Effect of enalapril on urinary glycosaminoglycan, heparan sulphate and microalbuminuria in type II diabetic patients

Abstract

Recent studies in diabetic humans have shown that angiotensin converting enzyme (ACE) inhibitors may provide additional renal benefit above and beyond conventional antihypertensive agents. We investigated the effect of enalapril on urinary glycosaminoglycans (GAG), heparan sulphate (HS) and microalbuminuria (MAU) in diabetic patients. Urinary GAG and HS levels were determined in controls (n=16, 41.3 +/- 12.9 years old) and in type II diabetics (n=18, 53 +/- 9.6 years old) who were not using ACE inhibitors. Four of these patients had also hypertension. The duration of diabetes was 5.5 +/- 3 years (mean +/- SD). Microalbuminuria was detected in seven patients. The subjects were treated with enalapril (5-10 mg day-1) for 6 weeks. The median values of GAG (n=18, 2.8 mg uronic acid g-1 crea. day-1) and HS (n=18, 1.36 mg glycosamine g-1 crea. day-1) in the pre-treatment group were significantly (p < 0.01) higher than the control group (n=16, 1.98 mg uronic acid g-1crea. day-1 and 0.87 mg glycosamine g-1crea. day-1, respectively. Before treatment, GAG and HS levels seemed to be not different between microalbuminuric and normoalbuminuric as well as hypertensive and normotensive patients. Following enalapril treatment, the median values of GAG (n=18, 1.35 mg uronic acid g-1 crea. day-1) and HS (n= 18, 0.99 mg glycosamine g-1 crea. day-1) tended to decrease to the levels which were not significantly different from the control group. Following treatment, significant reduction in urinary albumin excretion (from 15.45 to 11.1 mg day-1) (p < 0.0005) was also observed. When considering the pre- and post-treatment concentrations, there were positive correlations between urinary GAG and HS values (p < 0.05, r=0.6541 and p < 0.01, r=0.5984). These results suggest that measurement of urinary heparan sulphate may be another useful predictor of clinical diabetic nephropathy; and enalapril causes marked reduction in HS and GAG values in all patients independently by the presence of hypertension.