Abstract
Although multiple antihypertensive agents are required to control blood pressure (BP) in chronic renal disease, it remains undetermined whether the combination therapy with angiotensin receptor blockers (ARB) plus calcium antagonists or angiotensin-converting enzyme inhibitors (ACEI) confers more preferable action on renal disease than the ARB monotherapy. In the present study, we compared the effect of the combination therapy with ARB plus calcium antagonists/ACEI on proteinuria with that of the ARB monotherapy in chronic nondiabetic renal disease. At 1 month of the drug treatment, the candesartan monotherapy (n=19) reduced BP from 154±3/93±2 to 146±3/88±2 mmHg (P<0.05), and a similar magnitude of BP reductions was observed with the combination therapy with candesartan plus ACEI/amlodipine (from 153±2/95±2 to 144±2/88±2 mmHg, P<0.05, n=39). The depressor action of these therapies was sustained throughout the 12-month treatment. In contrast, the reduction in proteinuria was greater with the combination therapy (−52±3% at 12 months, n=39) than with the candesartan monotherapy (−25±3%, n=19), although the baseline values of proteinuria were nearly the same in the candesartan monotherapy group (1.74±0.22 g/day) and the combination therapy group (2.10±0.19 g/day, P>0.2). Of note, the proteinuria-sparing effect did not differ between the candesartan+ACEI group and the candesartan+amlodipine group. In conclusion, the present study suggests more beneficial action of the combination therapy with ARB plus ACEI/amlodipine than the ARB monotherapy in nondiabetic renal disease. Since the reduction in BP was achieved to the same level, the distinct proteinuria-sparing action of these therapies is attributed to BP-independent mechanisms, which should vary depending on the agents used.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 digital issues and online access to articles
$119.00 per year
only $9.92 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Shulman NB et al. Prognostic value of serum creatinine and effect of treatment of hypertension on renal function. Results from the hypertension detection and follow-up program. The Hypertension Detection and Follow-up Program Cooperative Group. Hypertension 1989; 13(5 Suppl): I80–I93.
Eddy AA . Interstitial nephritis induced by protein-overload proteinuria. Am J Pathol 1989; 135: 719–733.
Pedrini MT et al. The effect of dietary protein restriction on the progression of diabetic and nondiabetic renal disease: a meta-analysis. Ann Intern Med 1996; 124: 627–632.
Klahr S et al. The effects of dietary protein restriction and blood pressure control on the progression of chronic renal disease. N Engl J Med 1994; 330: 877–884.
Peterson JC et al. Blood pressure control, proteinuria, and the progression of renal disease. Ann Intern Med 1995; 123: 754–762.
Imanishi M et al. Mechanism of decreased albuminuria caused by angiotensin converting enzyme inhibitor in early diabetic nephropathy. Kidney Int Suppl 1997; 63: S198–S200.
Raij L, Shultz PJ, Tolins JP . Possible mechanism for the renoprotective effect of angiotensin converting enzyme inhibitors. J Hypertens Suppl 1989; 7: S33–S36.
Klag MJ et al. Blood pressure and end-stage renal disease in men. N Engl J Med 1996; 334: 13–18.
Bakris GL et al. Preserving renal function in adults with hypertension and diabetes: a consensus approach. Am J Kidney Dis 2000; 36: 646–661.
Russo D et al. Coadministration of losartan and enalapril exerts additive antiproteinuric effect in IgA nephropathy. Am J Kidney Dis 2001; 38: 18–25.
Nakao N et al. Combination treatment of angiotensin-II receptor blocker and angiotensin-converting-enzyme inhibitor in non-diabetic renal disease (COOPERATE): a randomized controlled trial. Lancet 2003; 361: 117–124.
Frohlich ED et al. Recommendations for human blood pressure determination by sphygmomanometers. Hypertension 1988; 11: 210A–216A.
Matsuda H, Hayashi K, Saruta T . Distinct time courses of renal protective action of angiotensin receptor antagonists and ACE inhibitors in chronic renal disease. J Hum Hypertens 2003; 17: 271–276.
Matsuda H et al. Zonal heterogeneity in action of angiotensin-converting enzyme inhibitor on renal microcirculation: role of intrarenal bradykinin. J Am Soc Nephrol 1999; 10: 2272–2282.
Endo Y et al. Function of angiotensin II type 2 receptor in the postglomerular efferent arteriole. Kidney Int Suppl 1997; 63: S205–S207.
Herlitz H et al. The effects of an ACE inhibitor and a calcium antagonist on the progression of renal disease: the Nephros Study. Nephrol Dial Transplant 2001; 16: 2158–2165.
Hayashi K et al. Disparate effects of calcium antagonist on renal microcirculation. Hypertens Res 1996; 19: 31–36.
Jinno T et al. Calcium channel blocker azelnidipine enhances vascular protective effect of AT1 receptor blocker olmesartan. Hypertension 2004; 43: 263–269.
Mogensen CE et al. Randomized controlled trial of dual blockade of renin–angiotensin system in patients with hypertension, microalbuminuria, and non-insulin dependent diabetes: the candesartan and lisinopril microalbuminuria (CALM) study. Br Med J 2000; 321: 1440–1444.
Kuriyama S et al. Antiproteinuric effects of combined antihypertensive therapies in patients with overt type 2 diabetic nephropathy. Hypertens Res 2002; 25: 849–855.
Staessen J et al. Rise in plasma concentration of aldosterone during long-term angiotensin II suppression. J Endocrinol 1981; 91: 457–465.
Rocha R, Chander PN, Zuckerman A, Stier Jr CT . Role of aldosterone in renal vascular injury in stroke-prone hypertensive rats. Hypertension 1999; 33(1 Part 2): 232–237.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Homma, K., Hayashi, K., Kanda, T. et al. Beneficial action of candesartan cilexetil plus amlodipine or ACE inhibitors in chronic nondiabetic renal disease. J Hum Hypertens 18, 879–884 (2004). https://doi.org/10.1038/sj.jhh.1001761
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.jhh.1001761
Keywords
This article is cited by
-
Targeting mechanisms of hypertensive vascular disease with dual calcium channel and renin–angiotensin system blockade
Journal of Human Hypertension (2007)
-
Combination therapy with renin-angiotensin system blockers: Will amlodipine replace hydrochlorothiazide?
Current Hypertension Reports (2007)