Long-term renoprotection by perindopril or nifedipine in non-hypertensive patients with Type 2 diabetes and microalbuminuria.
OBJECTIVE
To assess the efficacy of an angiotensin converting enzyme (ACE) inhibitor (perindopril), a dihydropyridine calcium channel blocker (sustained release nifedipine) and placebo in preventing the progression of albuminuria and decline in glomerular filtration rate (GFR) in patients with Type 2 diabetes and microalbuminaria.


METHODS
A prospective, randomized, open, blinded end point study of 77 patients allocated to three treatment groups (23 perindopril, 27 nifedipine, 27 placebo). Drug doses were adjusted to achieve a decrease in diastolic blood pressure (DBP) of 5 mmHg in the first 3 months and additional therapy was given if hypertension developed (supine DBP > 90 mmHg and/or systolic blood pressure (SBP) > 140 mmHg if < or = 40 years; supine DBP > 90 mmHg and/or SBP > 160 mmHg if > 40 years). Median follow-up was 66 months, with 37 patients being followed for at least 6 years.


RESULTS
Blood pressure remained within the non-hypertensive range in 83% of perindopril-, 95% of nifedipine- and 30% of placebo-treated patients (P < 0.01). In the first 12 months albumin excretion rate (AER) decreased by 47% only in the perindopril group (P = 0.04). From 12 to 72 months, AER gradients increased by 27% per year only in the placebo group (P < 0.01). After 6 years, macroalbuminuria had developed in 7/15 placebo compared with 2/11 in perindopril and 1/11 nifedipine-treated patients (P = 0.05). GFR did not change in the first 12 months, but thereafter the median GFR gradient (ml/min/1.73 m(2) per year) was -2.4 (P < 0.01) for perindopril-, -1.3 (P = 0.26) for nifedipine- and -4.2 (P = 0.01) for placebo-treated patients. The rate of decline in GFR for the study group as a whole from 12 months to the end of follow-up correlated negatively with mean arterial pressure (MAP) (r = -0.38, P < 0.01). During a 3-month treatment pause in 29 patients AER tended to increase only in the perindopril group (P < 0.07).


CONCLUSIONS
Long-term control of blood pressure with perindopril or nifedipine stabilizes AER and attenuates GFR decline in proportion to MAP in non-hypertensive patients with Type 2 diabetes and microalbuminuria.
Jerums
G
G
Department of Medicine, University of Melbourne, and Endocrinology Unit, Austin Health, Studley Road, Heidelberg, 3084 Victoria, Australia. endo@austin.unimelb.edu.au
Allen
T J
TJ
Campbell
D J
DJ
Cooper
M E
ME
Gilbert
R E
RE
Hammond
J J
JJ
O'Brien
R C
RC
Raffaele
J
J
Tsalamandris
C
C
D000328:Adult; D000419:Albuminuria / Q000188:drug therapy* / Q000503:physiopathology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000503:physiopathology; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000627:therapeutic use*; D020913:Perindopril / Q000627:therapeutic use*; D011446:Prospective Studies
D000806:Angiotensin-Converting Enzyme Inhibitors; D002121:Calcium Channel Blockers; D009543:Nifedipine; D020913:Perindopril