Current Heart Failure Reports

, Volume 15, Issue 5, pp 307–314 | Cite as

Cardiorenal Interactions Revisited: How to Improve Heart Failure Outcomes in Patients With Chronic Kidney Disease

  • Mattia ArrigoEmail author
  • Pietro E. Cippà
  • Alexandre Mebazaa
Comorbidities of Heart Failure (C. Angermann, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Comorbidities of Heart Failure


Purpose of the Review

To summarize current advances in the understanding and management of heart failure (HF) in patients with advanced chronic kidney disease (CKD).

Recent Findings

Diagnosis of HF and treatment of congestion are crucial in the management of patients with advanced CKD to reduce symptoms, preserve organ function, and improve outcomes. Echocardiography and cardiovascular biomarkers may help to differentiate cardiac from non-cardiac components of overhydration. Renal replacement therapy or ultrafiltration may be required to treat congestion. Furthermore, patients with advanced CKD are frequently undertreated with disease-modifying HF therapies, but the use of beta-blockers and ACEi should be considered under close monitoring of kidney function and serum potassium. The use of the new oral potassium binders may translate into improved outcomes.


The treatment of HF in patients with advanced CKD requires a multi-disciplinary approach. New diagnostic and therapeutic strategies are under evaluation and may contribute to improved outcomes.


Heart failure Chronic kidney disease Renal failure Cardiorenal Outcome 


Compliance with Ethical Standards

Conflict of Interest

Pietro E. Cippà declares no conflict of interest. Dr. Arrigo reports personal fees from Orion Pharma, outside the submitted work. Dr. Mebazaa reports personal fees from Novartis, Orion, Roche, Servier, Cardiorentis, Neuro Tronik, and Zs Pharma and grants and personal fees from Adrenomed. He also reports grants from MyCartis and Critical diagnostics, grants and personal fees from Abbott, and grants and personal fees from Sphyngotec, all of which are outside the submitted work. In addition, Dr. Mebazaa has a patent WO2017077117 issued.

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.


Papers of particular interest, published recently, have been highlighted as: • Of importance Of major importance

  1. 1.
    • Schefold JC, Filippatos G, Hasenfuss G, Anker SD. Haehling von S. Heart failure and kidney dysfunction: epidemiology, mechanisms and management. Nat Rev Nephrol. 2016;12:610–23. Comprehensive review of the pathophysiology of concomitant heart and kidney failure with therapeutic considerations. CrossRefPubMedGoogle Scholar
  2. 2.
    Ronco C, Haapio M, House AA, Anavekar N, Bellomo R. Cardiorenal syndrome. J Am Coll Cardiol. 2008;52:1527–39.CrossRefPubMedGoogle Scholar
  3. 3.
    • Damman K, Tang WHW, Felker GM, Lassus J, Zannad F, Krum H, et al. Current evidence on treatment of patients with chronic systolic heart failure and renal insufficiency: practical considerations from published data. Journal of the American College of Cardiology. 2014;63:853–71. Systematic review of the literature with practical considerations on the use of disease-modifying heart failure treatments in patients with chronic kidney disease of different stages . CrossRefPubMedGoogle Scholar
  4. 4.
    Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JGF, Coats AJS, et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2016;37:2129–200.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Damman K, Tang WHW, Testani JM, McMurray JJV. Terminology and definition of changes renal function in heart failure. Eur Heart J. 2014;35:3413–6.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    • Eckardt K-U, Bansal N, Coresh J, Evans M, Grams ME, Herzog CA, James MT, Heerspink HJL, Pollock CA, Stevens PE, Tamura MK, Tonelli MA, Wheeler DC, Winkelmayer WC, Cheung M, Hemmelgarn BR, Conference Participants. Improving the prognosis of patients with severely decreased glomerular filtration rate (CKD G4+): conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney International 2018. Executive conclusions from the KDIGO conference on strategies to improve outcome of patients with advanced chronic kidney disease. Google Scholar
  7. 7.
    Tuegel C, Bansal N. Heart failure in patients with kidney disease. Heart. 2017;103:1848–53.CrossRefPubMedGoogle Scholar
  8. 8.
    Kottgen A, Russell SD, Loehr LR, Crainiceanu CM, Rosamond WD, Chang PP, et al. Reduced kidney function as a risk factor for incident heart failure: the atherosclerosis risk in communities (ARIC) study. J Am Soc Nephrol American Society of Nephrology. 2007;18:1307–15.CrossRefGoogle Scholar
  9. 9.
    Foley RN. Clinical epidemiology of cardiac disease in dialysis patients: left ventricular hypertrophy, ischemic heart disease, and cardiac failure. Semin Dial. 2003;16:111–7.CrossRefPubMedGoogle Scholar
  10. 10.
    Dubin RF, Deo R, Bansal N, Anderson AH, Yang P, Go AS, et al. Associations of conventional echocardiographic measures with incident heart failure and mortality: the chronic renal insufficiency cohort. Clin J Am Soc Nephrol American Society of Nephrology. 2017;12:60–8.CrossRefGoogle Scholar
  11. 11.
    Chen C, Yang X, Lei Y, Zha Y, Liu H, Ma C, et al. Urinary biomarkers at the time of AKI diagnosis as predictors of progression of AKI among patients with acute cardiorenal syndrome. Clin J Am Soc Nephrol American Society of Nephrology. 2016;11:1536–44.CrossRefGoogle Scholar
  12. 12.
    Erickson KF, Winkelmayer WC, Chertow GM, Bhattacharya J. Physician visits and 30-day hospital readmissions in patients receiving hemodialysis. J Am Soc Nephrol. 2014;25:2079–87.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    • Arrigo M, Parissis JT, Akiyama E, Mebazaa A. Understanding acute heart failure: pathophysiology and diagnosis. Eur Heart J Suppl. 2016;18:G11–8. Review of the current understanding of the pathophysiology of heart failure with special focus on systemic congestion and its diagnosis . CrossRefGoogle Scholar
  14. 14.
    • Chawla LS, Herzog CA, Costanzo MR, Tumlin J, Kellum JA, Mc Cullough PA, et al. Proposal for a functional classification system of heart failure in patients with end-stage renal disease: proceedings of the acute dialysis quality initiative (ADQI) XI workgroup. Journal of the American College of Cardiology. 2014;63:1246–52. Workgroup report with proposal for a functional classification system of heart failure in patients with advanced chronic kidney disease. This paper includes also echocardiographic criteria suggestive of heart disease in patients on hemodialysis. CrossRefPubMedGoogle Scholar
  15. 15.
    Davies SJ, Davenport A. The role of bioimpedance and biomarkers in helping to aid clinical decision-making of volume assessments in dialysis patients. Kidney Int. 2014;86:489–96.CrossRefPubMedGoogle Scholar
  16. 16.
    Wizemann V, Wabel P, Chamney P, Zaluska W, Moissl U, Rode C, et al. The mortality risk of overhydration in haemodialysis patients. Nephrology Dialysis Transplantation. 2009;24:1574–9.CrossRefPubMedCentralGoogle Scholar
  17. 17.
    Agarwal R. Hypervolemia is associated with increased mortality among hemodialysis patients. Hypertension. 2010;56:512–7.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Onofriescu M, Siriopol D, Voroneanu L, Hogaş S, Nistor I, Apetrii M, Florea L, Veisa G, Mititiuc I, Kanbay M, Sascău R, Covic A. Overhydration, cardiac function and survival in hemodialysis patients. Lionetti V, ed. PLoS One 2015;10:e0135691.Google Scholar
  19. 19.
    Caetano C, Valente A, Oliveira T, Garagarza C. Body composition and mortality predictors in hemodialysis patients. J Ren Nutr. 2016;26:81–6.CrossRefPubMedGoogle Scholar
  20. 20.
    Kim E-J, Choi M-J, Lee J-H, Oh J-E, Seo J-W, Lee Y-K, Yoon J-W, Kim H-J, Noh J-W, Koo J-R. Extracellular fluid/intracellular fluid volume ratio as a novel risk indicator for all-cause mortality and cardiovascular disease in hemodialysis patients. Shimosawa T, ed. PLoS One 2017;12:e0170272.Google Scholar
  21. 21.
    Arrigo M, Moos Von S, Gerritsen K, Sadoune M, Tangvoraphonkchai K, Davenport A, et al. Soluble CD146 and B-type natriuretic peptide dissect overhydration into functional components of prognostic relevance in haemodialysis patients. Nephrol Dial Transplant. 2018;
  22. 22.
    Mallamaci F, Zoccali C, Tripepi G, Benedetto FA, Parlongo S, Cataliotti A, et al. Diagnostic potential of cardiac natriuretic peptides in dialysis patients. Kidney Int. 2001;59:1559–66.CrossRefPubMedGoogle Scholar
  23. 23.
    Zoccali C, Mallamaci F, Benedetto FA, Tripepi G, Parlongo S, Cataliotti A, et al. Cardiac natriuretic peptides are related to left ventricular mass and function and predict mortality in dialysis patients. J Am Soc Nephrol. 2001;12:1508–15.PubMedGoogle Scholar
  24. 24.
    Gayat E, Caillard A, Laribi S, Mueller C, Sadoune M, Seronde M-F, et al. Soluble CD146, a new endothelial biomarker of acutely decompensated heart failure. Int J Cardiol. 2015;199:241–7.CrossRefPubMedGoogle Scholar
  25. 25.
    Arrigo M, Truong QA, Onat D, Szymonifka J, Gayat E, Tolppanen H, et al. Soluble CD146 is a novel marker of systemic congestion in heart failure patients: an experimental mechanistic and transcardiac clinical study. Clin Chem. 2017;63:386–93.CrossRefPubMedGoogle Scholar
  26. 26.
    Kubena P, Arrigo M, Parenica J, Gayat E, Sadoune M, Ganovska E, et al. Plasma levels of soluble CD146 reflect the severity of pulmonary congestion better than brain Natriuretic peptide in acute coronary syndrome. Ann Lab Med. 2016;36:300.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Chazot C, Rozes M, Vo-Van C, Deleaval P, Hurot J-M, Lorriaux C, et al. Brain natriuretic peptide is a marker of fluid overload in incident hemodialysis patients. Cardiorenal Med Karger Publishers. 2017;7:218–26.CrossRefGoogle Scholar
  28. 28.
    Mullens W, Abrahams Z, Skouri HN, Francis GS, Taylor DO, Starling RC, et al. Elevated intra-abdominal pressure in acute decompensated heart failure. J Am Coll Cardiol. 2008;51:300–6.CrossRefPubMedGoogle Scholar
  29. 29.
    Mullens W, Abrahams Z, Francis GS, Sokos G, Taylor DO, Starling RC, et al. Importance of venous congestion for worsening of renal function in advanced decompensated heart failure. J Am Coll Cardiol. 2009;53:589–96.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Ishihara S, Gayat E, Sato N, Arrigo M, Laribi S, Legrand M, et al. Similar hemodynamic decongestion with vasodilators and inotropes: systematic review, meta-analysis, and meta-regression of 35 studies on acute heart failure. Clin Res Cardiol. 2016;105:971–80.CrossRefPubMedGoogle Scholar
  31. 31.
    Van Aelst LNL, Arrigo M, Placido R, Akiyama E, Girerd N, Zannad F, et al. Acutely decompensated heart failure with preserved and reduced ejection fraction present with comparable haemodynamic congestion. Eur J Heart Fail. 2018;20:738–47.CrossRefPubMedGoogle Scholar
  32. 32.
    Bart BA, Goldsmith SR, Lee KL, Givertz MM, O’Connor CM, Bull DA, et al. Ultrafiltration in decompensated heart failure with cardiorenal syndrome. N Engl J Med. 2012;367:2296–304.CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Costanzo MR, Ronco C, Abraham WT, Agostoni P, Barasch J, Fonarow GC, et al. Extracorporeal ultrafiltration for fluid overload in heart failure. J Am Coll Cardiol. 2017;69:2428–45.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Morpurgo M, Pasqualini M, Brunazzi MC, Vianello G, Valle R, Roncon L, et al. A multicenter feasibility study on ultrafiltration via a single peripheral venous access in acute heart failure with overt fluid overload. Int J Cardiol. 2017;240:253–7.CrossRefPubMedGoogle Scholar
  35. 35.
    Grodin JL, Carter S, Bart BA, Goldsmith SR, Drazner MH, Tang WHW. Direct comparison of ultrafiltration to pharmacological decongestion in heart failure: a per-protocol analysis of CARRESS-HF. Eur J Heart Fail. 2018;57:2233.Google Scholar
  36. 36.
    Trespalacios FC, Taylor AJ, Agodoa LY, Bakris GL, Abbott KC. Heart failure as a cause for hospitalization in chronic dialysis patients. Am J Kidney Dis. 2003;41:1267–77.CrossRefPubMedGoogle Scholar
  37. 37.
    Wang I-K, Lin C-L, Sung F-C. Lower risk of de novo congestive heart failure in peritoneal dialysis patients compared with hemodialysis patients. Int J Cardiol. 2017;229:123.CrossRefPubMedGoogle Scholar
  38. 38.
    Sens F, Schott-Pethelaz A-M, Labeeuw M, Colin C, Villar E, REIN Registry. Survival advantage of hemodialysis relative to peritoneal dialysis in patients with end-stage renal disease and congestive heart failure. Kidney Int. 2011;80:970–7.CrossRefPubMedGoogle Scholar
  39. 39.
    FHN Trial Group, Chertow GM, Levin NW, Beck GJ, Depner TA, Eggers PW, et al. In-center hemodialysis six times per week versus three times per week. N Engl J Med Massachusetts Medical Society. 2010;363:2287–300.Google Scholar
  40. 40.
    Chan CT, Greene T, Chertow GM, Kliger AS, Stokes JB, Beck GJ, et al. Effects of frequent hemodialysis on ventricular volumes and left ventricular remodeling. Clin J Am Soc Nephrol American Society of Nephrology. 2013;8:2106–16.CrossRefGoogle Scholar
  41. 41.
    Roy P, Bouchard J, Amyot R, Madore F. Prescription patterns of pharmacological agents for left ventricular systolic dysfunction among hemodialysis patients. Am J Kidney Dis. 2006;48:645–51.CrossRefPubMedGoogle Scholar
  42. 42.
    Tseng W-C, Liu J-S, Hung S-C, Kuo K-L, Chen Y-H, Tarng D-C, et al. Effect of spironolactone on the risks of mortality and hospitalization for heart failure in pre-dialysis advanced chronic kidney disease: a nationwide population-based study. Int J Cardiol. 2017;238:72–8.CrossRefPubMedGoogle Scholar
  43. 43.
    McMurray JJV, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, et al. Angiotensin–neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014;371:993–1004.CrossRefPubMedGoogle Scholar
  44. 44.
    Damman K, Gori M, Claggett B, Jhund PS, Senni M, Lefkowitz MP, et al. Renal effects and associated outcomes during angiotensin-neprilysin inhibition in heart failure. JACC: Heart Failure. 2018;6:489–98.PubMedGoogle Scholar
  45. 45.
    Arrigo M, Vodovar N, Nougué H, Sadoune M, Pemberton CJ, Ballan P, et al. The heart regulates the endocrine response to heart failure: cardiac contribution to circulating neprilysin. Eur Heart J. 2018;39:1794–8.CrossRefPubMedGoogle Scholar
  46. 46.
    Vodovar N, Seronde M-F, Laribi S, Gayat E, Lassus J, Januzzi JL Jr, et al. Elevated plasma B-type natriuretic peptide concentrations directly inhibit circulating neprilysin activity in heart failure. JACC: Heart Failure. 2015;3:629–36.PubMedGoogle Scholar
  47. 47.
    Emrich IE, Vodovar N, Feuer L, Untersteller K, Nougué H, Seiler-Mussler S, Fliser D, Launay J-M, Heine GH. Do plasma neprilysin activity and plasma neprilysin concentration predict cardiac events in chronic kidney disease patients? Nephrol Dial Transplant 2018.Google Scholar
  48. 48.
    UK HARP-III Collaborative Group. Randomized multicentre pilot study of sacubitril/valsartan versus irbesartan in patients with chronic kidney disease: United Kingdom Heart and Renal Protection (HARP)-III-rationale, trial design and baseline data. Nephrol Dial Transplant. 2017;32:2043–51.Google Scholar
  49. 49.
    Holtkamp FA, de Zeeuw D, Thomas MC, Cooper ME, de Graeff PA, Hillege HJL, et al. An acute fall in estimated glomerular filtration rate during treatment with losartan predicts a slower decrease in long-term renal function. Kidney Int. 2011;80:282–7.CrossRefPubMedGoogle Scholar
  50. 50.
    Juurlink DN, Mamdani MM, Lee DS, Kopp A, Austin PC, Laupacis A, et al. Rates of hyperkalemia after publication of the randomized aldactone evaluation study. N Engl J Med Massachusetts Medical Society. 2004;351:543–51.CrossRefGoogle Scholar
  51. 51.
    Eschalier R, McMurray JJV, Swedberg K, Van Veldhuisen DJ, Krum H, Pocock SJ, et al. Safety and efficacy of eplerenone in patients at high risk for hyperkalemia and/or worsening renal function: analyses of the EMPHASIS-HF study subgroups (Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure). J Am Coll Cardiol. 2013;62:1585–93.CrossRefPubMedGoogle Scholar
  52. 52.
    Desai AS, Vardeny O, Claggett B, McMurray JJV, Packer M, Swedberg K, et al. Reduced risk of hyperkalemia during treatment of heart failure with mineralocorticoid receptor antagonists by use of sacubitril/valsartan compared with enalapril. JAMA Cardiol. 2017;2:79.CrossRefPubMedGoogle Scholar
  53. 53.
    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;372:211–21.CrossRefPubMedGoogle Scholar
  54. 54.
    Pitt B, Anker SD, Bushinsky DA, Kitzman DW, Zannad F, Huang I-Z, et al. Evaluation of the efficacy and safety of RLY5016, a polymeric potassium binder, in a double-blind, placebo-controlled study in patients with chronic heart failure (the PEARL-HF) trial. Eur Heart J. 2011;32:820–8.CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Sarwar CMS, Papadimitriou L, Pitt B, Pina I, Zannad F, Anker SD, et al. Hyperkalemia in heart failure. J Am Coll Cardiol. 2016;68:1575–89.CrossRefPubMedGoogle Scholar
  56. 56.
    Morris AA, Cole RT, Butler J, Gupta D. Oral sodium and potassium binders in heart failure. Curr Heart Fail Rep. 2015;12:107–11.CrossRefPubMedGoogle Scholar
  57. 57.
    Wali RK, Wang GS, Gottlieb SS, Bellumkonda L, Hansalia R, Ramos E, et al. Effect of kidney transplantation on left ventricular systolic dysfunction and congestive heart failure in patients with end-stage renal disease. J Am Coll Cardiol. 2005;45:1051–60.CrossRefPubMedGoogle Scholar
  58. 58.
    Abbott KC, Trespalacios FC, Agodoa LY, Taylor AJ, Bakris GL. Beta-blocker use in long-term dialysis patients: association with hospitalized heart failure and mortality. Arch Intern Med. 2004;164:2465–71.CrossRefPubMedGoogle Scholar
  59. 59.
    Cice G, Ferrara L, D’Andrea A, D’Isa S, Di Benedetto A, Cittadini A, et al. Carvedilol increases two-year survivalin dialysis patients with dilated cardiomyopathy: a prospective, placebo-controlled trial. J Am Coll Cardiol. 2003;41:1438–44.CrossRefPubMedGoogle Scholar
  60. 60.
    Cice G, Di Benedetto A, D’Isa S, D’Andrea A, Marcelli D, Gatti E, et al. Effects of telmisartan added to angiotensin-converting enzyme inhibitors on mortality and morbidity in hemodialysis patients with chronic heart failure a double-blind, placebo-controlled trial. J Am Coll Cardiol. 2010;56:1701–8.CrossRefPubMedGoogle Scholar
  61. 61.
    Matsumoto Y, Mori Y, Kageyama S, Arihara K, Sugiyama T, Ohmura H, et al. Spironolactone reduces cardiovascular and cerebrovascular morbidity and mortality in hemodialysis patients. J Am Coll Cardiol. 2014;63:528–36.CrossRefPubMedGoogle Scholar
  62. 62.
    Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373:2117–28.CrossRefPubMedGoogle Scholar
  63. 63.
    Butler J, Hamo CE, Filippatos G, Pocock SJ, Bernstein RA, Brueckmann M, et al. The potential role and rationale for treatment of heart failure with sodium-glucose co-transporter 2 inhibitors. Eur J Heart Fail. 2017;19:1390–400.CrossRefPubMedGoogle Scholar
  64. 64.
    Wanner C, Inzucchi SE, Lachin JM, Fitchett D, von Eynatten M, Mattheus M, et al. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med. 2016;375:323–34.CrossRefPubMedGoogle Scholar
  65. 65.
    Summary of recommendation statements. Kidney Int Suppl (2011). 2013;3:5–14.Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Mattia Arrigo
    • 1
    Email author
  • Pietro E. Cippà
    • 2
  • Alexandre Mebazaa
    • 3
    • 4
    • 5
  1. 1.Department of Cardiology, University Heart CenterUniversity Hospital ZurichZurichSwitzerland
  2. 2.Center for Regenerative Medicine and Stem Cell ResearchUniversity of Southern CaliforniaLos AngelesUSA
  3. 3.INSERM UMR-S 942ParisFrance
  4. 4.University Paris Diderot, Sorbonne Paris CitéParisFrance
  5. 5.Department of Anesthesiology and Critical Care MedicineSt. Louis and Lariboisère University HospitalsParisFrance

Personalised recommendations