Low-dose ramipril reduces microalbuminuria in type 1 diabetic patients without hypertension: results of a randomized controlled trial.
OBJECTIVE
To assess if low (1.25 mg) and/or standard (5 mg) doses of the ACE inhibitor ramipril could prevent progression of microalbuminuria (incipient diabetic nephropathy) in normotensive type 1 diabetic patients.


METHODS
This study, using a multicenter randomized placebo-controlled double-blind parallel group, was conducted over 2 years in 28 outpatient diabetic clinics in the U.K. and Ireland. We screened 334 type 1 diabetic patients with suspected microalbuminuria and normal blood pressure; of these, 140 patients 18-65 years of age with a diagnosis of type 1 diabetes and persistent microalbuminuria, defined as urinary albumin excretion rate (AER) of 20-200 microg/min, were enrolled in the study.


RESULTS
The proportion of patients progressing to macroalbuminuria was reduced in the ramipril groups but did not reach statistical significance over 2 years. AER was significantly lower at year 2 in the combined ramipril-treated patients versus placebo (P = 0.013). More patients on ramipril regressed to normoalbuminuria (<20 microg/min), with 11% for 1.25 mg ramipril, 20% for 5 mg ramipril, and 4% for placebo (P = 0.053). Blood pressure was significantly reduced to a similar extent with both 1.25 and 5 mg ramipril. Supine systolic blood pressure increased from 130 to 134 mmHg in the placebo group and fell in the 1.25 mg ramipril group (from 132 to 129 mmHg) and in the 5 mg ramipril group (from 134 to 130 mmHg) (P = 0.003, compared with placebo). No statistically significant changes were observed in glomerular filtration rate (GFR) between the placebo- and ramipril-treated groups during the 2-year period.


CONCLUSIONS
Microalbuminuria is reduced significantly by ramipril treatment in type 1 diabetic patients without hypertension. Although the magnitude of the response was greater, there is no significant difference between responses to 1.25 or 5 mg ramipril. Small but highly significant reductions in systolic and mean arterial pressures occur in ramipril-treated patients. GFR is stable at this stage of the evolution of diabetic nephropathy and is unaffected by ramipril treatment for 2 years.
O'Hare
P
P
Sir Quentin Hazel Institute of Molecular Medicine, University of Warwick, Gibbet Hill, Coventry, CV47AL, England, U.K.
Bilbous
R
R
Mitchell
T
T
O' Callaghan
C J
CJ
Viberti
G C
GC
D000293:Adolescent; D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000188:drug therapy* / Q000503:physiopathology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D001794:Blood Pressure; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000652:urine; D004311:Double-Blind Method; D005260:Female; D005919:Glomerular Filtration Rate; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007494:Ireland; D008297:Male; D008875:Middle Aged; D010919:Placebos; D017257:Ramipril / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D006113:United Kingdom
D000806:Angiotensin-Converting Enzyme Inhibitors; D006442:Glycated Hemoglobin; D010919:Placebos; D017257:Ramipril