An Update on the Pathophysiology and Treatment of Cardiorenal Syndrome

Rupesh Raina, Nikhil Nair, Ronith Chakraborty, Lena Nemer, Rahul Dasgupta, Kenneth Varian, Rupesh Raina, Nikhil Nair, Ronith Chakraborty, Lena Nemer, Rahul Dasgupta, Kenneth Varian

Abstract

Cardiorenal syndrome (CRS) encompasses various disorders of the heart and kidneys; dysfunction of one organ leads to acute or chronic dysfunction of the other. It incorporates the intersection of heart-kidney interactions across several mediums, hemodynamically, through the alterations in neurohormonal markers, and increased venous and renal pressure, all of which are hallmarks of its clinical phenotypes. This article explores the epidemiology, pathology, classification and treatment of each type of CRS.

Keywords: Cardiorenal syndrome; Chronic kidney disease; Heart failure.

Conflict of interest statement

The authors have no conflict of interest to declare.

Copyright 2020, Raina et al.

Figures

Figure 1
Figure 1
Mechanism of damage in CRS-1. ACE, angiotensin-converting enzyme; CKD, chronic kidney disease; CRS, cardiorenal syndrome; RAA, rennin-angiotensin-aldosterone.
Figure 2
Figure 2
Mechanism of damage in CRS-2. CKD, chronic kidney disease; CRS, cardiorenal syndrome.
Figure 3
Figure 3
Mechanism of damage in CRS-3. CRS, cardiorenal syndrome; GFR, glomerular filtration rate; RAAS, renin-angiotensin-aldosterone system.
Figure 4
Figure 4
Mechanism of damage in CRS-4. CKD, chronic kidney disease; CRS, cardiorenal syndrome; EPO, erythropoietin; LDL, low-density lipoprotein.
Figure 5
Figure 5
Mechanism of damage in CRS-5. CRS, cardiorenal syndrome.

References

    1. Rangaswami J, Bhalla V, Blair JEA, Chang TI, Costa S, Lentine KL, Lerma EV. et al. Cardiorenal syndrome: classification, pathophysiology, diagnosis, and treatment strategies: a scientific statement from the American Heart Association. Circulation. 2019;139(16):e840–e878. doi: 10.1161/CIR.0000000000000664.
    1. Chrysohoou C, Bougatsos G, Magkas N, Skoumas J, Kapota A, Kopelias J, Bliouras N. et al. Peritoneal dialysis as a therapeutic solution in elderly patients with cardiorenal syndrome and heart failure: A case-series report. Hellenic J Cardiol. 2019 doi: 10.1016/j.hjc.2019.04.010.
    1. Ronco C, McCullough PA, Anker SD, Anand I, Aspromonte N, Bagshaw SM, Bellomo R. et al. Cardiorenal syndromes: an executive summary from the consensus conference of the Acute Dialysis Quality Initiative (ADQI) Contrib Nephrol. 2010;165:54–67. doi: 10.1159/000313745.
    1. Di Lullo L, Reeves PB, Bellasi A, Ronco C. Cardiorenal Syndrome in Acute Kidney Injury. Semin Nephrol. 2019;39(1):31–40. doi: 10.1016/j.semnephrol.2018.10.003.
    1. Hadjiphilippou S, Kon SP. Cardiorenal syndrome: review of our current understanding. J R Soc Med. 2016;109(1):12–17. doi: 10.1177/0141076815616091.
    1. Mullens W, Abrahams Z, Francis GS, Sokos G, Taylor DO, Starling RC, Young JB. et al. Importance of venous congestion for worsening of renal function in advanced decompensated heart failure. J Am Coll Cardiol. 2009;53(7):589–596. doi: 10.1016/j.jacc.2008.05.068.
    1. Ichikawa I, Pfeffer JM, Pfeffer MA, Hostetter TH, Brenner BM. Role of angiotensin II in the altered renal function of congestive heart failure. Circ Res. 1984;55(5):669–675. doi: 10.1161/01.RES.55.5.669.
    1. Takahama H, Kitakaze M. Pathophysiology of cardiorenal syndrome in patients with heart failure: potential therapeutic targets. Am J Physiol Heart Circ Physiol. 2017;313(4):H715–H721. doi: 10.1152/ajpheart.00215.2017.
    1. 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(4):433–440. doi: 10.1093/eurjhf/hfs209.
    1. Wallquist C, Mansouri L, Norrback M, Hylander B, Jacobson SH, Lundahl J. Early Changes in monocyte adhesion molecule expression and tumor necrosis factor-alpha levels in chronic kidney disease - a 5-year prospective study. Am J Nephrol. 2016;44(4):268–275. doi: 10.1159/000449290.
    1. Wen H, Gwathmey JK, Xie LH. Oxidative stress-mediated effects of angiotensin II in the cardiovascular system. World J Hypertens. 2012;2(4):34–44. doi: 10.5494/wjh.v2.i4.34.
    1. Ronco C, Bellasi A, Di Lullo L. Cardiorenal syndrome: an overview. Adv Chronic Kidney Dis. 2018;25(5):382–390. doi: 10.1053/j.ackd.2018.08.004.
    1. Heywood JT, Fonarow GC, Costanzo MR, Mathur VS, Wigneswaran JR, Wynne J, Committee ASA. et al. High prevalence of renal dysfunction and its impact on outcome in 118,465 patients hospitalized with acute decompensated heart failure: a report from the ADHERE database. J Card Fail. 2007;13(6):422–430. doi: 10.1016/j.cardfail.2007.03.011.
    1. Palazzuoli A, Silverberg DS, Iovine F, Calabro A, Campagna MS, Gallotta M, Nuti R. 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(4):645. doi: 10.1016/j.ahj.2007.07.022. e649-615.
    1. Odutayo A, Wong CX, Farkouh M, Altman DG, Hopewell S, Emdin CA, Hunn BH. AKI and long-term risk for cardiovascular events and mortality. J Am Soc Nephrol. 2017;28(1):377–387. doi: 10.1681/ASN.2016010105.
    1. Uduman J. Epidemiology of Cardiorenal Syndrome. Adv Chronic Kidney Dis. 2018;25(5):391–399. doi: 10.1053/j.ackd.2018.08.009.
    1. Mentzer RM Jr, Oz MC, Sladen RN, Graeve AH, Hebeler RF Jr, Luber JM Jr, Smedira NG. et al. Effects of perioperative nesiritide in patients with left ventricular dysfunction undergoing cardiac surgery:the NAPA Trial. J Am Coll Cardiol. 2007;49(6):716–726. doi: 10.1016/j.jacc.2006.10.048.
    1. Martinez-Gallardo R, Ferreira-Morong F, Garcia-Pino G, Cerezo-Arias I, Hernandez-Gallego R, Caravaca F. Congestive heart failure in patients with advanced chronic kidney disease: association with pre-emptive vascular access placement. Nefrologia. 2012;32(2):206–212.
    1. Anavekar NS, McMurray JJ, Velazquez EJ, Solomon SD, Kober L, Rouleau JL, White HD. et al. Relation between renal dysfunction and cardiovascular outcomes after myocardial infarction. N Engl J Med. 2004;351(13):1285–1295. doi: 10.1056/NEJMoa041365.
    1. Cheung AK, Sarnak MJ, Yan G, Berkoben M, Heyka R, Kaufman A, Lewis J. et al. Cardiac diseases in maintenance hemodialysis patients: results of the HEMO Study. Kidney Int. 2004;65(6):2380–2389. doi: 10.1111/j.1523-1755.2004.00657.x.
    1. Gerstein HC, Mann JF, Yi Q, Zinman B, Dinneen SF, Hoogwerf B, Halle JP. et al. Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals. JAMA. 2001;286(4):421–426. doi: 10.1001/jama.286.4.421.
    1. Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, Reinhart K. et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med. 2008;36(1):296–327. doi: 10.1097/01.CCM.0000298158.12101.41.
    1. Mehta RL, Bouchard J, Soroko SB, Ikizler TA, Paganini EP, Chertow GM, Himmelfarb J. et al. Sepsis as a cause and consequence of acute kidney injury: program to improve care in acute renal disease. Intensive Care Med. 2011;37(2):241–248. doi: 10.1007/s00134-010-2089-9.
    1. Cowie MR, Komajda M, Murray-Thomas T, Underwood J, Ticho B, Investigators P. Prevalence and impact of worsening renal function in patients hospitalized with decompensated heart failure: results of the prospective outcomes study in heart failure (POSH) Eur Heart J. 2006;27(10):1216–1222. doi: 10.1093/eurheartj/ehi859.
    1. Nohria A, Hasselblad V, Stebbins A, Pauly DF, Fonarow GC, Shah M, Yancy CW. et al. Cardiorenal interactions: insights from the ESCAPE trial. J Am Coll Cardiol. 2008;51(13):1268–1274. doi: 10.1016/j.jacc.2007.08.072.
    1. Palmer BF. Renal dysfunction complicating the treatment of hypertension. N Engl J Med. 2002;347(16):1256–1261. doi: 10.1056/NEJMra020676.
    1. Forman DE, Butler J, Wang Y, Abraham WT, O'Connor CM, Gottlieb SS, Loh E. et al. Incidence, predictors at admission, and impact of worsening renal function among patients hospitalized with heart failure. J Am Coll Cardiol. 2004;43(1):61–67. doi: 10.1016/j.jacc.2003.07.031.
    1. Hsu CY, McCulloch CE, Iribarren C, Darbinian J, Go AS. Body mass index and risk for end-stage renal disease. Ann Intern Med. 2006;144(1):21–28. doi: 10.7326/0003-4819-144-1-200601030-00006.
    1. Orvalho JS, Cowgill LD. Cardiorenal Syndrome: Diagnosis and Management. Vet Clin North Am Small Anim Pract. 2017;47(5):1083–1102. doi: 10.1016/j.cvsm.2017.05.004.
    1. Blecker S, Matsushita K, Kottgen A, Loehr LR, Bertoni AG, Boulware LE, Coresh J. High-normal albuminuria and risk of heart failure in the community. Am J Kidney Dis. 2011;58(1):47–55. doi: 10.1053/j.ajkd.2011.02.391.
    1. Chen HH, Anstrom KJ, Givertz MM, Stevenson LW, Semigran MJ, Goldsmith SR, Bart BA. 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(23):2533–2543. doi: 10.1001/jama.2013.282190.
    1. Bart BA, Goldsmith SR, Lee KL, Givertz MM, O'Connor CM, Bull DA, Redfield MM. et al. Ultrafiltration in decompensated heart failure with cardiorenal syndrome. N Engl J Med. 2012;367(24):2296–2304. doi: 10.1056/NEJMoa1210357.
    1. Wan SH, Stevens SR, Borlaug BA, Anstrom KJ, Deswal A, Felker GM, Givertz MM. et al. Differential response to low-dose dopamine or low-dose nesiritide in acute heart failure with reduced or preserved ejection fraction: results from the rose AHF trial (Renal optimization strategies evaluation in acute heart failure) Circ Heart Fail. 2016;9(8):e002593. doi: 10.1161/CIRCHEARTFAILURE.115.002593.
    1. Testani, Jeffrey M. et al. Influence of diuretic dose and route of administration on loop diuretic efficiency: insights from the diuretic optimization strategies evaluation in acute heart failure (DOSE-AHF) trial. Journal of Cardiac Failure. 2014;20:8. doi: 10.1016/j.cardfail.2014.06.115.
    1. Felker GM, Lee KL, Bull DA, Redfield MM, Stevenson LW, Goldsmith SR, LeWinter MM. et al. Diuretic strategies in patients with acute decompensated heart failure. N Engl J Med. 2011;364(9):797–805. doi: 10.1056/NEJMoa1005419.
    1. Belziti CA, Bagnati R, Ledesma P, Vulcano N, Fernandez S. Worsening renal function in patients admitted with acute decompensated heart failure: incidence, risk factors and prognostic implications. Rev Esp Cardiol. 2010;63(3):294–302. doi: 10.1016/S0300-8932(10)70088-9.
    1. Hoorn EJ, Ellison DH. Diuretic Resistance. Am J Kidney Dis. 2017;69(1):136–142. doi: 10.1053/j.ajkd.2016.08.027.
    1. Wilcox CS, Mitch WE, Kelly RA, Skorecki K, Meyer TW, Friedman PA, Souney PF. Response of the kidney to furosemide. I. Effects of salt intake and renal compensation. J Lab Clin Med. 1983;102(3):450–458.
    1. Ali SS, Olinger CC, Sobotka PA, Dahle TG, Bunte MC, Blake D, Boyle AJ. Loop diuretics can cause clinical natriuretic failure: a prescription for volume expansion. Congest Heart Fail. 2009;15(1):1–4. doi: 10.1111/j.1751-7133.2008.00037.x.
    1. Ter Maaten JM, Damman K, Verhaar MC, Paulus WJ, Duncker DJ, Cheng C, van Heerebeek L. et al. Connecting heart failure with preserved ejection fraction and renal dysfunction: the role of endothelial dysfunction and inflammation. Eur J Heart Fail. 2016;18(6):588–598. doi: 10.1002/ejhf.497.
    1. Mukherjee M, Sharma K, Madrazo JA, Tedford RJ, Russell SD, Hays AG. Right-sided cardiac dysfunction in heart failure with preserved ejection fraction and worsening renal function. Am J Cardiol. 2017;120(2):274–278. doi: 10.1016/j.amjcard.2017.04.019.
    1. Doty JM, Saggi BH, Sugerman HJ, Blocher CR, Pin R, Fakhry I, Gehr TW. et al. Effect of increased renal venous pressure on renal function. J Trauma. 1999;47(6):1000–1003. doi: 10.1097/00005373-199912000-00002.
    1. Konstam MA, Neaton JD, Dickstein K, Drexler H, Komajda M, Martinez FA, Riegger GA. et al. Effects of high-dose versus low-dose losartan on clinical outcomes in patients with heart failure (HEAAL study): a randomised, double-blind trial. Lancet. 2009;374(9704):1840–1848. doi: 10.1016/S0140-6736(09)61913-9.
    1. 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(6):685–691. doi: 10.1161/CIRCHEARTFAILURE.111.963256.
    1. Ahmed A, Fonarow GC, Zhang Y, Sanders PW, Allman RM, Arnett DK, Feller MA. et al. Renin-angiotensin inhibition in systolic heart failure and chronic kidney disease. Am J Med. 2012;125(4):399–410. doi: 10.1016/j.amjmed.2011.10.013.
    1. Heart Failure Society of A, Lindenfeld J, Albert NM, Boehmer JP, Collins SP, Ezekowitz JA, Givertz MM. et al. HFSA 2010 comprehensive heart failure practice guideline. J Card Fail. 2010;16(6):e1–194. doi: 10.1016/j.cardfail.2010.04.004.
    1. Vinod P, Krishnappa V, Chauvin AM, Khare A, Raina R. Cardiorenal syndrome: role of arginine vasopressin and vaptans in heart failure. Cardiol Res. 2017;8(3):87–95. doi: 10.14740/cr553w.
    1. Mullens W, Abrahams Z, Francis GS, Skouri HN, Starling RC, Young JB, Taylor DO. et al. Sodium nitroprusside for advanced low-output heart failure. J Am Coll Cardiol. 2008;52(3):200–207. doi: 10.1016/j.jacc.2008.02.083.
    1. Gheorghiade M, Konstam MA, Burnett JC Jr, Grinfeld L, Maggioni AP, Swedberg K, Udelson JE. et al. Short-term clinical effects of tolvaptan, an oral vasopressin antagonist, in patients hospitalized for heart failure: the EVEREST Clinical Status Trials. JAMA. 2007;297(12):1332–1343. doi: 10.1001/jama.297.12.1332.
    1. Massie BM, O'Connor CM, Metra M, Ponikowski P, Teerlink JR, Cotter G, Weatherley BD. et al. Rolofylline, an adenosine A1-receptor antagonist, in acute heart failure. N Engl J Med. 2010;363(15):1419–1428. doi: 10.1056/NEJMoa0912613.
    1. Pitt B, Remme W, Zannad F, Neaton J, Martinez F, Roniker B, Bittman R. et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 2003;348(14):1309–1321. doi: 10.1056/NEJMoa030207.
    1. Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, Palensky J. et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med. 1999;341(10):709–717. doi: 10.1056/NEJM199909023411001.
    1. Zannad F, McMurray JJ, Krum H, van Veldhuisen DJ, Swedberg K, Shi H, Vincent J. et al. Eplerenone in patients with systolic heart failure and mild symptoms. N Engl J Med. 2011;364(1):11–21. doi: 10.1056/NEJMoa1009492.
    1. McAlister FA, Ezekowitz J, Hooton N, Vandermeer B, Spooner C, Dryden DM, Page RL. et al. Cardiac resynchronization therapy for patients with left ventricular systolic dysfunction: a systematic review. JAMA. 2007;297(22):2502–2514. doi: 10.1001/jama.297.22.2502.
    1. Boerrigter G, Costello-Boerrigter LC, Abraham WT, Sutton MG, Heublein DM, Kruger KM, Hill MR. et al. Cardiac resynchronization therapy improves renal function in human heart failure with reduced glomerular filtration rate. J Card Fail. 2008;14(7):539–546. doi: 10.1016/j.cardfail.2008.03.009.
    1. Bazoukis G, Letsas KP, Korantzopoulos P, Thomopoulos C, Vlachos K, Georgopoulos S, Karamichalakis N. et al. Impact of baseline renal function on all-cause mortality in patients who underwent cardiac resynchronization therapy: A systematic review and meta-analysis. J Arrhythm. 2017;33(5):417–423. doi: 10.1016/j.joa.2017.04.005.
    1. Flaherty MP, Pant S, Patel SV, Kilgore T, Dassanayaka S, Loughran JH, Rawasia W. et al. Hemodynamic support with a Microaxial percutaneous left ventricular assist device (Impella) protects against acute kidney injury in patients undergoing high-risk percutaneous coronary intervention. Circ Res. 2017;120(4):692–700. doi: 10.1161/CIRCRESAHA.116.309738.
    1. Nemoto M. Experimental evaluation of the influence of complete artificial circulation on renal circulation and tissue metabolism -comparative study of pulsatile vs nonpulsatile circulation. Ann Thorac Cardiovasc Surg. 2003;9(6):355–364.
    1. Welp H, Rukosujew A, Tjan TD, Hoffmeier A, Kosek V, Scheld HH, Drees G. Effect of pulsatile and non-pulsatile left ventricular assist devices on the renin-angiotensin system in patients with end-stage heart failure. Thorac Cardiovasc Surg. 2010;58(Suppl 2):S185–188. doi: 10.1055/s-0029-1240709.
    1. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Drazner MH, Fonarow GC. et al. 2013 ACCF/AHA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2013;128(16):1810–1852. doi: 10.1161/CIR.0b013e31829e8807.
    1. Ghali JK, Wikstrand J, Van Veldhuisen DJ, Fagerberg B, Goldstein S, Hjalmarson A, Johansson P. et al. The influence of renal function on clinical outcome and response to beta-blockade in systolic heart failure: insights from Metoprolol CR/XL Randomized Intervention Trial in Chronic HF (MERIT-HF) J Card Fail. 2009;15(4):310–318. doi: 10.1016/j.cardfail.2008.11.003.
    1. Cohen-Solal A, Kotecha D, van Veldhuisen DJ, Babalis D, Bohm M, Coats AJ, Roughton M. et al. Efficacy and safety of nebivolol in elderly heart failure patients with impaired renal function: insights from the SENIORS trial. Eur J Heart Fail. 2009;11(9):872–880. doi: 10.1093/eurjhf/hfp104.
    1. Badve SV, Roberts MA, Hawley CM, Cass A, Garg AX, Krum H, Tonkin A. et al. Effects of beta-adrenergic antagonists in patients with chronic kidney disease: a systematic review and meta-analysis. J Am Coll Cardiol. 2011;58(11):1152–1161. doi: 10.1016/j.jacc.2011.04.041.

Source: PubMed

Спонсоры и соавторы

Заболевания

Медикаментозные вмешательства

Подписаться