Background: The management of the cardiorenal syndrome (CRS) in decompensated heart failure (HF) is challenging, with high-quality evidence lacking. Summary: The pathophysiology of CRS in decompensated HF is complex, with glomerular filtration rate (GFR) and urine output representing different aspects of kidney function. GFR depends on structural factors (number of functional nephrons and integrity of the glomerular membrane) versus hemodynamic alterations (volume status, renal perfusion, arterial blood pressure, central venous pressure or intra-abdominal pressure) and neurohumoral activation. In contrast, urine output and volume homeostasis are mainly a function of the renal tubules. Treatment of CRS in decompensated HF patients should be individualized based on the underlying pathophysiological processes. Key Messages: Congestion, defined as elevated cardiac filling pressures, is not a surrogate for volume overload. Transient decreases in GFR might be accepted during decongestion, but hypotension must be avoided. Paracentesis and compression therapy are essential to remove fluid overload from third spaces. Increasing the effective circulatory volume improves renal function when cardiac output is depressed. As mechanical support is invasive and inotropes are related to increased mortality, afterload reduction through vasodilator therapy remains the preferred strategy in patients who are normo- or hypertensive. Specific therapies to augment renal perfusion (rolofylline, dopamine or nesiritide) have rendered disappointing results, but recently, serelaxin has been shown to improve renal function, even with a trend towards reduced all-cause mortality in selected patients. Diuretic resistance is associated with worse outcomes, independent of the underlying GFR. Combinational diuretic therapy, with ultrafiltration as a bail-out strategy, is indicated in case of diuretic resistance. i 2014 S. Karger AG, Basel

1.
Adams KF Jr, Fonarow GC, Emerman CL, LeJemtel TH, Costanzo MR, Abraham WT, et al: Characteristics and outcomes of patients hospitalized for heart failure in the United States: rationale, design, and preliminary observations from the first 100,000 cases in the Acute Decompensated Heart Failure National Registry (ADHERE). Am Heart J 2005;149:209-216.
2.
Gheorghiade M, Vaduganathan M, Fonarow GC, Bonow RO: Rehospitalization for heart failure: problems and perspectives. J Am Coll Cardiol 2013;61:391-403.
3.
McKie PM, Schirger JA, Costello-Boerrigter LC, Benike SL, Harstad LK, Bailey KR, et al: Impaired natriuretic and renal endocrine response to acute volume expansion in pre-clinical systolic and diastolic dysfunction. J Am Coll Cardiol 2011;58:2095-2103.
4.
Verbrugge FH, Dupont M, Steels P, Grieten L, Swennen Q, Tang WH, et al: The kidney in congestive heart failure: ‘are natriuresis, sodium, and diuretics really the good, the bad and the ugly?'. Eur J Heart Fail 2014;16:133-142.
5.
Fonarow GC, Adams KF Jr, Abraham WT, Yancy CW, Boscardin WJ: Risk stratification for in-hospital mortality in acutely decompensated heart failure: classification and regression tree analysis. JAMA 2005;293:572-580.
6.
Ronco C, Haapio M, House AA, Anavekar N, Bellomo R: Cardiorenal syndrome. J Am Coll Cardiol 2008;52:1527-1539.
7.
Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P: Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care 2004;8:R204-R212.
8.
Gottlieb SS, Abraham W, Butler J, Forman DE, Loh E, Massie BM, et al: The prognostic importance of different definitions of worsening renal function in congestive heart failure. J Card Fail 2002;8:136-141.
9.
Forman DE, Butler J, Wang Y, Abraham WT, O'Connor CM, Gottlieb SS, et al: Incidence, predictors at admission, and impact of worsening renal function among patients hospitalized with heart failure. J Am Coll Cardiol 2004;43:61-67.
10.
Testani JM, Chen J, McCauley BD, Kimmel SE, Shannon RP: Potential effects of aggressive decongestion during the treatment of decompensated heart failure on renal function and survival. Circulation 2010;122:265-272.
11.
Testani JM, Kimmel SE, Dries DL, Coca SG: Prognostic importance of early worsening renal function after initiation of angiotensin-converting enzyme inhibitor therapy in patients with cardiac dysfunction. Circ Heart Fail 2011;4:685-691.
12.
Costanzo MR, Guglin ME, Saltzberg MT, Jessup ML, Bart BA, Teerlink JR, et al: Ultrafiltration versus intravenous diuretics for patients hospitalized for acute decompensated heart failure. J Am Coll Cardiol 2007;49:675-683.
13.
Metra M, Davison B, Bettari L, Sun H, Edwards C, Lazzarini V, et al: Is worsening renal function an ominous prognostic sign in patients with acute heart failure? The role of congestion and its interaction with renal function. Circ Heart Fail 2012;5:54-62.
14.
Mullens W, Verbrugge FH: Increasing diuresis in congestive heart failure: ready for prime time? J Am Coll Cardiol 2013;62:1184-1186.
15.
Hillege HL, Girbes AR, de Kam PJ, Boomsma F, de Zeeuw D, Charlesworth A, et al: Renal function, neurohormonal activation, and survival in patients with chronic heart failure. Circulation 2000;102:203-210.
16.
Barreto FC, Barreto DV, Liabeuf S, Meert N, Glorieux G, Temmar M, et al: Serum indoxyl sulfate is associated with vascular disease and mortality in chronic kidney disease patients. Clin J Am Soc Nephrol 2009;4:1551-1558.
17.
Sato B, Yoshikawa D, Ishii H, Suzuki S, Inoue Y, Takeshita K, et al: Relation of plasma indoxyl sulfate levels and estimated glomerular filtration rate to left ventricular diastolic dysfunction. Am J Cardiol 2013;111:712-716.
18.
Braam B, Cupples WA, Joles JA, Gaillard C: Systemic arterial and venous determinants of renal hemodynamics in congestive heart failure. Heart Fail Rev 2012;17:161-175.
19.
Mullens W, Abrahams Z, Skouri HN, Francis GS, Taylor DO, Starling RC, et al: Elevated intra-abdominal pressure in acute decompensated heart failure: a potential contributor to worsening renal function? J Am Coll Cardiol 2008;51:300-306.
20.
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.
21.
Testani JM, Coca SG, McCauley BD, Shannon RP, Kimmel SE: Impact of changes in blood pressure during the treatment of acute decompensated heart failure on renal and clinical outcomes. Eur J Heart Fail 2011;13:877-884.
22.
Dupont M, Mullens W, Finucan M, Taylor DO, Starling RC, Tang WH: Determinants of dynamic changes in serum creatinine in acute decompensated heart failure: the importance of blood pressure reduction during treatment. Eur J Heart Fail 2013;15:433-440.
23.
Blair JE, Pang PS, Schrier RW, Metra M, Traver B, Cook T, et al: Changes in renal function during hospitalization and soon after discharge in patients admitted for worsening heart failure in the placebo group of the EVEREST trial. Eur Heart J 2011;32:2563-2572.
24.
Damman K, Van Veldhuisen DJ, Navis G, Vaidya VS, Smilde TD, Westenbrink BD, et al: Tubular damage in chronic systolic heart failure is associated with reduced survival independent of glomerular filtration rate. Heart 2010;96:1297-1302.
25.
Damman K, Masson S, Hillege HL, Maggioni AP, Voors AA, Opasich C, et al: Clinical outcome of renal tubular damage in chronic heart failure. Eur Heart J 2011;32:2705-2712.
26.
Dupont M, Shrestha K, Singh D, Awad A, Kovach C, Scarcipino M, et al: Lack of significant renal tubular injury despite acute kidney injury in acute decompensated heart failure. Eur J Heart Fail 2012;14:597-604.
27.
Verbrugge FH, Dupont M, Shao Z, Shrestha K, Singh D, Finucan M, et al: Novel urinary biomarkers in detecting acute kidney injury, persistent renal impairment, and all-cause mortality following decongestive therapy in acute decompensated heart failure. J Card Fail 2013;19:621-628.
28.
Verbrugge FH, Dupont M, Steels P, Grieten L, Malbrain M, Tang WH, et al: Abdominal contributions to cardiorenal dysfunction in congestive heart failure. J Am Coll Cardiol 2013;62:485-495.
29.
Schnermann J: Juxtaglomerular cell complex in the regulation of renal salt excretion. Am J Physiol 1998;274:R263-R279.
30.
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;325:293-302.
31.
Cohn JN, Tognoni G: A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med 2001;345:1667-1675.
32.
Francis GS, Benedict C, Johnstone DE, Kirlin PC, Nicklas J, Liang CS, et al: Comparison of neuroendocrine activation in patients with left ventricular dysfunction with and without congestive heart failure. A substudy of the Studies of Left Ventricular Dysfunction (SOLVD). Circulation 1990;82:1724-1729.
33.
Verbrugge FH, Grieten L, Mullens W: New insights into combinational drug therapy to manage congestion in heart failure. Curr Heart Fail Rep 2014;11:1-9.
34.
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, discussion 22-24.
35.
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;53:582-588.
36.
Chaudhry SI, Wang Y, Concato J, Gill TM, Krumholz HM: Patterns of weight change preceding hospitalization for heart failure. Circulation 2007;116:1549-1554.
37.
Marik PE, Baram M, Vahid B: Does central venous pressure predict fluid responsiveness? A systematic review of the literature and the tale of seven mares. Chest 2008;134:172-178.
38.
Gelman S, Mushlin PS: Catecholamine-induced changes in the splanchnic circulation affecting systemic hemodynamics. Anesthesiology 2004;100:434-439.
39.
Fallick C, Sobotka PA, Dunlap ME: Sympathetically mediated changes in capacitance: redistribution of the venous reservoir as a cause of decompensation. Circ Heart Fail 2011;4:669-765.
40.
Stevenson LW, Perloff JK: The limited reliability of physical signs for estimating hemodynamics in chronic heart failure. JAMA 1989;261:884-888.
41.
Shah MR, Hasselblad V, Tasissa G, Christenson RH, Binanay C, O'Connor CM, et al: Rapid assay brain natriuretic peptide and troponin I in patients hospitalized with decompensated heart failure (from the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness Trial). Am J Cardiol 2007;100:1427-1433.
42.
Binanay C, Califf RM, Hasselblad V, O'Connor CM, Shah MR, Sopko G, et al: Evaluation study of congestive heart failure and pulmonary artery catheterization effectiveness: the ESCAPE trial. JAMA 2005;294:1625-1633.
43.
Asfar P, Meziani F, Hamel JF, Grelon F, Megarbane B, Anguel N, et al: High versus low blood-pressure target in patients with septic shock. N Engl J Med 2014;370:1583-1593.
44.
Palmer BF: Impaired renal autoregulation: implications for the genesis of hypertension and hypertension-induced renal injury. Am J Med Sci 2001;321:388-400.
45.
Mullens W, Abrahams Z, Francis GS, Taylor DO, Starling RC, Tang WH: Prompt reduction in intra-abdominal pressure following large-volume mechanical fluid removal improves renal insufficiency in refractory decompensated heart failure. J Card Fail 2008;14:508-514.
46.
Sandner SE, Zimpfer D, Zrunek P, Rajek A, Schima H, Dunkler D, et al: Renal function and outcome after continuous flow left ventricular assist device implantation. Ann Thorac Surg 2009;87:1072-1078.
47.
Hasin T, Topilsky Y, Schirger JA, Li Z, Zhao Y, Boilson BA, et al: Changes in renal function after implantation of continuous-flow left ventricular assist devices. J Am Coll Cardiol 2012;59:26-36.
48.
Packer M, Carver JR, Rodeheffer RJ, Ivanhoe RJ, DiBianco R, Zeldis SM, et al: Effect of oral milrinone on mortality in severe chronic heart failure. The PROMISE Study Research Group. N Engl J Med 1991;325:1468-1475.
49.
O'Connor CM, Gattis WA, Uretsky BF, Adams KF Jr, McNulty SE, Grossman SH, et al: Continuous intravenous dobutamine is associated with an increased risk of death in patients with advanced heart failure: insights from the Flolan International Randomized Survival Trial (FIRST). Am Heart J 1999;138:78-86.
50.
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.
51.
Mullens W, Abrahams Z, Francis GS, Sokos G, Starling RC, Young JB, et al: Usefulness of Isosorbide Dinitrate and Hydralazine as add-on therapy in patients discharged for advanced decompensated heart failure. Am J Cardiol 2009;103:1113-1119.
52.
Mebazaa A, Parissis J, Porcher R, Gayat E, Nikolaou M, Boas FV, et al: Short-term survival by treatment among patients hospitalized with acute heart failure: the global ALARM-HF registry using propensity scoring methods. Intensive Care Med 2011;37:290-301.
53.
Follath F, Cleland JG, Just H, Papp JG, Scholz H, Peuhkurinen K, et al: Efficacy and safety of intravenous levosimendan compared with dobutamine in severe low-output heart failure (the LIDO study): a randomised double-blind trial. Lancet 2002;360:196-202.
54.
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.
55.
Cleland JG, Teerlink JR, Senior R, Nifontov EM, Mc Murray JJ, Lang CC, et al: The effects of the cardiac myosin activator, omecamtiv mecarbil, on cardiac function in systolic heart failure: a double-blind, placebo-controlled, crossover, dose-ranging phase 2 trial. Lancet 2011;378:676-683.
56.
Massie BM, O'Connor CM, Metra M, Ponikowski P, Teerlink JR, Cotter G, et al: Rolofylline, an adenosine A1-receptor antagonist, in acute heart failure. N Engl J Med 2010;363:1419-1428.
57.
Chen HH, Anstrom KJ, Givertz MM, Stevenson LW, Semigran MJ, Goldsmith SR, et al: Low-dose dopamine or low-dose nesiritide in acute heart failure with renal dysfunction: the ROSE acute heart failure randomized trial. JAMA 2013;310:2533-2543.
58.
Conrad KP: Maternal vasodilation in pregnancy: the emerging role of relaxin. Am J Physiol Regul Integr Comp Physiol 2011;301:R267-R275.
59.
Teerlink JR, Cotter G, Davison BA, Felker GM, Filippatos G, Greenberg BH, et al: Serelaxin, recombinant human relaxin-2, for treatment of acute heart failure (RELAX-AHF): a randomised, placebo-controlled trial. Lancet 2013;381:29-39.
60.
Metra M, Cotter G, Davison BA, Felker GM, Filippatos G, Greenberg BH, et al: Effect of serelaxin on cardiac, renal, and hepatic biomarkers in the Relaxin in Acute Heart Failure (RELAX-AHF) development program: correlation with outcomes. J Am Coll Cardiol 2013;61:196-206.
61.
Fonarow GC, Corday E: Overview of acutely decompensated congestive heart failure (ADHF): a report from the ADHERE registry. Heart Fail Rev 2004;9:179-185.
62.
Felker GM, Lee KL, Bull DA, Redfield MM, Stevenson LW, Goldsmith SR, et al: Diuretic strategies in patients with acute decompensated heart failure. N Engl J Med 2011;364:797-805.
63.
Testani JM, Brisco MA, Turner JM, Spatz ES, Bellumkonda L, Parikh CR, et al: Loop diuretic efficiency: a metric of diuretic responsiveness with prognostic importance in acute decompensated heart failure. Circ Heart Fail 2014;7:261-270.
64.
Singh D, Shrestha K, Testani JM, Verbrugge FH, Dupont M, Mullens W, et al: Insufficient natriuretic response to continuous intravenous furosemide is associated with poor long-term outcomes in acute decompensated heart failure. J Card Fail 2014;20:392-399.
65.
Jentzer JC, DeWald TA, Hernandez AF: Combination of loop diuretics with thiazide-type diuretics in heart failure. J Am Coll Cardiol 2010;56:1527-1534.
66.
Knauf H, Mutschler E: Functional state of the nephron and diuretic dose-response - rationale for low-dose combination therapy. Cardiology 1994;84(suppl 2):18-26.
67.
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;367:2296-2304.
68.
Ali SS, Olinger CC, Sobotka PA, Dahle TG, Bunte MC, Blake D, et al: Loop diuretics can cause clinical natriuretic failure: a prescription for volume expansion. Congest Heart Fail 2009;15:1-4.
69.
Patarroyo M, Wehbe E, Hanna M, Taylor DO, Starling RC, Demirjian S, et al: Cardiorenal outcomes after slow continuous ultrafiltration therapy in refractory patients with advanced decompensated heart failure. J Am Coll Cardiol 2012;60:1906-1912.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.