Electrolyte Blood Press.  2013 Jun;11(1):17-23. 10.5049/EBP.2013.11.1.17.

Pharmacologic Management of the Cardio-renal Syndrome

• Kim CS

• KMID: 2168396
• DOI: http://doi.org/10.5049/EBP.2013.11.1.17

Abstract

Cardio-renal syndromes are disorders of the heart and kidney wherein acute or long-term dysfunction in one organ may induce acute or long-term dysfunction of the other. Because of this complex organ interaction, management of cardiorenal syndrome must be tailored to the underlying pathophysiology. Clinical guidelines exist for the treatment of heart failure or renal failure as separate conditions. Thus far, however, there has been no consensus about managing patients with cardio-renal and reno-cardiac syndromes. Pharmacologic treatment remains a controversial subject. Standard cardiac drugs such as diuretics and inotropes may have limited effect because resistance often develops after long-term use. Recent studies of patients with acute cardio-renal syndromes have focused on newer therapies, including phosphodiesterase inhibitors, vasopressin antagonists, adenosine A1 receptor antagonists, and renal protective dopamine. Initial clinical trials of these agents have shown encouraging results in some patients with heart failure, but have failed to demonstrate a clear superiority over more conventional treatments. Similarly, the benefits of diuretics, aspirin, erythropoietin agents, and iron supplements for management of chronic cardiorenal syndromes are unknown.

Keyword

Cardio-renal syndrome; Management; Drug

MeSH Terms

Adenosine A1 Receptor Antagonists
Aspirin
Cardio-Renal Syndrome
Consensus
Diuretics
Dopamine
Erythropoietin
Heart
Heart Failure
Humans
Iron
Kidney
Phosphodiesterase Inhibitors
Renal Insufficiency
Vasopressins
Adenosine A1 Receptor Antagonists
Aspirin
Diuretics
Dopamine
Erythropoietin
Iron
Phosphodiesterase Inhibitors
Vasopressins

Reference

1. Elsayed EF, Tighiouart H, Griffith J, Kurth T, Levey AS, Salem D, et al. Cardiovascular disease and subsequent kidney disease. Arch Intern Med. 2007; 167:1130–1136. PMID: 17563020.

2. Hillege HL, Nitsch D, Pfeffer MA, Swedberg K, McMurray JJ, Yusuf S, et al. Renal function as a predictor of outcome in a broad spectrum of patients with heart failure. Circulation. 2006; 113:671–678. PMID: 16461840.

3. Ronco C, House AA, Haapio M. Cardiorenal syndrome: refining the definition of a complex symbiosis gone wrong. Intensive Care Med. 2008; 34:957–962. PMID: 18251008.

4. Bongartz LG, Cramer MJ, Doevendans PA, Joles JA, Braam B. The severe cardiorenal syndrome: 'Guyton revisited'. Eur Heart J. 2005; 26:11–17. PMID: 15615794.

5. Ronco C, McCullough P, Anker SD, Anand I, Aspromonte N, Bagshaw SM, et al. Cardio-renal syndromes: report from the consensus conference of the acute dialysis quality initiative. Eur Heart J. 2010; 31:703–711. PMID: 20037146.

6. Shlipak MG. Pharmacotherapy for heart failure in patients with renal insufficiency. Ann Intern Med. 2003; 138:917–924. PMID: 12779302.

7. Klein L, Massie BM, Leimberger JD, O'Connor CM, Pina IL, Adams KF Jr, et al. Admission or changes in renal function during hospitalization for worsening heart failure predict postdischarge survival: results from the Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure (OPTIME-CHF). Circ Heart Fail. 2008; 1:25–33. PMID: 19808267.

8. Marik PE. Low-dose dopamine: a systematic review. Intensive Care Med. 2002; 28:877–883. PMID: 12122525.

9. Lauschke A, Teichgraber UK, Frei U, Eckardt KU. 'Low-dose' dopamine worsens renal perfusion in patients with acute renal failure. Kidney Int. 2006; 69:1669–1674. PMID: 16572117.

10. Giamouzis G, Butler J, Starling RC, Karayannis G, Nastas J, Parisis C, et al. Impact of dopamine infusion on renal function in hospitalized heart failure patients: results of the Dopamine in Acute Decompensated Heart Failure (DAD-HF) Trial. J Card Fail. 2010; 16:922–930. PMID: 21111980.

11. Mebazaa A, Nieminen MS, Packer M, Cohen-Solal A, Kleber FX, Pocock SJ, et al. Levosimendan vs dobutamine for patients with acute decompensated heart failure: the SURVIVE Randomized Trial. JAMA. 2007; 297:1883–1891. PMID: 17473298.

12. 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; 53:589–596. PMID: 19215833.

13. den Uil CA, Lagrand WK, Spronk PE, van der Ent M, Jewbali LS, Brugts JJ, et al. Low-dose nitroglycerin improves microcirculation in hospitalized patients with acute heart failure. Eur J Heart Fail. 2009; 11:386–390. PMID: 19211570.

14. Mullens W, Abrahams Z, Francis GS, Skouri HN, Starling RC, Young JB, et al. Sodium nitroprusside for advanced low-output heart failure. J Am Coll Cardiol. 2008; 52:200–207. PMID: 18617068.

15. Sackner-Bernstein JD, Skopicki HA, Aaronson KD. Risk of worsening renal function with nesiritide in patients with acutely decompensated heart failure. Circulation. 2005; 111:1487–1491. PMID: 15781736.

16. Witteles RM, Kao D, Christopherson D, Matsuda K, Vagelos RH, Schreiber D, et al. Impact of nesiritide on renal function in patients with acute decompensated heart failure and pre-existing renal dysfunction a randomized, double-blind, placebo-controlled clinical trial. J Am Coll Cardiol. 2007; 50:1835–1840. PMID: 17980248.

17. Yancy CW, Krum H, Massie BM, Silver MA, Stevenson LW, Cheng M, et al. Safety and efficacy of outpatient nesiritide in patients with advanced heart failure: results of the Second Follow-Up Serial Infusions of Nesiritide (FUSION II) trial. Circ Heart Fail. 2008; 1:9–16. PMID: 19808265.

18. O'Connor CM, Starling RC, Hernandez AF, Armstrong PW, Dickstein K, Hasselblad V, et al. Effect of nesiritide in patients with acute decompensated heart failure. N Engl J Med. 2011; 365:32–43. PMID: 21732835.

19. Lemmens-Gruber R, Kamyar M. Vasopressin antagonists. Cell Mol Life Sci. 2006; 63:1766–1779. PMID: 16794787.

20. Konstam MA, Gheorghiade M, Burnett JC Jr, Grinfeld L, Maggioni AP, Swedberg K, et al. Effects of oral tolvaptan in patients hospitalized for worsening heart failure: the EVEREST Outcome Trial. JAMA. 2007; 297:1319–1331. PMID: 17384437.

21. Givertz MM, Massie BM, Fields TK, Pearson LL, Dittrich HC. The effects of KW-3902, an adenosine A1-receptor antagonist,on diuresis and renal function in patients with acute decompensated heart failure and renal impairment or diuretic resistance. J Am Coll Cardiol. 2007; 50:1551–1560. PMID: 17936154.

22. Voors AA, Dittrich HC, Massie BM, DeLucca P, Mansoor GA, Metra M, et al. Effects of the adenosine A1 receptor antagonist rolofylline on renal function in patients with acute heart failure and renal dysfunction: results from PROTECT(Placebo-Controlled Randomized Study of the Selective Adenosine A1 Receptor Antagonist Rolofylline for Patients Hospitalized with Acute Decompensated Heart Failure and Volume Overload to Assess Treatment Effect on Congestion and Renal Function). J Am Coll Cardiol. 2011; 57:1899–1907. PMID: 21545947.

23. Gottlieb SS, Givertz MM, Metra M, Gergich K, Bird S, Jones-Burton C, et al. The effects of adenosine A(1) receptor antagonism in patients with acute decompensated heart failure and worsening renal function: the REACH UP study. J Card Fail. 2010; 16:714–719. PMID: 20797594.

24. 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; 70:479–487. PMID: 1642186.

25. Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, et al. Randomized Aldactone Evaluation Study Investigators. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med. 1999; 341:709–717. PMID: 10471456.

26. Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 2003; 348:1309–1321. PMID: 12668699.

27. Bakris GL, Hart P, Ritz E. Beta blockers in the management of chronic kidney disease. Kidney Int. 2006; 70:1905–1913. PMID: 17021610.

28. Baigent C, Landray M, Leaper C, Altmann P, Armitage J, Baxter A, et al. First United Kingdom Heart and Renal Protection (UK-HARP-I) study: biochemical efficacy and safety of simvastatin and safety of low-dose aspirin in chronic kidney disease. Am J Kidney Dis. 2005; 45:473–484. PMID: 15754269.

29. Keltai M, Tonelli M, Mann JF, Sitkei E, Lewis BS, Hawken S, et al. Renal function and outcomes in acute coronary syndrome: impact of clopidogrel. Eur J Cardiovasc Prev Rehabil. 2007; 14:312–318. PMID: 17446813.

30. Best PJ, Steinhubl SR, Berger PB, Dasgupta A, Brennan DM, Szczech LA, et al. The efficacy and safety of short- and long-term dual antiplatelet therapy in patients with mild or moderate chronic kidney disease: results from the Clopidogrel for the Reduction of Events During Observation (CREDO) trial. Am Heart J. 2008; 155:687–693. PMID: 18371477.

31. Silva RP, Barbosa PH, Kimura OS, Sobrinho CR, Sousa Neto JD, Silva FA, et al. Prevalance of anemia and its association with cardio-renal syndrome. Int J Cardiol. 2007; 120:232–236. PMID: 17174420.

32. Kazory A, Ross EA. Anemia: the point of convergence or divergence for kidney disease and heart failure? J Am Coll Cardiol. 2009; 53:639–647. PMID: 19232895.

33. George J, Patal S, Wexler D, Abashidze A, Shmilovich H, Barak T, et al. Circulating erythropoietin levels and prognosis in patients with congestive heart failure: comparison with neurohormonal and inflammatory markers. Arch Intern Med. 2005; 165:1304–1309. PMID: 15956012.

34. van der Meer P, Lok DJ, Januzzi JL, de la Porte PW, Lipsic E, van Wijngaarden J, et al. Adequacy of endogenous erythropoietin levels and mortality in anaemic heart failure patients. Eur Heart J. 2008; 29:1510–1515. PMID: 18495690.

35. Silverberg DS, Wexler D, Iaina A, Steinbruch S, Wollman Y, Schwartz D. Anemia, chronic renal disease and congestive heart failure--the cardio renal anemia syndrome: the need for cooperation between cardiologists and nephrologists. Int Urol Nephrol. 2006; 38:295–310. PMID: 16868702.

36. Palazzuoli A, Silverberg DS, Iovine F, Calabrò A, Campagna MS, Gallotta M, et al. Effects of beta-erythropoietin treatment on left ventricular remodeling, systolic function, and B-type natriuretic peptide levels in patients with the cardiorenal anemia syndrome. Am Heart J. 2007; 154:645.e9–645.e15. PMID: 17892986.

37. Okonko DO, Grzeslo A, Witkowski T, Mandal AK, Slater RM, Roughton M, et al. Effect of intravenous iron sucrose on exercise tolerance in anemic and nonanemic patients with symptomatic chronic heart failure and iron deficiency FERRIC-HF: a randomized, controlled, observer-blinded trial. J Am Coll Cardiol. 2008; 51:103–112. PMID: 18191732.

38. Anker SD, Comin Colet J, Filippatos G, Willenheimer R, Dickstein K, Drexler H, et al. Ferric carboxymaltose in patients with heart failure and iron deficiency. N Engl J Med. 2009; 361:2436–2448. PMID: 19920054.