American Journal of Kidney Diseases
Volume 51, Issue 2 , Pages 199-211 , February 2008

Change in Proteinuria After Adding Aldosterone Blockers to ACE Inhibitors or Angiotensin Receptor Blockers in CKD: A Systematic Review

  • Andrew S. Bomback, MD

      Affiliations

    • Department of Medicine, Division of Nephrology and Hypertension, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC
    • Department of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC.
    • Corresponding Author InformationAddress correspondence to Andrew S. Bomback, MD, University of North Carolina Kidney Center, 7024 Burnett-Womack Bldg, Campus Box 7155, Chapel Hill, NC 27599-7155.
    • ,
  • Abhijit V. Kshirsagar, MD, MPH

      Affiliations

    • Department of Medicine, Division of Nephrology and Hypertension, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC
    • ,
  • M. Ahinee Amamoo, MS

      Affiliations

    • Department of Medicine, Division of Nephrology and Hypertension, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC
    • Department of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC.
    • ,
  • Philip J. Klemmer, MD

      Affiliations

    • Department of Medicine, Division of Nephrology and Hypertension, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC

Received 25 June 2007 ,Accepted 31 October 2007.

References 

  1. National Kidney Foundation. K/DOQI Clinical Practice Guidelines on Hypertension and Antihypertensive Agents in Chronic Kidney Disease. Am J Kidney Dis. 2004;43(suppl 1):S1–S290
  2. 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;329:1456–1462
  3. Lewis EJ, Hunsicker LG, Clarke WR, et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001;345:851–860
  4. Nakao N, Yoshimura A, Morita H, Takada M, Kayano T, Ideura T. Combination treatment of angiotensin-II receptor blocker and angiotensin-converting-enzyme inhibitor in non-diabetic renal disease (COOPERATE): A randomised controlled trial. Lancet. 2003;361:117–124
  5. MacKinnon M, Shurraw S, Akbari A, Knoll GA, Jaffey J, Clark HD. Combination therapy with an angiotensin receptor blocker and an ACE inhibitor in proteinuric renal disease: A systematic review of the efficacy and safety data. Am J Kidney Dis. 2006;48:8–20
  6. Lysaght MJ. Maintenance dialysis population dynamics: Current trends and long-term implications. J Am Soc Nephrol. 2002;13(suppl 1):S37–S40
  7. Coresh J, Astor BC, Greene T, Eknoyan G, Levey AS. Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and Nutrition Examination Survey. Am J Kidney Dis. 2003;41:1–12
  8. Staessen J, Lijnen P, Fagard R, Verschueren LJ, Amery A. Rise in plasma concentration of aldosterone during long-term angiotensin II suppression. J Endocrinol. 1981;91:457–465
  9. Biollaz J, Brunner HR, Gavras I, Waeber B, Gavras H. Antihypertensive therapy with MK 421: Angiotensin II–renin relationships to evaluate efficacy of converting enzyme blockade. J Cardiovasc Pharmacol. 1982;4:966–972
  10. Lee AF, MacFadyen RJ, Struthers AD. Neurohormonal reactivation in heart failure patients on chronic ACE inhibitor therapy: A longitudinal study. Eur J Heart Fail. 1999;1:401–406
  11. McKelvie RS, Yusuf S, Pericak D, et al. Comparison of candesartan, enalapril, and their combination in congestive heart failure: Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) Pilot Study (The RESOLVD Pilot Study Investigators). Circulation. 1999;100:1056–1064
  12. Cicoira M, Zanolla L, Rossi A, et al. Failure of aldosterone suppression despite angiotensin-converting enzyme (ACE) inhibitor administration in chronic heart failure is associated with ACE DD genotype. J Am Coll Cardiol. 2001;37:1808–1812
  13. Schjoedt KJ, Andersen S, Rossing P, Tarnow L, Parving HH. Aldosterone escape during blockade of the renin-angiotensin-aldosterone system in diabetic nephropathy is associated with enhanced decline in glomerular filtration rate. Diabetologia. 2004;47:1936–1939
  14. Rocha R, Stier CT, Kifor I, et al. Aldosterone: A mediator of myocardial necrosis and renal arteriopathy. Endocrinology. 2000;141:3871–3878
  15. Hollenberg NK. Aldosterone in the development and progression of renal injury. Kidney Int. 2004;66:1–9
  16. Rocha R, Chander PN, Zuckerman A, Stier CT. Role of aldosterone in renal vascular injury in stroke-prone hypertensive rats. Hypertension. 1999;33:232–237
  17. Greene EL, Kren S, Hostetter TH. Role of aldosterone in the remnant kidney model in the rat. J Clin Invest. 1996;98:1063–1068
  18. Conn JW, Knopf RF, Nesbit RM. Clinical characteristics of primary aldosteronism from an analysis of 145 cases. Am J Surg. 1964;107:159–172
  19. Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: Is blinding necessary?. Control Clin Trials. 1996;17:1–12
  20. Chrysostomou A, Becker G. Spironolactone in addition to ACE inhibition to reduce proteinuria in patients with chronic renal disease. N Engl J Med. 2001;345:925–926
  21. Epstein M, Buckalew V, Martinez F, et al. Antiproteinuric efficacy of eplerenone, enalapril, and eplerenone/enalapril combination therapy in diabetic hypertensives with microalbuminuria. Am J Hypertens. 2002;15:24A;(abstr)
  22. White WB, Duprez D, St Hillaire R, et al. Effects of the selective aldosterone blocker eplerenone versus the calcium antagonist amlodipine in systolic hypertension. Hypertension. 2003;41:1021–1026
  23. Flack JM, Oparil S, Pratt JH, et al. Efficacy and tolerability of eplerenone and losartan in hypertensive black and white patients. J Am Coll Cardiol. 2003;41:1148–1155
  24. Furumatsu Y, Shoji T, Tomida K, et al. Antiproteinuric effect of triple blockade with angiotensin-converting-enzyme inhibitor, angiotensin-II receptor blocker, and spironolactone. J Am Soc Nephrol. 2003;14:762A;(abstr)
  25. Nowicki M, Muskala P, Bald E, Chwatko G. Nephroprotective effect of combined converting enzyme and aldosterone blockade in hypertensive patients with target organ damage is blood pressure-dependent. J Am Soc Nephrol. 2003;14:21A;(abstr)
  26. Shiigai T, Kuwana H, Kobayashi T, Maeda Y. Effect of spironolactone added to angiotensin receptor blocker in renal failure patients. J Am Soc Nephrol. 2003;1:763A;(abstr)
  27. Sato A, Hayashi K, Naruse M, Saruta T. Effectiveness of aldosterone blockade in patients with diabetic nephropathy. Hypertension. 2003;41:64–68
  28. Pitt B, Reichek N, Willenbrock R, et al. Effects of eplerenone, enalapril, and eplerenone/enalapril in patients with essential hypertension and left ventricular hypertrophy: The 4E-left ventricular hypertrophy study. Circulation. 2003;108:1831–1838
  29. Williams GH, Burgess E, Kolloch RE, et al. Efficacy of eplerenone versus enalapril as monotherapy in systemic hypertension. Am J Cardiol. 2004;93:990–996
  30. Rachmani R, Slavachevsky I, Amit M, et al. The effect of spironolactone, cilazapril and their combination on albuminuria in patients with hypertension and diabetic nephropathy is independent of blood pressure reduction: A randomized controlled study. Diabet Med. 2004;21:471–475
  31. Nitta K, Uchida K, Nihei H: Spironolactone and angiotensin receptor blocker in nondiabetic renal diseases. Am J Med 117:444-445, 200
  32. Furumatsu Y, Shoji T, Hayashi D, et al. Antiproteinuric effect of triple blockade with angiotensin-converting-enzyme inhibitor, angiotensin-II receptor blocker, and spironolactone: One year follow up. J Am Soc Nephrol. 2004;15:58A;(abstr)
  33. Bianchi S, Bigazzi R, Campese VM. Antagonists of aldosterone and proteinuria in patients with CKD: An uncontrolled pilot study. Am J Kidney Dis. 2005;46:45–51
  34. Sato A, Hayashi K, Saruta T. Antiproteinuric effects of mineralocorticoid receptor blockade in patients with chronic renal disease. Am J Hypertens. 2005;18:44–49
  35. Schjoedt KJ, Rossing K, Juhl TR, et al. Beneficial impact of spironolactone in diabetic nephropathy. Kidney Int. 2005;68:2829–2836
  36. Rossing K, Schjoedt KJ, Smidt UM, Boomsma F, Parving HH. Beneficial effects of adding spironolactone to recommended antihypertensive treatment in diabetic nephropathy: A randomized, double-masked, cross-over study. Diabetes Care. 2005;28:2106–2112
  37. Schjoedt KJ, Rossing K, Tarnow L, Parving HH. Beneficial impact of spironolactone on nephrotic range albuminuria in diabetic nephropathy. J Am Soc Nephrol. 2005;16:57A;(abstr)
  38. van den Meiracker AH, Baggen RG, Pauli S, et al. Spironolactone in type 2 diabetic nephropathy: Effects on proteinuria, blood pressure and renal function. J Hypertens. 2006;24:2285–2292
  39. Bianchi S, Bigazzi R, Campese VM. Long-term effects of spironolactone on proteinuria and kidney function in patients with chronic kidney disease. Kidney Int. 2006;70:2116–2123
  40. Schjoedt KJ, Rossing K, Juhl TR, et al. Beneficial impact of spironolactone on nephrotic range albuminuria in diabetic nephropathy. Kidney Int. 2006;70:536–542
  41. Chrysostomou A, Pedagogos E, MacGregor A, Becker GJ. Double-blind, placebo-controlled study on the effect of 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. 2006;1:256–262
  42. Epstein M, Williams GH, Weinberger M, et al. Selective aldosterone blockade with eplerenone reduces proteinuria in patients with type 2 diabetes. Clin J Am Soc Nephrol. 2006;1:940–951
  43. Takebayashi K, Matsumoto S, Aso Y, Inukai T. Aldosterone blockade attenuates urinary monocyte chemoattractant protein-1 and oxidative stress in patients with type 2 diabetes complicated by diabetic nephropathy. J Clin Endocrinol Metab. 2006;91:2214–2217
  44. Schulz KF, Chalmers I, Hayes RJ, Altman DG. Empirical evidence of bias (Dimensions of methodological quality associated with estimates of treatment effects in controlled trials). JAMA. 1995;273:408–412
  45. Moher D, Pham B, Jones A, et al. Does quality of reports of randomised trials affect estimates of intervention efficacy reported in meta-analyses?. Lancet. 1998;352:609–613
  46. Smith GD, Egger M. Who benefits from medical interventions?. BMJ. 1994;308:72–74
  47. Glasziou PP, Irwig LM. An evidence based approach to individualising treatment. BMJ. 1995;311:1356–1359
  48. Pitt B. “Escape” of aldosterone production in patients with left ventricular dysfunction treated with an angiotensin converting enzyme inhibitor: Implications for therapy. Cardiovasc Drugs Ther. 1995;9:145–149
  49. Fullerton MJ, Funder JW. Aldosterone and cardiac fibrosis: In vitro studies. Cardiovasc Res. 1994;28:1863–1867
  50. Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure (Randomized Aldactone Evaluation Study Investigators). N Engl J Med. 1999;341:709–717
  51. Pitt B, Remme W, Zannad F, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 2003;348:1309–1321
  52. Nishiyama A, Abe Y. Molecular mechanisms and therapeutic strategies of chronic renal injury: Renoprotective effects of aldosterone blockade. J Pharmacol Sci. 2006;100:9–16
  53. Zhou X, Ono H, Ono Y, Frohlich ED. Aldosterone antagonism ameliorates proteinuria and nephrosclerosis independent of glomerular dynamics in L-NAME/SHR model. Am J Nephrol. 2004;24:242–249
  54. Asai M, Monkawa T, Marumo T, et al. Spironolactone in combination with cilazapril ameliorates proteinuria and renal interstitial fibrosis in rats with anti-Thy-1 irreversible nephritis. Hypertens Res. 2004;27:971–978
  55. Nagase M, Shibata S, Yoshida S, Nagase T, Gotoda T, Fujita T. Podocyte injury underlies the glomerulopathy of Dahl salt-hypertensive rats and is reversed by aldosterone blocker. Hypertension. 2006;47:1084–1093
  56. Struthers AD. Aldosterone escape during angiotensin-converting enzyme inhibitor therapy in chronic heart failure. J Card Fail. 1996;2:47–54
  57. Sato A, Saruta T. Aldosterone escape during angiotensin-converting enzyme inhibitor therapy in essential hypertensive patients with left ventricular hypertrophy. J Int Med Res. 2001;29:13–21
  58. Lakkis J, Lu WX, Weir MR. RAAS escape: A real clinical entity that may be important in the progression of cardiovascular and renal disease. Curr Hypertens Rep. 2003;5:408–417
  59. 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;11:462–466
  60. Juurlink DN, Mamdani MM, Lee DS, et al. Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study. N Engl J Med. 2004;351:543–551
  61. Prakash ES. “Aldosterone escape” or refractory hyperaldosteronism?. MedGenMed. 2005;7:25

 Originally published online as doi:10.1053/j.ajkd.2007.10.040 on January 4, 2008.

PII: S0272-6386(07)01491-6

doi: 10.1053/j.ajkd.2007.10.040

American Journal of Kidney Diseases
Volume 51, Issue 2 , Pages 199-211 , February 2008

Article Tools

* Image Usage & Resolution