Chronic Kidney Disease and Cardiovascular Disease: Is there Any Relationship?

Author(s): Natalia G. Vallianou*, Shah Mitesh, Agathoniki Gkogkou, Eleni Geladari.

Journal Name: Current Cardiology Reviews

Volume 15 , Issue 1 , 2019

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Graphical Abstract:


Introduction: Chronic Kidney Disease is a growing health burden world wide. Traditional and mutual risk factors between CVD and CKD are age, hypertension, diabetes mellitus, dyslipidemia, tobacco use, family history and male gender. In this review, we will focus on whether or not early CKD is an important risk factor for the presence, severity and progression of CVD. Specifically, we will examine both traditional and novel risk factors of both CKD and CVD and how they relate to each other.

Conclusion: We will also assess if early treatment of CKD, intensive compared to standard, has an important effect on the halt of the development of CKD as well as CVD. Insights into the pathogenesis and early recognition of CKD as well as the importance of novel kidney biomarkers will be pointed out. Also, common pathogenetic mechanisms between CKD and CVD will be discussed.

Keywords: CKD, CVD, pathogenesis, early detection, kidney biomarkers, United States.

Sarnak MJ, Levey AS, Schoolwerth AC, et al. Kidney disease as a risk factor for development of cardiovascular disease. A Statement From the American Heart Association Councils on kidney in cardiovascular disease, high blood pressure research, clinical cardiology, and epidemiology and prevention. Circulation 2003; 108: 2154-69.
Eknoyan G. Chronic kidney disease definition and classification: The quest for refinements. Kidney Int 2007; 72: 1183-5.
National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: Evaluation, classification and stratification. Am J Kidney Dis 2002; 39(2)(Suppl. 1): S1-S266.
Stenvinkel P. Chronic kidney disease: A public health priority and harbinger of premature cardiovascular disease. J Intern Med 2010; 268(5): 456-67.
Centers for Disease Control and Prevention Age-adjusted prevalence of CKD Stages 1-4 by Gender 1999-2012. Chronic Kidney Disease (CKD) Surveillance Project website. Available at: . External Link Disclaimer. Accessed on: December 6, 2016.
Briasoulis A, Bakris GL. Chronic kidney disease as a coronary artery disease risk equivalent. Curr Cardiol Rep 2013; 15(3): 340.
Husain-Syed F, McCullough PA, Birk HW, et al. Cardio-Pulmonary-renal interactions: A multidisciplinary approach. J Am Coll Cardiol 2015; 65(22): 2433-48.
Centers for Disease Control and Prevention National Center for Health Statistics. “Leading Causes of Death: Deaths: Final Data for 2013, Table 10.” Available at: . leading-causes-of-death.htm Accessed on: September 4, 2015.
Perk J, De Backer G, Gohlke H, et al. European Association for Cardiovascular Prevention & Rehabilitation (EACPR); ESC Committee for Practice Guidelines (CPG). 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 (constituted by representatives of nine societies and by invited experts). Eur Heart J 2012; 33(17): 1635-701.
Manjunath G, Tighiouart H, Ibrahim H, et al. Level of kidney function as a risk factor for atherosclerotic cardiovascular outcomes in the community. J Am Coll Cardiol 2003; 41: 47-55.
Menon V, Gul A, Sarnak MJ. Cardiovascular risk factors in chronic kidney disease. Kidney Int 2005; 68(4): 1413-8.
Subbiah AK, Chhabra YK, Mahajan S. Cardiovascular disease in patients with chronic kidney disease: A neglected subgroup. Heart Asia 2016; 8: 56-61.
Keith DS, Nichols GA, Gullion CM, Brown JB, Smith DH. Longitudinal follow-up and outcomes among a population with chronic kidney disease in a large managed care organization. Arch Intern Med 2004; 164(6): 659-63.
Daly C. Is early chronic kidney disease an important risk factor for cardiovascular disease? A background paper prepared for the UK Consensus Conference on early chronic kidney disease. Nephrol Dial Transplant 2007; 22(Suppl. 9): ix19-25.
Archibald G, Bartlett W, Brown A, et al. UK Consensus Conference on early chronic kidney disease. Nephrol Dial Transplant 2007; 22(Suppl. 9): ix4-5.
Varma PP, Raman DK, Ramakrishnan TS. Pragnya Singh. Prevalence of early stages of chronic kidney disease in healthy army personnel. Med J Armed Forces 2011; 67: 9-14.
Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: A new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 1999; 130: 461-70.
Levey AS, Eckardt KU, Tsukamoto Y, et al. Definition and classification of chronic kidney disease: A position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2005; 67: 2089-100.
Culleton BF, Larson MG, Parfrey PS, Kannel WB, Levy D. Proteinuria as a risk factor for cardiovascular disease and mortality in older people: A prospective study. Am J Med 2000; 109: 1-8.
Grimm RH Jr, Svendsen KH, Kasiske B, Keane WF, Wahi MM. Proteinuria is a risk factor for mortality over 10 years of follow-up. MRFIT Research Group. Multiple risk factor intervention trial. Kidney Int 1997; 63: S10-4.
American Diabetes Association. Standards of medical care in diabetes-2018. Abridged for primary care providers. Diabetes Care 2018; 41(Suppl. 1): S1-S59.
Dell’Omo G, Penno G, Giorgi D, Mariani M, Pedrinelli R. Association between high-normal albuminuria and risk factors for cardiovascular and renal disease in essential hypertensive men. Am J Kidney Dis 2002; 40: 1-8.
Orth SR, Stein I, Hallan SI. Smoking: A risk factor for progression of chronic kidney disease and for cardiovascular morbidity and mortality in renal patients-absence of evidence or evidence of absence? Clin J Am Soc Nephrol 2008; 3(1): 1-8.
Jager A, Kostense PJ, Ruhe HG, et al. Microalbuminuria and peripheral arterial disease are independent predictors of cardiovascular and all-cause mortality, especially among hypertensive subjects: Five-year follow-up of the Hoorn Study. Arterioscler Thromb Vasc Biol 1999; 19: 617-24.
Diercks GF, Hillege HL, van Boven A. Relation between albumin in the urine and electrocardiographic markers of myocardial ischemia in patients without diabetes mellitus. Am J Cardiol 2001; 88: 771-4.
Wachtell K, Olsen MH, Dahlof B, et al. Microalbuminuria in hypertensive patients with electrocardiographic left ventricular hypertrophy: The LIFE study. J Hypertens 2002; 20: 405-12.
Smink PA, Lambers Heerspink HJ, Gansevoort RT, et al. Albuminuria, estimated GFR, traditional risk factors, and incident cardiovascular disease: The PREVEND (Prevention of Renal and Vascular Endstage Disease) study. Am J Kidney Dis 2012; 60(5): 804-11.
Klausen K, Borch-Johnsen K, Feldt-Rasmussen B, et al. Very low levels of microalbuminuria are associated with increased risk of coronary heart disease and death independently of renal function, hypertension, and diabetes. Circulation 2004; 110: 32-5.
Spoelstra-de Man AME, Brouwer TB, Stehouwer CDA, Smulders YM. Rapid progression of albumin excretion is an independent predictor of cardiovascular mortality in patients with type 2 diabetes and microalbuminuria. Diabetes Care 2001; 24: 2097-101.
Yuyun MF, Dinneen SF, Edwards OM, Wood E, Wareham NJ. Absolute level and rate of change of albuminuria over 1 year independently predict mortality and cardiovascular events in patients with diabetic nephropathy. Diabet Med 2003; 20: 277-82.
Ibsen H, Olsen MH, Wachtell K, et al. Reduction in albuminuria translates to reduction in cardiovascular events in hypertensive patients: Losartan Intervention for Endpoint Reduction in Hypertension Study. Hypertension 2005; 45: 198-202.
Matsushita K, van der Velde M, Astor BC, et al. Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality: A collaborative meta-analysis of general population cohorts. Lancet 2010; 375(9731): 2073-81.
Stehouwer CDA, Smulders YM. Microalbuminuria and risk for cardiovascular disease: Analysis of potential mechanisms. J Am Soc Nephrol 2006; 17: 2106-11.
Paisley KE, Beaman M, Tooke JE, Vidya Mohamed-Ali V, Lowe GDO, Shore AC. Endothelial dysfunction and inflammation in asymptomatic proteinuria. Kidney Int 2003; 63: 624-33.
Henry RMA, Ferreira I, Kostense PJ, et al. Type 2 diabetes is associated with impaired endothelium-dependent, flow-mediated dilation, but impaired glucose metabolism is not. The Hoorn Study. Atherosclerosis 2004; 174: 49-56.
Nieuwdorp M, Meuwese MC, Vink H, Hoekstra JB, Kastelein JJP, Stroes ES. The endothelial glycocalix: A potential barrier between health and vascular disease. Curr Opin Lipidol 2005; 16: 507-11.
Heart Outcomes Prevention Evaluation Study Investigators. Yusuf S, Dagenais G, Pogue J, Bosch J, Sleight P. Vitamin E supplementation and cardiovascular events in high-risk patients. N Engl J Med 2000; 342(3): 154-60.
Eidelman RS, Hollar D, Hebert PR, Lamas GA, Hennekens CH. Randomized trials of vitamin E in the treatment and prevention of cardiovascular disease. Arch Intern Med 2004; 164(14): 1552-6.
Subbiah AK, Chhabra YK, Sandeep Mahajan S. Cardiovascular disease in patients with chronic kidney disease: A neglected subgroup. Heart Asia 2016; 8(2): 56-61.
Jager A, van Hinsbergh VW, Kostense PJ, et al. C-reactive protein and soluble vascular cell adhesion molecule-1 are associated with elevated urinary albumin excretion but do not explain its link with cardiovascular risk. Arterioscler Thromb Vasc Biol 2002; 22: 593-8.
Schram MT, Chaturvedi N, Schalkwijk CG, Fuller JH, Stehouwer CDA. the EURODIAB Prospective Complications Study Group. Markers of inflammation are cross-sectionally associated with microvascular complications and cardiovascular disease in type 1 diabetes: The EURODIAB Prospective Complications Study. Diabetologia 2005; 48: 370-8.
Miller WG, Bruns DE, Hortin GL, et al. Current issues in measurement and reporting of urinary albumin excretion. Clin Chem 2009; 55: 24-38.
Uchida HA, Norii H, Hanayama Y, et al. Steroid pulse therapy impaired endothelial function while increasing plasma high molecule adiponectin concentration in patients with IgA nephropathy. Nephrol Dial Transplant 2006; 21: 3475-80.
Schwedhelm E, Böger RH. The role of asymmetric and symmetric dimethylarginines in renal disease. Nat Rev Nephrol 2011; 7(5): 275-85.
Kielstein JT, Frölich JC, Haller H, Ritz E, Fliser D. Marked increase of asymmetric dimethylarginine in patients with incipient primary chronic renal disease. J Am Soc Nephrol 2003; 13: 170-6.
Schepers E, Glorieux G, Dhondt A, Leybaert L, Vanholder R. Role of symmetric dimethylarginine in vascular damage by increasing ROS via store-operated calcium influx in monocytes. Nephrol Dial Transplant 2009; 24: 1429-35.
Böger RH, Darius H, Atzler D, et al. Asymmetric dimethylarginine as independent risk marker for mortality in ambulatory patients with peripheral arterial disease. J Intern Med 2011; 269: 349-61.
Schulze F, Wesemann R, Schwedhelm E, et al. Symmetric dimethylarginine predicts all-cause mortality following ischemic stroke. Atherosclerosis 2010; 208: 518-23.
Puschett JB, Agunanne E, Uddin MN. Emerging role of the bufadienolides in cardiovascular and kidney diseases. Am J Kidney Dis 2010; 56: 359-70.
Bagrov AY, Agalakova NI, Kashkin VA, Fedorova OV. Endogenous cardiotonic steroids and differential patterns of sodium pump inhibition in NaCl-loaded salt-sensitive and normotensive rats. Am J Hypertens 2009; 22(5): 559-63.
Meneton P, Jeunemaitre X, de Wardener HE, MacGregor GA. Links between dietary salt intake, renal salt handling, blood pressure, and cardiovascular diseases. Physiol Rev 2005; 85: 679-715.
Elkareh J, Periyasamy SM, Shidyak A, et al. Marinobufagenin induces increases in procollagen expression in a process involving protein kinase C and Fli-1: implications for uremic cardiomyopathy. Am J Physiol Renal Physiol 2009; 296: F1219-26.
Fedorova LV, Raju V, El-Okdi N. The cardiotonic steroid hormone marinobufagenin induces renal fibrosis: Implication of epithelial-to-mesenchymal transition. Am J Physiol Renal Physiol 2009; 296: F922-34.
Cerasola G, Nardi E, Palermo A, Mulè G, Cottone S. Epidemiology and pathophysiology of left ventricular abnormalities in chronic kidney disease: A review. J Nephrol 2011; 24: 1.
Nardi E, Palermo A, Mulè G, Cusimano P, Cottone S, Cerasola G. Left ventricular hypertrophy and geometry in hypertensive patients with chronic kidney disease. J Hypertens 2009; 27: 633-41.
Cerasola G, Nardi E, Mulè G. Left ventricular mass in hypertensive patients with mild-to-moderate reduction of renal function. Nephrology 2010; 15: 203-10.
Weiner DE, Tighiouart H, Vlagopoulos PT, et al. Effects of anemia and left ventricular hypertrophy on cardiovascular disease in patients with chronic kidney disease. J Am Soc Nephrol 2005; 16(6): 1803-10.
Gutierrez O, Isakova T, Rhee E. Fibroblast growth factor-23 mitigates hyperphosphatemia but accentuates calcitriol deficiency in chronic kidney disease. J Am Soc Nephrol 2005; 16: 2205-15.
Gutiérrez OM, Januzzi JL, Isakova T. Fibroblast growth factor-23 and left ventricular hypertrophy in chronic kidney disease. Circulation 2009; 119: 2545-52.
Mirza M, Larsson A, Melhus H, Lind L, Larsson T. Serum intact FGF-23 associate with left ventricular mass, hypertrophy and geometry in an elderly population. Atherosclerosis 2009; 207: 546-51.
Aoki J, Ikari Y, Nakajima H. Clinical and pathologic characteristics of dilated cardiomyopathy in hemodialysis patients. Kidney Int 2005; 67: 333-40.
Astor BC, Shafi T, Hoogeveen RC, et al. Novel markers of kidney function as predictors of esrd, cardiovascular disease, and mortality in the general population. Am J Kidney Dis 2012; 59: 653-62.
ACCORD Study Group. Gerstein HC, Miller ME, et al Long-term effects of intensive glucose lowering on cardiovascular outcomes. N Engl J Med 2011; 364(9): 818-28.
Papademetriou V, Zaheer M, Doumas M, et al. Cardiovascular outcomes in action to control cardiovascular risk in diabetes: Impact of blood pressure level and presence of kidney disease. Am J Nephrol 2016; 43(4): 271-80.
ORIGIN Trial Investigators. Gerstein HC, Bosch J, et al. Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med 2012; 367(4): 319-28.
Berlowitz DR, Foy CG, Kazis LE, et al. Effect of intensive blood-pressure treatment on patient-reported outcomes. N Engl J Med 2017; 377(8): 733-44.
Jellinger PS, Handelsman Y, Rosenblit PD, et al. American association of clinical endocrinologists and American college of endocrinology guidelines for management of dyslipidemia and prevention of cardiovascular disease. Endocr Pract 2017; 23(Suppl. 2): 1-87.
Papademetriou V, Lovato L, Tsioufis C, et al. Effects of high density lipoprotein raising therapies on cardiovascular outcomes in patients with type 2 diabetes mellitus, with or without renal impairment: The action to control cardiovascular risk in diabetes study. Am J Nephrol 2017; 45(2): 136-45.
Wanner C, Inzucchi SE, Lachin JM, et al. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med 2016; 375(4): 323-34.
Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med 2017; 377(7): 644-57.

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Year: 2019
Page: [55 - 63]
Pages: 9
DOI: 10.2174/1573403X14666180711124825
Price: $58

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