab fragments) reduce elevated plasma concentration, or irrelevant murine IgG (MIg). Relative nondiabetics, (MIg treated) manifested proteinuria (3.35 +/- 0.15 vs 0.87 0.1 mg albumin/mg creatinine), 3.8-fold increase matrix fraction, renal cortical overexpression mRNAs encoding alpha 1(IV) collagen (2.6-fold increase) fibronectin (3.8-fold increase). Treatment significantly reduced (1.52 0.3 mg/mg inhibited expansion, attenuated mRNAs. The nephropathic protective effects independent any change blood glucose concentrations. Antibodies unreactive did not duplicate beneficial A717. Thus, abrogating biologic increased a salutary influence on nephropathy novel therapeutic potential its management.