Obesity, anemia, and cardiovascular risk in patients with chronic kidney disease: Overview and pathophysiologic insights

  • Andrew C. Miller
  • Brandon Smaglo
  • Samy I. McFarlane
Article

Abstract

Obesity is a well-established risk factor for cardiovascular disease (CVD) and is increasingly being recognized as a risk factor for chronic kidney disease (CKD). Anemia that is associated with rapid CKD progression is also associated with increased CVD risk. The common soil hypothesis linking obesity, anemia, CKD, and CVD includes increased inflammation and oxidative stress. We present an overview of CKD and CVD risk associated with obesity and anemia highlighting the pathogenetic pathways linking these rapidly growing disorders. We also discuss the therapeutic strategies for obesity reduction and anemia treatment and their impact on CVD and CKD risk, highlighting the contemporary issues and questions raised by recent clinical trials.

References and Recommended Reading

  1. 1.
    Coresh J, Selvin E, Stevens LA, et al.: Prevalence of chronic kidney disease in the United States. JAMA 2007, 298:2038–2047.PubMedCrossRefGoogle Scholar
  2. 2.
    McCullough PA, Li S, Jurkovitz CT, et al.: Chronic kidney disease, prevalence of premature cardiovascular disease, and relationship to short-term mortality. Am Heart J 2008, 156:277–283.PubMedCrossRefGoogle Scholar
  3. 3.
    Minami J, Ishimitsu T, Sudo Y, Matsuoka H: Chronic kidney disease (CKD) as an independent risk factor for cardiovascular disease (CVD) [in Japanese]. Nippon Rinsho 2008, 66:1657–1663.PubMedGoogle Scholar
  4. 4.
    Ronco C, House AA, Haapio M: Cardiorenal syndrome: refining the definition of a complex symbiosis gone wrong. Intensive Care Med 2008, 34:957–962.PubMedCrossRefGoogle Scholar
  5. 5.
    Whaley-Connell AT, Sowers JR, Stevens LA, et al.: CKD in the United States: Kidney Early Evaluation Program (KEEP) and National Health and Nutrition Examination Survey (NHANES) 1999–2004. Am J Kidney Dis 2008, 51:S13–S20.PubMedCrossRefGoogle Scholar
  6. 6.
    McFarlane SI, Chen SC, Whaley-Connell AT, et al.: Prevalence and associations of anemia of CKD: Kidney Early Evaluation Program (KEEP) and National Health and Nutrition Examination Survey (NHANES) 1999–2004. Am J Kidney Dis 2008, 51:S46–S55.PubMedCrossRefGoogle Scholar
  7. 7.
    McFarlane SI, Salifu MO, Makaryus J, Sowers JR: Anemia and cardiovascular disease in diabetic nephropathy. Curr Diab Rep 2006, 6:213–218.PubMedCrossRefGoogle Scholar
  8. 8.
    Axelsson J: Obesity in chronic kidney disease: good or bad? Blood Purif 2008, 26:23–29.PubMedCrossRefGoogle Scholar
  9. 9.
    Iseki K, Kohagura K: Anemia as a risk factor for chronic kidney disease. Kidney Int Suppl 2007, Nov:S4–S9.Google Scholar
  10. 10.
    Kramer H, Luke A: Obesity and kidney disease: a big dilemma. Curr Opin Nephrol Hypertens 2007, 16:237–241.PubMedCrossRefGoogle Scholar
  11. 11.
    Smith SC Jr: Multiple risk factors for cardiovascular disease and diabetes mellitus. Am J Med 2007, 120:S3–S11.PubMedCrossRefGoogle Scholar
  12. 12.
    Tsuruya K, Hirakata H: Anemia as a risk factor for CKD and CVD [in Japanese]. Nippon Rinsho 2008, 66:1786–1793.PubMedGoogle Scholar
  13. 13.
    McFarlane SI, Banerji M, Sowers JR: Insulin resistance and cardiovascular disease. J Clin Endocrinol Metab 2001, 86:713–718.PubMedCrossRefGoogle Scholar
  14. 14.
    Meigs JB, D’Agostino RB Sr, Wilson PW, et al.: Risk variable clustering in the insulin resistance syndrome. The Framingham Offspring Study. Diabetes 1997, 46:1594–1600.PubMedCrossRefGoogle Scholar
  15. 15.
    Lamarche B, Despres JP, Moorjani S, et al.: Triglycerides and HDL-cholesterol as risk factors for ischemic heart disease. Results from the Quebec cardiovascular study. Atherosclerosis 1996, 119:235–245.PubMedCrossRefGoogle Scholar
  16. 16.
    Lamarche B, Lemieux S, Dagenais GR, Despres JP: Visceral obesity and the risk of ischaemic heart disease: insights from the Quebec Cardiovascular Study. Growth Horm IGF Res 1998, 8(Suppl B):1–8.PubMedCrossRefGoogle Scholar
  17. 17.
    Lamarche B, Moorjani S, Cantin B, et al.: Cardiovascular study in Quebec: importance of apolipoprotein B and insulinemia in the risk evaluation for myocardial ischemia [in French]. Union Med Can 1995, 124:17–21.PubMedGoogle Scholar
  18. 18.
    El-Atat FA, Stas SN, McFarlane SI, Sowers JR: The relationship between hyperinsulinemia, hypertension and progressive renal disease. J Am Soc Nephrol 2004, 15:2816–2827.PubMedCrossRefGoogle Scholar
  19. 19.
    Bachorzewska-Gajewska H, Malyszko J, Poniatowski B, et al.: Obesity as a risk factor of chronic kidney disease in patients undergoing primary angioplasty [in Polish]. Pol Arch Med Wewn 2006, 116:916–923.PubMedGoogle Scholar
  20. 20.
    Cases A: New cardiovascular risk factors and chronic kidney disease. Hypertrophy of the left ventricle. Atrial fibrillation. Smoking. Obesity. Emerging cardiovascular risk factors: homocysteine, reactive C protein. Fibrinogen [in Spanish]. Nefrologia 2004, 24(Suppl):62–72, 187–235.PubMedGoogle Scholar
  21. 21.
    Wahba IM, Mak RH: Obesity and obesity-initiated metabolic syndrome: mechanistic links to chronic kidney disease. Clin J Am Soc Nephrol 2007, 2:550–562.PubMedCrossRefGoogle Scholar
  22. 22.
    Whaley-Connell A, Pavey BS, Afroze A, Bakris GL: Obesity and insulin resistance as risk factors for chronic kidney disease. J Cardiometab Syndr 2006, 1:209–214; quiz 215–206.PubMedCrossRefGoogle Scholar
  23. 23.
    Hsu CY, McCulloch CE, Iribarren C, et al.: Body mass index and risk for end-stage renal disease. Ann Intern Med 2006, 144:21–28.PubMedGoogle Scholar
  24. 24.
    Axelsson J, Qureshi AR, Heimburger O, et al.: Body fat mass and serum leptin levels influence epoetin sensitivity in patients with ESRD. Am J Kidney Dis 2005, 46:628–634.PubMedCrossRefGoogle Scholar
  25. 25.
    Naugler WE, Karin M: The wolf in sheep’s clothing: the role of interleukin-6 in immunity, inflammation and cancer. Trends Mol Med 2008, 14:109–119.PubMedCrossRefGoogle Scholar
  26. 26.
    Pachaly MA, do Nascimento MM, Suliman ME, et al.: Interleukin-6 is a better predictor of mortality as compared to C-reactive protein, homocysteine, pentosidine and advanced oxidation protein products in hemodialysis patients. Blood Purif 2008, 26:204–210.PubMedCrossRefGoogle Scholar
  27. 27.
    Carter KW, Hung J, Powell BL, et al.: Association of interleukin-1 gene polymorphisms with central obesity and metabolic syndrome in a coronary heart disease population. Hum Genet 2008, 124:199–206.PubMedCrossRefGoogle Scholar
  28. 28.
    Mito N, Hiyoshi T, Hosoda T, et al.: Effect of obesity and insulin on immunity in non-insulin-dependent diabetes mellitus. Eur J Clin Nutr 2002, 56:347–351.PubMedCrossRefGoogle Scholar
  29. 29.
    Kammerer J, Ratican M, Elzein H, Mapes D: Anemia in CKD: prevalence, diagnosis, and treatment. Case study of the anemic patient. Nephrol Nurs J 2002, 29:371–374.PubMedGoogle Scholar
  30. 30.
    Robinson BE: Epidemiology of chronic kidney disease and anemia. J Am Med Dir Assoc 2006, 7:S3–S6; quiz S17–S21.PubMedCrossRefGoogle Scholar
  31. 31.
    Johnson ES, Thorp ML, Platt RW, Smith DH: Predicting the risk of dialysis and transplant among patients with CKD: a retrospective cohort study. Am J Kidney Dis 2008, 52:653–660.PubMedCrossRefGoogle Scholar
  32. 32.
    Levin A: Identification of patients and risk factors in chronic kidney disease—evaluating risk factors and therapeutic strategies. Nephrol Dial Transplant 2002, 16(Suppl 7):57–60.Google Scholar
  33. 33.
    Collins AJ, Li S, St Peter W, et al.: Death, hospitalization, and economic associations among incident hemodialysis patients with hematocrit values of 36 to 39%. J Am Soc Nephrol 2001, 12:2465–2473.PubMedGoogle Scholar
  34. 34.
    Foley RN, Parfrey PS, Harnett JD, et al.: The impact of anemia on cardiomyopathy, morbidity, and and mortality in end-stage renal disease. Am J Kidney Dis 1996, 28:53–61.PubMedCrossRefGoogle Scholar
  35. 35.
    Levin A, Singer J, Thompson CR, et al.: Prevalent left ventricular hypertrophy in the predialysis population: identifying opportunities for intervention. Am J Kidney Dis 1996, 27:347–354.PubMedCrossRefGoogle Scholar
  36. 36.
    Hayashi T, Suzuki A, Shoji T, et al.: Cardiovascular effect of normalizing the hematocrit level during erythropoietin therapy in predialysis patients with chronic renal failure. Am J Kidney Dis 2000, 35:250–256.PubMedCrossRefGoogle Scholar
  37. 37.
    Portoles J, Torralbo A, Martin P, et al.: Cardiovascular effects of recombinant human erythropoietin in predialysis patients. Am J Kidney Dis 1997, 29:541–548.PubMedCrossRefGoogle Scholar
  38. 38.
    London GM, Pannier B, Guerin AP, et al.: Alterations of left ventricular hypertrophy in and survival of patients receiving hemodialysis: follow-up of an interventional study. J Am Soc Nephrol 2001, 12:2759–2767.PubMedGoogle Scholar
  39. 39.
    Thomas MC, MacIsaac RJ, Tsalamandris C, et al.: Unrecognized anemia in patients with diabetes: a cross-sectional survey. Diabetes Care 2003, 26:1164–1169.PubMedCrossRefGoogle Scholar
  40. 40.
    Horl WH, Macdougall IC, Rossert J, et al.: Predialysis Survey on Anemia Management: patient referral. Am J Kidney Dis 2003, 41:49–61.PubMedCrossRefGoogle Scholar
  41. 41.
    Voulgari PV, Kolios G, Papadopoulos GK, et al.: Role of cytokines in the pathogenesis of anemia of chronic disease in rheumatoid arthritis. Clin Immunol 1999, 92:153–160.PubMedCrossRefGoogle Scholar
  42. 42.
    Bosman DR, Winkler AS, Marsden JT, et al.: Anemia with erythropoietin deficiency occurs early in diabetic nephropathy. Diabetes Care 2001, 24:495–499.PubMedCrossRefGoogle Scholar
  43. 43.
    Stenvinkel P, Barany P: Anaemia, rHuEPO resistance, and cardiovascular disease in end-stage renal failure; links to inflammation and oxidative stress. Nephrol Dial Transplant 2002, 17(Suppl 5):32–37.PubMedCrossRefGoogle Scholar
  44. 44.
    Krajewski J, Batmunkh C, Jelkmann W, Hellwig-Burgel T: Interleukin-1beta inhibits the hypoxic inducibility of the erythropoietin enhancer by suppressing hepatocyte nuclear factor-4alpha. Cell Mol Life Sci 2007, 64:989–998.PubMedCrossRefGoogle Scholar
  45. 45.
    Imagawa S, Nakano Y, Obara N, et al.: A GATA-specific inhibitor (K-7174) rescues anemia induced by IL-1beta, TNF-alpha, or L-NMMA. FASEB J 2003, 17:1742–1744.PubMedGoogle Scholar
  46. 46.
    Sela S, Shurtz-Swirski R, Sharon R, et al.: The polymorphonuclear leukocyte—a new target for erythropoietin. Nephron 2001, 88:205–210.PubMedCrossRefGoogle Scholar
  47. 47.
    Eftimovska N, Stojceva-Taneva O, Polenakovic M: Slow progression of chronic kidney disease and what it is associated with. Prilozi 2008, 29:153–165.PubMedGoogle Scholar
  48. 48.
    Shah S, Iqbal M, Karam J, et al.: Oxidative stress, glucose metabolism, and the prevention of type 2 diabetes: pathophysiological insights. Antioxid Redox Signal 2007, 9:911–929.PubMedCrossRefGoogle Scholar
  49. 49.
    Akimoto T, Kusano E, Inaba T, et al.: Erythropoietin regulates vascular smooth muscle cell apoptosis by a phosphatidylinositol 3 kinase-dependent pathway. Kidney Int 2000, 58:269–282.PubMedCrossRefGoogle Scholar
  50. 50.
    Vaziri ND: Anemia and anemia correction: surrogate markers or causes of morbidity in chronic kidney disease? Nat Clin Pract Nephrol 2008, 4:436–445.PubMedCrossRefGoogle Scholar
  51. 51.
    Singh AK, Szczech L, Tang KL, et al.: Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med 2006, 355:2085–2098.PubMedCrossRefGoogle Scholar
  52. 52.
    Drueke TB, Locatelli F, Clyne N, et al.: Normalization of hemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med 2006, 355:2071–2084.PubMedCrossRefGoogle Scholar
  53. 53.
    KDOQI Clinical Practice Guideline and Clinical Practice Recommendations for anemia in chronic kidney disease: 2007 update of hemoglobin target. Am J Kidney Dis 2007, 50:471–530.Google Scholar
  54. 54.
    Bagg W, Whalley GA, Doughty RN: Mechanisms of benefit of sustained weight reduction in morbid obesity: beyond reduction in conventional cardiovascular risk factors. J Hypertens 2007, 25:295–297.PubMedCrossRefGoogle Scholar
  55. 55.
    Pfohl M, Luft D, Blomberg I, Schmulling RM: Long-term changes of body weight and cardiovascular risk factors after weight reduction with group therapy and dexfenfluramine. Int J Obes Relat Metab Disord 1994, 18:391–395.PubMedGoogle Scholar

Copyright information

© Current Medicine Group, LLC 2009

Authors and Affiliations

  • Andrew C. Miller
  • Brandon Smaglo
  • Samy I. McFarlane
    • 1
  1. 1.Division of Endocrinology, Department of Medicine, College of MedicineState University of New York-Downstate Medical CenterBrooklynUSA

Personalised recommendations