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Mechanisms of the cardiorenal syndromes

Nature Reviews Nephrology volume 5, pages 641–649 (2009)Cite this article

Abstract

The kidney and heart have essential roles in maintaining blood volume homeostasis and in the regulation of systemic blood pressure. Acute or chronic dysfunction in either the heart or kidneys can induce dysfunction in the other organ, resulting in the so-called cardiorenal syndromes, which are classified into five different types. Abrupt worsening of cardiac function predisposes an individual to acute kidney injury from renal hypoperfusion or renal congestion. Progressive, sometimes permanent, chronic kidney impairment can result from chronic renal hypoperfusion or congestion. Heart failure is common in patients with acute kidney injury. Chronic kidney disease predisposes individuals to atherosclerotic, arteriosclerotic and cardiomyopathic disease. Finally, both cardiac and renal disease can also occur secondary to systemic conditions, such as diabetes or autoimmune disease. This Review examines the mechanisms presiding over the first four types of cardiorenal syndromes. These mechanisms provide a template that accounts for the heart–kidney interactions that occur in patients whose concomitant cardiac and renal conditions result from a third cause.

Key Points

  • A bidirectional complex relationship exists between the heart and the kidney to maintain homeostasis of blood volume and regulate blood pressure

  • Acute or chronic dysfunction in the heart or kidneys can induce dysfunction in the other organ by several mechanisms

  • Abrupt worsening of cardiac function predisposes individuals to acute kidney injury from renal hypoperfusion or renal congestion

  • Chronically low cardiac output can be associated with hypotension and hypoperfusion, which can cause progressive, sometimes permanent, chronic kidney impairment

  • Acute kidney injury leads to hemodynamic stresses and proinflammatory reactions that might induce heart failure

  • Chronic kidney disease predisposes individuals to atherosclerotic, arteriosclerotic and cardiomyopathic disease

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Figure 1: The role of renal hypoperfusion and congestion in cardiorenal syndromes type I and II (acute and chronic cardiorenal syndrome).
Figure 2: The pathogenesis of cardiovascular disease in cardiorenal syndrome type IV (chronic renocardiac syndrome).

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References

  1. Ronco, C., House, A. A. & Haapio, M. Cardiorenal syndrome: refining the definition of a complex symbiosis gone wrong. Intensive Care Med. 34, 957–962 (2008).

    Article  PubMed  Google Scholar 

  2. Haldeman, G. A., Croft, J. B., Giles, W. H. & Rashidee, A. Hospitalization of patients with heart failure: National Hospital Discharge Survey, 1985 to 1995. Am. Heart J. 137, 352–360 (1999).

    Article  CAS  PubMed  Google Scholar 

  3. Uchino, S., Bellomo, R., Goldsmith, D., Bates, S. & Ronco, C. An assessment of the RIFLE criteria for acute renal failure in hospitalized patients. Crit. Care Med. 34, 1913–1917 (2006).

    Article  PubMed  Google Scholar 

  4. Bagshaw, S. M., George, C., Dinu, I. & Bellomo R. A multi-centre evaluation of the RIFLE criteria for early acute kidney injury in critically ill patients. Nephrol. Dial. Transplant. 23, 1203–1210 (2008).

    Article  PubMed  Google Scholar 

  5. Coresh, J., Astor, B. C., Greene, T., Eknoyan, G. & Levey, A. S. Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and Nutrition Examination Survey. Am. J. Kidney Dis. 41, 1–12 (2003).

    Article  PubMed  Google Scholar 

  6. Wencker, D. Acute cardio-renal syndrome: progression from congestive heart failure to congestive kidney failure. Curr. Heart Fail. Rep. 4, 134–138 (2007).

    Article  PubMed  Google Scholar 

  7. Forman, D. et al. Incidence, predictors at admission, and impact of worsening renal function among patients hospitalized with heart failure. J. Am. Coll. Cardiol. 43, 61–67 (2004).

    Article  PubMed  Google Scholar 

  8. Adams, K. F. Jr 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. 149, 209–216 (2005).

    Article  PubMed  Google Scholar 

  9. Fonarow, G. C. et al. Characteristics, treatments, and outcomes of patients with preserved systolic function hospitalized for heart failure: a report from the OPTIMIZE-HF registry. J. Am. Coll. Cardiol. 50, 768–777 (2007).

    Article  PubMed  Google Scholar 

  10. Jose, P. et al. Increase in creatinine and cardiovascular risk in patients with systolic dysfunction after myocardial infarction. J. Am. Soc. Nephrol. 17, 2886–2891 (2006).

    Article  CAS  PubMed  Google Scholar 

  11. Goldberg, A. et al. Inhospital and 1-year mortality of patients who develop worsening renal function following acute ST-elevation myocardial infarction. Am. Heart J. 150, 330–337 (2005).

    Article  PubMed  Google Scholar 

  12. Fonarow, G. C. et al. Risk stratification for in-hospital mortality in acutely decompensated heart failure: classification and regression tree analysis. JAMA 293, 572–580 (2005).

    Article  CAS  PubMed  Google Scholar 

  13. Smith, G. L. et al. Renal impairment and outcomes in heart failure: systematic review and meta-analysis. J. Am. Coll. Cardiol. 47, 1987–1996 (2006).

    Article  PubMed  Google Scholar 

  14. Hillege, H. L. et al. Renal function as a predictor of outcome in a broad spectrum of patients with heart failure. Circulation 113, 671–678 (2006).

    Article  PubMed  Google Scholar 

  15. Bhatia, R. S. et al. Outcome of heart failure with preserved ejection fraction in a population-based study. N. Engl. J. Med. 355, 260–269 (2006).

    Article  CAS  PubMed  Google Scholar 

  16. Kelly, K. J. Acute renal failure: much more than a kidney disease. Semin. Nephrol. 26, 105–113 (2006).

    Article  CAS  PubMed  Google Scholar 

  17. Foley, R. N. et al. Chronic kidney disease and the risk for cardiovascular disease, renal replacement, and death in the United States Medicare population, 1998 to 1999. J. Am. Soc. Nephrol. 16, 489–495 (2005).

    Article  PubMed  Google Scholar 

  18. Rigatto, C. et al. Congestive heart failure in renal transplant recipients: risk factors, outcomes, and relationship with ischemic heart disease. J. Am. Soc. Nephrol. 13, 1084–1090 (2002).

    PubMed  Google Scholar 

  19. Tonelli, M. et al. Chronic kidney disease and mortality risk: a systematic review. J. Am. Soc. Nephrol. 17, 2034–2047 (2006).

    Article  PubMed  Google Scholar 

  20. Foley, R. N. et al. Clinical and echocardiographic cardiovascular disease in patients starting end-stage renal disease therapy: Prevalence, associations and prognosis. Kidney Int. 47, 186–192 (1995).

    Article  CAS  PubMed  Google Scholar 

  21. Herzog, C. A., Ma, J. Z. & Collins, A. J. Poor long-term survival after acute myocardial infarction among patients on long-term dialysis. N. Engl. J. Med. 339, 799–805 (1998).

    Article  CAS  PubMed  Google Scholar 

  22. deFilippi, C. et al. Cardiac troponin T and C-reactive protein for predicting prognosis, coronary atherosclerosis, and cardiomyopathy in patients undergoing long-term hemodialysis. JAMA 290, 353–359 (2003).

    Article  CAS  PubMed  Google Scholar 

  23. Ohtake, T. et al. High prevalence of occult coronary artery stenosis in patients with chronic kidney disease at the initiation of renal replacement therapy: An angiographic examination. J. Am. Soc. Nephrol. 16, 1141–1148 (2005).

    Article  PubMed  Google Scholar 

  24. Harnett, J. D. et al. Congestive heart failure in dialysis patients: Prevalence, incidence, prognosis and risk factors. Kidney Int. 47, 884–890 (1995).

    Article  CAS  PubMed  Google Scholar 

  25. Foley, R. N., Parfrey, P. S. & Sarnak, M. J. Clinical epidemiology of cardiovascular disease in chronic renal disease. Am. J. Kidney Dis. 32 (5 Suppl. 3), S112–S119 (1998).

    Article  CAS  PubMed  Google Scholar 

  26. Johnson, D. W., Craven, A. M. & Isbel, N. M. Modification of cardiovascular risk in hemodialysis patients: an evidence-based review. Hemodial. Int. 11, 1–14 (2007).

    Article  PubMed  Google Scholar 

  27. Bongartz, L. G., Cramer, M. J., Doevendans, P. A., Joles, J. A. & Braam, B. The severe cardiorenal syndrome: 'Guyton revisited'. Eur. Heart J. 26, 11–17 (2005).

    Article  PubMed  Google Scholar 

  28. Domanovits, H. et al. Acute renal failure after successful cardiopulmonary resuscitation. Intensive Care Med. 27, 1194–1199 (2001).

    Article  CAS  PubMed  Google Scholar 

  29. Howard, P. A. & Dunn, M. I. Aggressive diuresis for severe heart failure in the elderly. Chest 119, 807–810 (2001).

    Article  CAS  PubMed  Google Scholar 

  30. Koracevic, G. P., Sakac, D. & Obradovic, S. Pathophysiological mechanisms and drugs leading to decrease in renal function in congestive heart failure. Medicine and Biology 12, 123–129 (2005).

    Google Scholar 

  31. Neuhofer, W. & Pittrow, D. Role of endothelin and endothelin receptor antagonists in renal disease. Eur. J. Clin. Invest. 36 (Suppl. 3), 78–88 (2006).

    Article  CAS  PubMed  Google Scholar 

  32. Nohria, A. et al. Cardiorenal interactions: insights form the ESCAPE trial. J. Am. Coll. Cardiol. 51, 1268–1274 (2008).

    Article  PubMed  Google Scholar 

  33. Weinfeld, M. S., Chertow, G. M. & Stevenson, L. W. Aggravated renal dysfunction during intensive therapy for advanced chronic heart failure. Am. Heart J. 138, 285–290 (1999).

    Article  CAS  PubMed  Google Scholar 

  34. Winton, F. R. The influence of venous pressure on the isolated mammalian kidney. J. Physiol. 72, 49–61 (1931).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Firth, J. D., Raine, A. E. & Ledingham, J. G. Raised venous pressure: a direct cause of renal sodium retention in oedema? Lancet 1, 1033–1035 (1988).

    Article  CAS  PubMed  Google Scholar 

  36. Mullens, W. et al. Elevated intra-abdominal pressure in acute decompensated heart failure: a potential contributor to worsening renal function? J. Am. Coll. Cardiol. 51, 300–306 (2008).

    Article  PubMed  Google Scholar 

  37. Mullens, W. et al. Prompt reduction in intra-abdominal pressure following large-volume mechanical fluid removal improves renal insufficiency in refractory decompensated heart failure. J. Card. Fail. 14, 508–514 (2008).

    Article  PubMed  Google Scholar 

  38. Shlipak, M. G., Smith, G. L., Rathore, S. S., Massie, B. M. & Krumholz, H. M. Renal function, digoxin therapy, and heart failure outcomes: evidence from the digoxin intervention group trial. J. Am. Soc. Nephrol. 15, 2195–2203 (2004).

    Article  CAS  PubMed  Google Scholar 

  39. Ellison, D. H. Diuretic resistance: physiology and therapeutics. Semin. Nephrol. 19, 581–597 (1999).

    CAS  PubMed  Google Scholar 

  40. Almeshari, K., Ahlstrom, N. G., Capraro, F. E. & Wilcox, C. S. A volume independent component to postdiuretic sodium retention in humans. J. Am. Soc. Nephrol. 3, 1878–1883 (1993).

    CAS  PubMed  Google Scholar 

  41. Pitt, B. 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. 341, 709–717 (1999).

    Article  CAS  PubMed  Google Scholar 

  42. Tamirisa, K. P., Aaronson, K. D. & Koelling, T. K. Spironolactone-induced renal insufficiency and hyperkalemia in patients with heart failure. Am. Heart J. 148, 971–978 (2004).

    Article  CAS  PubMed  Google Scholar 

  43. Parfrey, P. S. Inhibitors of the renin angiotensin system: proven benefits, unproven safety. Ann. Intern. Med. 148, 76–77 (2008).

    Article  PubMed  Google Scholar 

  44. Juurlink, D. N. et al. Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study. N. Engl. J. Med. 351, 543–551 (2004).

    Article  CAS  PubMed  Google Scholar 

  45. Butler, J. et al. Relationship between heart failure treatment and development of worsening renal function among hospitalized patients. Am. Heart J. 147, 331–338 (2004).

    Article  PubMed  Google Scholar 

  46. Buller, C. E. et al. The profile of cardiac patients with renal artery stenosis. J. Am. Coll. Cardiol. 43, 1606–1613 (2004).

    Article  PubMed  Google Scholar 

  47. Maschio, G. et al. Effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of chronic renal insufficiency. The Angiotensin-Converting-Enzyme Inhibition in Progressive Renal Insufficiency Study Group. N. Engl. J. Med. 334, 939–945 (1996).

    Article  CAS  PubMed  Google Scholar 

  48. Sackner-Bernstein, J. D., Skopicki, H. A. & Aaronson, K. D. Risk of worsening renal function with nesiritide in patients with acutely decompensated heart failure. Circulation 111, 1487–1491 (2005).

    Article  CAS  PubMed  Google Scholar 

  49. Roghi, A. et al. Impact of acute renal failure following percutaneous coronary intervention on long-term mortality. J. Cardiovasc. Med. (Hagerstown) 9, 375–381 (2008).

    Article  Google Scholar 

  50. Kuitunen, A., Vento, A., Suojaranta-Ylinen, R. & Pettila, V. Acute renal failure after cardiac surgery: evaluation of the RIFLE classification. Ann. Thorac. Surg. 81, 542–546 (2006).

    Article  PubMed  Google Scholar 

  51. Schiele, F. et al. Impact of renal dysfunction on 1-year mortality after acute myocardial infarction. Am. Heart J. 151, 661–667 (2006).

    Article  CAS  PubMed  Google Scholar 

  52. Rea, M. E. & Dunlap, M. E. Renal hemodynamics in heart failure: implications for treatment. Curr. Opin. Nephrol. Hypertens. 17, 87–92 (2008).

    Article  PubMed  Google Scholar 

  53. Struthers, A. D. & MacDonald, T. M. Review of aldosterone- and angiotensin II-induced target organ damage and prevention. Cardiovasc. Res. 61, 663–670 (2004).

    Article  CAS  PubMed  Google Scholar 

  54. Onozato, M. L. et al. Dual blockade of aldosterone and angiotensin II additively suppresses TGF-beta and NADPH oxidase in the hypertensive kidney. Nephrol. Dial. Transplant. 22, 1314–1322 (2007).

    Article  CAS  PubMed  Google Scholar 

  55. Lee, C. Y. & Burnett, J. C. Jr. Natriuretic peptides and therapeutic applications. Heart Fail. Rev. 12, 131–142 (2007).

    Article  CAS  PubMed  Google Scholar 

  56. Nohria, A. et al. Cardiorenal interactions—insights from the ESCAPE trial. J. Am. Coll. Cardiol. 51, 1268–1274 (2007).

    Article  Google Scholar 

  57. Schrier, R. W. & Bansal, S. Pulmonary hypertension, right ventricular failure, and kidney: different from left ventricular failure? Clin. J. Am. Soc. Nephrol. 3, 1232–1237 (2008).

    Article  Google Scholar 

  58. Silverberg, D. S. et al. Anemia, chronic renal disease and congestive heart failure-the cardio renal anemia syndrome: the need for cooperation between cardiologists and nephrologists. Int. Urol. Nephrol. 38, 295–310 (2006).

    Article  PubMed  Google Scholar 

  59. Westenbrink, B. D. et al. Anaemia in chronic heart failure is not only related to impaired renal perfusion and blunted erythropoietin production, but to fluid retention as well. Eur. Heart J. 28, 166–171 (2007).

    Article  CAS  PubMed  Google Scholar 

  60. Palazzuoli, A., Gallotta, M., Iovine, F., Nuti, R. & Silverberg, D. S. Anaemia in heart failure: a common interaction with renal insufficiency called the cardio-renal anaemia Syndrome. Int. J. Clin. Pract. 62, 281–286 (2008).

    Article  CAS  PubMed  Google Scholar 

  61. Kazory, A. & Ross, E. A. Anemia: the point of convergence or divergence for kidney disease and heart failure? J. Am. Coll. Cardiol. 53, 639–647 (2009).

    Article  PubMed  Google Scholar 

  62. Jie, K. E. et al. Erythropoietin and the cardiorenal syndrome: Cellular mechanisms on the cardiorenal connectors. Am. J. Physiol. Renal Physiol. 291, F932–F944 (2006).

    Article  CAS  PubMed  Google Scholar 

  63. Gottlieb, S. S. et al. The prognostic importance of different definitions of worsening renal function in congestive heart failure. J. Card. Fail. 8, 136–141 (2002).

    Article  PubMed  Google Scholar 

  64. Hillege, H. et al. Renal function neurohormonal activation and survival in patients with chronic heart failure. Circulation 102, 203–210 (2000).

    Article  CAS  PubMed  Google Scholar 

  65. Palazzuoli, A. 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. 154, 645.e9–645.e15 (2007).

    Article  CAS  Google Scholar 

  66. Ghali, J. K. et al. Randomized double-blind trial of darbepoetin alfa in patients with symptomatic heart failure and anemia. Circulation 117, 526–535 (2008).

    Article  CAS  PubMed  Google Scholar 

  67. Mittalhenkle, A. et al. Cardiovascular risk factors and incident acute renal failure in older adults: the cardiovascular health study. Clin. J. Am. Soc. Nephrol. 3, 450–456 (2008).

    Article  Google Scholar 

  68. Payen, D. et al. A positive fluid balance is associated with a worse outcome in patients with acute renal failure. Crit. Care 12, R74 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  69. Rabb, H. et al. Acute renal failure leads to dysregulation of lung salt and water channels. Kidney Int. 63, 600–606 (2003).

    Article  CAS  PubMed  Google Scholar 

  70. Figueras, J., Stein, L., Diez, V., Weil, M. H. & Shubin, H. Relationship between pulmonary hemodynamics and arterial pH and carbon dioxide tension in critically ill patients. Chest 70, 466–472 (1976).

    Article  CAS  PubMed  Google Scholar 

  71. Blake, P. et al. Isolation of “myocardial depressant factor(s)” from the ultrafiltrate of heart failure patients with acute renal failure. ASAIO J. 42, M911–M915 (1996).

    Article  CAS  PubMed  Google Scholar 

  72. Meyer, T. W. & Hostetter, T. H. Uremia. N. Engl. J. Med. 357, 1316–1325 (2007).

    Article  CAS  PubMed  Google Scholar 

  73. Deswal, A. et al. Cytokines and cytokine receptors in advanced heart failure: an analysis of the cytokine database from the Vesnarinone trial (VEST). Circulation 103, 2055–2059 (2001).

    Article  CAS  PubMed  Google Scholar 

  74. Selby, N. M. & McIntyre, C. W. The acute cardiac effects of dialysis. Semin. Dial. 20, 220–228 (2007).

    Article  PubMed  Google Scholar 

  75. Ronco, C., Bellomo, R. & Ricci, Z. Continuous renal replacement therapy in critically ill patients. Nephrol. Dial. Transplant. 16 (Suppl. 5), 67–72 (2001).

    Article  PubMed  Google Scholar 

  76. Mann, J. F., Gerstein, H. C., Pogue, J. Bosch, J. & Yusuf, S. Renal insufficiency as a predictor of cardiovascular outcome and the impact of Ramipril. The HOPE randomized trial. Ann. Intern. Med. 134, 629–636 (2001).

    Article  CAS  PubMed  Google Scholar 

  77. Mann, J. F. et al. Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial. Lancet 372, 547–553 (2008).

    Article  CAS  PubMed  Google Scholar 

  78. McMahon, L. P. & Parfrey, P. S. in Brenner & Rector's The Kidney 8th edn Vol. 2 (eds Brenner, B. M. & Rector, F. C.) 1697–1727 (Saunders Elsevier, Philadelpia, 2008).

    Google Scholar 

  79. Manjunath, G. et al. Level of Kidney function as a risk factor for cardiovascular outcomes in the elderly. Kidney Int. 63, 1121–1129 (2003).

    Article  PubMed  Google Scholar 

  80. London, G. M. et al. Associations of bone activity, calcium load, aortic stiffness and calcifications in ESRD. J. Am. Soc. Nephrol. 19, 1827–1835 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Parfrey, P. S. et al. Double-blind comparison of full and partial anemia correction in incident hemodialysis patients without symptomatic heart disease. J. Am. Soc. Nephrol. 16, 2180–2189 (2005).

    Article  PubMed  Google Scholar 

  82. Rigatto, C., Foley, R. N., Kent, G. M., Guttmann, R. & Parfrey, P. S. Long-term changes in left ventricular hypertrophy after renal transplantation. Transplantation 70, 570–575 (2000).

    Article  CAS  PubMed  Google Scholar 

  83. Parfrey, P. S., Harnett, J. D., Griffiths, S., Gault, M. H. & Barre, P. E. Congestive heart failure in dialysis patients. Arch. Intern. Med. 148, 1519–1525 (1988).

    Article  CAS  PubMed  Google Scholar 

  84. Rucker, D. & Tonelli, M. Cardiovascular risk and management in chronic kidney disease. Nat. Rev. Nephrol. 5, 287–296 (2009).

    Article  PubMed  Google Scholar 

  85. Fort, J. Chronic renal failure: a cardiovascular risk factor. Kidney Int. Suppl. S25–S29 (2005).

  86. Schiffrin, E. L., Lipman, M. L. & Mann, J. F. Chronic kidney disease: effects on the cardiovascular system. Circulation 116, 85–97 (2007).

    Article  PubMed  Google Scholar 

  87. Ravani, P. et al. Asymmetrical dimethylarginine predicts progression to dialysis and death in patients with chronic kidney disease: a competing risks modeling approach. J. Am. Soc. Nephrol. 16, 2449–2455 (2005).

    Article  CAS  PubMed  Google Scholar 

  88. Mallamaci, F. et al. Hyperhomocysteinemia predicts cardiovascular outcomes in hemodialysis patients. Kidney Int. 61, 609–614 (2002).

    Article  PubMed  Google Scholar 

  89. Moe, S. M. et al. Medial artery calcification in ESRD patients is associated with deposition of bone matrix proteins. Kidney Int. 61, 638–647 (2002).

    Article  PubMed  Google Scholar 

  90. Chertow, G. M., Burke, S. K., Raggi, P. & Treat to Goal Working Group. Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients. Kidney Int. 62, 245–252 (2002).

    Article  CAS  PubMed  Google Scholar 

  91. Krane, V. et al. Effect of atorvastatin on inflammation and outcome in patients with type 2 diabetes mellitus on hemodialysis. Kidney Int. 74, 1461–1467 (2008).

    Article  CAS  PubMed  Google Scholar 

  92. Westenfeld, R. et al. Fetuin-A protects against atherosclerotic calcification in CKD. J. Am. Soc. Nephrol. 20, 1264–1274 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Amann, K. Media calcification and intima calcification are distinct entities in chronic kidney disease. Clin. J. Am. Soc. Nephrol. 3, 1599–1605 (2008).

    Article  PubMed  Google Scholar 

  94. McCullough, P. A., Agrawal, V., Danielewicz, E. & Abela, G. S. Accelerated atherosclerotic calcification and Monckeberg's sclerosis: a continuum of advanced vascular pathology in chronic kidney disease. Clin. J. Am. Soc. Nephrol. 3, 1585–1598 (2008).

    Article  CAS  PubMed  Google Scholar 

  95. Berl, T. & Henrich, W. Kidney–heart interactions: epidemiology, pathogenesis, and treatment. Clin. J. Am. Soc. Nephrol. 1, 8–18 (2006).

    Article  CAS  PubMed  Google Scholar 

  96. Chertow, G. M. et al. Evaluation of Cinacalcet Therapy to Lower Cardiovascular Events (EVOLVE): rationale and design overview. Clin. J. Am. Soc. Nephrol. 2, 898–905 (2007).

    Article  CAS  Google Scholar 

  97. Roberts, M. A. et al. B-type natriuretic peptides strongly predict mortality in patients who are treated with long-term dialysis. Clin. J. Am. Soc. Nephrol. 3, 1057–1065 (2008).

    Article  CAS  Google Scholar 

  98. Spanaus, K. S. et al. B-type natriuretic peptide concentrations predict the progression of nondiabetic chronic kidney disease: the Mild-to-Moderate Kidney Disease Study. Clin. Chem. 53, 1264–1272 (2007).

    Article  CAS  PubMed  Google Scholar 

  99. Longitano, J. P. et al. Correlation of N-terminal pro brain natriuretic peptide (NT-pronBNP) with depressed left ventricular function and mortality in chronic hemodialysis patients: Results of a two-year outcomes study [abstract]. J. Am. Soc. Nephrol. 12, 223A (2001).

    Google Scholar 

  100. Foley, R. N. et al. Advance prediction of early death in dialysis patients. Am. J. Kidney Dis. 23, 836–845 (1994).

    Article  CAS  PubMed  Google Scholar 

  101. Rigatto, C. et al. Electrocardiographic left ventricular hypertrophy in renal transplant recipients: prognostic value and impact of blood pressure and anemia. J. Am. Soc. Nephrol. 14, 462–468 (2003).

    Article  PubMed  Google Scholar 

  102. Parfrey, P. S., Lauve, M., Latremouille-Viau, D. & Lefebvre, P. Erythropoietin therapy and left ventricular mass index in CKD and ESRD patients: a meta-analysis. Clin. J. Am. Soc. Nephrol. 4, 755–762 (2009).

    Article  CAS  Google Scholar 

  103. Phrommintikul, A., Haas, S. J., Elsik, M. & Krum, H. Mortality and target haemoglobin concentrations in anemic patients with chronic kidney disease treated with erythropoietin: a meta-analysis. Lancet 369, 381–388 (2007).

    Article  CAS  PubMed  Google Scholar 

  104. Pfeffer, M. A. et al. Baseline characteristics in the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT). Am. J. Kidney Dis. 54, 59–69 (2009).

    Article  CAS  PubMed  Google Scholar 

  105. Siedlecki, A. M., Jin, X. & Muslin, A. J. Uremic cardiac hypertrophy is reversed by rapamycin but not by lowering of blood pressure. Kidney Int. 75, 800–808 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Raine, A. E. Acquired aortic stenosis in dialysis patients. Nephron 68, 159–168 (1994).

    Article  CAS  PubMed  Google Scholar 

  107. Rufino, M. et al. Heart valve calcification and calcium x phosphorus product in hemodialysis patients: analysis of optimum values for its prevention. Kidney Int. Suppl. 85, S115–S118 (2003).

    Article  Google Scholar 

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  1. Division of Nephrology, Memorial University of Newfoundland, St John's, NL, Canada

    M. Khaled Shamseddin & Patrick S. Parfrey

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P. S. Parfrey declares associations with Amgen, Ortho Clinical Diagnostics and Merck as consultant and recipient of grant/research support. M. K. Shamseddin declares no competing interests.

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Shamseddin, M., Parfrey, P. Mechanisms of the cardiorenal syndromes. Nat Rev Nephrol 5, 641–649 (2009). https://doi.org/10.1038/nrneph.2009.156

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