Skip to main content

Preventing Progression of Chronic Kidney Disease: Renin–Angiotensin–Aldosterone System Blockade Beyond Blood Pressure

  • Chapter
  • First Online:
Management of Chronic Kidney Disease
  • 332 Accesses

Abstract

There is clear evidence for the pathogenic role of the renin–angiotensin–aldosterone system (RAAS) in the development and progression of CKD. Treatment with either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker has been shown to reduce proteinuria and preserve kidney function in patients with established chronic kidney disease, beyond blood pressure lowering. Such findings have led to widespread recommendations for early and sustained blockade of the RAAS to be considered as the first-line treatment for the management of established CKD. Some of these benefits may reflect the better tolerability, efficacy, and side-effect profile of RAAS blockers, compared to other antihypertensive agents. Specific actions on kidney hemodynamics, oxidative stress, inflammation, and other pathogenic elements may also contribute to “BP-independent effect” of RAAS blockade in the setting of CKD. This chapter specifically explores the utility of RAAS blockade to prevent the development and slow the progression of chronic kidney disease, beyond their actions to lower blood pressure.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Seikaly MG, Arant BS, Seney FD. Endogenous angiotensin concentrations in specific intrarenal fluid compartments of the rat. J Clin Invest. 1990;86(4):1352.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Matchar DB, McCrory DC, Orlando LA, et al. Systemic review: comparative effectiveness of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers for treating essential hypertension. Ann Intern Med. 2008;148(1):16.

    Article  PubMed  Google Scholar 

  3. ONTARGET Investigators. Telmisartan, Ramipril or both in patients at high risk for vascular events. NEJM. 2008;358(1):1547.

    Google Scholar 

  4. Kunz R, Friedrich C, Wolbers M, Mann JF. Meta-analysis: effect of monotherapy and combination therapy with inhibitors of the renin angiotensin system on proteinuria in renal disease. Ann Intern Med. 2008;148(1):30.

    Article  PubMed  Google Scholar 

  5. Barnett AH, Bain SC, Bouter P, Karlberg B, Madsbad S, Jervell J, Mustonen J. Angiotensin-receptor blockade versus converting-enzyme inhibition in type 2 diabetes and nephropathy. N Engl J Med. 2004;351:1952–61.

    Article  CAS  PubMed  Google Scholar 

  6. Xie X, Liu Y, Perkovic V, Li X, Ninomiya T, Hou W, Zhao N, Liu L, Lv J, Zhang H, Wang H. Renin-angiotensin system inhibitors and kidney and cardiovascular outcomes in patients with CKD: a Bayesian network meta-analysis of randomized clinical trials. Am J Kidney Dis. 2016;67(5):728–41.

    Article  CAS  PubMed  Google Scholar 

  7. Lewis EJ, Hunsicker LG, Bain RP, Rohde RD. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The collaborative study group. N Engl J Med. 1993;329(20):1456–62.

    Article  CAS  PubMed  Google Scholar 

  8. Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, Remuzzi G, Snapinn SM, Zhang Z, Shahinfar S, RENAAL Study Investigators. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001;345(12):861–9.

    Article  CAS  PubMed  Google Scholar 

  9. Parving HH, Lehnert H, Bröchner-Mortensen J, Gomis R, Andersen S, Arner P, Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria Study Group. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med. 2001;345(12):870–8.

    Article  CAS  PubMed  Google Scholar 

  10. Jafar TH, Scmid CH, Landa M, et al. Ann Intern Med. 2001;135(2):73.

    Article  CAS  PubMed  Google Scholar 

  11. Li PK, Leung CB, Chow KM, Cheng YL, Fung SK, Mak SK, Tang AW, Wong TY, Yung CY, Yung JC, Yu AW, Szeto CC; HKVIN Study Group. Hong Kong study using valsartan in IgA nephropathy (HKVIN): a double-blind, randomized, placebo-controlled study. Am J Kidney Dis. 2006;47(5):751–60.

    Google Scholar 

  12. Strippoli GF, Craig M, Deeks JJ, Schena FP, Craig JC. Effects of angiotensin converting enzyme inhibitors and angiotensin ii receptor antagonists on mortality and renal outcomes in diabetic nephropathy: systematic review. BMJ. 2004;329:828.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Price DA, De’Oliveira JM, Fisher ND, Williams GH, Hollenberg NK. The state and responsiveness of the renin-angiotensin-aldosterone system in patients with type II diabetes mellitus. Am J Hypertens. 1999;12:348–55.

    Article  CAS  PubMed  Google Scholar 

  14. Heart Outcomes Prevention Evaluation Study Investigators. Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the hope study and micro-hope sub-study. Lancet. 2000;355:253–9.

    Article  Google Scholar 

  15. Kilpatrick ES, Rigby AS, Atkin SL. The role of blood pressure variability in the development of nephropathy in type 1 diabetes. Diabetes Care. 2010;33:2442–7.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Gerstein HC, Mann JF, Pogue J, Dinneen SF, Halle JP, Hoogwerf B, Joyce C, Rashkow A, Young J, Zinman B, Yusuf S, Prevalence and determinants of microalbuminuria in high-risk diabetic and nondiabetic patients in the heart outcomes prevention evaluation study. The Hope Study Investigators. Diabetes Care. 2000;23(Suppl 2):B35–9.

    PubMed  Google Scholar 

  17. Bilous RCN, Sjølie AK, Fuller J, Klein R, Orchard T, et al. Effect of candesartan on microalbuminuria and albumin excretion rate in diabetes. Three randomized trials. Ann Intern Med. 2009;151:11–20.

    Article  PubMed  Google Scholar 

  18. Casas JP, Chua W, Loukogeorgakis S, Vallance P, Smeeth L, Hingorani AD, MacAllister RJ. Effect of inhibitors of the renin-angiotensin system and other antihypertensive drugs on renal outcomes: systematic review and meta-analysis. Lancet. 2005;366:2026–33.

    Article  CAS  PubMed  Google Scholar 

  19. Eijkelkamp WB, Zhang Z, Remuzzi G, Parving HH, Cooper ME, Keane WF, Shahinfar S, Gleim GW, Weir MR, Brenner BM, de Zeeuw D. Albuminuria is a target for renoprotective therapy independent from blood pressure in patients with type 2 diabetic nephropathy: post hoc analysis from the reduction of endpoints in NIDDM with the angiotensin II antagonist losartan (RENAAL) trial. J Am Soc Nephrol. 2007;18(5):1540–6.

    Article  CAS  PubMed  Google Scholar 

  20. Kronish IM, Woodward M, Sergie Z, Ogedegbe G, Falzon L, Mann DM. Meta-analysis: impact of drug class on adherence to antihypertensives. Circulation. 2011;123:1611–21.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Kidney Disease: Improving Global Outcomes (KDIGO) Blood Pressure Work Group. KDIGO 2021 Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease. Kidney Int. 2021;99(3S):S1–S87. https://kdigo.org/guidelines/blood-pressure-in-ckd/.

    Google Scholar 

  22. KDIGO. Guidelines for the management of diabetic kidney disease; 2022.

    Google Scholar 

  23. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int. 2013;3(Suppl):1–150. http://www.kdigo.org/clinical_practice_guidelines/pdf/CKD/KDIGO_2012_CKD_GL.pdf.

    Google Scholar 

  24. Horita Y, Taura K, Taguchi T, Furusu A, Kohno S. Aldosterone breakthrough during therapy with angiotensin-converting enzyme inhibitors and angiotensin ii receptor blockers in proteinuric patients with immunoglobulin a nephropathy. Nephrology (Carlton). 2006;11:462–6.

    Article  CAS  PubMed  Google Scholar 

  25. Strippoli G. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and combined therapy in patients with micro- and macroalbuminuria and other cardiovascular risk factors: a systematic review of randomized controlled trials. Nephrol Dial Transplant. 2011;26:2827–47.

    Article  PubMed  Google Scholar 

  26. Bilous R, Chaturvedi N, Sjølie AK, Fuller J, Klein R, Orchard T, Porta M, Parving H-H. Effect of candesartan on microalbuminuria and albumin excretion rate in diabetes: three randomized trials. Ann Intern Med. 2009;151(1):11–20, W3–4.

    Article  PubMed  Google Scholar 

  27. Nakayama T, Morimoto K, Uchiyama K, Kusahana E, Washida N, Azegami T, Kanda T, Yoshida T, Itoh H. Effects of renin-angiotensin system inhibitors on the incidence of unplanned dialysis. Hypertens Res. 2022;45(6):1018–27.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Merlin C. Thomas .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2023 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Thomas, M.C. (2023). Preventing Progression of Chronic Kidney Disease: Renin–Angiotensin–Aldosterone System Blockade Beyond Blood Pressure. In: Arıcı, M. (eds) Management of Chronic Kidney Disease. Springer, Cham. https://doi.org/10.1007/978-3-031-42045-0_10

Download citation

  • DOI: https://doi.org/10.1007/978-3-031-42045-0_10

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-031-42044-3

  • Online ISBN: 978-3-031-42045-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics