Maximal Dose of Angiotensin Converting Enzyme (ACE) Inhibitor for Treatment of Diabetic Kidney Disease

This is a randomized, double-blind cross-over study with three treatment periods consisting of 20, 40 and 60 mg lisinopril daily in random order. The endpoints of the study will be examined after each treatment period. There is no wash out between treatment periods. To minimize the risk of hypotension every treatment period starts with 20 mg lisinopril for two weeks. Thus, the risk of adverse effects is minimized and an increase in dose from 0 mg to 60 mg lisinopril is avoided. The patients usual antihypertensive treatments will be stopped in a period of 8 weeks (wash out) before randomization. Since diuretic drugs will be needed by almost every patient in the study to avoid oedema all patients will be treated with lasix retard 60 - 120 mg daily. Patients: 60 type 1 diabetic patients with diabetic nephropathy and hypertension (blood pressure \> 135 mm Hg systolic and/or 85 mm Hg diastolic). Methods: The endpoints of the study will be examined at baseline and after each treatment period corresponding to 8, 16, and 24 weeks after randomization. The following parameters are determined after each treatment period: Albuminuria (determined from three consecutive 24 hours urine collections), kidney function (GFR - by plasma clearance of 51Cr-EDTA ), and 24 hour ambulatory blood pressure (TM-2420/2421). Furthermore, the concentrations of TGF-ß, sodium, creatinine, and carbamide in the 24 hour urinary samples are determined. The plasma concentration of albumin, renin, angiotensin II, and aldosterone is measured. DNA is extracted from a blood sample and genetic variants in the renin-angiotensin system are measured including the ACE/ID genotype. Endpoints: Primary endpoint: albuminuria ; Secondary endpoints: blood pressure (24 hour ambulatory) and GFR; Tertiary: differences in response to treatment in patients with different ACE/ID and other renin angiotensin system genotypes.