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

Recent studies in diabetic humans have shown that angiotensin converting en zyme (ACE) inhibitors may provide additional renal benefit above and beyond conventional antihypertensive agents. We investigated the effect of enalap ril on urinary glycosaminoglycans (GAG), heparan sulphate (HS) and microalb uminuria (MAU) in diabetic patients. Urinary GAG and HS levels were determi ned 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 t hese 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 med ian 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 m g uronic acid g(-1) crea. day(-1) and 0.87 mg glycosamine g(-1) crea. day(- 1)), respectively. Before treatment, GAG and HS levels seemed to be not dif ferent between microalbuminuric and normoalbuminuric as well as hypertensiv e and normotensive patients. Following enalapril treatment, the median valu es 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 w hich were not significantly different from the control group. Following tre atment, significant reduction in urinary albumin excretion (from 15.45 to 1 1.1 mg day(-1)) (p < 0.0005) was also observed. When considering the pre- a nd 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 a nother useful predictor of clinical diabetic nephropathy; and enalapril cau ses marked reduction in HS and GAG values in all patients independently by the presence of hypertension.