Effects of ACE inhibition supplementary to beta blockers and diuretics in early diabetic nephropathy.
Angiotensin converting enzyme (ACE) inhibition has shown promising results in diabetic nephropathy, but long-term results on survival are not available. In a cohort of patients receiving antihypertensive treatment predominantly consisting of beta blockers in combination with diuretics, support for an improved survival has been presented. Addition of ACE inhibition to such a combination treatment may be favorable both due to the suggested renoprotective effects of ACE inhibitors and because diuretics activate the renin-angiotensin system. In 10 insulin-dependent diabetic patients with early diabetic nephropathy [urinary albumin excretion rate (UAE) less than 100o micrograms/min], who were receiving continuous therapy with metoprolol and bendroflumethiazide, a double-blind crossover study with four months addition of ramipril 5 mg (Ramace) and placebo was conducted. UAE (radioimmunoassay) and fractional albumin excretion were significantly reduced after the four months of ramipril administration [UAE: 114.1 x/divided by 1.3 (geometric mean x/divided by confidence factor] versus 174.6 x/divided by 1.2 micrograms/min, 2P less than 0.005). Renal plasma flow (clearance of 131I-hippuran) tended to increase [497 +/- 25 (mean +/- SE) vs. 464 +/- 28 ml/min/1.73 m2, 2P = 0.08], while GFR (125I-iothalamate) stayed unchanged (121 +/- 8 vs. 120 +/- 9 ml/min/1.73 m2). Mean arterial pressure during clearance studies fell moderately (95 +/- 3 vs. 101 +/- 1 mm Hg, 2P less than 0.05) and renal resistance was decreased (2P less than 0.03). ACE activity was suppressed in all patients. Twenty-four-hour ambulatory blood pressure measurements were not significantly different after the two periods (daytime averages: 91 +/- 2 vs. 93 +/- 2, nighttime 80 +/- 2 vs. 84 +/- 3 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)
Medical Department M. Diabetes and Endocrinology, Kommunehospitalet, University Hospital, Aarhus, Denmark.
M M
MM
Pedersen
K W
KW
Hansen
A
A
Schmitz
K
K
Sørensen
C K
CK
Christensen
C E
CE
Mogensen
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001794:Blood Pressure; D003928:Diabetic Nephropathies / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D004232:Diuretics / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004452:Echocardiography; D005260:Female; D006728:Hormones / Q000097:blood; D006801:Humans; D007668:Kidney / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000097:blood
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D004232:Diuretics; D006728:Hormones; D007703:Peptidyl-Dipeptidase A