Advertisement

Insulin Resistance and the Metabolic Syndrome in Kidney Disease (e.g., the Cardiorenal Metabolic Syndrome)

  • Vikram PatneyEmail author
  • Sivakumar Ardhanari
  • Adam Whaley-Connell
Chapter

Abstract

The cardiorenal metabolic syndrome is a collection of metabolic risk factors driven by obesity and insulin resistance that convey an increased risk for cardiovascular and kidney disease. In this context, there has been increasing interest in the impact of insulin resistance and the compensatory hyperinsulinemia on kidney disease, independent to that of the contribution of overt diabetes to the development of kidney disease. It is unknown whether there is a direct causal relationship between insulin resistance and progressive kidney disease or just the presence of known risk factors for the initiation and progression of chronic kidney disease (CKD) (i.e., hypertension and obesity), yet growing evidence supports that obesity and insulin resistance directly contribute to CKD.

Keywords

Insulin resistance Metabolic syndrome Kidney disease Cardiorenal syndrome 

References

  1. 1.
    Sarafadis PA, Nilsson PM. The metabolic syndrome: a glance at its history. J Hypertens. 2006;24(4):621–6.CrossRefGoogle Scholar
  2. 2.
    Hitzenberger K. Uber den Blutdruck bei diabetes mellitus. Wiener Arch Innere Med. 1921;2:461–6.Google Scholar
  3. 3.
    Kylin E. Hypertonie and Zuckerkrankheit. Zentralblatt fur Innere Medizin. 1921;42:873–7.Google Scholar
  4. 4.
    Maranon G. Uber Hypertonie and Zuckerkrankheit. Zentralblatt fur Innere Medizin. 1923;43:169–76.Google Scholar
  5. 5.
    Reaven GM. Role of insulin resistance in human disease. Diabetes. 1988;37:1595–607.PubMedCrossRefGoogle Scholar
  6. 6.
    Facchiini FS, et al. Insulin resistance as a predictor of age-related diseases. J Clin Endocrinol Metab. 2001;86(8):3574–8.CrossRefGoogle Scholar
  7. 7.
    Yip J, Facchini FS, Reaven GM. Resistance to insulin-mediated glucose disposal as a predictor of cardiovascular disease. J Clin Endocrinol Metab. 1998;83(8):2773–6.PubMedCrossRefGoogle Scholar
  8. 8.
    Whaley-Connell A, et al. Overnutrition and the cardiorenal syndrome: use of a rodent model to examine mechanisms. Cardiorenal Med. 2011;1:23–30.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Kurella M, Lo JC, Chertow GM. Metabolic syndrome and the risk for chronic kidney disease among nondiabetic adults. J Am Soc Nephrol. 2005;16(7):2134–40.PubMedCrossRefGoogle Scholar
  10. 10.
    Fox CS, et al. Glycemic status and development of kidney disease: the Framingham heart study. Diabetes Care. 2005;28(10):2436–40.PubMedCrossRefGoogle Scholar
  11. 11.
    Chen J, Muntner P, Hamm LL, et al. The metabolic syndrome and chronic kidney disease in US adults. Ann Intern Med. 2004;28(10):167–74.CrossRefGoogle Scholar
  12. 12.
    Fliser D, Pacini G, Enelleiter R, et al. Insulin resistance and hyperinsulinemia are already present in patients with incipient renal disease. Kidney Int. 1998;53(5):1343–7.PubMedCrossRefGoogle Scholar
  13. 13.
    Alberti KGMM, ZImmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications Part 1: diagnosis and classification of diabetes mellitus provisional report of WHO a consultation. Diabet Med. 1998;15:539–53.PubMedCrossRefGoogle Scholar
  14. 14.
    Balkau B, Charles MA, for the European Group for the Study of Insulin Resistance (EGIR). Comment on the provisional report from the WHO consultation. Diabet Med. 1999;16(5):442–3.PubMedCrossRefGoogle Scholar
  15. 15.
    Cleeman JI, et al. Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III). J Am Med Assoc. 2001;285(19):2486–97.CrossRefGoogle Scholar
  16. 16.
    Alberti K, Zimmet P, Shaw J. The metabolic syndrome- a new worldwide definition. Lancet. 2005;366:1059–61.PubMedCrossRefGoogle Scholar
  17. 17.
    The International Diabetes Federation. The IDF worldwide definition of the metabolic syndrome. The IDF consensus worldwide definition of the Metabolic Syndrome. [Online] 2005. http://www.idf.org/webdata/docs/IDF_Meta_def_final.pdf.
  18. 18.
    Beltran-Sanchez H, et al. Prevalence and trends of metabolic syndrome in the adult U.S. population, 1999-2010. J Am Coll Cardiol. 2013;62(8):697–703.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Gupta A, et al. Prevalence of diabetes, impaired fasting glucose and insulin resistance syndrome in an urban Indian population. Diabetes Res Clin Pract. 2003;61:69–76.PubMedCrossRefGoogle Scholar
  20. 20.
    Li J-B, et al. Metabolic syndrome: prevalence and risk factors in southern China. J Int Med Res. 2010;38:1142–8.PubMedCrossRefGoogle Scholar
  21. 21.
    Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults. JAMA. 2002;287(3):356–9.PubMedCrossRefGoogle Scholar
  22. 22.
    Chen J, Muntner P, Hamm LL, et al. Insulin resistance and risk of chronic kidney disease in nondiabetic US adults. J Am Soc Nephrol. 2003;14(2):469–77.PubMedCrossRefGoogle Scholar
  23. 23.
    Mottillo S, et al. The metabolic syndrome and cardiovascular risk. J Am Coll Cardiol. 2010;56(14):1113–32.PubMedCrossRefGoogle Scholar
  24. 24.
    Wilson PWF, et al. Metabolic syndrome as a precursor of cardiovascular disease and type 2 diabetes mellitus. Circulation. 2005;112:3066–72.PubMedCrossRefGoogle Scholar
  25. 25.
    Hoenher CM, et al. Association of the insulin resistance syndrome and microalbuminuria among nondiabetic Native Americans. The Inter-Tribal Heart Project. J Am Soc Nephrol. 2002;13:1626–34.CrossRefGoogle Scholar
  26. 26.
    Cheng J, et al. The metabolic syndrome and chronic kidney disease in U.S. adults. Ann Intern Med. 2004;140(3):167–74.CrossRefGoogle Scholar
  27. 27.
    Mykannen L, et al. Microalbuminuria is associated with insulin resistance in nondiabetic subjects: the insulin resistance atherosclerosis study. Diabetes. 1998;47(5):793–800.CrossRefGoogle Scholar
  28. 28.
    Hoehner CM, et al. Association of the insulin resistance syndrome and microalbuminuria among nondiabetic Native Americans. The Inter-Tribal Heart Project et al. J Am Soc Nephrol. 2002;13(6):1626–34.PubMedCrossRefGoogle Scholar
  29. 29.
    Palaniappan L, Carnetheon M, Fortmann S. P. Association between microalbuminuria and the metabolic syndrome: NHANES III. Am J Hypertens. 2003;16(11 Pt 1):952–8.PubMedCrossRefGoogle Scholar
  30. 30.
    Fujikawa R, et al. Insulin resistance precedes the appearance of albuminuria in non-diabetic subjects: 6 year follow up study. Diabetes Res Clin Pract. 2001;53(2):99–106.PubMedCrossRefGoogle Scholar
  31. 31.
    Abuaisha B, et al. Relationship of elevated urinary albumin excretion to components of the metabolic syndrome in non-insulin-dependent diabetes mellitus. Diabetes Res Clin Pract. 1998;39(2):93–9.PubMedCrossRefGoogle Scholar
  32. 32.
    Ballantyne CM, et al. Metabolic syndrome risk of cardiovascular disease and diabetes in the ARIC study. Int J Obes. 2008;32(Suppl 2):S21–4.CrossRefGoogle Scholar
  33. 33.
    Wahba IM, Mak RH. Obesity and obesity-initiated metabolic syndrome: mechanistic links to chronic kidney disease. Clin J Am Soc Nephrol. 2007;2(3):550–62.PubMedCrossRefGoogle Scholar
  34. 34.
    Bagby SP. Obesity-initiated metabolic syndrome and the kidney: a recipe for chronic kidney disease. J Am Soc Nephrol. 2004;15(11):2775–91.PubMedCrossRefGoogle Scholar
  35. 35.
    Whaley-Connell A, Johnson MS, Sowers JR. Aldosterone: role in cardiometabolic syndrome and resistant hypertension. Prog Cardiovasc Dis. 2010;52(5):401–9.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Cusumano AM, Bodkin NL, Hansen BC, et al. Glomerular hypertrophy is associated with hyperinsulinemia and precedes overt diabetes in aging rhesus monkeys. Am J Kidney Dis. 2002;40(5):1075–85.PubMedCrossRefGoogle Scholar
  37. 37.
    Shulman GI. Ectopic fat in insulin resistance, dyslipidemia, and cardiometabolic disease. N Engl J Med. 2014;371(12):1131–41.PubMedCrossRefGoogle Scholar
  38. 38.
    Morino K, et al. Regulation of mitochondrial biogenesis by lipoprotein lipase in muscle of insulin-resistant offspring of parents with type 2 diabetes. Diabetes. 2012;61:877–87.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Shulman GI, et al. Mitochondrial dysfunction in the elderly: possible role in insulin resistance. Science. 2003;300:1140–1.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Cohen AJ, McCarthy DM, Stoff JS. Direct hemodynamic effect of insulin in the isolated perfused kidney. Am J Physiol. 1989;257(4 Pt 2):F580–5.PubMedGoogle Scholar
  41. 41.
    Dengel DR, et al. Insulin resistance, elevated glomerular filtration fraction, and renal injury. Hypertension. 1996;28(1):127–32.PubMedCrossRefGoogle Scholar
  42. 42.
    Catalano C, Muscelli E, Quinones Galvan A, et al. Effect of insulin on systemic and renal handling of albumin in nondiabetic and NIDDM subjects. Diabetes. 1997;46(5):868–75.PubMedCrossRefGoogle Scholar
  43. 43.
    McFarlane SI, Banerji M, Sowers JR. Insulin resistance and cardiovascular disease. J Clin Endocrinol Metab. 2001;86(2):713–8.PubMedGoogle Scholar
  44. 44.
    Young BA, Johnson RJ, Alpers CE, et al. Cellular events in the evolution of experimental diabetic nephropathy. Kidney Int. 1995;47(3):935–44.PubMedCrossRefGoogle Scholar
  45. 45.
    Conti FJ, et al. Studies on binding and mitogenic effect of insulin and insulin-like growth factor I in glomerular mesangial cells. Endocrinology. 1988;122(6):2788–95.PubMedCrossRefGoogle Scholar
  46. 46.
    Anderson PW, Zhang XY, Tian J, et al. Insulin and Angiotensin II are additive in stimulating TGF-beta 1 and matrix mRNAs in mesangial cells. Kidney Int. 1996;50(3):745–53.PubMedCrossRefGoogle Scholar
  47. 47.
    Weisberg SP, et al. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest. 2003;112(12):1796–808.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Nonogaki K, et al. Interleukin-6 stimulates hepatic triglyceride secretion in rats. Endocrinology. 1995;136:2143–9.PubMedCrossRefGoogle Scholar
  49. 49.
    Wisse BE. The inflammatory syndrome: the role of adipose tissue cytokines in metabolic disorders linked to obesity. J Am Soc Nephrol. 2004;15:2792–800.PubMedCrossRefGoogle Scholar
  50. 50.
    Flier JS. Obesity wars: molecular progress confronts an expanding epidemic. Cell. 2004;116(2):337–50.PubMedCrossRefGoogle Scholar
  51. 51.
    Lord G. Role of leptin in immunology. Nutr Rev. 2002;60(Suppl):S35–S8.PubMedCrossRefGoogle Scholar
  52. 52.
    Wallace AM, et al. Plasma leptin and the risk of cardiovascular disease in the west of Scotland coronary prevention study (WOSCOPS). Circulation. 2001;104:3052–6.PubMedCrossRefGoogle Scholar
  53. 53.
    Beddhu S, et al. Associations of metabolic syndrome with inflammation in CKD: results from the third National Health and nutrition examination survey (NHANES III). Am J Kidney Dis. 2005;46(4):577–86.PubMedCrossRefGoogle Scholar
  54. 54.
    Maury E, Brichard SM. Adipokine dysregulation, adipose tissue inflammation and metabolic syndrome. Mol Cell Endocrinol. 2010;314:1–16.PubMedCrossRefGoogle Scholar
  55. 55.
    Sweiss N, Sharma K. Adiponectin effects on the kidney. Best Pract Res Clin Endocrinol Metab. 2014;28:71–9.PubMedCrossRefGoogle Scholar
  56. 56.
    Yano Y, Hoshide S, Ishikawa J, et al. Differential impacts of adiponectin on low-grade albuminuria between obese and nonobese individuals without diabetes. J Clin Hypertens. 2007;9(10):775–82.CrossRefGoogle Scholar
  57. 57.
    Sharma K, Ramachandrarao S, Qiu G, et al. Adiponectin regulates albuminuria and podocyte function in mice. J Clin Invest. 2008;118(5):1645–56.PubMedPubMedCentralGoogle Scholar
  58. 58.
    Jia T, et al. The complex role of adiponectin in chronic kidney disease. Biochimie. 2012;94:2150–6.PubMedCrossRefGoogle Scholar
  59. 59.
    Menon V, et al. Adiponectin and mortality in patients with chronic kidney disease. J Am Soc Nephrol. 2006;17:2599–606.PubMedCrossRefGoogle Scholar
  60. 60.
    Paul M, Poyan Mehr A, Kreutz R. Physiology of local renin-angiotensin systems. Physiol Rev. 2006;86(3):747–803.PubMedCrossRefGoogle Scholar
  61. 61.
    Seikaly MG, Arant BS Jr, Seney FD Jr. Endogenous angiotensin concentrations in specific intrarenal fluid compartments of the rat. J Clin Invest. 1990;86(4):1352–7.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Price DA, et al. The paradox of the low-renin state in diabetic nephropathy. J Am Soc Nephrol. 1999;10(11):2382–91.PubMedGoogle Scholar
  63. 63.
    Hall JE, Henegar JR, Dwyer TM, et al. Is obesity a major cause of chronic kidney disease? Adv Ren Replace Ther. 2004;11(1):41–54.PubMedCrossRefGoogle Scholar
  64. 64.
    Ruster C, Wolf G. Renin-angiotensin-aldosterone system and progression of renal disease. J Am Soc Nephrol. 2006;17(11):2985–91.PubMedCrossRefGoogle Scholar
  65. 65.
    Wolf G, Neilson EG. Angiotensin II induces cellular hypertrophy in cultured murine proximal tubular cells. Am J Physiol. 1990;259(5 Pt 2):F768–77.PubMedGoogle Scholar
  66. 66.
    Rodriguez-Vita J, et al. Angiotensin II activates the Smad pathway in vascular smooth muscle cells by a transforming growth factor-beta-independent mechanism. Circulation. 2005;111(19):2509–17.PubMedCrossRefGoogle Scholar
  67. 67.
    Sarzani R, et al. Renin-angiotensin system, natriuretic peptides, obesity, metabolic syndrome, and hypertension: an integrated view in humans. J Hypertens. 2008;26(5):831–43.PubMedCrossRefGoogle Scholar
  68. 68.
    de Kloet AD, Krause EG, Woods SC. The renin angiotensin system and the metabolic syndrome. Physiol Behav. 2010;100(5):525–34.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Putnam K, et al. The renin-angiotensin system: a target of and a contributor to dyslipidemias, altered glucose homeostasis, and hypertension of the metabolic syndrome. Am J Physiol Heart Circ Physiol. 2012;302(6):H1219–30.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Kishi T, Hirooka Y. Sympathoexcitation associated with renin-angiotensin system in metabolic syndrome. Int J Hypertens. 2013;2013:406897.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Kalupahana PS, Moustaid-Moussa N. The renin-angiotensin system: the link between obesity, inflammation and insulin resistance. Obes Rev. 2012;13(2):136–49.PubMedCrossRefGoogle Scholar
  72. 72.
    Skov J, et al. Tissue renin-angiotensin systems: a unifying hypothesis of metabolic disease. Front Endocrinol. 2014;5:23.CrossRefGoogle Scholar
  73. 73.
    Herrera CL, et al. Association of polymorphisms within the renin-angiotensin system with metabolic syndrome in a cohort of Chilean subjects. Arch Endocrinol Metab. 2016;60(3):190–8.PubMedCrossRefGoogle Scholar
  74. 74.
    Singh R, et al. Mechanism of increased angiotensin II levels in glomerular mesangial cells cultured in high glucose. J Am Soc Nephrol. 2003;14(4):873–80.PubMedCrossRefGoogle Scholar
  75. 75.
    Zhang SL, et al. High levels of glucose stimulate angiotensinogen gene expression via the p38 mitogen-activated protein kinase pathway in rat kidney proximal tubular cells. Endocrinology. 2000;141(12):4637–46.PubMedCrossRefGoogle Scholar
  76. 76.
    Peti-Peterdi J. High glucose and renin release: the role of succinate and GPR91. Kidney Int. 2010;78(12):1214–7.PubMedCrossRefGoogle Scholar
  77. 77.
    Singh VP, et al. High glucose induced regulation of intracellular ANG II synthesis and nuclear redistribution in cardiac myocytes. Am J Physiol Heart Circ Physiol. 2007;293(2):H939–48.PubMedCrossRefGoogle Scholar
  78. 78.
    van der Zijl NJ, et al. Valsartan improves {Beta}-cell function and insulin sensitivity in subjects with impaired glucose metabolism: a randomized controlled trial. Diabetes Care. 2011;34(4):845–51.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    The Navigator Study Group. Effect of valsartan on the incidence of diabetes and cardiovascular events. N Engl J Med. 2010;362(16):1477–90.CrossRefGoogle Scholar
  80. 80.
    The Dream trial investigators. Effect of ramipril on the incidence of diabetes. N Engl J Med. 2006;355(15):1551–62.CrossRefGoogle Scholar
  81. 81.
    Scheen AJ. Renin-angiotensin system inhibition prevents type 2 diabetes mellitus. Part 1. A meta-analysis of randomised clinical trials. Diabetes Metab. 2004;30(6):487–96.PubMedCrossRefGoogle Scholar
  82. 82.
    Yvan-Charvet L, Quignard-Boulange A. Role of adipose tissue with renin-angiotensin system and inflammatory diseases associated with obesity. Kidney Int. 2011;79(2):162–8.PubMedCrossRefGoogle Scholar
  83. 83.
    Engeli S, et al. The adipose tissue renin-angiotensin system: role in the metabolic syndrome? Int J Biochem Cell Biol. 2003;35(6):807–25.PubMedCrossRefGoogle Scholar
  84. 84.
    Yasue S, et al. Adipose tissue-specific regulation of angiotensinogen in obese humans and mice: impact of nutritional status and adipocyte hypertrophy. Am J Hypertens. 2010;23(4):425–31.PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Massiera F, et al. Adipose angiotensinogen is involved in adipose tissue growth and blood pressure regulation. FASEB J. 2001;15(14):2727–9.PubMedCrossRefGoogle Scholar
  86. 86.
    Gorzelniak K, et al. Hormonal regulation of the human adipose-tissue angiotensin system: relationship to obesity and hypertension. J Hypertens. 2002;20(5):965–73.PubMedCrossRefGoogle Scholar
  87. 87.
    Engeli S, et al. Weight loss and the renin-angiotensin-aldosterone system. Hypertension. 2005;45(3):356–62.PubMedCrossRefGoogle Scholar
  88. 88.
    Cassis S, et al. Angiotensin II regulates oxygen consumption. Am J Physiol Regul Integr Comp Physiol. 2002;282(2):R445–53.PubMedCrossRefGoogle Scholar
  89. 89.
    Fogari R, et al. Comparison of the effects of valsartan and Felodipine on plasma leptin and insulin sensitivity in hypertensive obese patients. Hypertens Res. 2005;28(3):209–14.PubMedCrossRefGoogle Scholar
  90. 90.
    Corson MA, et al. Phosphorylation of endothelial nitric oxide synthase in response to fluid shear stress. Circ Res. 1996;79(5):984–91.PubMedCrossRefGoogle Scholar
  91. 91.
    Govers R, Rabelink TJ. Cellular regulation of endothelial nitric oxide synthase. Am J Physiol Renal Physiol. 2001;280(2):F193–206.PubMedCrossRefGoogle Scholar
  92. 92.
    Deanfield JE, Halcox JP, Rabelink TJ. Endothelial function and dysfunction: testing and clinical relevance. Circulation. 2007;115(10):1285–95.PubMedCrossRefGoogle Scholar
  93. 93.
    Tziomalos K, et al. Endothelial dysfunction in metabolic syndrome: prevalence, pathogenesis, and management. Nutr Metab Cardiovasc Dis. 2010;20(2):140–6.PubMedCrossRefGoogle Scholar
  94. 94.
    Barac A, Campia U, Panza JA. Methods for evaluating endothelial function in humans. Hypertension. 2007;49(4):748–60.PubMedCrossRefGoogle Scholar
  95. 95.
    Festa A, et al. Relative contribution of insulin and its precursors to fibrinogen and PAI-1 in a study (IRAS). Arterioscler Thromb Vasc Biol. 1999;19(3):562–8.PubMedCrossRefGoogle Scholar
  96. 96.
    Potter van loon BJ, et al. The cardiovascular risk factor plasminogen activator inhibitor type 1 is related to insulin resistance. Metabolism. 1993;42(8):945–9.PubMedCrossRefGoogle Scholar
  97. 97.
    Bahia L, et al. Relationship between adipokines, inflammation, and vascular reactivity in lean controls and obese subjects with metabolic syndrome. Clinics (Sao Paulo). 2006;61(5):433–40.CrossRefGoogle Scholar
  98. 98.
    Benjamin EJ, et al. Clinical correlates and heritability of flow-mediated dilation in the community: the Framingham Heart Study. Circulation. 2004;109(5):613–9.PubMedCrossRefGoogle Scholar
  99. 99.
    McVeigh GE, et al. Impaired endothelium-dependent and independent vasodilation in patients with type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia. 1992;35(8):771–6.PubMedGoogle Scholar
  100. 100.
    Panza JA, et al. Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension. N Engl J Med. 1990;323(1):22–7.PubMedCrossRefGoogle Scholar
  101. 101.
    Williams SB, et al. Impaired nitric-oxide mediated vasodilation in patients with non-insulin dependent diabetes mellitus. J Am College Cardiol. 1996;27(3):567–74.CrossRefGoogle Scholar
  102. 102.
    Hamburg NM, et al. Metabolic syndrome, insulin resistance, and brachial artery vasodilator function in Framingham offspring participants without clinical evidence of cardiovascular disease. Am J Cardiol. 2008;101(1):82–8.PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Lteif AA, Han K, Mather KJ. Obesity, insulin resistance and the metabolic syndrome: determinants of endothelial dysfunction in whites and blacks. Circulation. 2005;112(1):32–8.PubMedCrossRefGoogle Scholar
  104. 104.
    Blanco-Colio LM, et al. Elevated ICAM-1, MCP-1 plasma levels in subjects at high cardiovascular risk are diminished by atorvastatin treatment. Atorvastatin on inflammatory markers study: a subsidy of achieve targets fast with atorvastatin stratified titration. Am Heart J. 2007;153(5):881–8.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Vikram Patney
    • 1
    Email author
  • Sivakumar Ardhanari
    • 1
    • 2
  • Adam Whaley-Connell
    • 1
    • 2
    • 3
  1. 1.Division of Nephrology and Hypertension, Department of MedicineUniversity of Missouri-Columbia School of MedicineColumbiaUSA
  2. 2.Division of Cardiovascular MedicineUniversity of Missouri-Columbia School of MedicineColumbiaUSA
  3. 3.Research Service, University of Missouri School of Medicine, Harry S. Truman VA Medical CenterColumbiaUSA

Personalised recommendations