Prevention of diabetic nephropathy with enalapril in normotensive diabetics with microalbuminuria.

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Abstract
STUDY OBJECTIVE--To assess the effectiveness of inhibition of angiotensin converting enzyme in preventing diabetic nephropathy. DESIGN--Randomised follow up study of normotensive diabetics with persistent microalbuminuria (30-300 mg/24 hours) treated with enalapril or its matched placebo for one year. Double blind for first six months, single blind for last six months. SETTING--Diabetic clinic in tertiary referral centre. PATIENTS--Treatment group and placebo group each comprised 10 normotensive diabetics with persistent microalbuminuria. INTERVENTIONS--Treatment group was given enalapril 20 mg daily and controls matched placebo. Patients were given antihypertensive treatment after one year. END POINT--Albumin excretion, arterial pressure, and renal function. MAIN RESULTS--In last three months of trial three of 10 patients taking placebo had diabetic nephropathy (albumin excretion greater than 300 mg/24 hours). No patients taking enalapril developed nephropathy and five showed normal albumin excretion (less than 30 mg/24 hours) (p = 0.005, Mann-Whitney test). Mean arterial pressure was reduced by enalapril throughout study (p less than 0.005) but increased linearly with placebo (p less than 0.05). Albumin excretion decreased linearly with enalapril but not placebo. An increase in albumin excretion with placebo was positively related to the increase in mean arterial pressure (r = 0.709, p less than 0.05, Spearman's rank test). With enalapril total renal resistances and fractional albumin clearances improved progressively (time effect, p = 0.0001). CONCLUSION--Inhibition of angiotensin converting enzyme prevents development of nephropathy in normotensive diabetics with persistent microalbuminuria. This may be due to reduction in intraglomerular pressure and to prevention of increased systemic blood pressure. Future studies should compare long term effects of inhibitors of converting enzyme with other antihypertensive drugs.