UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Renal effects of ACE inhibitors in heart failure

Author
Wilson S Colucci, MD
Section Editors
Richard H Sterns, MD
Stephen S Gottlieb, MD
Deputy Editor
John P Forman, MD, MSc

INTRODUCTION

Angiotensin-converting enzyme (ACE) inhibitors are widely used in the treatment of heart failure. These agents decrease the formation of angiotensin II, thereby decreasing both arteriolar and venous resistance. This "unloading" effect on the left ventricle results in an elevation in cardiac output, symptomatic improvement, and an approximately 25 percent decrease in cardiovascular mortality at one to three years, due primarily to a slower rate of progressive cardiac dysfunction [1-4]. In addition, the administration of an ACE inhibitor after an acute myocardial infarction can preserve cardiac function (as evidenced by an increased ejection fraction and slowed ventricular enlargement) and improve long-term survival [5]. (See "ACE inhibitors in heart failure with reduced ejection fraction: Therapeutic use" and "Angiotensin converting enzyme inhibitors and receptor blockers in acute myocardial infarction: Recommendations for use".)

An ACE inhibitor given with a loop diuretic may have the additional advantage of raising the plasma sodium concentration in patients with heart failure and hyponatremia [6]. This synergism may reflect factors that result in an increase in free water excretion. (See "Hyponatremia in patients with heart failure".)

In addition to a possible elevation in free water excretion, ACE inhibitors have other renal actions in heart failure, including changes in the glomerular filtration rate (GFR), reduced potassium excretion that can lead to hyperkalemia, and a variable alteration in the natriuretic response to diuretics.

EFFECT ON GLOMERULAR FILTRATION RATE

In view of the improvement in cardiac output and in renal blood flow, it might be assumed that angiotensin-converting enzyme (ACE) inhibitors would also increase the glomerular filtration rate (GFR). However, this expected response occurs in only 10 to 25 percent of patients, while an increase in the plasma creatinine concentration is a more common finding [7-9]. As an example, the CONSENSUS trial of patients with severe heart failure noted a mean elevation in the plasma creatinine concentration of 0.1 to 0.2 mg/dL (10 to 20 µmol/L); furthermore, 11 percent of patients had more than a 100 percent rise in the plasma creatinine concentration [8]. This usually modest decline in GFR occurs within the first week; renal function then tends to be stable unless a complicating factor, such as worsening of cardiac function, is superimposed [8].

A reduction in GFR in heart failure is most likely to occur in those settings in which maintenance of the GFR is dependent upon high ambient angiotensin II levels [6-10]:

     

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Nov 2016. | This topic last updated: Mon Jul 06 00:00:00 GMT 2015.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
References
Top
  1. Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). The CONSENSUS Trial Study Group. N Engl J Med 1987; 316:1429.
  2. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. The SOLVD Investigators. N Engl J Med 1991; 325:293.
  3. Comparative effects of therapy with captopril and digoxin in patients with mild to moderate heart failure. The Captopril-Digoxin Multicenter Research Group. JAMA 1988; 259:539.
  4. Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. The SOLVD Investigattors. N Engl J Med 1992; 327:685.
  5. Pfeffer MA, Braunwald E, Moyé LA, et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. The SAVE Investigators. N Engl J Med 1992; 327:669.
  6. Oster JR, Materson BJ. Renal and electrolyte complications of congestive heart failure and effects of therapy with angiotensin-converting enzyme inhibitors. Arch Intern Med 1992; 152:704.
  7. Packer M, Lee WH, Medina N, et al. Functional renal insufficiency during long-term therapy with captopril and enalapril in severe chronic heart failure. Ann Intern Med 1987; 106:346.
  8. Ljungman S, Kjekshus J, Swedberg K. Renal function in severe congestive heart failure during treatment with enalapril (the Cooperative North Scandinavian Enalapril Survival Study [CONSENSUS] Trial). Am J Cardiol 1992; 70:479.
  9. Packer M, Lee WH, Kessler PD, et al. Identification of hyponatremia as a risk factor for the development of functional renal insufficiency during converting enzyme inhibition in severe chronic heart failure. J Am Coll Cardiol 1987; 10:837.
  10. MacDowall P, Kalra PA, O'Donoghue DJ, et al. Risk of morbidity from renovascular disease in elderly patients with congestive cardiac failure. Lancet 1998; 352:13.
  11. Dzau VJ, Colucci WS, Hollenberg NK, Williams GH. Relation of the renin-angiotensin-aldosterone system to clinical state in congestive heart failure. Circulation 1981; 63:645.
  12. Schunkert H, Ingelfinger JR, Hirsch AT, et al. Evidence for tissue-specific activation of renal angiotensinogen mRNA expression in chronic stable experimental heart failure. J Clin Invest 1992; 90:1523.
  13. Packer M, Lee WH, Yushak M, Medina N. Comparison of captopril and enalapril in patients with severe chronic heart failure. N Engl J Med 1986; 315:847.
  14. Giles TD, Katz R, Sullivan JM, et al. Short- and long-acting angiotensin-converting enzyme inhibitors: a randomized trial of lisinopril versus captopril in the treatment of congestive heart failure. The Multicenter Lisinopril-Captopril Congestive Heart Failure Study Group. J Am Coll Cardiol 1989; 13:1240.
  15. Hirsch AT, Talsness CE, Smith AD, et al. Differential effects of captopril and enalapril on tissue renin-angiotensin systems in experimental heart failure. Circulation 1992; 86:1566.
  16. Ahmed A, Fonarow GC, Zhang Y, et al. Renin-angiotensin inhibition in systolic heart failure and chronic kidney disease. Am J Med 2012; 125:399.
  17. Packer M, Lee WH, Medina N, Yushak M. Influence of renal function on the hemodynamic and clinical responses to long-term captopril therapy in severe chronic heart failure. Ann Intern Med 1986; 104:147.
  18. Textor SC, Bravo EL, Fouad FM, Tarazi RC. Hyperkalemia in azotemic patients during angiotensin-converting enzyme inhibition and aldosterone reduction with captopril. Am J Med 1982; 73:719.
  19. Motwani JG, Fenwick MK, Morton JJ, Struthers AD. Furosemide-induced natriuresis is augmented by ultra-low-dose captopril but not by standard doses of captopril in chronic heart failure. Circulation 1992; 86:439.
  20. McLay JS, McMurray JJ, Bridges AB, et al. Acute effects of captopril on the renal actions of furosemide in patients with chronic heart failure. Am Heart J 1993; 126:879.
  21. Good JM, Brady AJ, Noormohamed FH, et al. Effect of intense angiotensin II suppression on the diuretic response to furosemide during chronic ACE inhibition. Circulation 1994; 90:220.