Skip to main content
Log in

Therapeutic advantage of angiotensin-converting enzyme inhibitors in patients with proteinuric chronic kidney disease

  • Original Article
  • Published:
Heart and Vessels Aims and scope Submit manuscript

Abstract

Angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) is recommended for the treatment of hypertension in patients with chronic kidney disease (CKD). The relation of ACEI to renal prognosis was investigated in CKD patients in a retrospective cohort study. The objectives were patients with nondiabetic CKD of stage 4 or below receiving monotherapy with calcium channel blocker (CCB), ACEI, or ARB, and combination therapy. For the endpoint of progression to CKD stage 5, Cox’s proportional hazards analysis was conducted with explanatory variables of age, sex, baseline estimated GFR (eGFR), and proteinuria (UP) at the start of the observation period, and final blood pressure (BP) and UP at completion of the observation period. Analyzed patients comprised 131 males and 117 females, with mean age of 47.8 years. Patients were observed for 44.2 months, and the parameters of final SBP, DBP, eGFR, and UP were 127.6 ± 6.9 mmHg, 77.8 ± 5.8 mmHg, 38.1 ± 10.6 ml/min/1.73 m2, and 1.08 ± 0.57 g/gCr, respectively, where 42 patients progressed to CKD stage 5. Drugs of CCB, ACEI, and ARB types were administered to 93, 85, and 127 patients, respectively. In the multivariate analysis, extracted common prognostic factors included the baseline eGFR and final UP, the odds ratio of which was 0.876 (every increase by 1 ml/min of eGFR) and 2.229 (every increase by 1 g of UP), respectively. Among drugs in use, ACEI was an independent prognostic factor, whose odds ratio was 0.147. The present study suggests that ACEI is a prognostic factor independent of hypotensive action and UP in CKD patients.

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

Access this article

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. Liu H, Yu J, Chen F, Li J, Hu D (2007) Inpatients with coronary heart disease have a high prevalence of chronic kidney disease based on estimated glomerular filtration rate (eGFR) in China. Heart Vessels 22:223–228

    Article  CAS  PubMed  Google Scholar 

  2. Norris K, Vaughn C (2003) The role of renin-angiotensin-aldosterone system inhibition in chronic kidney disease. Expert Rev Cardiovasc Ther 1:51–63

    Article  CAS  PubMed  Google Scholar 

  3. Vogt L, Kocks MJ, Navis G (2004) Renoprotection by blockade of the renin-angiotensin-aldosterone system in diabetic and nondiabetic chronic kidney disease. Specific involvement of intra-renal angiotensin-converting enzyme activity in therapy resistance? Minerva Med 95:395–409

    CAS  PubMed  Google Scholar 

  4. Ruggenenti P (2004) Angiotensin-converting enzyme inhibition and angiotensin II antagonism in nondiabetic chronic nephropathies. Semin Nephrol 24:158–167

    Article  CAS  PubMed  Google Scholar 

  5. Noda M, Fukuda R, Matsuo T (1997) Effects of candesartan cilexetil (TCV-116) and enalapril in 5/6 nephrectomized rats. Kidney Int 63(suppl):S136–S139

    CAS  Google Scholar 

  6. Ots M, Mackenzie HS, Brenner BM (1998) Effects of combination therapy with enalapril and losartan on the rate of progression of renal injury in rats with 5/6 renal mass ablation. J Am Soc Nephrol 9:224–230

    CAS  PubMed  Google Scholar 

  7. Ishimitsu T, Kameda T, Akashiba A (2007) Efonidipine reduces proteinuria and plasma aldosterone in patients with chronic glomerulonephritis. Hypertens Res 30:621–626

    Article  CAS  PubMed  Google Scholar 

  8. Fujita T, Ando K, Nishimura H, Ideura T, Tasuda G, Isshiki M, Takahashi K; Cilnidipine versus Amlodipine Randomised Trial for Renal Disease (CARTER) Study Invesigators (2007) Antiproteinuric effect of calcium channel blocker cilnidipine added to renninangiotensin inhibition in hypertensive patients with chronic renal disease. Kidney Int 72:1543–1549

    Article  CAS  PubMed  Google Scholar 

  9. Gryglewski RJ, Uracz W, Marcinkiewicz E (2002) Bradykinin as a major endogenous regulator of endothelial function. Pediatr Pathol Mol Med 21:279–290

    Article  CAS  PubMed  Google Scholar 

  10. Padia SH, Howell NL, Carey RM (2006) Renal angiotensin type 2 receptors mediate natriuresis via angiotensin III in the angiotensin II type 1 receptor-blocked rat. Hypertension 47:537–544

    Article  CAS  PubMed  Google Scholar 

  11. Miura S, Kiya Y, Saku K (2008) Differential bonding interactions of inverse agonists of angiotensin II type 1 receptor in stabilizing the inactive state. Mol Endocrinol 22:139–146

    Article  CAS  PubMed  Google Scholar 

  12. Ginsberg JM, Chang BS, Matarese RA, Garella S (1983) Use of single voided urine samples to estimate quantitative proteinuria. N Engl J Med 309:1543–1546

    CAS  PubMed  Google Scholar 

  13. Imai E, Horio M, Nitta K, Yamagata K, Iseki K, Tsukamoto Y, Ito S, Makino H, Hishida A, Matsuo S (2007) Modification of the Modification of Diet in Renal Disease (MDRD) Study equation for Japan. Am J Kidney Dis 50:927–937

    Article  PubMed  Google Scholar 

  14. Segura J, Garcia-Donaire JA, Ruilope LM (2005) Calcium channel blockers and renal protection: insights from the latest clinical trials. J Am Soc Nephrol 16(suppl 1):S64–S66

    Article  CAS  PubMed  Google Scholar 

  15. Wright JT Jr, Bakris G, Greene T, Agodoa LY, Appel LJ, Charleston J, Cheek D, Douglas-Baltimore JG, Gassman J, Glassock R, Hebert L, Jamerson K, Lewis J, Phillips RA, Toto RD, Middleton JP, Rostang SG; African American Study of Kidney Disease and Hypertension Study Group (2002) Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial. JAMA 288:2421–2431

    Article  CAS  PubMed  Google Scholar 

  16. Campbell R, Remuzzi G, Ruggenenti P (2003) Effects of combined ACE inhibitor and angiotensin II antagonist treatment in human chronic nephropathies. Kidney Int 63:1094–1103

    Article  CAS  PubMed  Google Scholar 

  17. Ferrari P, Marti HP, Pfister M, Frey FJ (2002) Additive antiproteinuric effect of combined ACE inhibitor and angiotensin II receptor blockade. J Hypertens 20:125–130

    Article  CAS  PubMed  Google Scholar 

  18. Weir MR, Henrich WL (2000) Theoretical basis and clinical evidence for differential effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor subtype 1 blockers. Curr Opin Nephrol Hypertens 9:403–411

    Article  CAS  PubMed  Google Scholar 

  19. Barnett AH, Bain SC, Bouter P, Karlberg B, Madsbad S, Jervell J, Mustonen J; Diabetics Exposed to Telmisartan and Enalapril Study Group (2004) Angiotensin-receptor blockade versus converting-enzyme inhibition in type 2 diabetes and nephropathy. N Engl J Med 351:1952–1961

    Article  CAS  PubMed  Google Scholar 

  20. Ichikawa I (1996) Will angiotensin II receptor antagonists be renoprotective in humans? Kidney Int 50:684–692

    Article  CAS  PubMed  Google Scholar 

  21. Hutchison FN, Cui X, Webster SK (1995) The antiproteinuric action of angiotensin-converting enzyme is dependent on kinin. J Am Soc Nephrol 6:1216–1222

    CAS  PubMed  Google Scholar 

  22. Shoda J, Kanno Y, Suzuki H (2006) A five-year comparison of the renal protective effects of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in patients with nondiabetic nephropathy. Intern Med 45:193–198

    Article  PubMed  Google Scholar 

  23. Hou FF, Zhang X, Zhang GH, Xie D, Chen PY, Zhang WR, Jiang JP, Liang M, Wang GB, Liu ZR, Geng RW (2006) Efficacy and safety of benazepril for advanced chronic renal insufficiency. N Engl J Med 354:131–140

    Article  CAS  PubMed  Google Scholar 

  24. Schanstra JP, Bachvarova M, Neau E (2007) Gene expression profiling in the remnant kidney model of wild type and kinin B1 and B2 receptor knockout mice. Kidney Int 72:442–454

    Article  CAS  PubMed  Google Scholar 

  25. MacLaughlin M, Monserrat AJ, Muller A (1998) Role of kinins in the renoprotective effect of angiotensin-converting enzyme inhibitors in experimental chronic renal failure. Kidney Blood Press Res 21:329–334

    Article  CAS  PubMed  Google Scholar 

  26. Tschöpe C, Seidl U, Reinecke A (2003) Kinins are involved in the antiproteinuric effect of angiotensin-converting enzyme inhibition in experimental diabetic nephropathy. Int Immunopharmacol 3:335–344

    Article  PubMed  Google Scholar 

  27. Allard J, Buléon M, Cellier E (2007) ACE inhibitor reduces growth factor receptor expression and signaling but also albuminuria through B2-kinin glomerular receptor activation in diabetic rats. Am J Physiol Renal Physiol 293:F1083–F1092

    Article  CAS  PubMed  Google Scholar 

  28. Okada H, Watanabe Y, Suzuki H (2004) Bradykinin decreases plasminogen activator inhibitor-1 expression and facilitates matrix degradation in the renal tubulointerstitium under angiotensin-converting enzyme blockade. J Am Soc Nephrol 15:2404–2413

    Article  CAS  PubMed  Google Scholar 

  29. Kimura H (2005) Increased expression of plasminogen activator inhibitor-1 in hypoxic renal injury and its pathological significance in progression of advanced renal disease (in Japanese). Rinsho Byori 53:749–758

    CAS  PubMed  Google Scholar 

  30. Eddy AA, Fogo AB (2006) Plasminogen activator inhibitor-1 in chronic kidney disease: evidence and mechanisms of action. J Am Soc Nephrol 17:2999–3012

    Article  CAS  PubMed  Google Scholar 

  31. Skurk T, Lee YM, Hauner H (2001) Angiotensin II and its metabolites stimulate PAI-1 protein release from human adipocytes in primary culture. Hypertension 37:1336–1340

    CAS  PubMed  Google Scholar 

  32. Gesualdo L, Ranieri E, Monno R (1999) Angiotensin IV stimulates plasminogen activator inhibitor-1 expression in proximal tubular epithelial cells. Kidney Int 56:461–470

    Article  CAS  PubMed  Google Scholar 

  33. Yoshida M, Naito Y, Takada Y (2002) L-158,809 and (D-Ala(7))-angiotensin I/II (1-7) decrease PAI-1 release from human umbilical vein endothelial cells. Thromb Res 105:531–536

    Article  CAS  PubMed  Google Scholar 

  34. Jungers P, Hannedouche T, Itakura Y, Albouze G, Descamps-Latscha B, Man NK (1995) Progression rate to end-stage renal failure in non-diabetic kidney diseases: a multivariate analysis of determinant factors. Nephrol Dial Transplant 10:1353–1360

    CAS  PubMed  Google Scholar 

  35. Morita S, Fukuhara S, Akizawa T, Asano Y, Koshikawa S, Koide K, Kurokawa K (2006) Prognostic factors for a composite endpoint of renal outcomes in patients with chronic kidney disease. Ther Apher Dial 10:72–77

    Article  PubMed  Google Scholar 

  36. Radford MG Jr, Donadio JV Jr, Bergstralh EJ, Grande JP (1997) Predicting renal outcome in IgA nephropathy. J Am Soc Nephrol 8:199–207

    PubMed  Google Scholar 

  37. Ruggenenti P, Perna A, Mosconi L, Pisoni R, Remuzzi G (1998) Urinary protein excretion rate is the best independent predictor of ESRF in non-diabetic proteinuric chronic nephropathies. Kidney Int 53:1209–1216

    Article  CAS  PubMed  Google Scholar 

  38. Donadio JV, Bergstralh EJ, Grande JP, Rademcher DM (2002) Proteinuria patterns and their association with subsequent endstage renal disease in IgA nephropathy. Nephrol Dial Transplant 17:1197–1203

    Article  CAS  PubMed  Google Scholar 

  39. Vikse BE, Aasarod K, Bostad L, Iversen BM (2003) Clinical prognostic factors in biopsy-proven benign nephrosclerosis. Nephrol Dial Transplant 18:517–523

    Article  CAS  PubMed  Google Scholar 

  40. Jafar TH, Stark PC, Schmid CH, Strandgaard S, Kamper AL, Maschio G, Becker G, Perrone RD, Levey AS; ACE Inhibition in Progressive Renal Disease (AIPRD) Study Group (2005) The effect of angiotensin-converting-enzyme inhibitors on progression of advanced polycystic kidney disease. Kidney Int 67:265–271

    Article  CAS  PubMed  Google Scholar 

  41. Hsu SI, Couser WG (2003) Chronic progression of tubulointerstitial damage in proteinuric renal disease is mediated by complement activation: a therapeutic role for complement inhibitors? J Am Soc Nephrol 14(suppl 2):S186–S191

    Article  CAS  PubMed  Google Scholar 

  42. Klahr S, Levey AS, Beck GJ, Caggiula AW, Hunsicker L, Kusek JW, Striker G (1994) 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 330:877–884

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Tetsuya Ogawa.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Omae, K., Ogawa, T. & Nitta, K. Therapeutic advantage of angiotensin-converting enzyme inhibitors in patients with proteinuric chronic kidney disease. Heart Vessels 25, 203–208 (2010). https://doi.org/10.1007/s00380-009-1188-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00380-009-1188-4

Key words

Navigation