BACKGROUND: Albuminuria is the best and most readily available marker for glomerular damage and progressive renal function loss in patients with diabetic nephropathy. Recently, administration of the oral glycosaminoglycan sulodexide (a mixture of 80% fast-moving heparin and 20% dermatan sulphate) was shown to effectively decrease albumin excretion rate in diabetics with nephropathy. AIMS: To evaluate whether the hypoalbuminuric effect of sulodexide is associated with improvement of the renal vascular or tubule function. METHODS: Forty-five type 1 diabetic patients, affected by diabetic nephropathy with albuminuria for at least 5 years, were randomly allocated to sulodexide or untreated. Those allocated to sulodexide were given 100 mg of sulodexide daily for 120 days. Renal vascular function (DIR) and N-acetyl-beta-D-glucosaminidase (NAG) excretion were estimated before and at the end of the study, the former in thesulodexide group only. DIR was measured as two Cr(cl) lasting 120 min (before and during 2 mug/kg b.w. i.v. dopamine). RESULTS: The analysis of trends during the study demonstrated a marked reduction of albuminuria in the sulodexide group (from 126.1 +/- 15.41 to 93.6 +/- 13.7 mg/day). DIR rose from 13.2 +/- 2.1% to 15.44 +/- 1.9% (relative increase: +16.9%), and NAG excretion showed a decreasing trend decreased in the sulodexide group only (from 5.1 +/- 0.62 to 4.7 +/- 0.40 U/g(creat)). CONCLUSION: The findings presented in this study indicate for the first time that orally available sulodexide may favorably affect the renal vascular function in type 1 diabetic patients with nephropathy and microalbuminuria. The effect of sulodexide on NAG is strongly influenced by the baseline NAG values, with a significant NAG reduction in the patients with the highest baseline NAG values.