Skip to main content
SpringerLink
Log in

Current dilemmas in inhibiting the renin–angiotensin system: do not forget real life

  • Original Article
  • Published:
International Urology and Nephrology Aims and scope Submit manuscript

Abstract

For a long time, the inhibition of the renin–angiotensin–aldosterone (RAA) axis has been considered a must in almost all patients with progressive chronic kidney disease (CKD), with the aim of reducing the rate of progression to end-stage renal disease (ESRD). However, recent data from a meta-analysis, including the ALLHAT study, and a study in Canadian diabetic patients questioned the usefulness of angiotensin converting enzyme (ACE) inhibition in delaying the onset of dialysis. Publication of these data led to an intensive recent debate among reputed nephrologists, with numerous pros and cons regarding the pharmacological influence of CKD progression. The authors of the present review critically discuss the arguments and counterarguments of this challenging debate. Finally, a cautious view for the practicing nephrologist is expressed, highlighting the difference between study patients and real-life patients, and the possible overlooked aspects of recent renal protection studies (the importance of central blood pressure, of ambulatory blood pressure monitoring and possible, the impact of angiotensin converting inhibitors on stroke), are presented.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Casas JP, Chua W, Loukogeorgakis S et al (2005) Effect of inhibitors of the renin-angiotensin system and other antihypertensive drugs on renal outcomes: systematic review and meta-analysis. Lancet 366:2026–2033

    Article  PubMed  CAS  Google Scholar 

  2. Suissa S, Hutchinson T, Brophy JM, Kezouh A (2006) ACE-inhibitor use and the long-term risk of renal failure in diabetes. Kidney Int 69:913–919

    Article  PubMed  CAS  Google Scholar 

  3. Mann JF, McClellan WM, Kunz R et al (2006) Progression of renal disease—can we forget about inhibition of the renin-angiotensin system? Nephrol Dial Transplant 21:2348–2351

    Article  PubMed  CAS  Google Scholar 

  4. Ritz E, Dikow R (2006) Hypertension and antihypertensive treatment of diabetic nephropathy. Nat Clin Pract Nephrol 2:562–567

    Article  PubMed  Google Scholar 

  5. Leenen FH, Nwachuku CE, Black HR et al (2006) Clinical events in high-risk hypertensive patients randomly assigned to calcium channel blocker versus angiotensin-converting enzyme inhibitor in the antihypertensive and lipid-lowering treatment to prevent heart attack trial. Hypertension 48:374–384

    Article  PubMed  CAS  Google Scholar 

  6. Rossing P, Parving H-H, de Zeeuw D (2006) Renoprotection by blocking the RAS in diabetic nephropathy—fact or fiction? Nephrol Dial Transplant 21:2354–2357

    Article  PubMed  Google Scholar 

  7. Jafar TH, Stark PC, Schmid CH et al (2003) Progression of chronic kidney disease: the role of blood pressure control, proteinuria, and angiotensin-converting enzyme inhibition: a patient-level meta-analysis. Ann Intern Med 139:244–252

    PubMed  CAS  Google Scholar 

  8. Dahlöf B, Sever PS, Poulter NR et al (2005) Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian cardiac outcomes trial-blood pressure lowering arm (ASCOT-BPLA): a multicentre randomised controlled trial. Lancet 366:895–906

    Article  PubMed  Google Scholar 

  9. Remuzzi G, Perico N, Macia M et al (2005) The role of renin-angiotensin-aldosterone system in the progression of chronic kidney disease. Kidney Int 99:S57–S65

    Article  CAS  Google Scholar 

  10. Bianchi S, Bigazzi R, Campese VM (2006) Long-term effects of spironolactone on proteinuria and kidney function in patients with chronic kidney disease. Kidney Int 70:2116–2123

    PubMed  CAS  Google Scholar 

  11. Lit YZ, Meyer TW (2006) Work to do on renin-angiotensin system blockade. Clin J Am Soc Nephrol 1:611–612

    Article  Google Scholar 

  12. Cryosostomou A, Pedagogos E, MacGregor L, Becker GJ (2006) Double-blind, placebo-controlled study on the effect of the aldosterone receptor antagonist spironolactone in patients who have persistent proteinuria and are on long-term angiotensin-converting enzyme inhibitor therapy, with or without an angiotensin II receptor blocker. Clin J Am Soc Nephrol 1:256–262

    Article  Google Scholar 

  13. Casas JP, Hingorani AD, MacAllister RJ, Smeeth L (2006) Progression of renal disease—can we forget about inhibition of the renin-angiotensin system? Author’s reply. Nephrol Dial Transplant 21:2352–2353

    Article  CAS  Google Scholar 

  14. Rahman M, Pressel S, Davis BR et al (2005) Renal outcomes in high-risk hypertensive patients treated with an angiotensin-converting enzyme inhibitor or a calcium channel blocker vs a diuretic: a report from the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT). Arch Intern Med 165:936–946

    Article  PubMed  CAS  Google Scholar 

  15. Suissa S (2006) Renoprotection by blocking the RAS in diabetic nephropathy—fact or fiction? Author’s reply. Nephrol Dial Transplant 21:2357–2358

    Article  Google Scholar 

  16. Gilbertson DT, Liu J, Xue JL et al (2005) Projecting the number of patients with end-stage renal disease in the United States to the year 2015. J Am Soc Nephrol 16:3736–3741

    Article  PubMed  Google Scholar 

  17. Foley RN, Murray AM, Li S et al (2005) Chronic kidney disease and the risk for cardiovascular disease, renal replacement, and death in the United States Medicare population, 1998 to 1999. J Am Soc Nephrol 16:489–495

    Article  PubMed  Google Scholar 

  18. Covic A, Haydar AA, Goldsmith DJ (2003) Recent insights from studies using ambulatory blood pressure monitoring in patients with renal disease. Curr Opin Nephrol Hypertens 12:645–648

    Article  PubMed  Google Scholar 

  19. Williams B, Lacy PS, Thom SM et al (2006) Differential impact of blood pressure-lowering drugs on central aortic pressure and clinical outcomes: principal results of the conduit artery function evaluation (CAFE) study. Circulation 113:1213–1225

    Article  PubMed  CAS  Google Scholar 

  20. London GM, Marchais SJ, Guérin AP et al (2002) Impairment of arterial function in chronic renal disease: prognostic impact and therapeutic approach. Nephrol Dial Transplant 17:13–15

    PubMed  CAS  Google Scholar 

  21. Covic A, Mardare N, Gusbeth-Tatomir P et al (2006) Arterial wave reflections and mortality in haemodialysis patients—only relevant in elderly, cardiovascularly compromised? Nephrol Dial Transplant 21:2859–2866

    Article  PubMed  Google Scholar 

  22. Fournier A, Messerli FH, Achard JM et al (2004) Cerebroprotection mediated by angiotensin II: a hypothesis supported by recent randomized clinical trials. J Am Coll Cardiol 43:1343–1347

    Article  PubMed  Google Scholar 

  23. Pitt B, Zannad F, Remme WJ et al (1999) The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized aldactone evaluation study investigators. N Engl J Med 341:709–717

    Article  PubMed  CAS  Google Scholar 

  24. Juurlink DN, Mamdani MM, Lee DS et al (2004) Rates of hyperkalemia after publication of the randomized aldactone evaluation study. N Engl J Med 351:543–551

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Nephrology Clinic, Parhon University Hospital, Carol 1st Blvd. Nr. 50, Iasi, 700503, Romania

    Adrian Covic & Paul Gusbeth-Tatomir

  2. Department of Renal Medicine, Guy’s and St Thomas’ Hospitals, London, UK

    David J. A. Goldsmith

Authors
  1. Adrian Covic
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paul Gusbeth-Tatomir
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. David J. A. Goldsmith
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Adrian Covic.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Covic, A., Gusbeth-Tatomir, P. & Goldsmith, D.J.A. Current dilemmas in inhibiting the renin–angiotensin system: do not forget real life. Int Urol Nephrol 39, 571–576 (2007). https://doi.org/10.1007/s11255-007-9211-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11255-007-9211-0

Keywords

Search

Navigation