Annals
Established in 1927 by the American College of Physicians
:
Advanced search
Originally published on November 5, 2007.
box Article
 arrow  Table of Contents                
space
 arrow  Full Text of this article Free
space
 arrow  PDF of this article
space
All Versions of this Article:
  arrow 148/1/30 (most recent)
  arrow 0000605-200801010-00190v1
 arrow  Figures/Tables List
space
 arrow  Audio Summary
space
 arrow  Related articles in Annals
space
box Services
 arrow 
pier article
Related Clinical
Content
space
 arrow  Send comment/rapid response letter
space
 arrow  Notify a friend about this article
space
 arrow  Alert me when this article is cited
space
 arrow  Add to Personal Archive
space
 arrow  Download to Citation Manager
space
 arrow  ACP Search
space
 arrow  Get Permissions
space
box Google Scholar
 arrow  Search for Related Content
space
box Social Bookmarking
 Add to CiteULike Add to Complore Add to Connotea Add to Del.icio.us Add to Digg Add to Facebook Add to Reddit Add to Technorati Add to Twitter
What's this?
box PubMed
Articles in PubMed by Author:
 arrow  Kunz, R.
space
 arrow  Mann, J. F.E.
space
 arrow  Related Articles in PubMed
space
 arrow  PubMed Citation
space
 arrow  PubMed
space

REVIEW

Meta-analysis: Effect of Monotherapy and Combination Therapy with Inhibitors of the Renin–Angiotensin System on Proteinuria in Renal Disease

right arrow Regina Kunz, MD, MSc(Epi); Chris Friedrich, MD; Marcel Wolbers, PhD; and Johannes F.E. Mann, MD

1 January 2008 | Volume 148 Issue 1 | Pages 30-48

Background: Reduction of proteinuria is associated with delayed progression of chronic kidney disease. Reports suggest that angiotensin-receptor blockers (ARBs) reduce proteinuria, but results are variable. The relative effect of ARBs and angiotensin-converting enzyme (ACE) inhibitors, and their combined administration, remains uncertain.

Purpose: To establish the effect of ARBs versus placebo and alternative treatments, and the effect of combined treatment with ARBs and ACE inhibitors, on proteinuria.

Data Sources: English-language studies in MEDLINE and the Cochrane Library Central Register of Controlled Trials (January 1990 to September 2006), reference lists, and expert contacts.

Study Selection: Randomized trials of ARBs versus placebo, ACE inhibitors, calcium-channel blockers, or the combination of ARBs and ACE inhibitors in patients with or without diabetes and with microalbuminuria or proteinuria for whom data were available on urinary protein excretion at baseline and at 1 to 12 months.

Data Extraction: Two investigators independently searched and abstracted studies.

Data Synthesis: Forty-nine studies involving 6181 participants reported results of 72 comparisons with 1 to 4 months of follow-up and 38 comparisons with 5 to 12 months of follow-up. The ARBs reduced proteinuria compared with placebo or calcium-channel blockers over 1 to 4 months (ratio of means, 0.57 [95% CI, 0.47 to 0.68] and 0.69 [CI, 0.62 to 0.77], respectively) and 5 to 12 months (ratio of means, 0.66 [CI, 0.63 to 0.69] and 0.62 [CI, 0.55 to 0.70], respectively). The ARBs and ACE inhibitors reduced proteinuria to a similar degree. The combination of ARBs and ACE inhibitors further reduced proteinuria more than either agent alone: The ratio of means for combination therapy versus ARBs was 0.76 (CI, 0.68 to 0.85) over 1 to 4 months and 0.75 (CI, 0.61 to 0.92) over 5 to 12 months; for combination therapy versus ACE inhibitors, the ratio of means was 0.78 (CI, 0.72 to 0.84) over 1 to 4 months and 0.82 (CI, 0.67 to 1.01) over 5 to 12 months. The antiproteinuric effect was consistent across subgroups.

Limitations: Most studies were small, varied in quality, and did not provide reliable data on adverse drug reactions. Proteinuria reduction is only a surrogate for important progression of renal failure.

Conclusion: The ARBs reduce proteinuria, independent of the degree of proteinuria and of underlying disease. The magnitude of effect is similar regardless of whether the comparator is placebo or calcium-channel blocker. Reduction in proteinuria from ARBs and ACE inhibitors is similar, but their combination is more effective than either drug alone. Uncertainty concerning adverse effects and outcomes that are important to patients limits applicability of findings to clinical practice.


Editors' Notes
space

Context

  • Although evidence suggests that both angiotensin-receptor blockers (ARBs) and angiotensin-converting enzyme (ACE) inhibitors reduce proteinuria, the relative effects of ARBs compared with ACE inhibitors and whether the effect of these agents is greater when they are used in combination are unclear.

Contribution

  • This meta-analysis of 49 randomized trials showed that ARBs delay progression of proteinuria over the short (1 to 4 months) and longer (5 to 12 months) terms and that ARBs reduce proteinuria to a similar degree as ACE inhibitors. Although data were limited, the combination of the 2 drugs seems to reduce proteinuria more than either drug alone.

Caution

  • Data on adverse effects and long-term outcomes are limited.

—The Editors

 

Author and Article Information
space

From Basel Institute for Clinical Epidemiology and Clinic for Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland, and Munich General Hospitals, Ludwig Maximilian University, Munich, Germany.

Acknowledgment: The authors thank Gordon Guyatt for constructive discussions and Jan Friedrich for sharing details regarding the methods of generating ratios of means.

Potential Financial Conflicts of Interest: Honoraria: J.F.E. Mann (Boehringer-Ingelheim, Novartis, Aventis). Grants received: J.F.E. Mann (Aventis, Novartis).

Reproducible Research Statement: For information on the protocol, statistical code, and data, contact Dr. Regina Kunz at rkunz{at}uhbs.ch.

Requests for Single Reprints: Regina Kunz, MD, MSc, Basel Institute for Clinical Epidemiology, University Hospital Basel, Hebelstrasse 10, 4031 Basel, Switzerland; e-mail, rkunz{at}uhbs.ch.

Current Author Addresses: Drs. Kunz and Wolbers: Basel Institute for Clinical Epidemiology, University Hospital Basel, Hebelstrasse 10, 4031 Basel, Switzerland.

Drs. Friedrich and Mann: Munich General Hospital, Ludwig Maxmilian University, Kölner Platz 1, 80804 Munich, Germany

 

Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?

Related articles in Annals:

Reviews
Systematic Review: Comparative Effectiveness of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers for Treating Essential Hypertension
David B. Matchar, Douglas C. McCrory, Lori A. Orlando, Manesh R. Patel, Uptal D. Patel, Meenal B. Patwardhan, Benjamin Powers, Gregory P. Samsa, AND Rebecca N. Gray
Annals 2008 148: 16-29. [ABSTRACT][Full Text]  

Editorials
Inhibitors of the Renin–Angiotensin System: Proven Benefits, Unproven Safety
Patrick S. Parfrey
Annals 2008 148: 76-77. [Full Text]  



This article has been cited by other articles:


Home page
Am J EpidemiolHome page
E. E. K. Nang, C. M. Khoo, E. S. Tai, S. C. Lim, S. Tavintharan, T. Y. Wong, D. Heng, and J. Lee
Is There a Clear Threshold for Fasting Plasma Glucose That Differentiates Between Those With and Without Neuropathy and Chronic Kidney Disease?: The Singapore Prospective Study Program
Am. J. Epidemiol., June 15, 2009; 169(12): 1454 - 1462.
[Abstract] [Full Text] [PDF]


Home page
Arch Intern MedHome page
E. Ku, J. Park, J. Vidhun, and V. Campese
The Hazards of Dual Renin-Angiotensin Blockade in Chronic Kidney Disease
Arch Intern Med, June 8, 2009; 169(11): 1015 - 1018.
[Full Text] [PDF]


Home page
Journal of Renin-Angiotensin-Aldosterone SystemHome page
P. S Sever, A. H Gradman, and M. Azizi
Managing cardiovascular and renal risk: the potential of direct renin inhibition
Journal of Renin-Angiotensin-Aldosterone System, June 1, 2009; 10(2): 65 - 76.
[Abstract] [PDF]


Home page
ANN INTERN MEDHome page
J. F.E. Mann, R. E. Schmieder, L. Dyal, M. J. McQueen, H. Schumacher, J. Pogue, X. Wang, J. L. Probstfield, A. Avezum, E. Cardona-Munoz, et al.
Effect of Telmisartan on Renal Outcomes: A Randomized Trial
Ann Intern Med, May 18, 2009; (2009) 0000605-200907070-00120.
[Abstract] [Full Text]


Home page
Journal of Renin-Angiotensin-Aldosterone SystemHome page
T. Berl
Review: Renal protection by inhibition of the renin-angiotensin-aldosterone system
Journal of Renin-Angiotensin-Aldosterone System, March 1, 2009; 10(1): 1 - 8.
[Abstract] [PDF]


Home page
QJMHome page
M.A.C. Onuigbo
Reno-prevention vs. reno-protection: a critical re-appraisal of the evidence-base from the large RAAS blockade trials after ontarget--a call for more circumspection
QJM, March 1, 2009; 102(3): 155 - 167.
[Abstract] [Full Text] [PDF]


Home page
J Am Coll CardiolHome page
F. H. Messerli
The sudden demise of dual renin-angiotensin system blockade or the soft science of the surrogate end point.
J. Am. Coll. Cardiol., February 10, 2009; 53(6): 468 - 470.
[Abstract] [Full Text] [PDF]


Home page
Evid. Based Med.Home page
A. K Jain and M. A Weir
A combination of telmisartan and ramipril increased renal outcomes in vascular disease or diabetes
Evid. Based Med., February 1, 2009; 14(1): 11 - 11.
[Full Text] [PDF]


Home page
Mayo Clin Proc.Home page
N. M. Paige and G. T. Nagami
The Top 10 Things Nephrologists Wish Every Primary Care Physician Knew
Mayo Clin. Proc., February 1, 2009; 84(2): 180 - 186.
[Abstract] [Full Text] [PDF]


Home page
Cleveland Clinic Journal of MedicineHome page
M. J. SCHREIBER JR,
Preventing renal disease progression: Can complete renin-angiotensin-aldosterone blockade work?
Cleveland Clinic Journal of Medicine, October 1, 2008; 75(10): 699 - 704.
[Full Text] [PDF]


Home page
HypertensionHome page
N. M. Kaplan
Recent Clinical Trials: The Good, the Bad, and the Misleading
Hypertension, October 1, 2008; 52(4): 608 - 609.
[Full Text] [PDF]


Home page
Nephrol Dial TransplantHome page
T. Berl
Maximizing inhibition of the renin-angiotensin system with high doses of converting enzyme inhibitors or angiotensin receptor blockers
Nephrol. Dial. Transplant., August 1, 2008; 23(8): 2443 - 2447.
[Full Text] [PDF]


Home page
Nephrol Dial TransplantHome page
J. F. E. Mann
What's new in hypertension 2007?
Nephrol. Dial. Transplant., February 1, 2008; 23(2): 466 - 470.
[Full Text] [PDF]


Home page
ANN INTERN MEDHome page
P. S. Parfrey
Inhibitors of the Renin-Angiotensin System: Proven Benefits, Unproven Safety
Ann Intern Med, January 1, 2008; 148(1): 76 - 77.
[Full Text] [PDF]




 Home | Current Issue | Past Issues | In the Clinic | ACP Journal Club | CME | Collections | Audio/Video | Mobile | Subscribe | Tools | Help | ACP Online 

Copyright © 2008 by the American College of Physicians.