Background: It is well established that a large number of hospitalized patients present various degrees of heart and kidney dysfunction; primary disease of the heart or kidney often involves dysfunction or injury to the other. Summary: Based on above-cited organ cross-talk, the term cardiorenal syndrome (CRS) was proposed. Although CRS was usually referred to as abruption of kidney function following heart injury, it is now clearly established that it can describe negative effects of an impaired renal function on the heart and circulation. The historical lack of clear syndrome definition and complexity of diseases contributed to a waste of precious time especially concerning diagnosis and therapeutic strategies. The effective classification of CRS proposed in a Consensus Conference by the Acute Dialysis Quality Group essentially divides CRS into two main groups, cardiorenal and renocardiac CRS, on the basis of primum movens of disease (cardiac or renal); both cardiorenal and renocardiac CRS are then divided into acute and chronic according to disease onset. Type 5 CRS integrates all cardiorenal involvement induced by systemic disease. Key Messages: Prevalence and incidence data show a widespread increase of CRS also due to an increasing incidence of acute and chronic cardiovascular disease, such as acute decompensated heart failure, arterial hypertension and valvular heart disease. Patients with chronic kidney disease present various degrees of cardiovascular involvement especially due to chronic inflammatory status, volume and pressure overload and secondary hyperparathyroidism leading to a higher incidence of calcific heart disease. The following review will focus on the main aspects (epidemiology, risk factors, diagnostic tools and protocols, therapeutic approaches) of CRS in Western countries (Europe and United States).

1.
Ronco C: Cardiorenal and renocardiac syndromes: clinical disorders in search of a systematic definition. Int J Artif Organs 2008;31:1-2.
2.
Bargshaw SM, Cruz DM, Aspromonte N, et al; the Acute Dialysis Quality Initiative (ADQI) Consensus Group: Epidemiology of cardio-renal syndromes: workgroup statements from the 7th ADQI Consensus Conference. Nephrol Dial Transplant 2010;25:1406-1416.
3.
Dar O, Cowie MR: Acute heart failure in the intensive care unit: epidemiology. Crit Care Med 2008;36:S3-S8.
4.
Van Sloten TT, Pijpers E, Steouwer CD, Brouwers MC: Metformin-associated lactic acidosis in a patient with normal kidney function. Diabetes Res Clinic Pract 2012;96x:57-58.
5.
Prawle JR, Liu YI, Licari E, et al: Oliguria as predictive biomarker of acute kidney injury in critically ill patients. Crit Care 2011;15:R172.
6.
Prowle JR, Echeverri JE, Ligabo EV, Ronco C, Bellomo R: Fluid balance and acute kidney injury. Nat Rev Nephrol 2010;6:107-115.
7.
Lassus JP, Nieminen MS, Peuhkurinen K, Pulkki K, Siirilä-Waris K, Sund R, Harjola VP; FINN-AKVA Study Group: Markers of renal function and acute kidney injury in acute heart failure: definitions and impact on outcomes of the cardiorenal syndrome. Eur Heart J 2010;31:2791-2798.
8.
Cruz DN, Gaiao S, Maisel A, Ronco C, Devarajan P: Neutrophil gelatinase-associated lipocalin as a biomarker of cardiovascular disease: a systematic review. Clin Chem Lab Med 2012;50:1533-1545.
9.
Di Lullo L, Floccari F, Granata A, D'Amelio A, Rivera R, Fiorini F, Malaguti M, Timio M: Ultrasonography: Ariadne's thread in the diagnosis of cardiorenal syndrome. Cardiorenal Med 2012;2:11-17.
10.
Hollenberg SM, Kevinsky CJ, Parrillo JE: Cardiogenic shock. Ann Intern Med 1999;131:47-59.
11.
Hebert K, Dias A, Delgado MC, Franco E, Tamariz L, Steen D, Trahan P, Major B, Arcement LM: Epidemiology and survival of the five stages of chronic kidney disease in a systolic heart failure population. Eur J Heart Fail 2010;12:861-865.
12.
Hillege HL, Nitsch D, Pfeffer MA, Swedberg K, McMurray JJ, Yusuf S, Granger CB, Michelson EL, Ostergren J, Cornel JH, et al: Renal function as a predictor of outcome in a broad spectrum of patients with heart failure. Circulation 2006;113:671-678.
13.
Halbesma N, Jansen DF, Heymans MW, Stolk RP, de Jong PE, Gansevoort RT: Development and validation of a general population renal risk score. Clin J Am Soc Nephrol 2011;6:1731-1738.
14.
Cruz DN, Fard A, Clementi A, Ronco C, Maisel A: Role of biomarkers in the diagnosis and management of cardio-renal syndromes. Semin Nephrol 2012;32:79-92.
15.
Liang KV, Williams AW, Greene EL, Redfield MM: Acute decompensated heart failure and the cardiorenal syndrome. Crit Care Med 2008;36(suppl):S75-S88.
16.
Costanzo MR, Guglin ME, Saltzberg MT, et al; UNLOAD Trial Investigators: Ultrafiltration versus intravenous diuretics for patients hospitalized for acute decompensated heart failure. J Am Coll Cardiol 2007;49:675-683.
17.
Shah SU, Anjum S, Littler WA: Use of diuretics in cardiovascular diseases: (1) heart failure. Postgrad Med J 2004;80:201-205.
18.
Butler J, Forman DE, Abraham WT, et al: Relationship between heart failure treatment and development of worsening renal function among hospitalized patients. Am Heart J 2004;147:331-338.
19.
Costanzo MR: Ultrafiltration in the management of heart failure. Curr Opin Crit Care 2008;14:524-530.
20.
Hunt SA, Abraham WT, Chin MH, et al; American College of Cardiology Foundation; American Heart Association: 2009 Focused update incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults. A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration with the International Society for Heart and Lung Transplantation. J Am Coll Cardiol 2009;53:e1-e90.
21.
Fiaccadori E, Regolisti G, Maggiore U, et al: Ultrafiltration in heart failure. Am Heart J 2011;161:439-449.
22.
Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky PM; the ADQI Workgroup: 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.
23.
Mehta RL, Kellum JA, Shah SV, et al: Acute kidney injury network (AKIN): report of an initiative to improve outcomes in acute kidney injury. Crit Care 2007;11:R31.
24.
Uchino S, Kellum JA, Bellomo R, et al: Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) investigators. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA 2005;294:813-818.
25.
Gheorghiade M, Zannad F, Sopko G, et al: Failure syndromes: current state and framework for future research. Circulation 2005;112:3958-3968.
26.
Sharabas I, Siddiqi N: Cardiovascular disease risk profiles comparison among dialysis patients. Saudi J Kidney Dis Transpl 2016;27:692-700.
27.
Siirila-Waris K, Lassus J, Melin J, et al: Characteristics, outcomes, and predictors of 1 year mortality in patients hospitalized for acute heart failure. Eur Heart J 2006;27:3011-3017.
28.
Ali T, Khan I, Simpson W, et al: Incidence and outcomes in acute kidney injury: a comprehensive population-based study. J Am Soc Nephrol 2007;18:1292-1298.
29.
De Abreu KLS, Silva Junior GB, Carreto AGC, et al: Acute kidney injury after trauma: prevalence, clinical characteristics and RIFLE classification. Indian J Crit Care Med 2010;14:121-128.
30.
Hillege HL, Girbes AR, de Kam PJ, et al: Renal function, neurohormonal activation and survival in patients with chronic heart failure. Circulation 2000;102:203-210.
31.
Di Lullo L, Barbera V, Santoboni A, Bellasi A, Cozzolino M, De Pascalis A, Rivera R, Balducci A, Russo D, Ronco C: Troponins and chronic kidney disease. G Ital Nefrol 2015;32.
32.
Chuasuwan A, Kellum JA: Cardio-renal syndrome type 3: epidemiology, pathophysiology, and treatment. Semin Nephrol 2012;32:31-39.
33.
Bellomo R, Kellum JA, Ronco C: Acute kidney injury. Lancet 2012;380:756-766.
34.
Karvellas CJ, Farhat MR, Sajjad I, Mogensen SS, Leung AA, Wald R, et al: A comparison of early versus late initiation of renal replacement therapy in critically ill patients with acute kidney injury: a systematic review and meta-analysis. Crit Care 2011;15:R72.
35.
Schneider AG, Bellomo R, Bagshaw SM, Glassford NJ, Lo S, Jun M, et al: Choice of renal replacement therapy modality and dialysis dependence after acute kidney injury: a systematic review and meta-analysis. Intensive Care Med 2013;39:987-997.
36.
Wu VC, Wang CH, Wang WJ, Lin YF, Hu FC, Chen YW, et al: Sustained low-efficiency dialysis versus continuous veno-venous hemofiltration for postsurgical acute renal failure. Am J Surg 2010;199:466-476.
37.
Bellomo R, Cass A, Cole L, Finfer S, Gallagher M, Lo S, et al: Intensity of continuous renal-replacement therapy in critically ill patients. N Engl J Med 2009;361:1627-1638.
38.
Tonelli M, Wiebe N, Culleton B, House A, Rabbat C, Fok M, McAlister F, Garg AX: Chronic kidney disease and mortality risk: a systematic review. J Am Soc Nephrol 2006;17:2034-2047.
39.
Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY: Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med 2004;351:1296-1305.
40.
Bansal N, Keane M, Delafontaine P, Dries D, Foster E, Gadegbeku CA, Go AS, Hamm LL, Kusek JW, Ojo AO, Rahman M, Tao K, Wright JT, Xie D, Hsu CY; CRIC Study Investigators: A longitudinal study of left ventricular function and structure from CKD to ESRD: the CRIC study. Clin J Am Soc Nephrol 2013;8:355-362.
41.
Di Lullo L, House A, Gorini A, Santoboni A, Russo D, Ronco C: Chronic kidney disease and cardiovascular complications. Heart Fail Rev 2015;20:259-272.
42.
Di Lullo L, Rivera R, Barbera V, Bellasi A, Cozzolino M, Russo D, De Pascalis A, Banerjee D, Floccari F, Ronco C: Sudden cardiac death and chronic kidney disease: from pathophysiology to treatment strategies. Int J Cardiol 2016;217:16-27.
43.
Ronco C, Di Lullo L: Cardiorenal syndrome. Heart Fail Clin 2014;10:251-280.
44.
Di Lullo L, Floccari F, Rivera R, Barbera V, Granata A, Otranto G, Mudoni A, Malaguti M, Santoboni A, Ronco C: Pulmonary hypertension and right heart failure in chronic kidney disease: new challenge for 21st-century cardionephrologists. Cardiorenal Med 2013;3:96-103.
45.
Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, Remuzzi G, Snapinn SM, Zhang Z, Shahinfar S; RENAAL Study Investigators: Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001;345:861-869.
46.
Lewis EJ, Hunsicker LG, Clarke WR, Berl T, Pohl MA, Lewis JB, Ritz E, Atkins RC, Rohde R, Raz I; Collaborative Study Group: Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 2001;345:851-860.
47.
Lesogor A, Cohn JN, Latini R, Tognoni G, Krum H, Massie B, Zalewski A, Kandra A, Hua TA, Gimpelewicz C: Interaction between baseline and early worsening of renal function and efficacy of renin-angiotensin-aldosterone system blockade in patients with heart failure: insights from the Val-HeFT study. Eur J Heart Fail 2013;15:1236-1244.
48.
Cice G, Ferrara L, D'Andrea A, D'Isa S, Di Benedetto A, Cittadini A, Russo PE, Golino P, Calabro R: Carvedilol increases two-year survival in dialysis patients with dilated cardiomyopathy: a prospective, placebo-controlled trial. J Am Coll Cardiol 2003;41:1438-1444.
49.
EVOLVE Trial Investigators; Chertow GM, Block GA, Correa-Rotter R, Drueke TB, Floege J, Goodman WG, Herzog CA, Kubo Y, London GM, Mahaffey KW, Mix TC, Moe SM, Trotman ML, Wheeler DC, Parfrey PS: Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis. N Engl J Med 2012;367:2482-2494.
50.
Di Lullo L, Floccari F, Santoboni A, Barbera V, Rivera RF, Granata A, Morrone L, Russo D: Progression of cardiac valve calcification and decline of renal function in CKD patients. J Nephrol 2013;26:739-744.
51.
Sharp Collaborative Group: Study of Heart and Renal Protection (SHARP): randomized trial to assess the effects of lowering low-density lipoprotein cholesterol among 9,438 patients with chronic kidney disease. Am Heart J 2010;160:785-794.
52.
Tateishi Y, et al: Depressed heart rate variability is associated with high IL-6 blood level and decline in the blood pressure in septic patients. Shock 2007;28:549-553.
53.
Stengl M, et al: Reduced L-type calcium current in ventricular myocytes from pigs with hyperdynamic septic shock. Crit Care Med 2010;38:579-587.
54.
Reinhart K, et al: New approaches to sepsis: molecular diagnostics and biomarkers. Clin Microbiol Rev 2012;25:609-634.
55.
Nakamura M, et al: Treatment of severe sepsis and septic shock by CHDF using a PMMA membrane hemofilter as a cytokine modulator. Contrib Nephrol 2010;166:73-82.
56.
Bellomo R, Wan L, May C: Vasoactive drugs and acute kidney injury. Crit Care Med 2008;36(4 suppl):S179-S186.
57.
Landoni G, et al: Fenoldopam in cardiac surgery-associated acute kidney injury. Int J Artif Organs 2008;31:561.
58.
Nigwekar SU, Waikar SS: Diuretics in acute kidney injury. Semin Nephrol 2011;31:523-534.
59.
Chou YH, et al: Impact of timing of renal replacement therapy initiation on outcome of septic acute kidney injury. Crit Care 2011;15:R134.
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.