Aldosterone breakthrough during angiotensin II receptor blockade in hypertensive patients with diabetes mellitus.
BACKGROUND
Aldosterone is an important pathogenetic factor, independent of the renin-angiotensin system in cardiovascular and renal disease. Aldosterone breakthrough during angiotensin-converting enzyme (ACE) inhibitor therapy was reported in hypertension, diabetes mellitus, and chronic renal disease. It is unclear whether the angiotensin II receptor blocker (ARB) causes aldosterone breakthrough in patients with hypertension and diabetes mellitus, and whether aldosterone breakthrough contributes to renal injury in these patients.


METHODS
We prospectively studied 95 hypertensive patients with diabetes mellitus. Patients were treated with candesartan (8 mg/day, n = 47) or valsartan (80 mg/day, n = 48) for 15 months. Blood pressure (BP), urinary albumin excretion (UAE), biochemical markers, plasma aldosterone concentration (PAC), and plasma renin activity (PRA) were measured before and at 3, 6, 12, and 15 months of treatment. Nine patients who exhibited aldosterone breakthrough after treatment with ARB were placed on spironolactone (25 mg/day) for 3 months, and BP, UAE, and biochemical markers were measured after treatment.


RESULTS
Although the overall PAC was significantly decreased (P < .05) in each group, it eventually increased in 21 (candesartan, 11 patients; valsartan, 10 patients) of 95 patients (22%; aldosterone breakthrough). Blood pressure, PRA, and biomedical markers did not differ between the two groups during treatment. Although UAE was significantly decreased in patients with or without aldosterone breakthrough at 6 months, it was increased again at 15 months of treatment in patients with aldosterone breakthrough. Treatment with spironolactone markedly reduced UAE in these patients.


CONCLUSIONS
Aldosterone breakthrough was seen to be equal in hypertensive patients with diabetes mellitus treated with candesartan or valsartan. Aldosterone blockade therapy may be effective in preventing renal injury in hypertensive patients with aldosterone breakthrough.
Department of Internal Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.
Takashi
T
Yoneda
Yoshiyu
Y
Takeda
Mikiya
M
Usukura
Nobushige
N
Oda
Hiroyuki
H
Takata
Yasuhiro
Y
Yamamoto
Shigehiro
S
Karashima
Masakaz
M
Yamagishi
D000368:Aged; D000419:Albuminuria / Q000175:diagnosis; D000450:Aldosterone / Q000097:blood*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects* / Q000627:therapeutic use; D001562:Benzimidazoles / Q000009:adverse effects / Q000627:therapeutic use; D001713:Biphenyl Compounds; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003925:Diabetic Angiopathies / Q000188:drug therapy*; D003928:Diabetic Nephropathies / Q000209:etiology*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D013777:Tetrazoles / Q000009:adverse effects / Q000627:therapeutic use; D014633:Valine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D000068756:Valsartan
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D000450:Aldosterone; D000068756:Valsartan; D014633:Valine; C081643:candesartan