Cardiorenal syndrome

Jump to navigation Jump to search

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate-Editor(s)-in-Chief: Yazan Daaboul; Rim Halaby; Dina Elantably, MD, MSc[2]

WikiDoc Resources for Cardiorenal syndrome


Most recent articles on Cardiorenal syndrome

Most cited articles on Cardiorenal syndrome

Review articles on Cardiorenal syndrome

Articles on Cardiorenal syndrome in N Eng J Med, Lancet, BMJ


Powerpoint slides on Cardiorenal syndrome

Images of Cardiorenal syndrome

Photos of Cardiorenal syndrome

Podcasts & MP3s on Cardiorenal syndrome

Videos on Cardiorenal syndrome

Evidence Based Medicine

Cochrane Collaboration on Cardiorenal syndrome

Bandolier on Cardiorenal syndrome

TRIP on Cardiorenal syndrome

Clinical Trials

Ongoing Trials on Cardiorenal syndrome at Clinical

Trial results on Cardiorenal syndrome

Clinical Trials on Cardiorenal syndrome at Google

Guidelines / Policies / Govt

US National Guidelines Clearinghouse on Cardiorenal syndrome

NICE Guidance on Cardiorenal syndrome


FDA on Cardiorenal syndrome

CDC on Cardiorenal syndrome


Books on Cardiorenal syndrome


Cardiorenal syndrome in the news

Be alerted to news on Cardiorenal syndrome

News trends on Cardiorenal syndrome


Blogs on Cardiorenal syndrome


Definitions of Cardiorenal syndrome

Patient Resources / Community

Patient resources on Cardiorenal syndrome

Discussion groups on Cardiorenal syndrome

Patient Handouts on Cardiorenal syndrome

Directions to Hospitals Treating Cardiorenal syndrome

Risk calculators and risk factors for Cardiorenal syndrome

Healthcare Provider Resources

Symptoms of Cardiorenal syndrome

Causes & Risk Factors for Cardiorenal syndrome

Diagnostic studies for Cardiorenal syndrome

Treatment of Cardiorenal syndrome

Continuing Medical Education (CME)

CME Programs on Cardiorenal syndrome


Cardiorenal syndrome en Espanol

Cardiorenal syndrome en Francais


Cardiorenal syndrome in the Marketplace

Patents on Cardiorenal syndrome

Experimental / Informatics

List of terms related to Cardiorenal syndrome


Cardiorenal syndrome (CRS) comprises a group of disease states that involve simultaneous kidney and heart failure. Because the kidney and the heart lead a “symbiotic” bi-directional relationship; the vitality of one organ ultimately and inevitably depends on the vitality of the other. In cardiorenal syndrome, an acute or chronic dysfunction in the heart or the kidneys causes an acute or chronic dysfunction of the other organ. Cardiorenal syndromes have recently earned major clinical significance because of their complex management challenges and their profound prognostic indication of mortality in patients suffering from concomitant heart and kidney diseases. The greatest challenge a clinician faces with cardiorenal syndromes is the therapeutic approach and pharmacological intervention required in favor of a CRS patient with known poor prognosis. Today’s management approaches, despite proven efficacy, remain notorious for their injurious effects on the target organs of CRS. Individualized treatment remains up till now an optimal modality of approach pending the understanding of CRS, pathophysiology, and effective prevention.


Five subgroups have been identified and further approved by the Acute Dialysis Quality Initiative (ADQI) in 2010 on the basis of the following:

  • Pathophysiology
  • Acute vs. chronic
  • Concomitance of cardiac and renal dysfunction

For descriptive purposes, the five cardiorenal syndromes have also been named differently [1] as shown in the table below:

Type Name Description
Type 1 Acute cardiorenal syndrome Acute heart failure leads to acute kidney injury (AKI)
Type 2 Chronic cardiorenal syndrome Chronic cardiac dysfunction leads to chronic kidney disease (CKD)
Type 3 Acute renocardiac syndrome Acute kidney injury leads to acute cardiac dysfunction
Type 4 Chronic renocardiac syndrome Chronic kidney injury leads to chronic cardiac dysfunction(eg; coronary disease, heart failure or arryhthmia)
Type 5 Secondary cardiorenal syndrome Acute or chronic systemic disorder (eg; diabetes mellitus, sepsis) leads to heart and kidney failure


The cardiorenal syndrome is the result of compensatory mechanisms of the body in order to maintain a good blood volume and organ perfusion in the face of heart failure or kidney failure. Regardless of the type of the cardiorenal syndrome, the following events are part of the underlying pathophysiology:

Shown below is an image summarizing the bidirectional relationship between the heart and the kidneys in the pathophysiology of the cardiorenal syndrome.
The bidirectional relationship between the heart and kidneys in the pathophysiology of the cardiorenal syndrome.
The bidirectional relationship between the heart and kidneys in the pathophysiology of the cardiorenal syndrome.
Shown below is an image showing the complex pathophysiological mechanisms involved in the cardiorenal syndrome.
The complex pathophysiological mechanisms involved in the cardiorenal syndrome.
The complex pathophysiological mechanisms involved in the cardiorenal syndrome.

Cardiorenal Syndrome Type 1

Cardiorenal Syndrome Type 2

  • Chronic heart dysfunction causing chronic kidney disease
  • Erythropoetin deficiency and anemia
  • Electrolyte imbalances[3][4]
  • Neurohormonal abnormalities with over production of vasoconstrictors
  • Altered sensitivity to endogenous vasodilators[1].

Cardiorenal Syndrome Type 3

Cardiorenal Syndrome Type 4

  • Primary chronic kidney disease leading to gradual decreased cardiac function
  • Electrolyte imbalances with chronic kidney disease
  • Fluid overload.

Cardiorenal Syndrome Type 5

  • Combined cardiac and renal dysfunction due to acute or chronic systemic disorders (Sepsis, diabetes, amyloidosis, lupus, sarcoidosis)
  • Primary trigger causes simultaneous or sequential damage to both organs
  • Injury to heart and kidneys cause of vicious cycle of further injury to each other. [1]

Risk Factors

Risk factors of worsening renal function in patients with heart failure includes[7]:

Epidemiology and Demographics

  • The prevalence of moderate to severe kidney impairement in patients with heart failure ranges from 30 to 60%.[8][9]
  • Among patients with acute decompensated heart failure , only 9% have normal renal function, whereas approximately 91 % have estimated GFR lower than 89 ml x min x 1.73 m2.[10]

Natural History, Complications and Prognosis

  • Renal failure is one of the most significant poor prognostic independent risk factors in patients with heart failure.[12]
  • Renal failure in the context of ambulatory patients with heart failure carries a poor prognostic sign and high mortality risks even at a creatinine level of 1.3 mg/dL.[13]
  • Worsening renal failure, evidenced by an increase in creatinine as low as 0.3 mg/dL, is a poor prognostic factor in hospitalized patients with heart failure. In fact, the increase in the creatinine level rather than the baseline creatinine in these patients correlated with frequent hospitalizations and higher mortality.[14]


Cardiorenal Syndrome Type 1

  • Blood and Urine Neutrophil gelatinase-associated lipocalin (NGAL) [15]
  • Cystatin C is a good early predictor of GFR[16][17]
  • Serum Creatinine elevates 48-72 h later[18]

Cardiorenal Syndrome Type 2

  • Serum creatinine to measure renal function
  • Classical makers of heart failure (eg. BNP) and measurement by ultrasound of systolic and diastolic ventricular dysfunction and ejection fraction [19]

Cardiorenal Syndrome Type 3

  • Cardiac troponins for ischemia[20] and BNP for heart failure[21]

Cardiorenal Syndrome Type 4

Cardiorenal Syndrome Type 5

  • Diagnosis of primary disease

Biomarkers of Cardiorenal Syndromes

  • Despite the efficient use of cardiac biomarkers that detect early injury, the detection of acute kidney injury before the consequential fall of GFR has not been possible with the current utilization of serum creatinine. It has become therefore imperative to search for new biomarkers that can readily identify renal damage and thus cardiorenal syndromes rapidly for prompt and efficient management.
  • Several novel biomarkers have been introduced to the literature. Nonetheless, none has yet effectively replaced the use of serum creatinine in clinical settings.

Catalytic Iron

  • Catalytic iron is based on the use of bleomycin detectable assay to detect catalytic iron in CRS at the level of generation of reactive oxygen species.
  • It is a potential diagnostic and therapeutic target for CRS[22].

Neutrophil Gelatinase-Associated Lipocalin (NGAL) or Siderocalin

  • It scavenges cellular and pericellular labile iron.
  • It has been studied extensively in animal and human models; it increases significantly in plasma and urine [23].

Cystatin C

  • It is a cysteine protease inhibitor.
  • At the level of the kidney, it is freely filtered, and completely reabsorbed.
  • Cystatin C is better than creatinine in estimating GFR and chronic kidney disease status[24].

Other Biomarkers

  • Other previous and emerging biomarkers for CRS include Kidney Injury Molecule 1 (KIM-1) [25], N-Acetyl-B-(D) Glucosaminidase (NAG)[26], Interleukin-18 (IL-18)[27], Liver Fatty Acid-Binding Protein (L-FABP) [28], and Tubular Enzymuria such as gamma glutamyl transpeptidase (GGT), alkaline phosphatase, lactate dehydrogenase, and α and π glutathione S-transferase (GST) [29][30].


Cardiorenal Syndrome Type 1

Cardiorenal Syndrome Type 2

Cardiorenal Syndrome Type 3

Cardiorenal Syndrome Type 4

Cardiorenal Syndrome Type 5

  • Treatment of primary disease.
  • Judicious IV fluids and pressor agents might be helpful.


  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 Ronco, C., Haapio, M., House, A., Anavekar, N., & Bellomo, R. (2008). Cardiorenal Syndrome. Journal of the American College of Cardiology, 52(19):1527-1539.
  2. Bongartz LG, Cramer MJ, Doevendans PA, Joles JA, Braam B (2005). "The severe cardiorenal syndrome: 'Guyton revisited'". Eur Heart J. 26 (1): 11–7. doi:10.1093/eurheartj/ehi020. PMID 15615794.
  3. Jie, J., Verhaar, M., Cramer, M., & et al. (2006). Erythropoietin and the cardiorenal syndrome: Cellular mechanisms on the cardiorenal connectors. American Journal of Physiology - Renal Physiology, 291:F932-F944.
  4. Fu, P., & Arcasoy, M. (2007). Erythropoietin protects cardiac myocytes against anthracycline-induced apoptosis. Biochemical and Biophysical Research Communications, 354:372-378.
  5. Blake, P., Hasegawa, Y., Khosla, M., Fouad-Tarazi, F., Sakura, N., & Paganini, E. (1996). Isolation of “myocardial depressant factor(s)” from the ultrafiltrate of heart failure patients with acute renal failure. ASAIO Journal, 42:M911-M915.
  6. Meyer, T., & Hostetter, T. (2007). Uremia. The New England Journal of Medicine, 257:1316-1325.
  7. Forman, Daniel E.; Butler, Javed; Wang, Yongfei; Abraham, William T.; O'Connor, Christopher M.; Gottlieb, Stephen S.; Loh, Evan; Massie, Barry M.; Rich, Michael W.; Stevenson, Lynne Warner; Young, James B.; Krumholz, Harlan M. (2004). "Incidence, predictors at admission, and impact of worsening renal function among patients hospitalized with heart failure". Journal of the American College of Cardiology. 43 (1): 61–67. doi:10.1016/j.jacc.2003.07.031. ISSN 0735-1097.
  8. Smith GL, Lichtman JH, Bracken MB, Shlipak MG, Phillips CO, DiCapua P; et al. (2006). "Renal impairment and outcomes in heart failure: systematic review and meta-analysis". J Am Coll Cardiol. 47 (10): 1987–96. doi:10.1016/j.jacc.2005.11.084. PMID 16697315.
  9. Heywood JT, Fonarow GC, Costanzo MR, Mathur VS, Wigneswaran JR, Wynne J; et al. (2007). "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. 13 (6): 422–30. doi:10.1016/j.cardfail.2007.03.011. PMID 17675055.
  10. Heywood, J. Thomas; Fonarow, Gregg C.; Costanzo, Maria Rosa; Mathur, Vandana S.; Wigneswaran, John R.; Wynne, Janet (2007). "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". Journal of Cardiac Failure. 13 (6): 422–430. doi:10.1016/j.cardfail.2007.03.011. ISSN 1071-9164.
  11. Foley RN, Parfrey PS, Sarnak MJ (1998). "Epidemiology of cardiovascular disease in chronic renal disease". J Am Soc Nephrol. 9 (12 Suppl): S16–23. PMID 11443763.
  12. Gottlieb SS, Abraham WT, Butler J, Forman DE, Loh E, Massie BM, O'Connor CM, Rich MW, Stevenson LW, Young J, Krumholz HM. The prognostic importance of different definitions of worsening renal function in congestive heart failure. J Card Fail. 2002; 8: 136–141.
  13. Dries DL, Exner DV, Domanski MJ, Greenberg B, Stevenson LW. The prognostic implications of renal insufficiency in asymptomatic and symptomatic patients with left ventricular systolic dysfunction. J Am Coll Cardiol. 2000; 35: 681–689.
  14. Hillege HL, Girbes AR, de Kam PJ, Boomsma F, de Zeeuw D, Charlesworth A, Hampton JR, van Veldhuisen DJ. Renal function, neurohormonal activation, and survival in patients with chronic heart failure. Circulation. 2000; 102: 203–210.
  15. Mishra, J., Ma, Q., Prada, A., & et al. (2003). Identification of neutrophil gelatinase-associated lipocalin as a novel early urinary biomarker for ischemic renal injury. Journal of American Society of Nephrology, 14: 2534-2543.
  16. Dharnidharka, V., Kwon, C., & Stevens, G. (2002). Serum cystatin C is superior to serum creatinine as a marker of kidney function: a meta-analysis. American Journal of Kidney Diseases, 40:221-226.
  17. Vandevoorde, R., Katlman, T., Ma, Q., & et al. (2006). Serum NGAL and cystatin C as predictive biomarkers for acute kidney injury. Journal of American Society of Nephrology, 17:404A.
  18. Wagener, G., Jan, M., Kim, M., & et al. (2006). Association between increases in urinary neutrophil gelatinase-associated lipocalin and acute renal dysfunction after adult cardiac surgery. Anesthesiology, 105:485-491.
  19. Palazzuoli, A., Silverberg, D., Iovine, F., & et al. (2007). Effects of beta-erythropoietin treatment on left ventricular remodeling, systolic function, and B-type natriuretic peptide levels in patients with the cardiorenal anemia syndrome. American Heart Journal, 154:645e9-15.
  20. Cameron, S., Sokoll, L., Laterza, O., Shah, S., & Green, G. (2007). A multi-marker approach for the prediction of adverse events in patients with acute coronary syndromes. Clinica Chimica Acta, 376:168-173.
  21. Forfia, P., Lee, M., Tunin, R., Mahmud, M., Champion, H., & Kass, D. (2007). Acute phosphodiesterase 5 inhibition mimics hemodynamic effects of B-type natriuretic peptide and potentiates B-type natriuretic peptide effects in failing but not normal canine heart. Journal of American College of Cardiology, 49:1079-1088.
  22. Lele, S., Shah, S., McCullough, P., & Rajapurkar, M. (2009). Serum catalytic iron as a novel biomarker of vascular injury in acute coronary syndromes. EuroIntervention, 5(3):336-342.
  23. Mori, K., & Nakao, K. (2007). Neutrophil gelatinase-associated lipocalin as the real-time indicator of active kidney damage. Kidney International, 71:967-970.
  24. McMurray, M., Trivax, J., & McCullough, P. (2009). Serum cystatin C, renal filtration function, and left ventricular remodeling. Circulation. Heart Failure, 2(2):86-89.
  25. Kobayashi, M., Hirawa, N., & Morita, S. (2010). Silent brain infarction and rapid decline of kidney function in patients with CKD: a prospective cohort study. American Journal of Kidney Diseases, 56(3):468-476.
  26. Wellwood, J., Ellis, B., Price, R., Hammond, K., Thompson, A., & Jones, N. (1975). Urinary N-acetyl- beta-D-glucosaminidase activities in patients with renal disease. British Medical Journal, 3(5980):408-411.
  27. Parikh, C., Abraham, E., Ancukiewicz, M., & Edelstein, C. (2005). Urine IL-18 is an early diagnostic marker for acute kidney injury and predicts mortality in the intensive care unit. Journal of the American Society of Nephrology, 16(10):3046-3052.
  28. Noiri, E., Doi, K., Negishi, K., & et al. (2009). Urinary fatty acid-binding protein 1: an early predictive biomarker of kidney injury. American Journal of Physiology—Renal Physiology, 296(4):F669-F-679.
  29. Liang, X., Liu, S., Chen, Y., & et al. (2010). Combination of urinary kidney injury molecule-1 and interleukin-18 as early biomarker for the diagnosis and progressive assessment of acute kidney injury following cardiopulmonary bypass surgery: a prospective nested casecontrol study. Biomarkers, 15(4):332-339.
  30. Endre, Z., & Westhuyzen, J. (2008). Early detection of acute kidney injury: emerging new biomarkers. Nephrology, 13(2):91-98.
  31. Howard, P., & Dunn, M. (2001). Aggressive diuresis for severe heart failure in the elderly. Chest, 119:807-810.
  32. 32.0 32.1 32.2 Ronco, C. (2008). NGAL: an emerging biomarker of acute kidney injury. International Journal of Artificial Organs, 199:200.
  33. Berger, A., Duval, S., & Krumholz, H. (2003). Aspirin, beta-blocker, and angiotensin-converting enzyme inhibitor therapy in patients with end-stage renal disease and an acute myocardial infarction. Journal of American College of Cardiology, 42:201-208.
  34. Butler, J., Forman, D., Abraham, W., & et al. (2004). Relationship between heart failure treatment and development of worsening renal function among hospitalized patients. American Heart Journal, 147:331-338.
  35. Hirsch, A., Haskal, Z., Hertzer, N., & et al. (2006). ACC/AHA guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society . Journal of American College of Cardiology, 47:e1-e192.