The breakdown of pre‐existing advanced glycation end products is associated with reduced renal fibrosis in experimental diabetes

Abstract

SPECIFIC AIMSThe aim of this study was to investigate the hypothesis that renal injury in diabetes is partly mediated by AGEs and that the cross-link breaker ALT-711 as a delayed intervention, once early renal injury is evident, is capable of improving renal structure and function. The potential molecular mediators of AGE-induced renal injury were assessed, including TGF-β, CTGF, as well as expression of collagens.PRINCIPAL FINDINGS 1. Systolic blood pressure was increased in diabetic animals compared with controls (C) (P<0.001 vs. C) Onset of treatment with ALT-711 either late after 24 wk of diabetes (DALT late) or early after 16 wk of diabetes (DALT early) was associated with a decrease in blood pressure (DALT early, wk 16 vs. wk 24, P<0.01; DALT late, wk 24 vs. wk 32, P<0.01) resulting in lower blood pressures for the treated groups when compared with untreated diabetic rats at 32 wk (P<0.01, DALT late vs. D; P<0.05, DALT early vs. D). 2. Twenty-four hour albumin excretion rate (AER) increased over tim...