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Pathophysiological Mechanisms and Prognostic Significance of Renal Functional Impairment in Cardiac Patients

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Cardiorenal Syndrome

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Abstract

Heart and kidney dysfunction are often associated, the primary disorder of one of these two organs being the cause of secondary involvement of the other. These interactions represent the pathophysiological basis of cardiorenal syndrome. Renal dysfunction is very common in heart failure patients, with a highly variable prevalence according to the subgroup of patients considered. The complex pathophysiologic interactions between heart and kidney are far from being completely understood. Several “cardiorenal connectors,” which represent the major players of the neurohumoral response in heart failure, have been identified. They act both through and independently from extracellular fluid volume control. Another mechanism, more recently taken into great consideration, is that of increased central venous pressure. Anemia, very frequent in both heart and renal failure, is most probably the third condition of this deadly syndrome, sometimes also called cardiorenal-anemia syndrome. In patients with heart failure, renal function has a powerful prognostic significance. This is true both in chronic heart failure over a long follow-up and in acutely decompensated heart failure for in-hospital mortality. In patients with advanced heart failure, baseline glomerular filtration rate has been reported to be even more powerful than left ventricular ejection fraction in predicting mortality. The prognostic meaning of worsening renal failure during hospitalization for acute decompensated heart failure is, on the contrary, less clear.

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References

  1. Ronco C, Haapio M, House AA et al (2008) Cardiorenal syndrome. J Am Coll Cardiol 52:1527–1539

    Article  PubMed  Google Scholar 

  2. van der Putten K, Bongartz LG, Braam B, Gaillard CA (2009) The cardiorenal syndrome a classification into 4 groups? J Am Coll Cardiol 53:1340

    Article  PubMed  Google Scholar 

  3. Smith GL, Lichtman JH, Bracken MB et al (2006) Renal impairment and outcomes in heart failure: systematic review and meta-analysis. J Am Coll Cardiol 47:1987–1996

    Article  PubMed  Google Scholar 

  4. Heywood JT, Fonarow GC, Costanzo MR 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 13:422–430

    Article  PubMed  Google Scholar 

  5. Heywood JT (2004) The cardiorenal syndrome: lessons from the ADHERE database and treatment options. Heart Fail Rev 9:195–201

    Article  PubMed  Google Scholar 

  6. Hillege HL, Nitsch D, Pfeffer MA et al (2006) Renal function as a predictor of outcome in a broad spectrum of patients with heart failure. Circulation 113:671–678

    Article  PubMed  Google Scholar 

  7. Bhatia RS, Tu JV, Lee DS et al (2006) Outcome of heart failure with preserved ejection fraction in a population-based study. N Engl J Med 355:260–269

    Article  CAS  PubMed  Google Scholar 

  8. Anavekar NS, McMurray JJ, Velazquez EJ et al (2004) Relation between renal dysfunction and cardiovascular outcomes after myocardial infarction. N Engl J Med 351:1285–1295

    Article  CAS  PubMed  Google Scholar 

  9. Guyton AC (1990) The surprising kidney-fluid mechanism for pressure control-its infinite gain! Hypertension 16:725–730

    CAS  PubMed  Google Scholar 

  10. Bongartz LG, Cramer MJ, Doevendans PA et al (2005) The severe cardiorenal syndrome: ‘Guyton revisited’. Eur Heart J 26:11–17

    Article  PubMed  Google Scholar 

  11. Binkley P, Nunziata E, Haas G et al (1991) Parasympathetic withdrawal is an integral component of autonomic imbalance in congestive heart failure: demonstration in human subjects and verification in a paced canine model of ventricular failure. J Am Coll Cardiol 18:464–472

    Article  CAS  PubMed  Google Scholar 

  12. Bell-Reuss E, Trevino DL, Gottschalk CW (1976) Effect of renal sympathetic nerve stimulation on proximal water and sodium reabsorption. J Clin Invest 57:1104–1107

    Article  CAS  PubMed  Google Scholar 

  13. Myers BD, Deen WM, Brenner BM (1983) Effects of norepinephrine and angiotensin II on the determinants of glomerular ultrafiltration and proximal tubule fluid reabsorption in the rat. Circ Res 37:101–110

    Google Scholar 

  14. Schrier RW, de Wardener HE (1971) Tubular reabsorption of sodium ion: influence of factors other than aldosterone and glomerular filtration rate. N Engl J Med 285:1231–1242

    Article  CAS  PubMed  Google Scholar 

  15. Schrier RW (1990) Body fluid volume regulation in health and disease: a unifying hypothesis. Ann Intern Med 113:155–159

    CAS  PubMed  Google Scholar 

  16. Schrier RW (2006) Role of diminished renal function in cardiovascular mortality: marker or pathogenetic factor? J Am Coll Cardiol 47:1–8

    Article  PubMed  Google Scholar 

  17. Castrop H, Schweda F, Mizel D et al (2004) Permissive role of nitric oxide in macula densa control of renin secretion. Am J Physiol 286:F848–F857

    Article  CAS  Google Scholar 

  18. Henry JP, Gauer OH, Reeves JS (1956) Evidence of atrial location of receptors in influencing urine flow. Circ Res 4:85–90

    CAS  PubMed  Google Scholar 

  19. Spinelli L, Petretta M, Marciano F et al (1999) Cardiac autonomic responses to volume overload in normal subjects and in patients with dilated cardiomyopathy. Am J Physiol 277:H1361–H1368

    CAS  PubMed  Google Scholar 

  20. Volpe M, Lembo G, Condorelli G et al (1990) Converting enzyme inhibition prevents the effects of atrial natriuretic factor on baroreflex responses in humans. Circulation 82:1214–1221

    CAS  PubMed  Google Scholar 

  21. Laragh, JH (1985) Atrial natriuretic hormone, the renin-aldosterone axis, and blood pressureelectrolyte homeostasis. N Engl J Med 313:1330–1336

    Article  CAS  PubMed  Google Scholar 

  22. Volpe M, Tritto C, De Luca N et al (1991) Failure of atrial natriuretic factor to increase with saline load in patients with dilated cardiomyopathy and mild heart failure. J Clin Invest 88:1481–1489

    Article  CAS  PubMed  Google Scholar 

  23. Braam B. (1999) Renal endothelial and macula densa NOS: integrated response to changes in extracellular fluid volume. Am J Physiol. 276(Pt 2):R1551–R1561

    CAS  PubMed  Google Scholar 

  24. Ren Y, Carretero OA, Garvin JL (2002) Mechanism by which superoxide potentiates tubuloglomerular feedback. Hypertension 39:624–628

    Article  CAS  PubMed  Google Scholar 

  25. Tojo A, Onozato ML, Kobayashi N et al (2002) Angiotensin II and oxidative stress in Dahl Salt-sensitive rat with heart failure. Hypertension 40:834–839

    Article  CAS  PubMed  Google Scholar 

  26. Heymes C, Bendall JK, Ratajczak P et al (2003) Increased myocardial NADPH oxidase activity in human heart failure. J Am Coll Cardiol 41:2164–2171

    Article  CAS  PubMed  Google Scholar 

  27. Nakagami H, Takemoto M, Liao JK (2003) NADPH oxidase-derived superoxide anion mediates angiotensin II-induced cardiac hypertrophy. J Mol Cell Cardiol 35:851–859

    Article  CAS  PubMed  Google Scholar 

  28. Pueyo ME, Gonzalez W, Nicoletti A et al (2000) Angiotensin II stimulates endothelial vascular cell adhesion molecule-1 via nuclear factorkappaB activation induced by intracellular oxidative stress. Arterioscler Thromb Vasc Biol 20:645–651

    CAS  PubMed  Google Scholar 

  29. Reid IA (1992) Interactions between ANG II, sympathetic nervous system, and baroreceptor reflexes in regulation of blood pressure. Am J Physiol 262:E763–E778

    CAS  PubMed  Google Scholar 

  30. Vallance P, Leone A, Calver A et al (1992) Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure. Lancet 339:572–575

    Article  CAS  PubMed  Google Scholar 

  31. Lin HH, Chen CH, Hsieh WK et al (2003) Hydrogen peroxide increases the activity of rat sympathetic preganglionic neurons in vivo and in vitro. Neuroscience 121:641–647

    Article  CAS  PubMed  Google Scholar 

  32. Testa M, Yeh M, Lee P et al (1996) Circulating levels of cytokines and their endogenous modulators in patients with mild to severe congestive heart failure due to coronary artery disease or hypertension. J Am Coll Cardiol 28:964–971

    Article  CAS  PubMed  Google Scholar 

  33. Zoccali C, Benedetto FA, Mallamaci F et al (2000) Inflammation is associated with carotid atherosclerosis in dialysis patients. Creed Investigators. Cardiovascular Risk Extended Evaluation in Dialysis Patients. J Hypertens 18:1207–1213

    Article  CAS  PubMed  Google Scholar 

  34. Zukowska-Grojec Z (1995) Neuropeptide Y A novel sympathetic stress hormone and more. Ann N Y Acad Sci 771:219–233

    Article  CAS  PubMed  Google Scholar 

  35. Jessup M, Costanzo MR (2009) The cardiorenal syndrome: do we need a change of strategy or a change of tactics? J Am Coll Cardiol 53:597–599

    Article  PubMed  Google Scholar 

  36. Mullens W, Abrahams Z, Francis GS et al (2009) Importance of venous congestion for worsening of renal function in advanced decompensated heart failure. J Am Coll Cardiol 53:589–589

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  38. Damman K, van Deursen VM, Navis G et al (2009) 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 53:582–588

    Article  PubMed  Google Scholar 

  39. Winton FR (1931) The influence of venous pressure on the isolated mammalian kidney. J Physiol 49–61

    Google Scholar 

  40. Firth JF, Raine AE, Ledingham JG (1988) Raised venous pressure: a direct cause of renal sodium retention in oedema? Lancet 1:1033–1035

    Article  CAS  PubMed  Google Scholar 

  41. Wathen RL, Selkurt EE (1969) Intrarenal regulatory factors of salt excretion during renal venous pressure elevation. Am J Physiol 216:1517–1524

    CAS  PubMed  Google Scholar 

  42. Burnett JC, Knox FR (1980) Renal interstitial pressure and sodium excretion during renal vein constriction. Am J Physiol 238:279–282

    Google Scholar 

  43. Burnett JC, Haas JA, Knox FG (1982) Segmental analysis of sodium reabsorption during renal vein constriction. Am J Physiol 243:19–22

    Google Scholar 

  44. Doty JM, Saggi BH, Sugerman HJ et al (1999) Effect of increased renal venous pressure on renal function. J Trauma 47:1000–1003

    Article  CAS  PubMed  Google Scholar 

  45. Fiksen-Olsen MJ, Strick DM, Hawley H, Romero JC (1992) Renal effects of angiotensin II inhibition during increases in renal venous pressure. Hypertension 19:137–141

    Google Scholar 

  46. Charkoudian N, Martin EA, Dinenno FA et al (2004) Influence of increased central venous pressure on baroreflex control of sympathetic activity in humans. Am J Physiol Heart Circ Physiol. 287:H1658–H1662

    Article  CAS  PubMed  Google Scholar 

  47. Tang YD, Katz SD (2006) Anemia in chronic heart failure: prevalence, etiology, clinical correlates, and treatment options. Circulation 113: 2454–2461

    Article  PubMed  Google Scholar 

  48. Tang YD, Katz SD (2008) The prevalence of anemia in chronic heart failure and its impact on the clinical outcomes. Heart Fail Rev 13:387–392

    Article  PubMed  Google Scholar 

  49. Komajda M, Anker SD, Charlesworth A et al (2006) The impact of new onset anaemia on morbidity and mortality in chronic heart failure: results from COMET. Eur Heart J 27: 1440–1446

    Article  PubMed  Google Scholar 

  50. Go AS, Yang J, Ackerson LM et al (2006) Hemoglobin level, chronic kidney disease, and the risks of death and hospitalization in adults with chronic heart failure: the Anemia in Chronic Heart Failure: Outcomes and Resource Utilization (ANCHOR) Study. Circulation 113:2713–2723

    Article  CAS  PubMed  Google Scholar 

  51. Young JB, Abraham WT, Albert NM et al (2008) Relation of low hemoglobin and anemia to morbidity and mortality in patients hospitalized with heart failure (insight from the OPTIMIZEHF registry). Am J Cardiol 15(101):223–230

    Article  Google Scholar 

  52. Opasich C, Cazzola M, Scelsi L et al (2005) Blunted erythropoietin production and defective iron supply for erythropoiesis as major causes of anaemia in patients with chronic heart failure. Eur Heart J 26: 2232–2237

    Article  CAS  PubMed  Google Scholar 

  53. Mitchell J (2007) Emerging role of anemia in heart failure. Am J Cardiol 99:15D–20D

    Article  PubMed  Google Scholar 

  54. Anand IS (2008) Heart failure and anemia: mechanisms and pathophysiology. Heart Fail Rev 13:379–386

    Article  PubMed  Google Scholar 

  55. Palazzuoli A, Gallotta M, Iovine F et al (2008) Anaemia in heart failure: a common interaction with renal insufficiency called the cardiorenalanaemia syndrome. Int J Clin Pract 62:281–286

    Article  CAS  PubMed  Google Scholar 

  56. George J, Patal S, Wexler D et al (2005) Circulating erythropoietin levels and prognosis in patients with congestive heart failure: comparison with neurohormonal and inflammatory markers. Arch Int Med 165:1304–1309

    Article  CAS  Google Scholar 

  57. van der Meer P, Voors AA, Lipsic E et al (2004) Prognostic value of plasma erythropoietin on mortality in patients with chronic heart failure. J Am Coll Cardiol 44:63–67

    Article  PubMed  Google Scholar 

  58. Volpe M, Tritto C, Testa U et al (1994) Blood levels of erythropoietin in congestive heart failure and correlation with clinical, hemodynamic, and hormonal profiles. Am J Cardiol 74:468–473

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  60. Singh AK, Szczech L, Tang KL et al (2006) Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med 355:2085–2098

    Article  CAS  PubMed  Google Scholar 

  61. Drüeke TB, Locatelli F, Clyne N et al (2006) Normalization of haemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med 355:2071–2084

    Article  PubMed  Google Scholar 

  62. Besarab A, Bolton K, Browne JK et al (1998) The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin. N Engl J Med 339:584–590

    Article  CAS  PubMed  Google Scholar 

  63. Mix TC, Brenner RM, Cooper ME et al (2005) Rationale—Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT): evolving the management of cardiovascular risk in patients with chronic kidney disease. Am Heart J 149:408–413

    Article  CAS  PubMed  Google Scholar 

  64. Szczech LA, Barnhart HX, Inrig JK et al (2008) Secondary analysis of the CHOIR trial epoetinalpha dose and achieved hemoglobin outcomes. Kidney Int 74:791–798

    Article  CAS  PubMed  Google Scholar 

  65. Murphy NF, McDonald K (2007) Treatment of anaemia in chronic heart failure— optimal approach still unclear. Eur Heart J 28:2185–2187

    Article  CAS  PubMed  Google Scholar 

  66. Ponikowski P, Anker SD, Szachniewicz J et al (2007) Effect of darbopoetin alfa on exercise tolerance in anemic patients with symptomatic chronic heart failure. J Am Coll Cardiol 49:753–762

    Article  CAS  PubMed  Google Scholar 

  67. van Veldhuisen DJ, Dickstein K, Cohen-Solal A et al (2007) Randomized, double-blind, placebocontrolled study to evaluate the effect of two dosing regimens of darbopoetin alfa in patients with heart failure and anaemia. Eur Heart J 28:2208–2216

    Article  PubMed  Google Scholar 

  68. Ghali JK, Anand IS, Abraham WT et al (2008) Randomized double-blind trial of darbopoetin alfa in patients with symptomatic heart failure and anemia. Circulation 117:526–535

    Article  CAS  PubMed  Google Scholar 

  69. Dries DL, Exner DV, Domanski MJ et al (2000) The prognostic implications of renal insufficiency in asymptomatic and symptomatic patients with left ventricular systolic dysfunction. J Am Coll Cardiol 35:681–689

    Article  CAS  PubMed  Google Scholar 

  70. Hillege HL, Girbes AR, de Kam PJ et al (2000) Renal function, neurohormonal activation, and survival in patients with chronic heart failure. Circulation 102:203–310

    CAS  PubMed  Google Scholar 

  71. Mahon NG, Blackstone EH, Francis GS et al (2002) The prognostic value of estimated creatinine clearance alongside functional capacity in ambulatory patients with chronic congestive heart failure. J Am Coll Cardiol 40:1106–1113

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  73. Abraham WT, Fonarow GC, Albert NM et al (2008) Predictors of in-hospital mortality in patients hospitalized for heart failure: insights from the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF). J Am Coll Cardiol 52:347–356

    Article  PubMed  Google Scholar 

  74. Nohria A, Hasselblad V, Stebbins A et al (2008) Cardiorenal interactions: insights from the ESCAPE trial. J Am Coll Cardiol 51:1268–1274

    Article  PubMed  Google Scholar 

  75. Weinrauch LA, Lin J, Solomon SD (2008) Mapping directions for the cardiorenal conundrum: where you end up depends upon where you started, so where do we go from here? J Am Coll Cardiol 51:1275–1276

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Cardiology, II Faculty of Medicine, University of Rome «La Sapienza», Sant’Andrea Hospital, Rome, Italy

    Massimo Volpe & Marco Testa

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  1. Massimo Volpe
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  2. Marco Testa
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  1. Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon

    Adel E. Berbari

  2. Clinica Medica Department of Clinical Medicine and Prevention, University of Milano-Bicocca San Gerardo Hospital, Monza, Milan, Italy

    Giuseppe Mancia

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Volpe, M., Testa, M. (2010). Pathophysiological Mechanisms and Prognostic Significance of Renal Functional Impairment in Cardiac Patients. In: Berbari, A.E., Mancia, G. (eds) Cardiorenal Syndrome. Springer, Milano. https://doi.org/10.1007/978-88-470-1463-3_14

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  • DOI: https://doi.org/10.1007/978-88-470-1463-3_14

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