Renoprotective effects of adding angiotensin II receptor blocker to maximal recommended doses of ACE inhibitor in diabetic nephropathy: a randomized double-blind crossover trial.
OBJECTIVE
We evaluated the renoprotective effects as reflected by short-term changes in albuminuria of dual blockade of the renin-angiotensin system (RAS) by adding an angiotensin II receptor blocker (ARB) to treatment with maximal recommended doses of an ACE inhibitor (ACEI) in patients with type 2 diabetes and nephropathy.


METHODS
A total of 20 patients (17 men and 3 women) with type 2 diabetes along with hypertension and nephropathy were enrolled in this double-blind, randomized, two-period, crossover trial of 8 weeks of treatment with the ARB candesartan 16 mg daily and placebo added in random order to existing treatment with lisinopril/enalapril 40 mg daily or captopril 150 mg daily. At the end of each treatment period, we evaluated albuminuria in three 24-h urinary collections by turbidimetry, 24-h ambulatory blood pressure (ABP) using the Takeda-TM2420, and glomerular filtration rate (GFR) by the (51)Cr-EDTA plasma-clearance technique.


RESULTS
During monoblockade of the RAS by ACEI treatment, albuminuria was 706 (349-1,219) mg/24 h [geometric mean (IQR)]; 24-h ABP was 138 +/- 3/72 +/- 2 mmHg (mean +/- SE); and GFR was 77 +/- 6 ml x min(-1) x 1.73 m(-2) (mean +/- SE). During dual blockade of the RAS by addition of candesartan 16 mg daily, there was a mean (95% CI) reduction in albuminuria of 28 (17-38) compared with ACEI alone (P < 0.001). There was a modest reduction in systolic/diastolic 24-h ABP of 3/2 mmHg (-2 to 8 systolic, -2 to 5 diastolic; NS). Changes in albuminuria did not correlate to changes in ABP. Addition of candesartan 16 mg daily induced a small, insignificant decrease in GFR of 4 (-1 to 9) ml x min(-1) x 1.73 m(-2).


CONCLUSIONS
Dual blockade of the RAS provides superior short-term renoprotection independent of systemic blood pressure changes in comparison with maximally recommended doses of ACEI in patients with type 2 diabetes as well as nephropathy.
Rossing
Kasper
K
Steno Diabetes Center, Gentofte, Denmark. krossing@dadlnet.dk
Jacobsen
Peter
P
Pietraszek
Lotte
L
Parving
Hans-Henrik
HH
D000368:Aged; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001562:Benzimidazoles / Q000008:administration & dosage*; D001713:Biphenyl Compounds; D002216:Captopril / Q000008:administration & dosage; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000209:etiology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects; D017706:Lisinopril / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D013777:Tetrazoles / Q000008:administration & dosage*; D016896:Treatment Outcome
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D004656:Enalapril; D002216:Captopril; D017706:Lisinopril; C081643:candesartan