AMINOGUANIDINE DECREASES URINARY ALBUMIN AND HIGH-MOLECULAR-WEIGHT PROTEINS IN DIABETIC RATS

The effect of aminoguanidine (AG) on diabetic proteinuria was studied in control rats ([C]), streptozotocin (SZ)-induced diabetic rats ([DM]), control rats treated with AG ([C + AG]), or diabetic rats treated with AG ([DM + AG]). Increased glycation of hemoglobin (HbA1c), and glomerular basement membrane (GBM) type IV collagen (IV-C) at 10 wk of stable diabetes were associated with the appearance of high-molecular-weight (HMW) cross-linked type I collagen and HMW proteinuria of 62 kD, 69 kD albumin and 77 kD proteins to the levels of 362, 381, and 408%, while 9.9, 13.5, 17, 18, and 23 kD proteins were decreased, respectively, to non-detectable, 37, 16, and 13%. AG decreased cross-linkage of type I collagen and significantly decreased urinary 62 kD protein to 54%, 69 kD albumin to 40%, and 77 kD protein to 49% at 10 wk in [DM + AG] compared to [DM] without changing diabetic control. It is suggested that glycation-derived late-stage protein modification is etiologically important for diabetic proteinuria, and that AG can potentially prevent diabetic HMW proteinuria.