Heart Failure Reviews

, Volume 9, Issue 3, pp 195–201 | Cite as

The Cardiorenal Syndrome: Lessons from the ADHERE Database and Treatment Options



Significant renal dysfunction is common in patients hospitalized for heart failure and carries a grim prognosis. Patients with heart failure who have or develop renal dysfunction while being treated for heart failure are said to have the cardiorenal syndrome. The Acute Decompensated Heart Failure National Registry (ADHERE®) database, which enrolled nonselected patients admitted to the hospital for acute decompensated heart failure (ADHF), was used to determine the causes for this renal dysfunction and whether treatment can optimize outcomes. Results show that the average patient admitted for ADHF is older than those typically enrolled in clinical trials and has at least moderate kidney damage, with significantly impaired glomerular filtration rates. Renal dysfunction in patients with heart failure is complex and often multifactorial in origin, but the syndrome may be reversible in some patients. Reduction of angiotensin II levels with angiotensin-converting enzyme (ACE) inhibitors may prevent glomerular hyperfiltration and ultimately preserve renal function; however, patients who are volume-depleted may be especially sensitive to ACE inhibitor–induced efferent arteriolar dilation, so ACE inhibitor therapy in patients with renal dysfunction should be initiated when the patient is volume replete. In conclusion, impaired renal function is common in heart failure patients and may be a key cause of the cascade involving fluid retention, decompensation, and eventual hospital admission. Future pharmacologic research should focus on therapies aimed at maintaining or improving renal function in heart failure patients to reduce the high mortality associated with the cardiorenal syndrome.


ACE inhibitors cardiorenal syndrome heart failure vasodilatory shock 


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  1. 1.
    American Heart Association, American Stroke Association. Heart Disease and Stroke Statistics—2004 Update. American Heart Association. Available at: http://www.americanheart.org/downloadable/heart/1072969766940HSStats2004Update.pdf. Accessed September 13, 2004.
  2. 2.
    O’Connell JB, Bristow MR. Economic impact of heart failure in the United States: Time for a different approach. J Heart Lung Transplant1994;13:S107–S112.PubMedGoogle Scholar
  3. 3.
    Parmley WW. Pathophysiology and current therapy of congestive heart failure. J Am Coll Cardiol 1989;13:771–785.PubMedGoogle Scholar
  4. 4.
    Nohria A, Tsang SW, Fang JC, et al. Clinical assessment identifies hemodynamic profiles that predict outcomes in patients admitted with heart failure. J Am Coll Cardiol 2003;41:1797–1804.PubMedGoogle Scholar
  5. 5.
    Adams KF, Fonarow GC, Emerman CL, et al. Characteristics and Outcomes of Patients Hospitalized for Heart Failure in the United States (2001–2003): Rationale, Design and Preliminary Observations from the Acute Decompensated Heart Failure National Registry (ADHERE®) . Am Heart J (In press).Google Scholar
  6. 6.
    Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976;16:31–41.PubMedGoogle Scholar
  7. 7.
    Hillege HL, Girbes ARJ, de Kam PJ, et al. Renal function, neurohormonal activation, and survival in patients with chronic heart failure. Circulation 2000;102:203–210.PubMedGoogle Scholar
  8. 8.
    Dries DL, Exner DV, Domanski MJ, Greenberg B, Stevenson LW. The prognostic implications of renal insufficiency in asymptomatic and symptomatic patients with left ventricular systolic dysfunction. J Am Coll Cardiol 2000;35:681–689.PubMedGoogle Scholar
  9. 9.
    SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med 1991;325:293–302.CrossRefGoogle Scholar
  10. 10.
    SOLVD Investigators T. Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. N Engl J Med 1992;327:685–691.CrossRefGoogle Scholar
  11. 11.
    Gottlieb SS, Abraham W, Butler J, et al. The prognostic importance of different definitions of worsening renal function in congestive heart failure. J Card Fail 2002;8:136–141.PubMedGoogle Scholar
  12. 12.
    Smith GL, Vaccarino V, Kosiborod M, et al. Worsening renal function: What is a clinically meaningful change in creatinine during hospitalization with heart failure? J Card Fail 2003;9:13–25.PubMedGoogle Scholar
  13. 13.
    Packer M, Coats AJ, Fowler MB, et al, for the Carvedilol Prospective Randomized Cumulative Survival Study Group. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med 2001;344:1651–1658.CrossRefPubMedGoogle Scholar
  14. 14.
    K/DOQI clinical practice guidelines for chronic kidney disease: Evaluation, classification, and stratification. Am J Kidney Dis 2002;39(2 suppl 1):S1–266.Google Scholar
  15. 15.
    Lemon SC, Roy J, Clark MA, Friedmann PD, Rakowski W. Classification and regression tree analysis in public health: Methodological review and comparison with logistic regression. Ann Behav Med 2003;26:172–181.PubMedGoogle Scholar
  16. 16.
    Fonarow GC, Adams KF, Abraham WT, ADHERE Investigators. Risk stratification for in-hospital mortality in heart failure using classification and regression tree (CART) methodology: Analysis of 33,046 patients in the ADHERE registry [abstract 290]. J Card Fail 2003;9(Suppl):S79.Google Scholar
  17. 17.
    Ljungman S, Laragh JH, Cody RJ. Role of the kidney in congestive heart failure. Relationship of cardiac index to kidney function. Drugs 1990;39(Suppl 4):10–21.PubMedGoogle Scholar
  18. 18.
    Firth JD, Raine AE, Ledingham JG. Raised venous pressure: A direct cause of renal sodium retention in oedema? Lancet 1988;1:1033–1035.PubMedGoogle Scholar
  19. 19.
    Schoolwerth AC, Sica DA, Ballermann BJ, Wilcox CS. Renal considerations in angiotensin converting enzyme inhibitor therapy: A statement for healthcare professionals from the Council on the Kidney in Cardiovascular Disease and the Council for High Blood Pressure Research of the American Heart Association. Circulation 2001;104:1985–1991.PubMedGoogle Scholar
  20. 20.
    Lewis EJ, Hunsicker LG, Bain RP, Rohde RD, for the Collaborative Study Group. The effect of angiotensin-converting–enzyme inhibition on diabetic nephropathy. N Engl J Med 1993;329:1456–1462.CrossRefPubMedGoogle Scholar
  21. 21.
    Ichikawa I, Pfeffer JM, Pfeffer MA, Hostetter TH, Brenner BM. Role of angiotensin II in the altered renal function of congestive heart failure. Circ Res 1984;55:669–675.PubMedGoogle Scholar
  22. 22.
    Packer M. Why do the kidneys release renin in patients with congestive heart failure? A nephrocentric view of converting-enzyme inhibition. Am J Cardiol 1987;60:179–184.PubMedGoogle Scholar
  23. 23.
    Chrysant SG, Dunn M, Marples D, DeMasters K. Severe reversible azotemia from captopril therapy. Report of three cases and review of the literature. Arch Intern Med 1983;143:437–441.PubMedGoogle Scholar
  24. 24.
    Kittleson M, Hurwitz S, Shah MR, et al. Development of circulatory-renal limitations to angiotensin-converting enzyme inhibitors identifies patients with severe heart failure and early mortality. J Am Coll Cardiol 2003;41:2029–2035.PubMedGoogle Scholar
  25. 25.
    Gottlieb SS, Brater DC, Thomas I, et al. BG9719 (CVT-124), an A1 adenosine receptor antagonist, protects against the decline in renal function observed with diuretic therapy. Circulation 2002;105:1348–1353.PubMedGoogle Scholar
  26. 26.
    Butman SM, Ewy GA, Standen JR, Kern KB, Hahn E. Bedside cardiovascular examination in patients with severe chronic heart failure: Importance of rest or inducible jugular venous distension. J Am Coll Cardiol 1993;22:968–974.PubMedCrossRefGoogle Scholar
  27. 27.
    Kircher BJ, Himelman RB, Schiller NB. Noninvasive estimation of right atrial pressure from the inspiratory collapse of the inferior vena cava. Am J Cardiol 1990;66:493–496.PubMedGoogle Scholar
  28. 28.
    Ommen SR, Nishimura RA, Appleton CP, et al. Clinical utility of Doppler echocardiography and tissue Doppler imaging in the estimation of left ventricular filling pressures: A comparative simultaneous Doppler-catheterization study. Circulation 2000;102:1788–1794.PubMedGoogle Scholar
  29. 29.
    Stevenson LW. Clinical use of inotropic therapy for heart failure: Looking backward or forward? Part I: Inotropic infusions during hospitalization. Circulation 2003;108:367–372.PubMedGoogle Scholar
  30. 30.
    Chatterjee K, Parmley WW, Cohn JN, et al. A cooperative multicenter study of captopril in congestive heart failure: Hemodynamic effects and long-term response. Am Heart J 1985;110:439–447.PubMedGoogle Scholar
  31. 31.
    Landry DW, Oliver JA. The pathogenesis of vasodilatory shock. N Engl J Med 2001;345:588–595.CrossRefPubMedGoogle Scholar
  32. 32.
    Argenziano M, Choudhri AF, Oz MC, Rose EA, Smith CR, Landry DW. A prospective randomized trial of arginine vasopressin in the treatment of vasodilatory shock after left ventricular assist device placement. Circulation 1997;96(9 suppl):II286–II290.Google Scholar
  33. 33.
    Khot UN, Mishra M, Yamani MH, et al. Severe renal dysfunction complicating cardiogenic shock is not a contraindication to mechanical support as a bridge to cardiac transplantation. J Am Coll Cardiol 2003;41:381–385.PubMedGoogle Scholar
  34. 34.
    Keane WF. Proteinuria: Its clinical importance and role in progressive renal disease. Am J Kidney Dis 2000;35:S97–105.PubMedGoogle Scholar
  35. 35.
    Stanton BA, Kaissling B. Adaptation of distal tubule and collecting duct to increased Na delivery. II. Na+ and K+ transport. Am J Physiol 1988;255:F1269–F1275.PubMedGoogle Scholar
  36. 36.
    Dormans TP, Gerlag PG, Russel FG, Smits P. Combination diuretic therapy in severe congestive heart failure. Drugs 1998;55:165–172.PubMedGoogle Scholar
  37. 37.
    Kiyingi A, Field MJ, Pawsey CC, Yiannikas J, Lawrence JR, Arter WJ. Metolazone in treatment of severe refractory congestive cardiac failure. Lancet 1990;335:29–31.PubMedGoogle Scholar
  38. 38.
    Neuberg GW, Miller AB, O’Connor CM, et al. Diuretic resistance predicts mortality in patients with advanced heart failure. Am Heart J 2002;144:31–38.PubMedGoogle Scholar
  39. 39.
    Rimondini A, Cipolla CM, Della BP, et al. Hemofiltration as short-term treatment for refractory congestive heart failure. Am J Med 1987;83:43–48.PubMedGoogle Scholar
  40. 40.
    Ramos R, Salem BI, DePawlikowski MP, et al. Outcome predictors of ultrafiltration in patients with refractory congestive heart failure and renal failure. Angiology 1996;47:447–454.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  1. 1.Cardiomyopathy ProgramLoma Linda University Medical CenterUSA
  2. 2.Loma LindaUSA

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