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Cardiorenal Syndrome: Pathophysiology and Treatment

  • Congestive Heart Failure (J Lindenfeld, Section Editor)
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Abstract

CRS is a common problem in patients with advanced heart failure. Arterial underfilling with consequent neurohormonal activation, systemic and intrarenal vasoconstriction, and salt and water retention cause the main clinical features of CRS which include a progressive decline in renal function, worsening renal function during treatment of heart failure (HF) decompensation and resistance to loop diuretics. Impaired renal function in HF patients often reflects more advanced stages of cardiac failure, and thus is associated with a worse prognosis. However, a transient fall in glomerular filtration rate may be a result of successful treatment of congestion, and thereby might not be associated with decreased survival in HF patients. This review covers basic pathophysiological mechanisms underlying the CRS and current trends in practical approaches to treat these patients.

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References

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  1. National Heart Lung Blood Institute: NHLBI Working Group. –cardiorenal connections in HF and cardiovascular disease – august 20, 2004. Available at http://www.Nhlbi.Nih.Gov/meeting/workshops/cardiorenalhf-hd.Htm.

  2. Liang KV, Williams AW, Greene EL, Redfield MM. Acute decompensated HF and the CRS. Crit Care Med. 2008;36:S75–88.

    Article  PubMed  Google Scholar 

  3. Bongartz LG, Cramer MJ, Doevedans PA, Joles JA, Braam B. The severe CRS: ‘Guyton revisited’. Eur Heart J. 2005;26:11–7.

    Article  PubMed  Google Scholar 

  4. Heywood JT. The CRS: lessons from the adhere database and treatment options. Heart Fail Rev. 2004;9:195–201.

    Article  PubMed  Google Scholar 

  5. Boerrigter G, Burnett Jr JC. CRS in decompensated HF: prognostic and therapeutic implications. Curr Heart Fail Rep. 2004;1:113–20.

    Article  PubMed  Google Scholar 

  6. Bock JS, Gottlieb SS. CRS: new perspectives. Circulation. 2010;121:2592.

    Article  PubMed  Google Scholar 

  7. Ronco C, Haapio M, House AA, et al. CRS. J Am Coll Cardiol. 2008;52:1527.

    Article  PubMed  Google Scholar 

  8. Schrier RW. Role of diminished renal function in cardiovascular mortality: marker or pathogenic factor? J Am Coll Cardiol. 2006;47:1–8.

    Article  PubMed  Google Scholar 

  9. Linden RJ, Kappagoda CT. Atrial receptors and renal blood flow. In: Linden RJ, Kappagoda CT, editors. Atrial Receptors. Cambridge: University Press; 1982. p. 235–9.

    Google Scholar 

  10. Packer M. Neurohormone interaction and adaptations in congestive HF. Circulation. 1988;77:721–30.

    Article  PubMed  CAS  Google Scholar 

  11. Sarraf M, Masoumi A, Schrier RW. CRS in Acute Decompensated HF. Clin J Am Soc Nephrol. 2009;4:2013–26.

    Article  PubMed  CAS  Google Scholar 

  12. Schrier RW. Body fluid volume regulation in health and disease: a unifying hypothesis. Ann Intern Med. 1990;113(2):155–9.

    Article  PubMed  CAS  Google Scholar 

  13. Blankstein R, Bakris GL. Renal hemodynamic changes in HF. Heart Fail Clin. 2008;4:411–23.

    Article  PubMed  Google Scholar 

  14. Schrier RW, Abraham WT. Hormones and hemodynamics in HF. N Engl J Med. 1999;341:577–8.

    Article  PubMed  CAS  Google Scholar 

  15. Weber K. Mechanisms of disease: aldosterone in chronic HF. N Engl J Med. 2001;345:1689–97.

    Article  PubMed  CAS  Google Scholar 

  16. Cohn JN, Levine TV, Olivari MT, et al. Plasma norepinephrine as a guide to prognosis in patients with chronic congestive HF. N Engl J Med. 1984;311:819–23.

    Article  PubMed  CAS  Google Scholar 

  17. Kramer RS, Mason DT, Braunwald E. Augmented sympathetic neurotransmitter activity in the peripheral vascular bed of patients with congestive HF and cardiac norepinephrine depletion. Circulation. 1966;33:629–34.

    Google Scholar 

  18. Schrier RW, Berl T, Anderson RJ. Osmotic and nonosmotic control of vasopressin release. Am J Physiol. 1979;236:F321–32.

    PubMed  CAS  Google Scholar 

  19. Schrier RW. Blood urea nitrogen and serum creatinine: not married in HF. Circ Heart Fail. 2008;1(1):2–5.

    Article  PubMed  CAS  Google Scholar 

  20. Ludwig C. Lehrbuch d. Physiol, 2nd edition, 1861.

  21. Winton FR. The influence of venous pressure on the isolated mammalian kidney. J Physiol. 1931;72(1):49–61.

    PubMed  CAS  Google Scholar 

  22. Mullens W, Abrahams GS, Francis GS, et al. Importance of venous congestion for worsening renal function in advanced decompensated HF. J Am Coll Card. 2009;53(7):589–96.

    Article  Google Scholar 

  23. Damman K, van Deursen VM, Navis G, Voors AA, van Veldhuisen DJ, Hillege HL. Increased central venous pressure is associated with impaired renal function and mortality in a broad spectrum of patients with cardiovascular disease. J Am Coll Cardiol. 2009;53(7):582–8.

    Article  PubMed  Google Scholar 

  24. Mullens W, Abrahams Z, Skouri HN, et al. Elevated intraabdominal pressure in acute decompensated HF. A potential contributor to worsening renal function? J Am Coll Cardiol. 2008;51(3):300–6.

    Article  PubMed  Google Scholar 

  25. Kirsch AJ, Kayton M, Hensle TW, et al. Renal effects of CO2 insufflation: oliguria and acute renal dysfunction in a rat pneumoperitoneum model. Urology. 1994;43:453–9.

    Article  PubMed  CAS  Google Scholar 

  26. Ezekowitz J, McAlisher FA, Humphries KH, et al. The association among renal insufficiency, pharmacotherapy, and outcomes in 6,427 patients with HF and coronary artery disease. J Am Coll Cardiol. 2004;44(8):1587–92.

    Article  PubMed  Google Scholar 

  27. Heywood JT, Fonarow GC, Costanzo MR, Mathur VS, Wigneswaran JR, Wynne J. High prevalence of renal dysfunction and its impact on outcome in 118,465 patients hospitalized with acute decompensated HF: a report from the ADHERE database. J Card Fail. 2007;13(6):422–30.

    Article  PubMed  Google Scholar 

  28. Aronson D, Mittlemann MA, Burger AJ. Elevated blood urea nitrogen level as a predictor of mortality in patients admitted for decompensated HF. Am J Med. 2004;116(7):466–73.

    Article  PubMed  CAS  Google Scholar 

  29. Filippatos G, Rossi J, Lloyd-Jones DM, et al. Prognostic value of blood urea nitrogen in patients hospitalized with worsening HF: insights from the Acute and chronic therapeutic impact of a vasopressin antagonists in chronic HF (ACTIV in CHF) study. J Card Fail. 2007;13(5):360–4.

    Article  PubMed  Google Scholar 

  30. Ismailov RM, Goldberg RJ, Lessard D, Spencer FA. Decompensated HF in the setting of kidney dysfunction: a community-wide perspective. Nephron Clin Pract. 2007;107(4):c147–55.

    Article  PubMed  Google Scholar 

  31. Gotsman I, Zwas D, Planer D, Admon D, Lotan C, Keren A. The significance of serum urea and renal function in patients with HF. Medicine (Baltimore). 2010;89(4):197–203.

    Article  CAS  Google Scholar 

  32. Brandimarte F, Vaduganathan M, Mureddu GF, et al. Prognostic implications of renal dysfunction in patients hospitalized with HF: data from the last decade of clinical investigations. Heart Fail Rev. 2012. doi:10.1007/s10741-012-9317-z. Excellent review on epidemiology and prognosis in CRS.

    Google Scholar 

  33. Gottlieb SS, Abraham W, Butler J, et al. The prognostic importance of different definitions of worsening renal function in congestive HF. J Card Fail. 2002;8(3):136–41.

    Article  PubMed  Google Scholar 

  34. Klein L, Massie BM, Leimberger JD, et al. Admission or changes in renal function during hospitalization for worsening HF predict postdischarge survival: results from the Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic HF (OPTIME-CHF). Circ Heart Fail. 2008;1(1):25–33.

    Article  PubMed  CAS  Google Scholar 

  35. Cowie MR, Komaja M, Murray-Thomas T, Underwood J, Tiko B. Prevalence and impact of worsening renal function in patients hospitalized with decompensated HF: results of the prospective outcomes study in HF (POSH). Eur Heart J. 2006;27(10):1216–22.

    Article  PubMed  Google Scholar 

  36. Forman DE, Butler J, Wang Y, et al. Incidence, predictors at admission, and impact of worsening renal function among patients hospitalized with HF. J Am Coll Cardiol. 2004;43:61–7.

    Article  PubMed  Google Scholar 

  37. Lanfear DE, Peterson EL, Campbell J, et al. Relation of worsening renal function during hospitalization for HF to long-term outcomes and rehospitalization. Am J Cardiol. 2011;107(1):74–8.

    Article  PubMed  Google Scholar 

  38. • Aronson D, Burger AJ. The relationship between transient and persistent worsening renal function and mortality in patients with acute decompensated HF. J Card Fail. 2010;16(7):541–7. The difference between transient and persistent WRF for prognosis.

    Article  PubMed  Google Scholar 

  39. Nohria A, Hasselblad V, Stebbins A, et al. Cardiorenal interactions: insight from the ESCAPE trial. J Am Coll Cardiol. 2008;51(13):1268–74.

    Article  PubMed  Google Scholar 

  40. Testani JM, Coca SG, McCauley BD, Shannon RP, Kimmel SE. Impact of changes in blood pressure during the treatment of acute decompensated HF on renal and clinical outcomes. Eur J Heart Fail. 2011;13(8):877–84.

    Article  PubMed  Google Scholar 

  41. •• Felker GM, Lee KL, Bull DA, et al. Diuretic strategies in patients with acute decompensated HF. N Engl J Med. 2011;364(9):797–805. First randomized study on diuretics in ADHF.

    Article  PubMed  CAS  Google Scholar 

  42. Blair JE, Pang PS, Schrier RW, et al. Changes in renal function during hospitalization and soon after discharge in patients admitted for worsening HF in the placebo group of the EVEREST trial. Eur Heart J. 2011;32(20):2563–72.

    Article  PubMed  Google Scholar 

  43. Ruggenenti P, Remuzzi G. Worsening kidney function in decompensated HF: treat the heart, don’t mind the kidney. Eur Heart J. 2011;32(20):2476–8.

    Article  PubMed  Google Scholar 

  44. Zile MR, Bennett TD, St John Sutton M, et al. Transition from chronic compensated to acute decompensated HF:pathophysiological insights obtained from continuous monitoring of intracardiac pressures. Circulation. 2008;118:1433–41.

    Article  PubMed  Google Scholar 

  45. Jain P, Massie BM, Gattis WA, Klein L, Gheorghiade M. Current medical treatment for the exacerbation of chronic HF resulting in hospitalization. Am Heart J. 2003;145(2 Suppl):S3–S17.

    Article  PubMed  Google Scholar 

  46. Fauchauld P. Effects of ultrafiltration of body fluid and transcapillary colloid osmotic gradient in hemodialysis patients, improvements in dialysis therapy. Contrib Nephrol. 1989;74:170–5.

    Google Scholar 

  47. Lindenfeld J, Albert NM, Boehmer JP, et al. Executive summary: HFSA 2010 comprehensive HF practice guidelines. J Card Fail. 2010;16(6):475–539.

    Article  Google Scholar 

  48. Shchekochikhin D, Lindenfeld J, Schrier RW. Increased Spironolactone in Advanced HF: Effect of Doses Greater Than 25 mg/day on Plasma Potassium Concentration. Cardiorenal Med. 2013;3:1–6.

    Article  PubMed  CAS  Google Scholar 

  49. Francis GS, Siegel RM, Goldsmith SR. Acute vasoconstrictior response to intravenous furosemide in patients with chronic congestive HF. Activation of the nuerohumoral axis. Ann Intern Med. 1985;103(1):1–6.

    Article  PubMed  CAS  Google Scholar 

  50. Silverstein ME, Ford CA, Lysaght MJ, Henderson LW. Treatment of severe fluid overload by ultrafiltration. N Engl J Med. 1974;291(15):747–51.

    Article  PubMed  CAS  Google Scholar 

  51. Constanzo MR, Guglin ME, Saltzberg MT, et al. Ultrafiltration versus intravenous diuretics for patients hospitalized for acute decompensated HF. J Am Coll Cardiol. 2007;49(6):675–83.

    Article  Google Scholar 

  52. Giglioi C, Landi D, Cecchi E, et al. Effect of ultrafiltration vs diuretics on clinical, biohumoral and haemodynamic variables in patients with decompensated HF : the ULTRADISCO study. Eur J Heart Fail. 2011;13(3):337–46.

    Article  Google Scholar 

  53. •• Bart BA, Goldsmith SR, Lee KL, et al. Ultrafiltration in decompensated HF with CRS. N Engl J Med. 2012;367(24):2296–304. Randomized study on UF versus pharmacological approach in CRS.

    Article  PubMed  CAS  Google Scholar 

  54. Marenzi G, Grazi S, Giraldi F, et al. Interrelation of humoral factors, hemodynamics, and fluid and salt metabolism in congestive HF: effects of extracorporeal ultrafiltration. Am J Med. 1993;94(1):49–56.

    Article  PubMed  CAS  Google Scholar 

  55. Rosario LB, Stevenson LW, Solomon SD, et al. The mechanism of decrease in dynamic mitral regurgitation during HF treatment: importance of reduction in the regurgitant orifice size. J Am Coll Cardiol. 1998;32:1819–24.

    Article  PubMed  CAS  Google Scholar 

  56. Stevenson LW, Brunken RC, Belil D, et al. Afterload reduction with vasodilators and diuretics decreases mitral regurgitation during upright exercise in advanced HF. J Am Coll Cardiol. 1990;15(1):174–80.

    Article  PubMed  CAS  Google Scholar 

  57. Publication Committee for the VMAC Investigators (Vasodilatation in the Management of Acute CHF). Intravenous nesiritide vs nitroglycerin for treatment of decompensated congestive HF: a randomized control trial. J Am Coll Cardiol. 2002;288(5):577–2002.

    Google Scholar 

  58. • Parissis JT, Rafouli-Stergiou P, Stasinos V, et al. Inotropes in cardiac patients: update 2011. Curr Opin Crit Care. 2010;16:432–41. Good review on inotropes in ADHF and CRS.

    Article  PubMed  Google Scholar 

  59. Follath F, Yilmaz MB, Delgado JF, et al. Clinical presentation, management and outcomes in the Acute HF Global Survey of Standard Treatment (ALARM-HF). Intensive Care Med. 2011;37:619–26.

    Article  PubMed  CAS  Google Scholar 

  60. Elkayam U, Tasissa G, Binanay C, et al. Use and impact of inotropes and vasodilator therapy in hospitalized patients with severe HF. Am Heart J. 2007;153:98–104.

    Article  PubMed  Google Scholar 

  61. Leier CV, Heban PT, Huss P, Bush CA, Lewis RP. Comparative Systemic and Regional Hemodynamic Effects of D opamine and Dobutamine in Patients with Cardiomyopathic HF. Circulation. 1978;58:466–75.

    Article  PubMed  CAS  Google Scholar 

  62. Friedrich JO, Adhikari N, Herridge MS, Beyene J. Meta-analysis: low-dose dopamine increases urine output but does not prevent renal dysfunction or death. Ann Intern Med. 2005;142(7):510–24.

    Article  PubMed  CAS  Google Scholar 

  63. Giamouzis G, Butler J, Starling RC, et al. Impact of dopamine infusion on renal function in hospitalized HF patients: results of the Dopamine in Acute Decompensated HF (DAD-HF) Trial. J Card Fail. 2010;16:922–30.

    Article  PubMed  CAS  Google Scholar 

  64. Zemljic G, Bunc M, Yazdanbakhsh AP, Vrtovec B. Levosimendan improves renal function in patients with advanced chronic HF awaiting cardiac transplantation. J Card Fail. 2007;13(6):417–21.

    Article  PubMed  CAS  Google Scholar 

  65. • Valika AA, Gheorghiade M. Ace inhibitor therapy for HF in patients with impaired renal function: a review of the literature. Heart Fail Rev. 2012. doi:10.1007/s10741-011-9295-6. Review on ACE inhibitors treatment in patients with CRS.

    Google Scholar 

  66. Ljungman S, Kjekshus J, Swedberg K. Renal function in severe congestive HF during treatment with enalapril (the Cooperative North Scandinavian Enalapril Survival Study [CONSENSUS] Trial). Am J Cardiol. 1992;70(4):479–87.

    Article  PubMed  CAS  Google Scholar 

  67. Oster JR, Meterson BJ. Renal and electrolyte complications of congestive HF and effects of therapy with angiotensin-converting enzyme inhibitors. Arch Intern Med. 1992;152(4):704–10.

    Article  PubMed  CAS  Google Scholar 

  68. Packer M. Functional renal insufficiency during long-term therapy with captopril and enalapril in severe chronic HF. Ann Intern Med. 1987;106(3):346–54.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

Dr. D. Shchekochikhin’s cardiorenal fellowship was sponsored by the Russian President’s Scholarship for Studying Abroad and Gambro UF Solutions, Inc.

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Conflict of Interest

Dmitry Shchekochikhin declares that he has no conflict of interest.

Robert Schrier has been a consultant for Otsuka Pharmaceutical, Janssen Pharmaceutical.

JoAnn Lindenfeld has been a consultant for St. Jude, Medtronic, Boston Scientific. She has received grant support from Zensun and Medtronic. She has received travel/accommodations expenses covered or reimbursed from FDA, NIH, AHA, ACC, HFSA, and University of Colorado.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Authors and Affiliations

  1. Department of Preventive and Emergency Cardiology, I.M.Setchenov’s First Moscow State Medical University, 119992, 6 (1), Bolshaya Pirogovskaya str., Moscow, Russia

    Dmitry Shchekochikhin

  2. University of Colorado Denver, 12700 East 19th Ave C281, Aurora, CO, 80045, USA

    Robert W. Schrier

  3. University of Colorado Denver, 1635 Aurora Ct F745, Room 7083, Aurora, CO, 80045, USA

    JoAnn Lindenfeld

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  1. Dmitry Shchekochikhin
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Correspondence to Dmitry Shchekochikhin.

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This article is part of the Topical Collection on Congestive Heart Failure

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Shchekochikhin, D., Schrier, R.W. & Lindenfeld, J. Cardiorenal Syndrome: Pathophysiology and Treatment. Curr Cardiol Rep 15, 380 (2013). https://doi.org/10.1007/s11886-013-0380-4

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