Cardiorenal syndrome in the context of diabetes mellitus

Authors: Marta Filková Karabová;  Ján Murín
Authors‘ workplace: I. interná klinika LF UK a Nemocnica Staré Mesto, UNB, Bratislava, prednostka doc. MUDr. Soňa Kiňová, PhD.
Published in: Forum Diab 2013; 2(1): 31-35


Cardiorenal syndrome is defined as a disorder of the heart and kidney whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other. From the recently introduced five-degree classification of cardiorenal syndrome, the fifth subtype, so called secondary cardiorenal syndrome, is a state where an acute or chronic systemic insult or illness leads to simultaneous heart and renal dysfunction. Diabetes mellitus represents such chronic systemic disease that affects the pathophysiology of cardiorenal axis. Diabetes is a well established risk factor for cardiovascular diseases and a significant proportion of diabetic patients go on to develop clinically significant nephropathy. In the diabetic state, the impairment of the heart and kidney function is caused by hemodynamic abnormalities, humoral factors, oxidative stress and endothelial dysfunction as well as a number of positive feedback loops existing in-between already established cardiac and renal dysfunction. In the therapy of diabetic cardiorenal syndrome the cornerstone remains the control of the primary disease and then concomitant cardiovascular risk factors.

Key words:
cardiorenal syndrome – diabetes mellitus – diabetic nephropathy


1. Heywood JT. The cardiorenal syndrome: lessons from the ADHERE database and treatment options. Heart Fail Rev 2004; 9(3): 195–201.

2. Ronco C, McCullough P, Anker SD et al. Cardio-renal syndromes: an executive summary from the consensus conference of the Acute Dialysis Quality Initiative. Contrib Nephrol 2010; 165: 54–67.

3. Ronco C, Cruz DN, Ronco F. Cardiorenal syndromes. Curr Opin Crit Care 2009; 15(5): 384–391.

4. Bock JS, Gottlieb SS. Cardiorenal syndrome – new perspectives. Circulation 2010; 121(23): 2592–2660.

5. Shah BN, Greaves K. The cardiorenal syndrome: a review. Int J Nephrol. 2011. Dostupné z WWW(DOI): 10.4061/2011/920195.

6. Metra M, Cotter G, Gheorgiade M et al. The role of the kidney damage in heart failure. Eur Heart J 2012; 33(17): 2135–2142.

7. Cannon PJ. The kidney in heart failure. New Engl J Med 1977; 296(1): 26–32.

8. Ljungman S, Laragh JH, Cody RJ. Role of the kidney in congestive heart-failure—relationship of cardiac index to kidney-function. Drugs 1990; 39(Suppl 4): 10–21.

9. Uthoff H, Breidthardt T, Klima T et al. Central venous pressure and impaired renal function in patients with acute heart failure. Eur J Heart Fail 2011; 13(4): 432–439.

10. Damman K, Navis G, Smilde TD et al. Decreased cardiac output, venous congestion and the association with renal impairment in patients with cardiac dysfunction. Eur J Heart Fail 2007; 9(9): 872–878.

11. Mullens W, Abrahams Z, Gary FS 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.

12. Mullens W, Abrahams Z, Skouri HN et al. Elevated intraabdominal pressure in acute decompensated heart failure. A potential contributor to worsening renal function? J Am Coll Cardiol 2008; 51(3): 300–306.

13. Ruiz-Ortega M, Ruperez M, Lorenzo O et al. Angiotensin II regulates the synthesis of proinflammatory cytokines and chemokines in the kidney. Kidney Int. 2002; 82(Suppl): S12–S22.

14. Remuzzi G, Perico N, Macia M et al. The role of the renin-angiotensin-aldosterone system in the progression of chronic kidney disease. Kidney Int. 2005; 99(Suppl): S57–S65.

15. Bristow MR, Ginsburg R, Minobe W et al. Decreased catecholamine sensitivity and β-adrenergic-receptor density in failing human hearts. New Engl J Med 1982; 307(4): 205–211.

16. Petersson M, Friberg P, Eisenhofer G et al. Long-term outcome in relation to renal sympathetic activity in patient with chronic heart failure. Eur Heart J 2005; 26(9): 906–913.

17. Schlaich MP, Sobotka PA, Krum H et al. Renal sympathetic-nerve ablation for uncontrolled hypertension. N Engl J Med 2009; 361(9): 932–934.

18. Pecháňová O. Reaktívne formy kyslíku a význam antioxidačných látok pri hypertenzii. Via pract 2007; 4(1): 11–14.

19. Silverberg DS, Wexler D, Blum M et al. The correction of anemia in severe resistant heart failure with erythropoietin and intravenous iron prevents the progression of both the heart and the renal failure and markedly reduces hospitalization. Clin Nephrol 2002; 58(Suppl 1): S37–S45.

20. Silva RP, Barbosa PHU, Kimura OS et al. Prevalance of anemia and its association with cardio-renal syndrome. Int J Cardiol 2007; 120(2): 232–236.

21. Nurko S. Anemia in chronic kidney diseases: causes, diagnosis, treatment. Cleveland Clin J Med 2006; 73(3): 289–297.

22. Deswal A, Petersen NJ, Feldman AM et al. Cytokines and cytokine receptors in advanced heart failure: an analysis of the cytokine database from the Vesnarinone trial (VEST). Circulation 2001; 103(16): 2055–2059.

23. Jelkmann W. Proinflammatory cytokines lowering erythropoietin production. J Interferon Cytokine Res 1998; 18(8): 555–559.

24. Anand IS. Anemia and chronic heart failure, implications and treatment options. J Am Coll Cardiol 2008; 52(7): 501–511.

25. Gotloib L, Silverberg D, Fudin R et al. Iron deficiency is a common cause of anemia in chronic kidney disease and can often be corrected with intravenous iron. Journal of Nephrology 2006; 19(2): 161–167.

26. Ziyadeh FN. Different roles for TGF-b and VEGF in the pathogenesis of the cardinal features of diabetic nephropathy. Diabetes Res Clin Pract 2008; 82 (Suppl 1): S38-S41.

27. Karnib HH. Cardiorenal Syndrome Type-5: The case of diabetes mellitus and the effect of nephropathy on the cardiovascular outcome. Journal of Clinical Metabolism and Diabetes 2011; 2(2): 54–60.

28. Pandolfi A, De Filippis EA. Chronic hyperglycemia and nitric oxide bioavailability play a pivotal role in pro-atherogenic vascular modifications. Genes Nutr. 2007; 2(2): 195–208.

29. Jakuš V, Rietbrock N. Intermediárne a koncové produkty neenzýmovej glykácie. Chem Listy 1999; 93(6): 375–381.

30. Satchell SC, Tooke JE. What is the mechanism of microalbuminuria in diabetes: a role for the glomerular endothelium? Diabetologia 2008; 51(5): 714–725.

31. Astrup AS, Tarnow L, Pietraszek L et al. Markers of endothelial dysfunction and inflammation in type 1 diabetic patients with or without diabetic nephropathy followed for 10 years: association with mortality and decline of glomerular filtration rate. Diabetes Care 2008; 31(6): 1170–1176.

32. Vallance P, Leone A, Calver A et al. Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure. Lancet 1992; 339(8793): 572–575.

33. Anderssohn M, Schwedhelm E, Lüneburg N et al. Asymmetric dimethylarginine as a mediator of vascular dysfunction and a marker of cardiovascular disease and mortality: an intriguing interaction with diabetes mellitus. Diabetes & Vascular Disease Research 2010; 7(2): 105–118.

34. Krzyzanowska K, Mittermayer F, Wolzt M, Schernthaner G. Asymmetric dimethylarginine predicts cardiovascular events in patients with type 2 diabetes. Diabetes Care 2007; 30(7): 1834–1839.

35. Hanai KO, Babazono T, Nyumura I et al. Asymmetric dimethylarginine is closely associated with the development and progression of nephropathy in patients with type 2 diabetes. Nephrol Dialysis Transplant 2009; 24(6): 1884–1888.

36. Kramer HJ, Nguyen QD, Curhan G, Hsu CY. Renal insufficiency in the absence of albuminuria and retinopathy among adults with type 2 diabetes mellitus. JAMA 2003; 289(24): 3273–3277.

37. Perkins BA, Nelson RG, Ostrander BE et al. Detection of renal function decline in patients with diabetes and normal or elevated GFR by serial measurements of serum cystatin C concentration: results of a 4-year follow-up study. J Am Soc Nephrol. 2005; 16(5): 1404–1412.

38. National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2002; 39(Suppl 1): S1-S266.

39. Molitch ME, DeFronzo RA, Franz MJ et al. Nephropathy in diabetes. Diabetes Care. 2004; 27(Suppl 1): S79-S83.

40. United States Renal Data System: Excerpts from the USRDS 2007 annual data report: atlas of end-stage renal disease in the United States. Minneapolis, MN 2007.

41. Coresh J, Astor BC, Greene T et al. 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 2003; 41(1):1–12.

42. Demeš M. Nefrologická aktivita v SR v roku 2007. Lek Obz 2009, 58(6): 268–269.

43. Whiteley L, Padmanabhan S, Hole D, Isles C. Should diabetes be considered a coronary heart disease risk equivalent? Results from 25 years of follow-up in the Renfrew and Paisley survey. Diabetes Care 2005; 28(7): 1588–1593.

44. Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in non diabetic subjects with and without prior myocardial infarction. N Engl J Med 1998; 339(4): 229–234.

45. Buse JB, Ginsberg HN, Bakris GL et al. Primary prevention of cardiovascular diseases in people with diabetes mellitus: a scientific statement from the American Heart Association and the American Diabetes Association. Circulation 2007; 115(1): 114–126.

46. Hillege HL, Girbes ARJ, de Kam PJ et al. Renal function, neurohormonal activation, and survival in patients with chronic heart failure. Circulation 2000; 102(2): 203–210.

47. Tonelli M, Wiebe N, Culleton B et al. Chronic kidney disease and mortality risk: a systematic review. J Am Soc Nephrol 2006; 17(7): 2034–2047.

48. European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice. Eur Heart J 2012; 33(13): 1635–1701.

49. Parfrey PS, Foley RN. The clinical epidemiology of cardiac disease in chronic renal failure. J Am Soc Nephrol 1999; 10(7): 1606–1615.

50. American Diabetes Association. Standards of medical care in diabetes – 2010. Diabetes Care 2010; 33(Suppl 1): S11-S61.

51. The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993; 329(14): 977–986.

52. The UK Prospective Diabetes Study (UKPDS) Group. Intensive blood glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998; 352(9131): 837–853.

53. Gerstein HC, Miller ME, Byington RP et al. Action to Control Cardiovascular Risk in Diabetes Study Group. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 2008; 358(24): 2545–2559.

54. Pyorala K, Pedersen TR, Kjekshus J et al. Cholesterol lowering with simvastatin improves prognosis of diabetic patients with coronary heart disease: a subgroup analysis of the Scandinavian Simvastatin Survival Study (4S). Diabetes Care. 1997; 20(4): 614–620.

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