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The MIAC (malnutrition, inflammation, atherosclerosis, calcification) syndrome


Authors: E. Mistrík;  V. Bláha;  S. Dusilová-Sulková;  L. Sobotka
Authors‘ workplace: Klinika gerontologická a metabolická Lékařské fakulty K a FN Hradec Králové, přednosta prof. MUDr. Luboš Sobotka, CSc.
Published in: Vnitř Lék 2007; 53(10): 1092-1099
Category: Reviews

Overview

The number of patients with chronic renal failure is on the rise; these patients have a 10 to 20 times higher risk of development and progression of cardiovascular diseases. Higher cardiovascular risk in such patients cannot be satisfactorily explained by traditional risk factors defined in the Framingham study. On the contrary, a concept of reverse epidemiology has been brought forward, designating a situation in which the incidence of obesity and hyperlipoproteinemia is associated with a higher survival rate of the patients concerned. Higher risk is today explained by the „MIAC (malnutrition, inflammation, atherosclerosis, calcification) syndrome“, which is present in patients with chronic kidney disease. New evidence has been recently obtained of different circulating molecules associated with atherosclerosis, the plasmatic levels of which are decreased or increased in such patients and which are in a way linked with the MIAC syndrome and the progression of atherosclerosis. Clinical management of the syndrome could increase survival in the future, and reduce morbidity and the number of hospitalisations. Circulating molecules could serve as markers evidencing the presence of the syndrome and its severity, as well as the success of treatment.

Key words:
inflammation – malnutrition – atherosclerosis – calcification – haemodialysis


Sources

1. Muntner P, He J, Hamm L et al. Renal insufficiency and subsequent death resulting from cardiovascular disease in the United States. J Am Soc Nephrol 2002; 13: 745-753.

2. Foley RN, Parfrey PS, Sarnak MJ. Clinical epidemiology of cardiovascular disease in chronic renal disease. Am J Kidney Dis 1998; 32: S112-S119.

3. United States Renal Data System. Excerpts from the USRDS 2005 Annual Data Report: Atlas of End-Stage Renal Disease in the United States, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. Am J Kid Dis 2006; 47(Suppl 1): 1-286.

4. Eknoyan G, Beck GJ, Cheung AK et al. Effect of dialysis dose and membrane flux in maintenance hemodialysis. N Engl J Med 2002; 347: 2010-2019.

5. O’Hare AM, Bertenthal D, Shlipak MG et al. Impact of renal insufficiency on mortality in advanced lower extremity peripheral arterial disease. J Am Soc Nephrol 2005; 16: 514-519.

6. Termorshuizen F, Dekker FW, van Manen JG et al. Relative Contribution of Residual Renal Function and Different Measures of Adequacy to Survival in Hemodialysis Patients: An analysis of the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD)-2. J Am Soc Nephrol 2004; 15: 1061-1070.

7. Harris T, Cook EF, Garrison R et al. Body mass index and mortality among nonsmoking older persons. The Framingham Heart Study. JAMA 1988; 259: 1520-1524.

8. Shea S, Cook EF, Kannel WB et al. Treatment of hypertension and its effect on cardiovascular risk factors: data from the Framingham Heart Study. Circulation 1985; 71: 22-30.

9. Cheung AK, Sarnak MJ, Yan G et al. Atherosclerotic cardiovascular disease risks in chronic hemodialysis patients. Kidney Int 2000; 58: 353-362.

10. Kalantar-Zadeh K, Block G, Humphreys MH et al. Reverse epidemiology of cardiovascular risk factors in maintenance dialysis patients. Kidney Int 2003; 63: 793-808.

11. Kalantar-Zadeh K, Abbott KC, Salahudeen AK et al. Survival advantages of obesity in dialysis patients. Am J Clin Nutr 2005; 81: 543-554.

12. Kalantar-Zadeh K Causes and consequences of the reverse epidemiology of body mass index in dialysis patients. J Ren Nutr 2005; 15: 142-147.

13. Kalantar-Zadeh K, Kopple JD, Kilpatrick RD et al. Association of morbid obesity and weight change on cardiovascular survival in hemodialysis population. Nephrol Dial Transplant 2005; 20: 1662-1669.

14. Stenvinkel P, Heimburger O, Paultre F et al. Strong association between malnutrition, inflammation, and atherosclerosis in chronic renal failure. Kidney Int 1999; 55: 1899-1911.

15. Wang A, Woo J, Wai-Kei Lam C et al. Associations of serum fetuin-A with malnutrition, inflammation, atherosclerosis and valvular calcification syndrome and outcome in peritoneal dialysis patients. Nephrol Dial Transplant 2005; 20: 1676-1685.

16. Papagianni A, Kokolina E, Kalovoulos M et al. Carotid atherosclerosis is associated with inflammation, malnutrition and intercellular adhesion molecule-1 in patients on continuos ambulatory peritoneal dialysis. Nephrol Dial Transplant 2004; 19: 1258-1263.

17. Tripepi G, Mallamaci F, Zoccali C Inflammation Markers, Adhesion Molecules, and All-Cause and Cardiovascular Mortality in Patients with ESRD: Searching for the Best Risk Marker by Multivariate Modeling. J Am Soc Nephrol 2005; 16: S83-S88.

18. Tzoulaki I, Murray GD, Lee AJ et al. C-reactive protein, interleukin-6, and soluble adhesion molecules as predictors of progressive peripheral atherosclerosis in the general population: Edinburgh artery study. Circ 2005; 112: 976-983.

19. Javaid K, Rahman A, Anwar KN et al. Tumor necrosis factor-α induces early-onset endothelial adhesivity by protein kinase Cζ- dependent activation of intercellular adhesion molecule-1. Circ Res 2003; 92: 1089-1097.

20. Seyrek N, Balal M, Karayaylali I et al. Is there any relationship between serum levels of IL-10 and atherosclerosis in hemodialysed patients? Hemodial Int 2004; 8: 90-91.

21. Malyszko J, Malyszko JS, Brzosko S et al. Adiponectin is related to CD146, a novel marker of endothelial cell activation/injury in chronic renal failure and peritoneally dialysed patients. J. Clin. Endocrinol. Metab 2004; 89: 4620-4627.

22. Yano A, Nakao K, Sarai A et al. Elevated serum interleukin-18 levels might reflect the high risk of hospitalization in patients on peritoneal dialysis. Nephrology 2005; 10: 576-582.

23. Zoccali C, Benedetto FA, Maas R et al. Asymmetric dimethylarginine, C-reactive protein, and carotid intima-media thickness in end stage renal disease. J Am Soc Nephrol 2002; 13: 490-496.

24. Ketteler M, Bongartz P, Westenfeld R et al. Association of low fetuin-A (AHSG) concentrations in serum with cardiovascular mortality in patients on dialysis: A cross-sectional study. Lancet 2003; 361: 827-833.

25. Himmelfarb J, Stenvinkel P, Ikizler TA et al. The elephant in uremia: oxidant stress as a unifying concept of cardiovascular disease in uremia. Kidney Int 2002; 62: 1524-1538.

26. Locatelli F, Canaud B, Eckardt KU et al. Oxidative stress in end-stage renal disease: An emerging threat to patient outcome. Nephrol Dial Transplant 2003; 18: 1272-1280.

27. Handelman GJ Current studies on oxidant stress in dialysis. Blood Purif 2003; 21: 46-50.

28. Sies H Oxidative stress: Oxidants and antioxidants. Exp Physiol 1997; 82: 291-295.

29. Descamps-Latscha B, Goldfarb B, Nguyen A et al. Establishing the relationship between complement activation and stimulation of phagocyte oxidative metabolism in hemodialyzed patients: A randomized prospective study. Nephron 1991; 59: 279-285.

30. Ward RA, McLeish KR. Polymorphonuclear leukocyte oxidative burst is enhanced in patients with chronic renal insufficiency. J Am Soc Nephrol 1994; 5: 1697-1702.

31. Morena M, Delbosc S, Dupuy AM et al. Overproduction of reactive oxygen species in end-stage renal disease patients: A potential component of hemodialysis associated inflammation; Hemodial Int 2005; 9: 37-46.

32. Cristol JP, Canaud B, Rabesandratana H et al. Enhancement of reactive oxygen species production and cell surface markers expression during hemodialysis. Nephrol Dial Transplant 1994; 9: 389-394.

33. Chen MF, Chang CL, Liou SY Increase in resting levels of superoxide anion in the whole blood of uremic patients on chronic hemodialysis. Blood Purif 1998; 16: 290-300.

34. Stenvinkel P, Lindholm B, Heimburger O Novel approaches in an integrated therapy of inflammatory-associated wasting in end-stage renal disease. Semin Dial 2004; 17: 505-515.

35. Endemann DH, Schiffrin EL Endothelial dysfunction. J Am Soc Nephro 2004; 15: 1983-1992.

36. Annuk M, Zilmer M, Lind L et al. Oxidative stress and endothelial function in chronic renal failure. J Am Soc Nephrol 2001; 12: 2747-2752.

37. Tauer A, Zhang X, Schaub TP et al. Formation of advanced glycation end products during CAPD. Am J Kidney Dis 2003; 41: S57-S60.

38. Zeier M, Schwenger V, Deppisch R et al. Glucose degradation products in PD fluids: Do they disappear from the peritoneal cavity and enter the systemic circulation? Kidney Int 2003; 63: 298-305.

39. Schwenger V, Morath C, Salava A et al. Damage to the peritoneal membrane by glucose degradation products is mediated by the receptor for advanced glycation end-products. J Am Soc Nephrol 2006; 17: 199-207.

40. Chung SH, Heimburger O, Stenvinkel P et al. Association between inflammation and changes in residual renal function and peritoneal transport rate during the first year of dialysis. Nephrol Dial Transplant 2001; 16: 2240-2245.

41. Chung SH, Heimburger O, Stenvinkel P et al. Association between residual renal function, inflammation and patient survival in new peritoneal dialysis patients. Nephrol Dial Transplant 2003; 18: 590-597.

42. Bolton CH, Downs LG, Victory JGG et al. Endothelial dysfunction in chronic renal failure, roles of lipoprotein oxidation and pro-inflammatory cytokines. Nephrol Dial Transplant 2001; 16: 1189-1197.

43. Zoccali C, Mallamaci F, Tripepi G Atherosclerosis in dialysis patients: does Chlamydia pneumoniae infection contribute to cardiovascular damage? Nephrol Dial Transplant 2002; 17 (Suppl 8): 25-28.

44. Yao Q, Lindholm B, Stenvinkel P Inflammation as a cause of malnutrition, atherosclerotic cardiovascular disease, and poor outcome in hemodialysis patients. Hemodial Int 2004; 8: 118-129.

45. Wiedermann CJ, Kiechl S, Dunzendorfer S et al. Association of endotoxemia with carotid atherosclerosis and cardiovascular disease. Prospective results from the Bruneck study. J Am Coll Cardiol 1999; 34: 1975-1981.

46. Rice JB, Stoll LL, Li WG et al. Low level endotoxin induces potent inflammatory activation of human blood vessels: inhibition by statins. Arterioscler Thromb Vasc Biol 2003; 23: 1576-1582.

47. Stoll LL, Denning GM, Li WG et al. Regulation of endotoxin-induced proinflammatory activation in human coronary artery cells: expression of functional membrane-bound CD14 by human coronary artery smooth muscle cells. J Immunol 2004; 173: 1336-1343.

48. Schratzberger P, Kiechl S, Dunzendorfer S et al. Plasma-induced endothelial activation associated with incident atherosclerosis: prospective results from a large population study. Circulation 2001; 103: 1064-1070.

49. Lehr HA, Sagban TA, Ihling C et al. Immunopathogenesis of atherosclerosis: endotoxin accelerates atherosclerosis in rabbits on hypercholesterolemic diet. Circulation 2001; 104: 914-920.

50. Ostos MA, Recalde D, Zakin MM et al. Implication of natural killer T cells in atherosclerosis development during a LPS-induced chronic inflammation. FEBS Lett 2002; 519: 23-29.

51. Stoll LL, Denning GM, Weintraub NL Potential role of endotoxin as a proinflammatory mediator of atherosclerosis. Arterioscler Thromb Vasc Biol 2004; 24: 2227-2236.

52. Guttridge DC, Mayo MW, Madrid LV et al. NF-κB-induced loss of MyoD messenger RNA: Possible role in muscle decay and cachexia. Science 2000; 289: 2363-2366.

53. Mitch WE, Du J, Bailey JL et al. Mechanisms causing muscle proteolysis in uremia: The influence of insulin and cytokines. Miner Electrolyte Metab 1999; 25: 216-219.

54. Grunfeld C, Zhao C, Fuller J et al. Endotoxin and cytokines induce expression of leptin, the ob gene product, in hamsters. J Clin Invest 1996; 97: 2152-2157.

55. Cheung W, Yu PX, Little BM et al. Role of leptin and melanocortin signaling in uraemia-associated cachexia. J Clin Invest 2005; 115: 1659-1665.

56. Chudek J, Adamczak M, Kania M et al. Does plasma leptin concentration predict the nutritional status of hemodialyzed patients with chronic renal failure? Med Sci Monit 2003; 9: CR377-CR382.

57. Haluzík M, Sulková S, Svobodová J et al. Serum leptin levels in diabetic patients on hemodialysis : the relationship to parameters of diabetes metabolic control. Endocr Res 2000; 26: 303-317.

58. Stenvinkel P, Heimburger O, Lindholm B et al. Are there two types of malnutrition in chronic renal failure? Evidence for relationships between malnutrition, inflammation and atherosclerosis (MIA syndrome). Nephrol Dial Transplant. 2000; 15: 953-960.

59. Leskinen Y, Lehtimaki T, Loimaala A et al. Carotid atherosclerosis in chronic renal failure- the central role of increased plaque burden. Atherosclerosis 2003; 171: 295-302.

60. Rohde LE, Lee RT, Rivero J et al. Circulating cell adhesion molecules are correlated with ultrasound- based assessment of carotid atherosclerosis. Arterioscler Thromb Vasc Biol 1998; 18: 1765-1770.

61. van der Meer IM, de Maat MPM, Bots ML et al. Inflammatory mediators and cell adhesion molecules as indicators of severity of atherosclerosis. The Rotterdam Study. Arterioscler Thromb Vasc Biol 2002; 22: 838-842.

62. London G, Marchais S, Guerin A et al. Arterial structure and function in end-stage renal disease. Nephrol Dial Transplant 2002; 17: 1713-1724.

63. Smržová J. Hyperfosfatemie jako závažná komplikace chronické renální insuficience a chronického selhání ledvin. I. Etiopatogeneze, důsledky a diagnostika. Vnitř Lék 2005; 51: 327-335.

64. Giachelli CM, Jono S, Shioi A et al. Vascular calcification and inorganic phosphate. Am J Kidney Dis 2001; 38: 34-37.

65. Giachelli CM Vascular calcification mechanisms. J Am Soc Nephrol 2004; 15: 2959-2964.

66. Luo GDP, McKee MD, Pinero GJ et al. Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein. Nature 1997; 386: 78-81.

67. Fiore CE, Celotta G, Politi GG et al. Association of high α2-Heremans-Schmid glycoprotein/fetuin concentration in serum and intima-media thickness in patients with atherosclerotic vascular disease and low bone mass. Atherosclerosis 2006; doi:10.1016/j.atherosclerosis.2006.08.052.

68. Hunt JL, Fairman R, Mitchell ME et al. Bone formation in carotid plaques: A clinicopathological study. Stroke 2002; 33: 1214-1219.

69. Mohler ER 3rd, Gannon F, Reynolds C et al. Bone formation and inflammation in cardiac valves. Circulation 2001; 103: 1522-1528.

70. Bostrom K, Watson KE, Horn S et al. Bone morphogenic protein expression in human atherosclerotic lesions. J Clin Invest 1993; 91: 1800-1809.

71. Proudfoot D, Skepper JN, Hegyi L et al. Apoptosis regulates human vascular calcification in vitro: Evidence for initiation of vascular calcification by apoptotic bodies. Circ Res 2000; 87: 1055-1062.

72. Huber SA, Sakkinen P, Conze D et al. Interleukin-6 exacerbates early atherosclerosis in mice. Arterioscler Thromb Vasc Biol 1999; 19: 2364-2367.

73. Harris TB, Ferrucci L, Tracy RP et al. Associations of elevated interleukin-6 and C-reactive protein levels with mortality in the elderly. Am J Med 1999; 106: 506-512.

74. Huo Y, Hafezi-Moghadam A, Ley K Role of vascular cell adhesion molecule-1 and fibronectin connecting segment-1 in monocyte rolling and adhesion on early atherosclerotic lesions. Circ Res 2000; 87: 153-159.

75. Pawlak K, Pawlak D, Brzosko S et al. Carotid atherosclerosis is associated with enhanced β-chemokine levels in patients on continuos ambulatory peritoneal dialysis. Atherosclerosis 2006; 186: 146-151.

76. Kalousová M, Kielstein JT, Hodková M et al. No benefit of hemodiafiltration over hemodialysis in lowering elevated levels of asymmetric dimethylarginine in ESRD patients. Blood Purificat 2006; 24: 439-444.

77. Vallance P. Importance of asymmetric dimethylarginine in cardiovascular risk. Lancet 2001; 358: 2096-2097.

78. Kielstein JT, Boeger RH, Bode-Boeger SM et al. Asymmetric dimethylarginine plasma concentrations differ in patients with end stage renal disease: Relationship to treatment method and atherosclerotic disease. J Am Soc Nephrol 1999; 10: 594-600.

79. Fliser D, Kronenberg F, Kielstein JT et al. Asymmetric dimethylarginine and progression of chronic kidney disease: The mild to moderate kidney disease study. J Am Soc Nephrol 2005; 16: 2456-2461.

80. Vallance P, Leiper J Asymmetric dimethylarginin and kidney disease- marker or mediator? J Am Soc Nephrol 2006; 16: 2254-2256.

81. Stenvinkel P Inflammation in end-stage renal disease: The hidden enemy. Nephrology 2006; 11: 36-41.

82. Stenvinkel P, Lindholm B, Heimbuerger O Novel approaches in an integrated therapy of inflammatory-associated wasting in end-stage renal disease. Semin dial 2004; 17: 505-515.

83. Kalantar-Zadeh K Recent advances in understanding the malnutrition-inflammation-cachexia syndrome in chronic kidney disease patients: What is next? Semin Dial 2005; 18: 365-369.

84. Boaz M, Smetana S, Weinstein T et al. Secondary prevention with antioxidants of cardiovascular disease in end stage renal disease (SPACE): randomised placebo-controlled trial. Lancet 2000; 356: 1213-1218.

85. Tepel M, van der Giet M, Statz M et al. The antioxidant acetylcysteine reduces cardiovascular events in patients with end-stage renal failure. Circulation 2003; 107: 992-995.

86. Mann JF, Gerstein HC, Pogue J et al. Renal insufficiency as a predictor of cardiovascular outcomes and the impact of ramipril: the HOPE randomized trial. Ann Intern Med 2001; 134: 629-636.

87. Smržová J Hyperfosfatemie jako závažná komplikace chronické renální insuficience a chronického selhání ledvin. II. Léčba. Vnitř Lék 2005; 51: 337-344.

88. Asmus HG, Braun J, Krause R et al. Two year comparison of sevelamer and calcium carbonate effects on cardiovascular calcification and bone density. Nephrol Dial Transplant 2005; 20: 1653-1661.

89. Chertow GM, Burke SK, Raggi P Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients. Kidney Int 2002; 62: 245-252.

90. Kalantar-Zadeh K, Ikizler A, Block G et al. Malnutrition-inflammation complex syndrome in dialysis patients: causes and consequences.Am J Kid Dis 2003; 42: 864-881.

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