Skip to main content
SpringerLink
Log in

Renoprotective effects of angiotensin II receptor blocker, candesartan cilexetil, in patients with stage 4–5 chronic kidney disease

  • Original Article
  • Published:
Clinical and Experimental Nephrology Aims and scope Submit manuscript

Abstract

Background

To investigate the renoprotective effects and safety of angiotensin II receptor blocker (ARB) for patients with stage 4–5 chronic kidney disease.

Methods

An ARB, candesartan cilexetil, was administered to 13 patients (ARB group, n = 7; control group, n = 6) with a serum creatinine level of 2.52–5.95 mg/dl whose blood pressure had been maintained below 140/90 mmHg by the use of drugs other than ARBs. Routine measurements were conducted for 48 weeks, and renal survival analysis was observed for up to 3 years with the endpoints being doubling of the serum creatinine level, entry to hemodialysis, or death. The results were compared with those of the control group that was not treated with ARB.

Results

No significant changes were observed in the blood pressure in either group. Proteinuria significantly decreased from 0.95 ± 0.51 to 0.39 ± 0.12 g/day (paired t test, P = 0.033) in the ARB group, but did not change in the control group. Creatinine clearance in the control group decreased significantly from 16.2 ± 5.7 to 10.4 ± 4.8 ml/min per 1.73 m2 (paired t test, P = 0.011), but did not change in the other group. Thus, the slopes of the reciprocal serum creatinine values became less steep in the ARB group as compared with the control (−0.002 ± 0.015 vs. −0.025 ± 0.015 dl/mg per month; unpaired t test, P = 0.019). Kaplan–Meier analysis revealed that ARB exhibited more favorable renal outcome at 3 years (log-rank, P = 0.025). No serious adverse events were noted in the study.

Conclusion

These results show that ARB reduces proteinuria and protects renal function even in the advanced renal failure.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001;345:861–9.

    Article  CAS  Google Scholar 

  2. Lewis EJ, Hunsicker LG, Clarke WR, Berl T, Pohl MA, Lewis JB et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001;345:851–60.

    Article  CAS  Google Scholar 

  3. European Society of Hypertension-European Society of Cardiology guidelines for the management of arterial hypertension. J Hypertens. 2003;21:1011–53.

    Article  Google Scholar 

  4. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42:1206–52.

    Article  CAS  Google Scholar 

  5. Japanese Society of Hypertension Guidelines for the Management of hypertension (JSH 2004) Guidelines Subcommittee: Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2004). Hypertens Res. 2006;29(Suppl):S1–105.

    Article  Google Scholar 

  6. Bakris GL, Siomos M, Richardson D, Janssen I, Bolton WK, Hebert L et al. ACE inhibition or angiotensin receptor blockade: impact on potassium in renal failure. VAL-K Study Group. Kidney Int. 2000;58:2084–92.

    Article  CAS  Google Scholar 

  7. Raebel MA, McClure DL, Simon SR, Chan KA, Feldstein A, Andrade SE et al. Laboratory monitoring of potassium and creatinine in ambulatory patients receiving angiotensin converting enzyme inhibitors and angiotensin receptor blockers. Pharmacoepidemiol Drug Saf. 2006;16:55–64.

    Article  Google Scholar 

  8. Palmer BF. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers: what to do if the serum creatinine and/or serum potassium concentration rises. Nephrol Dial Transplant. 2003;18:1973–5.

    Article  CAS  Google Scholar 

  9. Plum J, Bunten B, Nemeth R, Grabensee B. Effects of the angiotensin II antagonist valsartan on blood pressure, proteinuria, and renal hemodynamics in patients with chronic renal failure and hypertension. J Am Soc Nephrol. 1998;9:2223–34.

    CAS  PubMed  Google Scholar 

  10. Toto R, Shultz P, Raij L, Mitchell H, Shaw W, Ramjit D et al. Efficacy and tolerability of losartan in hypertensive patients with renal impairment. Collaborative Group. Hypertension. 1998;31:684–91.

    Article  CAS  Google Scholar 

  11. Hou FF, Zhang X, Zhang GH, Xie D, Chen PY, Zhang WR et al. Efficacy and safety of benazepril for advanced chronic renal insufficiency. N Engl J Med. 2006;354:131–40.

    Article  CAS  Google Scholar 

  12. Maroni BJ, Steinman TI, Mitch WE. A method for estimating nitrogen intake of patients with chronic renal failure. Kidney Int. 1985;27:58–65.

    Article  CAS  Google Scholar 

  13. Imai E, Horio M, Nitta K, Yamagata K, Iseki K, Hara S et al. Estimation of glomerular filtration rate by the MDRD study equation modified for Japanese patients with chronic kidney disease. Clin Exp Nephrol. 2007;11:41–50.

    Article  Google Scholar 

  14. Levey AS, Eckardt KU, Tsukamoto Y, Levin A, Coresh J, Rossert J et al. Definition and classification of chronic kidney disease: a position statement from kidney disease: improving global outcomes (KDIGO). Kidney Int. 2005;67:2089–100.

    Article  Google Scholar 

  15. Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004;351:1296–305.

    Article  CAS  Google Scholar 

  16. Kurtz A, Wagner C. Regulation of renin secretion by angiotensin II-AT1 receptors. J Am Soc Nephrol. 1999;10(Suppl 11):S162–8.

    CAS  PubMed  Google Scholar 

  17. Wada T, Inada Y, Sanada T, Ojima M, Shibouta Y, Noda M, et al. Effect of an angiotensin II receptor antagonist, CV-11974, and its prodrug, TCV-116, on production of aldosterone. Eur J Pharmacol. 1994;253:27–34.

    Article  CAS  Google Scholar 

  18. Naruse M, Tanabe A, Sato A, Takagi S, Tsuchiya K, Imaki T et al. Aldosterone breakthrough during angiotensin II receptor antagonist therapy in stroke-prone spontaneously hypertensive rats. Hypertension. 2002;40:28–33.

    Article  CAS  Google Scholar 

  19. Klahr S, Levey AS, Beck GJ, Caggiula AW, Hunsicker L, Kusek JW et al. The effects of dietary protein restriction and blood-pressure control on the progression of chronic renal disease. Modification of Diet in Renal Disease Study Group. N Engl J Med. 1994;330:877–84.

    Article  CAS  Google Scholar 

  20. Peterson JC, Adler S, Burkart JM, Greene T, Hebert LA, Hunsicker LG et al. Blood pressure control, proteinuria, and the progression of renal disease. The Modification of Diet in Renal Disease Study. Ann Intern Med. 1995;123:754–62.

    Article  CAS  Google Scholar 

  21. Klag MJ, Whelton PK, Randall BL, Neaton JD, Brancati FL, Ford CE et al. Blood pressure and end-stage renal disease in men. N Engl J Med. 1996;334:13–8.

    Article  CAS  Google Scholar 

  22. Kramer HJ, Horacek V, Backer A, Vaneckova I, Heller J. Relative roles of nitric oxide, prostanoids and angiotensin II in the regulation of canine glomerular hemodynamics. A micropuncture study. Kidney Blood Press Res. 2004;27:10–7.

    Article  CAS  Google Scholar 

  23. Nakamura Y, Ono H, Zhou X, Frohlich ED. Angiotensin type 1 receptor antagonism and ACE inhibition produce similar renoprotection in N(omega)-nitro-l>-arginine methyl ester/spontaneously hypertensive rats. Hypertension. 2001;37:1262–7.

    Article  CAS  Google Scholar 

  24. Perez De Lema G, De Wit C, Cohen CD, Nieto E, Molina A, Banas B et al. Angiotensin inhibition reduces glomerular damage and renal chemokine expression in MRL/lpr mice. J Pharmacol Exp Ther. 2003;307:275–81.

    Article  Google Scholar 

  25. Welch WJ, Wilcox CS. AT1 receptor antagonist combats oxidative stress and restores nitric oxide signaling in the SHR. Kidney Int. 2001;59:1257–63.

    Article  CAS  Google Scholar 

  26. Cao Z, Bonnet F, Candido R, Nesteroff SP, Burns WC, Kawachi H et al. Angiotensin type 2 receptor antagonism confers renal protection in a rat model of progressive renal injury. J Am Soc Nephrol. 2002;13:1773–87.

    Article  CAS  Google Scholar 

  27. Cooper ME, Mundel P, Boner G. Role of nephrin in renal disease including diabetic nephropathy. Semin Nephrol. 2002;22:393–8.

    Article  CAS  Google Scholar 

  28. Casas JP, Chua W, Loukogeorgakis S, Vallance P, Smeeth L, Hingorani AD et al. 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  Google Scholar 

  29. Ahmed A. Use of angiotensin-converting enzyme inhibitors in patients with heart failure and renal insufficiency: how concerned should we be by the rise in serum creatinine? J Am Geriatr Soc. 2002;50:1297–300.

    Article  Google Scholar 

  30. Hirsch S. Preventing end-stage renal disease: flexible strategies to overcome obstacles. Curr Opin Nephrol Hypertens. 2006;15:473–80.

    CAS  PubMed  Google Scholar 

  31. Mangrum AJ, Bakris GL. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in chronic renal disease: safety issues. Semin Nephrol. 2004;24:168–75.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Nephrology, Department of Internal Medicine, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi, Tokyo, 173-8605, Japan

    Yoshifuru Tamura, Masahiro Kosuga, Masahiro Yamashita, Satoru Tomioka, Michiko Sasaki, Tomoyuki Hikita, Hideaki Nakajima, Kenichiro Kojima & Shunya Uchida

Authors
  1. Yoshifuru Tamura
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Masahiro Kosuga
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Masahiro Yamashita
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Satoru Tomioka
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Michiko Sasaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Tomoyuki Hikita
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hideaki Nakajima
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kenichiro Kojima
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Shunya Uchida
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yoshifuru Tamura.

About this article

Cite this article

Tamura, Y., Kosuga, M., Yamashita, M. et al. Renoprotective effects of angiotensin II receptor blocker, candesartan cilexetil, in patients with stage 4–5 chronic kidney disease. Clin Exp Nephrol 12, 256–263 (2008). https://doi.org/10.1007/s10157-008-0040-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10157-008-0040-y

Keywords

Search

Navigation