Dual blockade of the rennin-angiotensin system versus maximal recommended dose of angiotensin II receptor blockade in chronic glomerulonephritis.
BACKGROUND
Proteinuria and hypertension are predictors of poor renal outcome in chronic glomerulonephritis (CGN). At the same level of blood pressure (BP) control, we evaluated which is superior, dual blockade of the rennin-angiotensin system (RAS) with both angiotensin-converting enzyme inhibitor (ACEI) and angiotensin II type 1 (AT-1) receptor blockade (ARB) or single blockade of ARB to reduce proteinuria and to preserve renal function in patients with CGN.


METHODS
In this prospective, parallel, open study of 86 patients with CGN, we compared the effects on proteinuria and renal functions of 36 months with comparable blood pressure (BP) control achieved by candesartan cilexetil (candesartan, 4-12 mg/day) or benazepril hydrochrolide (benazepril, 2.5-10 mg/day) with candesartan (4 mg/day). Aiming at BP 125/75 mmHg or less, the dose of candesartan (single blockade) or benazepril (dual blockade) was increased.


RESULTS
Dual blockade decreased proteinuria more than single blockade with ARB (-42.3 vs. -60.5%, P < 0.01). Renal plasma flow (RPF) and glomerular filtration fraction (GFR) did not change significantly in either group. The filtration fraction (FF) decreased dual blockade more than single blockade (-1.7 vs. -19.0%, P < 0.05). Decreased FF was associated with the reduction of proteinuria (P < 0.05). Six percent of patients with dual blockade were not able to continue the study because of a dry cough.


CONCLUSIONS
Long-term dual blockade decreased proteinuria more than single blockade with ARB. Although ARB and ACEI have a glomerular size-selective function for proteinuria, a greater antiproteinuric effect may depend on renal hemodynamics, especially FF. Increased levels of bradykinin after ACEI can decrease FF and ameliorate proteinuria. Dry cough is a significant adverse effect of ACE inhibitor.
Mori-Takeyama
Urara
U
Second Department of Internal Medicine, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan.
Minatoguchi
Shinya
S
Murata
Ichijirou
I
Fujiwara
Hisayoshi
H
Ozaki
Yoko
Y
Ohno
Michiya
M
Oda
Hiroshi
H
Ohashi
Hiroshige
H
D000328:Adult; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D001552:Benzazepines / Q000008:administration & dosage / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002908:Chronic Disease / Q000188:drug therapy; D004359:Drug Therapy, Combination; D005260:Female; D005921:Glomerulonephritis / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000188:drug therapy; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013777:Tetrazoles / Q000008:administration & dosage / Q000627:therapeutic use*
D047228:Angiotensin II Type 1 Receptor Blockers; D001552:Benzazepines; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; C077793:candesartan cilexetil; C044946:benazepril