ACE-inhibition and renoprotection in early diabetic nephropathy. Response to enalapril acutely and in long-term combination with conventional antihypertensive treatment.
Early antihypertensive treatment with beta1 blockers and diuretics has proved to delay progression in diabetic nephropathy. Application of angiotensin converting enzyme inhibitors (ACE-I) may also be relevant. To elucidate possible differences in acute renal response to ACE-I and beta-blockers, kidney function was investigated before and after enalaprilat (10 mg) and metoprolol (10 mg) i.v. in 8 microalbuminuric insulin-dependent diabetic patients on no antihypertensive therapy (Study A). Glomerular filtration rate (clearance of 125I-iothalamate) was unchanged with both agents. ACE-I gave rise to efferent renal vasodilation: renal resistance and filtration fraction fell, renal plasma flow (RPF; 131I-hippuran) tended to rise (2p = 0.07) and blood pressure and urinary albumin excretion rate (UAE; radioimmunoassay) were reduced. In contrast, metoprolol caused a decline in RPF, an increase in renal resistance and filtration fraction, and no change in blood pressure or UAE. In 10 diabetic, nephropathic patients undergoing treatment with metoprolol and thiazide (Study B), the acute response to enalaprilat corresponded closely to that observed in Study A, including a decrease in UAE and blood pressure. Over 6 months the addition of enalapril (20 mg/d) to metoprolol and thiazide produced a more pronounced UAE-reduction, although no significant decrease in blood pressure was observed. The present findings support that ACE-I may process specific renoprotective effects. A combination therapy with beta1 blockers, ACE-I, and diuretics is suggested.
Pedersen
M M
MM
Medical Department M (Diabetes & Endocrinology), Aarhus Kommunehospital, Denmark.
Christensen
C K
CK
Hansen
K W
KW
Christiansen
J S
JS
Mogensen
C E
CE
D000328:Adult; D000419:Albuminuria / Q000652:urine; D001794:Blood Pressure / Q000187:drug effects; D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D003928:Diabetic Nephropathies / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D004359:Drug Therapy, Combination; D015773:Enalaprilat / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D008790:Metoprolol / Q000494:pharmacology / Q000627:therapeutic use*; D008875:Middle Aged; D009318:Natriuresis / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
D008790:Metoprolol; D015773:Enalaprilat