The purpose of this study is to add to this body of evidence that Sulodexide may offer additional benefit in preventing or ameliorating more advanced diabetic nephropathy manifested as overt proteinuria and reduced GFR. Subjects with type 2 diabetes, moderately elevated serum creatinine and overt proteinuria will be treated with a standardized maximal recommended/tolerated dose of irbesartan 300 mg/day or losartan 100 mg/day plus additional concomitant non-ARB, non-ACEi antihypertensive drugs,for up to 2-3 months to establish adequate and stable blood pressure control and urine protein excretion. After establishing baseline serum creatinine and urine protein excretion they will be randomized to either Sulodexide 200 mg/d or matching placebo. Subjects will be seen every 3 months to monitor safety and efficacy parameters for up to 4 years. The primary outcome is a doubling of baseline serum creatinine (50% loss of kidney function) or end stage kidney disease (ESRD).