A five-year comparison of the renal protective effects of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in patients with non-diabetic nephropathy.
OBJECTIVE
Evidence suggests that the effectiveness of angiotensin-converting enzyme (ACE) inhibition diminishes with time, resulting in increasing angiotensin II levels, the action of which can be inhibited by the addition of an angiotensin receptor blocker (ARB). In the present study, the renal protective effects of ACE inhibitors and ARBs were compared over a five-year period in a prospective, randomized, open-blind study in 68 nondiabetic Japanese patients with elevated serum creatinine levels.


METHODS
Japanese patients with renal insufficiency were randomly assigned to receive either an ACE inhibitor (benazepril 1.25 to 5 mg daily or trandolapril 0.5 to 4 mg daily) or ARB (candesartan 2 to 8 mg daily or losartan 25 to 100 mg daily) at the Kidney Disease Center at Saitama Medical School Hospital. The primary study endpoint was a change in glomerular filtration rate (GFR) between the baseline value and the last available value obtained during the five-year treatment period, as estimated by the Cockcraft-Gault equation. Secondary endpoints included the annual changes in GFR, serum creatinine level, urinary protein excretion, and blood pressure, as well as the rate of development of endstage renal disease.


RESULTS
There were no significant differences in the primary endpoint between the two groups. However, after 4 years, the decline in GFR in patients treated with ARBs was significantly greater than that seen in patients treated with an ACE inhibitor (p<0.05). Furthermore, the rate of introduction of dialysis therapy was also significantly greater in the ARB-treated patients (52.7% in ACE inhibitor and 81.2% in ARB group at year 5. p<0.01).


CONCLUSIONS
While our data suggested that ARB, like ACE, treatment might slow the progression of renal dysfunction, it also pointed to the necessity to be alerted to the progression to endstage renal disease with longterm medication.
Department of Nephrology, Saitama Medical School, Iruma, Saitama.
Junko
J
Shoda
Yoshihiko
Y
Kanno
Hiromichi
H
Suzuki
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D001552:Benzazepines / Q000627:therapeutic use; D001562:Benzimidazoles / Q000627:therapeutic use; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D002908:Chronic Disease; D003404:Creatinine / Q000097:blood; D005260:Female; D005919:Glomerular Filtration Rate; D005921:Glomerulonephritis / Q000150:complications; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D019808:Losartan / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D051437:Renal Insufficiency / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D013777:Tetrazoles / Q000627:therapeutic use
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D001552:Benzazepines; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D007211:Indoles; D013777:Tetrazoles; C052035:trandolapril; D003404:Creatinine; D019808:Losartan; C081643:candesartan; C044946:benazepril