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Inhibition of the Renin–Angiotensin System: How Far Have We Come?

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Cardio-Nephrology

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Abstract

Inhibition of the renin–angiotensin–aldosterone system (RAAS) reduces the rate of progression of cardiovascular and renal disease in patients with established cardiac or renal dysfunction. The RAAS is complex with both autocrine, paracrine, and endocrine effects and there are multiple locations in this catalytic cascade which can be targeted with different therapies. Downstream metabolites of the cascade may have biological effects of clinical relevance. Optimal strategies to enhance the cardio renal benefits of RAAS inhibition are still being evaluated, given the evidence that angiotensin-converting enzyme inhibitors or angiotensin receptor blocker provide only a 20% relative risk reduction benefit of cardiorenal disease progression.

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References

  1. 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(5):408–17.

    Article  PubMed  Google Scholar 

  2. Rüster C, Wolf G. Renin–angiotensin–aldosterone system and progression of renal disease. J Am Soc Nephrol JASN. 2006;17(11):2985–91.

    Article  PubMed  CAS  Google Scholar 

  3. Wright JW, Krebs LT, Stobb JW, Harding JW. The angiotensin IV system: functional implications. Front Neuroendocrinol. 1995;16(1):23–52.

    Article  CAS  PubMed  Google Scholar 

  4. Fox CS, Matsushita K, Woodward M, Bilo HJG, Chalmers J, Heerspink HJL, et al. Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without diabetes: a meta-analysis. Lancet Lond Engl. 2012;380(9854):1662–73.

    Article  Google Scholar 

  5. Hallan SI, Matsushita K, Sang Y, Mahmoodi BK, Black C, Ishani A, et al. Age and association of kidney measures with mortality and end-stage renal disease. JAMA. 2012;308(22):2349–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Heerspink HJL, Kröpelin TF, Hoekman J, de Zeeuw D. Reducing albuminuria as surrogate endpoint (REASSURE) consortium. Drug-induced reduction in albuminuria is associated with subsequent renoprotection: a meta-analysis. J Am Soc Nephrol JASN. 2015;26(8):2055–64.

    Article  CAS  PubMed  Google Scholar 

  7. Khan UA, Garg AX, Parikh CR, Coca SG. Prevention of chronic kidney disease and subsequent effect on mortality: a systematic review and meta-analysis. PLoS ONE. 2013;8(8):e71784.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Remuzzi G, Perico N, Macia M, Ruggenenti P. The role of renin–angiotensin–aldosterone system in the progression of chronic kidney disease. Kidney Int Suppl. 2005;99:S57–65.

    Article  CAS  Google Scholar 

  9. Remuzzi G, Bertani T. Pathophysiology of progressive nephropathies. N Engl J Med. 1998;339(20):1448–56.

    Article  CAS  PubMed  Google Scholar 

  10. Remuzzi G, Ruggenenti P, Perico N. Chronic renal diseases: renoprotective benefits of renin–angiotensin system inhibition. Ann Intern Med. 2002;136(8):604–15.

    Article  CAS  PubMed  Google Scholar 

  11. Bakris GL, Weir MR. Angiotensin-converting enzyme inhibitor-associated elevations in serum creatinine: is this a cause for concern? Arch Intern Med. 2000;160(5):685–93.

    Article  CAS  PubMed  Google Scholar 

  12. Centers for Disease Control and Prevention (CDC). National Vital Statistics Report (NVSR). Deaths: final data for 2013. Atlanta, GA: US Department of Health and Human Services, Centers for Disease Control and Prevention; 2013.

    Google Scholar 

  13. Briasoulis A, Bakris GL. Chronic kidney disease as a coronary artery disease risk equivalent. Curr Cardiol Rep. 2013;15(3):340.

    Article  PubMed  Google Scholar 

  14. Favre GA, Esnault VLM, Van Obberghen E. Modulation of glucose metabolism by the renin–angiotensin–aldosterone system. Am J Physiol Endocrinol Metab. 2015;308(6):E435–49.

    Article  CAS  PubMed  Google Scholar 

  15. Becher UM, Endtmann C, Tiyerili V, Nickenig G, Werner N. Endothelial damage and regeneration: the role of the renin–angiotensin–aldosterone system. Curr Hypertens Rep. 2011;13(1):86–92.

    Article  CAS  PubMed  Google Scholar 

  16. Shahin Y, Khan JA, Samuel N, Chetter I. Angiotensin converting enzyme inhibitors effect on endothelial dysfunction: a meta-analysis of randomised controlled trials. Atherosclerosis. 2011;216(1):7–16.

    Article  CAS  PubMed  Google Scholar 

  17. Gallagher PE, Arter AL, Deng G, Tallant EA. Angiotensin-(1–7): a peptide hormone with anti-cancer activity. Curr Med Chem. 2014;21(21):2417–23.

    Article  CAS  PubMed  Google Scholar 

  18. Trask AJ, Ferrario CM. Angiotensin-(1–7): pharmacology and new perspectives in cardiovascular treatments. Cardiovasc Drug Rev. 2007;25(2):162–74.

    Article  CAS  PubMed  Google Scholar 

  19. Batlle D, Wysocki J, Soler MJ, Ranganath K. Angiotensin-converting enzyme 2: enhancing the degradation of angiotensin II as a potential therapy for diabetic nephropathy. Kidney Int. 2012;81(6):520–8.

    Article  CAS  PubMed  Google Scholar 

  20. Luther JM, Brown NJ. The renin–angiotensin–aldosterone system and glucose homeostasis. Trends Pharmacol Sci. 2011;32(12):734–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Scheen AJ. Prevention of type 2 diabetes mellitus through inhibition of the renin–angiotensin system. Drugs. 2004;64(22):2537–65.

    Article  CAS  PubMed  Google Scholar 

  22. Grams ME, Rabb H. The distant organ effects of acute kidney injury. Kidney Int. 2012;81(10):942–8.

    Article  PubMed  Google Scholar 

  23. Ronco C, Haapio M, House AA, Anavekar N, Bellomo R. Cardiorenal syndrome. J Am Coll Cardiol. 2008;52(19):1527–39.

    Article  PubMed  Google Scholar 

  24. Spanos G, Kalaitzidis RG, Karasavvidou DP, Zikou X, Siamopoulos KC. Aliskiren in an alternate-day administration schedule in hypertensive albuminuric patients. Blood Press Monit. 2014;19(6):359–65.

    Article  PubMed  Google Scholar 

  25. Parving H-H, Persson F, Lewis JB, Lewis EJ, Hollenberg NK. AVOID Study Investigators. Aliskiren combined with losartan in type 2 diabetes and nephropathy. N Engl J Med. 2008;358(23):2433–46.

    Article  CAS  PubMed  Google Scholar 

  26. James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311(5):507–20.

    Article  CAS  PubMed  Google Scholar 

  27. Kidney Disease: Improving Global Outcomes (KDIGO) Blood Pressure Work Group: KDIGO clinical practice guideline for the management of blood pressure in chronic kidney disease. Kidney Int Suppl. 2012;Suppl 2:337–414.

    Google Scholar 

  28. Verbeke F, Lindley E, Van Bortel L, Vanholder R, London G, Cochat P, et al. A European Renal Best Practice (ERBP) position statement on the Kidney Disease: improving Global Outcomes (KDIGO) clinical practice guideline for the management of blood pressure in non-dialysis-dependent chronic kidney disease: an endorsement with some caveats for real-life application. Nephrol Dial Transplant Off Publ Eur Dial Transpl Assoc Eur Ren Assoc. 2014;29(3):490–6.

    Google Scholar 

  29. Lakkis JI, Weir MR. Treatment-resistant hypertension in the transplant recipient. Semin Nephrol. 2014;34(5):560–70.

    Article  PubMed  Google Scholar 

  30. Chen Y, Meng L, Shao H, Yu F. Aliskiren vs. other antihypertensive drugs in the treatment of hypertension: a meta-analysis. Hypertens Res Off J Jpn Soc Hypertens. 2013;36(3):252–61.

    Article  CAS  Google Scholar 

  31. Abe M, Suzuki H, Okada K, Maruyama N, Inoshita A, Baba S, et al. Efficacy analysis of the renoprotective effects of aliskiren in hypertensive patients with chronic kidney disease. Heart Vessels. 2013;28(4):442–52.

    Article  PubMed  Google Scholar 

  32. National Kidney Foundation. KDOQI clinical practice guideline for diabetes and CKD: 2012 Update. Am J Kidney Dis Off J Natl Kidney Found. 2012;60(5):850–86.

    Article  Google Scholar 

  33. Qaseem A, Hopkins RH, Sweet DE, Starkey M, Shekelle P. Clinical Guidelines Committee of the American College of Physicians. Screening, monitoring, and treatment of stage 1 to 3 chronic kidney disease: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2013;159(12):835–47.

    PubMed  Google Scholar 

  34. Taler SJ, Agarwal R, Bakris GL, Flynn JT, Nilsson PM, Rahman M, et al. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for management of blood pressure in CKD. Am J Kidney Dis Off J Natl Kidney Found. 2013;62(2):201–13.

    Article  Google Scholar 

  35. Jafar TH, Stark PC, Schmid CH, Landa M, Maschio G, de Jong PE, et al. 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. 2003;139(4):244–52.

    Article  CAS  PubMed  Google Scholar 

  36. Keane WF. Proteinuria: its clinical importance and role in progressive renal disease. Am J Kidney Dis Off J Natl Kidney Found. 2000;35(4 Suppl 1):S97–105.

    Article  CAS  Google Scholar 

  37. Xie X, Liu Y, Perkovic V, Li X, Ninomiya T, Hou W, et al. 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 Off J Natl Kidney Found. 2015.

    Google Scholar 

  38. Sharma P, Blackburn RC, Parke CL, McCullough K, Marks A, Black C. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers for adults with early (stage 1 to 3) non-diabetic chronic kidney disease. Cochrane Database Syst Rev. 2011;10:CD007751.

    Google Scholar 

  39. Bolignano D, Palmer SC, Navaneethan SD, Strippoli GFM. Aldosterone antagonists for preventing the progression of chronic kidney disease. Cochrane Database Syst Rev. 2014;4:CD007004.

    Google Scholar 

  40. Navaneethan SD, Nigwekar SU, Sehgal AR, Strippoli GFM. Aldosterone antagonists for preventing the progression of chronic kidney disease: a systematic review and meta-analysis. Clin J Am Soc Nephrol CJASN. 2009;4(3):542–51.

    Article  CAS  PubMed  Google Scholar 

  41. Ritz E, Orth SR. Nephropathy in patients with type 2 diabetes mellitus. N Engl J Med. 1999;341(15):1127–33.

    Article  CAS  PubMed  Google Scholar 

  42. Dinneen SF, Gerstein HC. The association of microalbuminuria and mortality in non-insulin-dependent diabetes mellitus. A systematic overview of the literature. Arch Intern Med. 1997;157(13):1413–8.

    Article  CAS  PubMed  Google Scholar 

  43. Strippoli GFM, Bonifati C, Craig M, Navaneethan SD, Craig JC. Angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists for preventing the progression of diabetic kidney disease. Cochrane Database Syst Rev. 2006;4:CD006257.

    Google Scholar 

  44. DREAM Trial Investigators, Bosch J, Yusuf S, Gerstein HC, Pogue J, Sheridan P, et al. Effect of ramipril on the incidence of diabetes. N Engl J Med. 2006;355(15):1551–62.

    Article  Google Scholar 

  45. NAVIGATOR Study Group, McMurray JJ, Holman RR, Haffner SM, Bethel MA, Holzhauer B, et al. Effect of valsartan on the incidence of diabetes and cardiovascular events. N Engl J Med. 2010;362(16):1477–90.

    Article  Google Scholar 

  46. Abuissa H, Jones PG, Marso SP, O’Keefe JH. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers for prevention of type 2 diabetes: a meta-analysis of randomized clinical trials. J Am Coll Cardiol. 2005;46(5):821–6.

    Article  CAS  PubMed  Google Scholar 

  47. Andraws R, Brown DL. Effect of inhibition of the renin–angiotensin system on development of type 2 diabetes mellitus (meta-analysis of randomized trials). Am J Cardiol. 2007;99(7):1006–12.

    Article  CAS  PubMed  Google Scholar 

  48. Al-Mallah M, Khawaja O, Sinno M, Alzohaili O, Samra ABA. Do angiotensin converting enzyme inhibitors or angiotensin receptor blockers prevent diabetes mellitus? A meta-analysis. Cardiol J. 2010;17(5):448–56.

    PubMed  Google Scholar 

  49. Tocci G, Paneni F, Palano F, Sciarretta S, Ferrucci A, Kurtz T, et al. Angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers and diabetes: a meta-analysis of placebo-controlled clinical trials. Am J Hypertens. 2011;24(5):582–90.

    Article  CAS  PubMed  Google Scholar 

  50. Geng D, Jin D, Wu W, Xu Y, Wang J. Angiotensin receptor blockers for prevention of new-onset type 2 diabetes: a meta-analysis of 59,862 patients. Int J Cardiol. 2012;155(2):236–42.

    Article  PubMed  Google Scholar 

  51. Geng D, Jin D, Wu W, Liang Y, Wang J. Angiotensin converting enzyme inhibitors for prevention of new-onset type 2 diabetes mellitus: a meta-analysis of 72,128 patients. Int J Cardiol. 2013;167(6):2605–10.

    Article  PubMed  Google Scholar 

  52. Yang Y, Wei R-B, Wang Z-C, Wang N, Gao Y-W, Li M-X, et al. A meta-analysis of the effects of angiotensin converting enzyme inhibitors and angiotensin II receptor blockers on insulin sensitivity in hypertensive patients without diabetes. Diabetes Res Clin Pract. 2015;107(3):415–23.

    Article  CAS  PubMed  Google Scholar 

  53. Bolignano D, Palmer SC, Ruospo M, Zoccali C, Craig JC, Strippoli GFM. Interventions for preventing the progression of autosomal dominant polycystic kidney disease. Cochrane Database Syst Rev. 2015;7:CD010294.

    Google Scholar 

  54. Yang L-Y, Ge X, Wang Y-L, Ma K-L, Liu H, Zhang X-L, et al. Angiotensin receptor blockers reduce left ventricular hypertrophy in dialysis patients: a meta-analysis. Am J Med Sci. 2013;345(1):1–9.

    Article  PubMed  Google Scholar 

  55. Kanno Y, Kaneko K, Kaneko M, Kotaki S, Mimura T, Takane H, et al. Angiotensin receptor antagonist regresses left ventricular hypertrophy associated with diabetic nephropathy in dialysis patients. J Cardiovasc Pharmacol. 2004;43(3):380–6.

    Article  CAS  PubMed  Google Scholar 

  56. Agarwal R, Sinha AD, Pappas MK, Abraham TN, Tegegne GG. Hypertension in hemodialysis patients treated with atenolol or lisinopril: a randomized controlled trial. Nephrol Dial Transplant Off Publ Eur Dial Transpl Assoc Eur Ren Assoc. 2014;29(3):672–81.

    CAS  Google Scholar 

  57. Yang C-W, Tzeng N-S, Yin Y-J, Li C-H, Chen H-A, Chiu S-H, et al. Angiotensin receptor blockers decrease the risk of major adverse cardiovascular events in patients with end-stage renal disease on maintenance dialysis: a nationwide matched-cohort study. PloS One. 2015;10(10):e0140633.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  58. Zhang L, Zeng X, Fu P, Wu HM. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers for preserving residual kidney function in peritoneal dialysis patients. Cochrane Database Syst Rev. 2014;6:CD009120.

    Google Scholar 

  59. Akbari A, Knoll G, Ferguson D, McCormick B, Davis A, Biyani M. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in peritoneal dialysis: systematic review and meta-analysis of randomized controlled trials. Perit Dial Int J Int Soc Perit Dial. 2009;29(5):554–61.

    CAS  Google Scholar 

  60. Gossmann J, Burkhardt R, Harder S, Lenz T, Sedlmeyer A, Klinkhardt U, et al. Angiotensin II infusion increases plasma erythropoietin levels via an angiotensin II type 1 receptor-dependent pathway. Kidney Int. 2001;60(1):83–6.

    Article  CAS  PubMed  Google Scholar 

  61. Freudenthaler SM, Schenck T, Lucht I, Gleiter CH. Fenoterol stimulates human erythropoietin production via activation of the renin angiotensin system. Br J Clin Pharmacol. 1999;48(4):631–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Freudenthaler S, Benöhr P, Grenz A, Selzer T, Schmidt T, Mörike K, et al. Do alterations of endogenous angiotensin II levels regulate erythropoietin production in humans? Br J Clin Pharmacol. 2003;56(4):378–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Matsumura M, Nomura H, Koni I, Mabuchi H. Angiotensin-converting enzyme inhibitors are associated with the need for increased recombinant human erythropoietin maintenance doses in hemodialysis patients. Risks of Cardiac Disease in Dialysis Patients Study Group. Nephron. 1997;77(2):164–8.

    Article  CAS  PubMed  Google Scholar 

  64. Navarro JF, Mora C, Rivero A. Effect of angiotensin-converting enzyme inhibitors on hematological parameters and recombinant human erythropoietin doses in peritoneal dialysis patients. Nephron. 1998;80(2):239.

    Article  CAS  PubMed  Google Scholar 

  65. Curtis JJ, Laskow DA, Jones PA, Julian BA, Gaston RS, Luke RG. Captopril-induced fall in glomerular filtration rate in cyclosporine-treated hypertensive patients. J Am Soc Nephrol JASN. 1993;3(9):1570–4.

    CAS  PubMed  Google Scholar 

  66. Hiremath S, Fergusson D, Doucette S, Mulay AV, Knoll GA. Renin angiotensin system blockade in kidney transplantation: a systematic review of the evidence. Am J Transplant Off J Am Soc Transplant Am Soc Transpl Surg. 2007;7(10):2350–60.

    Article  CAS  Google Scholar 

  67. Ibrahim HN, Jackson S, Connaire J, Matas A, Ney A, Najafian B, et al. Angiotensin II blockade in kidney transplant recipients. J Am Soc Nephrol JASN. 2013;24(2):320–7.

    Article  CAS  PubMed  Google Scholar 

  68. Vlahakos DV, Marathias KP, Agroyannis B, Madias NE. Posttransplant erythrocytosis. Kidney Int. 2003;63(4):1187–94.

    Article  PubMed  Google Scholar 

  69. Li ECK, Heran BS, Wright JM. Angiotensin converting enzyme (ACE) inhibitors versus angiotensin receptor blockers for primary hypertension. Cochrane Database Syst Rev. 2014;8:CD009096.

    Google Scholar 

  70. SPRINT Research Group, Wright JT, Williamson JD, Whelton PK, Snyder JK, Sink KM, et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015;373(22):2103–16.

    Article  CAS  Google Scholar 

  71. Lu H, Rateri DL, Feldman DL Jr, Chamigo RJ, Fukamizu A, Ishida J, et al. Renin inhibition reduces hypercholesterolemia-induced atherosclerosis in mice. J Clin Investig. 2008;118(3):984–93.

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Wu H, Cheng XW, Hu L, Hao C-N, Hayashi M, Takeshita K, et al. Renin inhibition reduces atherosclerotic plaque neovessel formation and regresses advanced atherosclerotic plaques. Atherosclerosis. 2014;237(2):739–47.

    Article  CAS  PubMed  Google Scholar 

  73. Tokmakova MP, Skali H, Kenchaiah S, Braunwald E, Rouleau JL, Packer M, et al. Chronic kidney disease, cardiovascular risk, and response to angiotensin-converting enzyme inhibition after myocardial infarction: the Survival And Ventricular Enlargement (SAVE) study. Circulation. 2004;110(24):3667–73.

    Article  CAS  PubMed  Google Scholar 

  74. Guideline Development Group. Clinical Practice Guideline on management of patients with diabetes and chronic kidney disease stage 3b or higher (eGFR <45 mL/min). Nephrol Dial Transplant Off Publ Eur Dial Transpl Assoc Eur Ren Assoc. 2015;30(Suppl 2):ii1–142.

    Google Scholar 

  75. Hillege HL, Nitsch D, Pfeffer MA, Swedberg K, McMurray JJV, Yusuf S, et al. Renal function as a predictor of outcome in a broad spectrum of patients with heart failure. Circulation. 2006;113(5):671–8.

    Article  PubMed  Google Scholar 

  76. Damman K, Navis G, Voors AA, Asselbergs FW, Smilde TDJ, Cleland JGF, et al. Worsening renal function and prognosis in heart failure: systematic review and meta-analysis. J Card Fail. 2007;13(8):599–608.

    Article  PubMed  Google Scholar 

  77. Shlipak MG, Smith GL, Rathore SS, Massie BM, Krumholz HM. Renal function, digoxin therapy, and heart failure outcomes: evidence from the digoxin intervention group trial. J Am Soc Nephrol JASN. 2004;15(8):2195–203.

    Article  CAS  PubMed  Google Scholar 

  78. Smith GL, Lichtman JH, Bracken MB, Shlipak MG, Phillips CO, DiCapua P, et al. Renal impairment and outcomes in heart failure: systematic review and meta-analysis. J Am Coll Cardiol. 2006;47(10):1987–96.

    Article  PubMed  Google Scholar 

  79. Hillege HL, Girbes AR, de Kam PJ, Boomsma F, de Zeeuw D, Charlesworth A, et al. Renal function, neurohormonal activation, and survival in patients with chronic heart failure. Circulation. 2000;102(2):203–10.

    Article  CAS  PubMed  Google Scholar 

  80. McAlister FA, Ezekowitz J, Tonelli M, Armstrong PW. Renal insufficiency and heart failure: prognostic and therapeutic implications from a prospective cohort study. Circulation. 2004;109(8):1004–9.

    Article  PubMed  Google Scholar 

  81. Clark H, Krum H, Hopper I. Worsening renal function during renin–angiotensin–aldosterone system inhibitor initiation and long-term outcomes in patients with left ventricular systolic dysfunction. Eur J Heart Fail. 2014;16(1):41–8.

    Article  CAS  PubMed  Google Scholar 

  82. Schroten NF, Damman K, Hemmelder MH, Voors AA, Navis G, Gaillard CAJM, et al. Effect of additive renin inhibition with Aliskiren on renal blood flow in patients with chronic heart failure and renal dysfunction (additive renin inhibition with Aliskiren on renal blood flow and neurohormonal activation in patients with chronic heart failure and renal dysfunction). Am Heart J. 2015;169(5):693–701.e3.

    Article  CAS  PubMed  Google Scholar 

  83. Ezekowitz J, McAlister FA, Humphries KH, Norris CM, Tonelli M, Ghali WA, et al. The association among renal insufficiency, pharmacotherapy, and outcomes in 6,427 patients with heart failure and coronary artery disease. J Am Coll Cardiol. 2004;44(8):1587–92.

    Article  PubMed  Google Scholar 

  84. Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, 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(10):709–17.

    Article  CAS  PubMed  Google Scholar 

  85. Zannad F, McMurray JJV, Krum H, van Veldhuisen DJ, Swedberg K, Shi H, et al. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med. 2011;364(1):11–21.

    Article  CAS  PubMed  Google Scholar 

  86. Pun PH, Al-Khatib SM, Han JY, Edwards R, Bardy GH, Bigger JT, et al. Implantable cardioverter-defibrillators for primary prevention of sudden cardiac death in CKD: a meta-analysis of patient-level data from 3 randomized trials. Am J Kidney Dis Off J Natl Kidney Found. 2014;64(1):32–9.

    Article  Google Scholar 

  87. Azzalini L, Spagnoli V, Ly HQ. Contrast-induced nephropathy: from pathophysiology to preventive strategies. Can J Cardiol. 2015.

    Google Scholar 

  88. Silver SA, Shah PM, Chertow GM, Harel S, Wald R, Harel Z. Risk prediction models for contrast induced nephropathy: systematic review. BMJ. 2015;351:h4395.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  89. Zhang B, Liang L, Chen W, Liang C, Zhang S. The efficacy of sodium bicarbonate in preventing contrast-induced nephropathy in patients with pre-existing renal insufficiency: a meta-analysis. BMJ Open. 2015;5(3):e006989.

    Article  PubMed  PubMed Central  Google Scholar 

  90. Bainey KR, Rahim S, Etherington K, Rokoss ML, Natarajan MK, Velianou JL, et al. Effects of withdrawing vs continuing renin–angiotensin blockers on incidence of acute kidney injury in patients with renal insufficiency undergoing cardiac catheterization: results from the angiotensin converting enzyme inhibitor/angiotensin receptor blocker and contrast induced nephropathy in patients receiving cardiac catheterization (CAPTAIN) trial. Am Heart J. 2015;170(1):110–6.

    Article  CAS  PubMed  Google Scholar 

  91. Harel Z, Gilbert C, Wald R, Bell C, Perl J, Juurlink D, et al. The effect of combination treatment with aliskiren and blockers of the renin–angiotensin system on hyperkalaemia and acute kidney injury: systematic review and meta-analysis. BMJ. 2012;344:e42.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  92. Parving H-H, Brenner BM, McMurray JJV, de Zeeuw D, Haffner SM, Solomon SD, et al. Cardiorenal end points in a trial of aliskiren for type 2 diabetes. N Engl J Med. 2012;367(23):2204–13.

    Article  CAS  PubMed  Google Scholar 

  93. Mann JFE, Schmieder RE, McQueen M, Dyal L, Schumacher H, Pogue J, et al. Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial. Lancet Lond Engl. 2008;372(9638):547–53.

    Article  CAS  Google Scholar 

  94. ONTARGET Investigators, Yusuf S, Teo KK, Pogue J, Dyal L, Copland I, et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med. 2008;358(15):1547–59.

    Article  Google Scholar 

  95. Phillips CO, Kashani A, Ko DK, Francis G, Krumholz HM. Adverse effects of combination angiotensin II receptor blockers plus angiotensin-converting enzyme inhibitors for left ventricular dysfunction: a quantitative review of data from randomized clinical trials. Arch Intern Med. 2007;167(18):1930–6.

    Article  CAS  PubMed  Google Scholar 

  96. Makani H, Bangalore S, Desouza KA, Shah A, Messerli FH. Efficacy and safety of dual blockade of the renin–angiotensin system: meta-analysis of randomised trials. BMJ. 2013;346:f360.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  97. Susantitaphong P, Sewaralthahab K, Balk EM, Eiam-ong S, Madias NE, Jaber BL. Efficacy and safety of combined vs. single renin–angiotensin–aldosterone system blockade in chronic kidney disease: a meta-analysis. Am J Hypertens. 2013;26(3):424–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Bangalore S, Kumar S, Messerli FH. When conventional heart failure therapy is not enough: angiotensin receptor blocker, direct renin inhibitor, or aldosterone antagonist? Congest Heart Fail Greenwich Conn. 2013;19(3):107–15.

    Article  CAS  Google Scholar 

  99. Gheorghiade M, Böhm M, Greene SJ, Fonarow GC, Lewis EF, Zannad F, et al. Effect of aliskiren on postdischarge mortality and heart failure readmissions among patients hospitalized for heart failure: the ASTRONAUT randomized trial. JAMA. 2013;309(11):1125–35.

    Article  CAS  PubMed  Google Scholar 

  100. Arici M, Erdem Y. Dual blockade of the renin–angiotensin system for cardiorenal protection: an update. Am J Kidney Dis Off J Natl Kidney Found. 2009;53(2):332–45.

    Article  CAS  Google Scholar 

  101. Brewster LM, van Montfrans GA, Kleijnen J. Systematic review: antihypertensive drug therapy in black patients. Ann Intern Med. 2004;141(8):614–27.

    Article  PubMed  Google Scholar 

  102. Jamerson KA. Rationale for angiotensin II receptor blockers in patients with low-renin hypertension. Am J Kidney Dis Off J Natl Kidney Found. 2000;36(3 Suppl 1):S24–30.

    Article  CAS  Google Scholar 

  103. Flack JM, Mensah GA, Ferrario CM. Using angiotensin converting enzyme inhibitors in African-American hypertensives: a new approach to treating hypertension and preventing target-organ damage. Curr Med Res Opin. 2000;16(2):66–79.

    Article  CAS  PubMed  Google Scholar 

  104. Agodoa LY, Appel L, Bakris GL, Beck G, Bourgoignie J, Briggs JP, et al. Effect of ramipril vs amlodipine on renal outcomes in hypertensive nephrosclerosis: a randomized controlled trial. JAMA. 2001;285(21):2719–28.

    Article  CAS  PubMed  Google Scholar 

  105. Pinto YM, van Gilst WH, Kingma JH, Schunkert H. Deletion-type allele of the angiotensin-converting enzyme gene is associated with progressive ventricular dilation after anterior myocardial infarction. Captopril and Thrombolysis Study Investigators. J Am Coll Cardiol. 1995;25(7):1622–6.

    Article  CAS  PubMed  Google Scholar 

  106. Ruggenenti P, Bettinaglio P, Pinares F, Remuzzi G. Angiotensin converting enzyme insertion/deletion polymorphism and renoprotection in diabetic and nondiabetic nephropathies. Clin J Am Soc Nephrol CJASN. 2008;3(5):1511–25.

    Article  PubMed  Google Scholar 

  107. Gradman AH, Schmieder RE, Lins RL, Nussberger J, Chiang Y, Bedigian MP. Aliskiren, a novel orally effective renin inhibitor, provides dose-dependent antihypertensive efficacy and placebo-like tolerability in hypertensive patients. Circulation. 2005;111(8):1012–8.

    Article  CAS  PubMed  Google Scholar 

  108. Bezalel S, Mahlab-Guri K, Asher I, Werner B, Sthoeger ZM. Angiotensin-converting enzyme inhibitor-induced angioedema. Am J Med. 2015;128(2):120–5.

    Article  CAS  PubMed  Google Scholar 

  109. Bas M, Greve J, Strassen U, Khosravani F, Hoffmann TK, Kojda G. Angioedema induced by cardiovascular drugs: new players join old friends. Allergy. 2015;70(10):1196–200.

    Article  CAS  PubMed  Google Scholar 

  110. Craig TJ, Bernstein JA, Farkas H, Bouillet L, Boccon-Gibod I. Diagnosis and treatment of bradykinin-mediated angioedema: outcomes from an angioedema expert consensus meeting. Int Arch Allergy Immunol. 2014;165(2):119–27.

    Article  CAS  PubMed  Google Scholar 

  111. Rose LI, Underwood RH, Newmark SR, Kisch ES, Williams GH. Pathophysiology of spironolactone-induced gynecomastia. Ann Intern Med. 1977;87(4):398–403.

    Article  CAS  PubMed  Google Scholar 

  112. Buysse JM, Huang I-Z, Pitt B. PEARL-HF: prevention of hyperkalemia in patients with heart failure using a novel polymeric potassium binder, RLY5016. Future Cardiol. 2012;8(1):17–28.

    Article  CAS  PubMed  Google Scholar 

  113. Weir MR, Bakris GL, Bushinsky DA, Mayo MR, Garza D, Stasiv Y, et al. Patiromer in patients with kidney disease and hyperkalemia receiving RAAS inhibitors. N Engl J Med. 2015;372(3):211–21.

    Article  PubMed  CAS  Google Scholar 

  114. Bakris GL, Pitt B, Weir MR, Freeman MW, Mayo MR, Garza D, et al. Effect of patiromer on serum potassium level in patients with hyperkalemia and diabetic kidney disease: the AMETHYST-DN randomized clinical trial. JAMA. 2015;314(2):151–61.

    Article  CAS  PubMed  Google Scholar 

  115. Packham DK, Rasmussen HS, Lavin PT, El-Shahawy MA, Roger SD, Block G, et al. Sodium zirconium cyclosilicate in hyperkalemia. N Engl J Med. 2015;372(3):222–31.

    Article  PubMed  CAS  Google Scholar 

  116. Kosiborod M, Rasmussen HS, Lavin P, Qunibi WY, Spinowitz B, Packham D, et al. Effect of sodium zirconium cyclosilicate on potassium lowering for 28 days among outpatients with hyperkalemia: the HARMONIZE randomized clinical trial. JAMA. 2014;312(21):2223–33.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, John A. Burns School of Medicine, University of Hawaii at Manoa, Maui Memorial Medical Center, 21 Kamaiki Cir, Kahului, HI, 96732-3153, USA

    Jay Ian Lakkis

  2. Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, N3W 143 Nephrology, UMMC, Baltimore, MD, 21201, USA

    Matthew R. Weir

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  1. Jay Ian Lakkis
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  2. Matthew R. Weir
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Correspondence to Matthew R. Weir .

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Editors and Affiliations

  1. Department of Internal Medicine, Einstein Medical Center, Sidney Kimmel College of Thomas Jefferson University, Philadelphia, Pennsylvania, USA

    Janani Rangaswami

  2. Department of Medicine, Section of Nephrology, University of Illinois at Chicago, Chicago, Illinois, USA

    Edgar V. Lerma

  3. Department of Nephrology Dialysis and Transplantation, International Renal Research Institute, San Bortolo Hospital, Vicenza, Italy

    Claudio Ronco

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Lakkis, J.I., Weir, M.R. (2017). Inhibition of the Renin–Angiotensin System: How Far Have We Come?. In: Rangaswami, J., Lerma, E., Ronco, C. (eds) Cardio-Nephrology. Springer, Cham. https://doi.org/10.1007/978-3-319-56042-7_8

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