Skip to main content

Advertisement

Log in

Cardiovascular Implications of Chronic Kidney Disease in Older Adults

  • Review Article
  • Published:
Drugs & Aging Aims and scope Submit manuscript

Abstract

Because serum creatinine is an imprecise indicator of glomerular filtration rate (GFR), estimating equations derived from the Modification of Diet in Renal Diseases study are increasingly being used to estimate GFR. The notion that GFR declines with aging is based largely on the results of cross-sectional studies that have generally not differentiated the effects of senescence from those of coexisting conditions such as hypertension. Nevertheless, GFR probably declines in many, if not all, aging individuals. The introduction of automated reporting of estimated GFR may result in an over-diagnosis of chronic kidney disease (CKD). There is a large body of evidence to suggest that a decrease in GFR and/or albuminuria is associated with an increased risk of death, particularly from cardiovascular causes, and that this risk extends to the elderly. Although the data are not consistent with regard to the level of GFR at which the increase in cardiovascular risk becomes apparent, small amounts of urine albumin excretion (levels that do not meet the definition of microalbuminuria) are associated with a higher risk of death, even among the elderly. There is currently no evidence that aggressive control of blood pressure and/or use of medications that reduce proteinuria, such as those that block the renin-angiotensin-aldosterone system, reduce the risk of cardiovascular events or death among individuals with CKD. On the other hand, secondary analyses of at least two studies have documented the benefit of lipid lowering in CKD patients. Paradoxically, a recent study has raised concern that normalizing haemoglobin may enhance the cardiovascular risk associated with CKD. To conclude, the available evidence indicates that early identification of CKD may allow physicians to aggressively modify cardiovascular risk, which, in turn, has the potential to improve patient outcomes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Table I
Table II
Table III

Similar content being viewed by others

References

  1. Levey AS. Use of glomerular filtration rate measurements to assess the progression of renal disease. Semin Nephrol 1989; 9: 370–9

    PubMed  CAS  Google Scholar 

  2. Shemesh O, Golbetz H, Kriss JP, et al. Limitations of creatinine as a filtration marker in glomerulopathic patients. Kidney Int 1985; 28: 830–8

    Article  PubMed  CAS  Google Scholar 

  3. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16: 31–41

    Article  PubMed  CAS  Google Scholar 

  4. Goldberg TH, Finkelstein MS. Difficulties in estimating glomerular filtration rate in the elderly. Arch Intern Med 1987; 147: 1430–3

    Article  PubMed  CAS  Google Scholar 

  5. Nicoll SR, Sainsbury R, Bailey RR, et al. Assessment of creatinine clearance in healthy subjects over 65 years of age. Nephron 1991; 59: 621–5

    Article  PubMed  CAS  Google Scholar 

  6. National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis 2002 Feb; 39 (2 Suppl. 1): S1–266

    Article  Google Scholar 

  7. Levey AS, Bosch JP, Lewis JB, et al. 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

    PubMed  CAS  Google Scholar 

  8. Stevens LA, Coresh J, Greene T, et al. Assessing kidney function: measured and estimated glomerular filtration rate. N Engl J Med 2006; 354: 2473–83

    Article  PubMed  CAS  Google Scholar 

  9. Epstein M. Aging and the kidney. J Am Soc Nephrol 1996; 7: 1106–22

    PubMed  CAS  Google Scholar 

  10. Davies DF, Shock NW. Age changes in glomerular filtration rate, effective renal plasma flow, and tubular excretory capacity in adult males. J Clin Invest 1950; 29: 496–507

    Article  PubMed  CAS  Google Scholar 

  11. Lindeman RD, Tobin J, Shock NW. Longitudinal studies on the rate of decline of renal function with age. J Am Geriatr Soc 1985; 33: 278–85

    PubMed  CAS  Google Scholar 

  12. Bleyer AJ, Shemanski LR, Burke GL, et al. Tobacco, hypertension, and vascular disease: risk factors for renal functional decline in an older population. Kidney Int 2000; 57: 2072–9

    Article  PubMed  CAS  Google Scholar 

  13. Hemmelgarn BR, Zhang J, Manns BJ, et al. Progression of kidney dysfunction in the community-dwelling elderly. Kidney Int 2006; 69: 2155–61

    Article  PubMed  CAS  Google Scholar 

  14. 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

    Article  PubMed  Google Scholar 

  15. Garg AX, Clark WF, Haynes RB, et al. Moderate renal insufficiency and the risk of cardiovascular mortality: results from the NHANES I. Kidney Int 2002; 61: 1486–94

    Article  PubMed  Google Scholar 

  16. Rule AD, Larson TS, Bergstralh EJ, et al. Using serum creatinine to estimate glomerular filtration rate: accuracy in good health and in chronic kidney disease. Ann Intern Med 2004; 141: 929–3

    PubMed  CAS  Google Scholar 

  17. Froissait M, Rossert J, Jacquot C, et al. Predictive performance of the modification of diet in renal disease and Cockcroft-Gault equations for estimating renal function. J Am Soc Nephrol 2005; 16: 763–73

    Article  Google Scholar 

  18. Poggio ED, Wang X, Greene T, et al. Performance of the modification of diet in renal disease and Cockcroft-Gault equations in the estimation of GFR in health and in chronic kidney disease. J Am Soc Nephrol 2005; 16: 459–66

    Article  PubMed  Google Scholar 

  19. United States Renal Data System. Annual data report. Bethesda (MD): US Department of Public Health and Human Services, Public Health Service, National Institutes of Health, 2006

    Google Scholar 

  20. Hsu CY, Vittinghoff E, Lin F, et al. The incidence of end-stage renal disease is increasing faster than the prevalence of chronic renal insufficiency. Ann Intern Med 2004; 141: 95–101

    PubMed  Google Scholar 

  21. Muntner P, Coresh J, Powe NR, et al. The contribution of increased diabetes prevalence and improved myocardial infarction and stroke survival to the increase in treated end-stage renal disease. J Am Soc Nephrol 2003; 14: 1568–77

    Article  PubMed  Google Scholar 

  22. 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. Hypertension 2003; 42(5): 1050–65

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  24. Keith DS, Nichols GA, Gullion CM, et al. Longitudinal follow-up and outcomes among a population with chronic kidney disease in a large managed care organization. Arch Intern Med 2004; 164: 659–63

    Article  PubMed  Google Scholar 

  25. Rahman M, Pressel S, Davis BR, et al. Cardiovascular outcomes in high-risk hypertensive patients stratified by baseline glomerular filtration rate. Ann Intern Med 2006; 144: 172–80

    PubMed  Google Scholar 

  26. Manjunath G, Tighiouart H, Coresh J, et al. Level of kidney function as a risk factor for cardiovascular outcomes in the elderly. Kidney Int 2003; 63: 1121–9

    Article  PubMed  Google Scholar 

  27. Henry RM, Kostense PJ, Bos G, et al. Mild renal insufficiency is associated with increased cardiovascular mortality: The Hoorn Study. Kidney Int 2002; 62: 1402–7

    Article  PubMed  Google Scholar 

  28. 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: 629–36

    PubMed  CAS  Google Scholar 

  29. Ruilope LM, Salvetti A, Jamerson K, et al. Renal function and intensive lowering of blood pressure in hypertensive participants of the Hypertension Optimal Treatment (HOT) study. J Am Soc Nephrol 2001; 12: 218–25

    PubMed  CAS  Google Scholar 

  30. Shlipak MG, Simon JA, Grady D, et al. Renal insufficiency and cardiovascular events in postmenopausal women with coronary heart disease. J Am Coll Cardiol 2001; 38: 705–11

    Article  PubMed  CAS  Google Scholar 

  31. McClellan WM, Flanders WD, Langsten RD, et al. Anemia and renal insufficiency are independent risk factors for death among patients with congestive heart failure admitted to community hospitals: a population-based study. J Am Soc Nephrol 2002; 13: 1928–36

    Article  PubMed  Google Scholar 

  32. Smith GL, Shlipak MG, Havranek EP, et al. Race and renal impairment in heart failure: mortality in blacks versus whites. Circulation 2005; 111: 1270–7

    Article  PubMed  Google Scholar 

  33. Dries DL, Exner DV, Domanski MJ, et al. The prognostic implications of renal insufficiency in asymptomatic and symptomatic patients with left ventricular systolic dysfunction. J Am Coll Cardiol 2000; 35: 681–9

    Article  PubMed  CAS  Google Scholar 

  34. De Leeuw PW, Thijs L, Birkenhager WH, et al. Prognostic significance of renal function in elderly patients with isolated systolic hypertension: results from the Syst-Eur trial. J Am Soc Nephrol 2002; 13: 2213–22

    Article  PubMed  Google Scholar 

  35. Anavekar NS, McMurray JJ, Velazquez EJ, et al. Relation between renal dysfunction and cardiovascular outcomes after myocardial infarction. N Engl J Med 2004 Sep 23; 351(13): 1285–95

    Article  PubMed  CAS  Google Scholar 

  36. Dinneen SF, Gerstein HC. The association of microalbuminuria and mortality in non-insulin-dependent diabetes mellitus: a systematic overview of the literature. Arch Intern Med 1997; 157(13): 1413–8

    Article  PubMed  CAS  Google Scholar 

  37. Anavekar NS, Gans DJ, Berl T, et al. Predictors of cardiovascular events in patients with type 2 diabetic nephropathy and hypertension: a case for albuminuria. Kidney Int Suppl 2004 Nov; 92: S50–5

    Article  PubMed  Google Scholar 

  38. Damsgaard EM, Froland A, Jorgensen OD, et al. Microalbuminuria as predictor of increased mortality in elderly people. BMJ 1990; 3: 297–300

    Article  Google Scholar 

  39. Yuyun MF, Khaw KT, Luben R, et al. Microalbuminuria independently predicts all-cause and cardiovascular mortality in a British population: the European Prospective Investigation into Cancer in Norfolk (EPIC-Norfolk) population study. Int J Epidemiol 2004; 33: 189–98

    Article  PubMed  Google Scholar 

  40. Culleton BF, Larson MG, Parfrey PS, et al. Proteinuria as a risk factor for cardiovascular disease and mortality in older people: a prospective study. Am J Med 2000; 109: 1–8

    Article  PubMed  CAS  Google Scholar 

  41. Arnlov J, Evans JC, Meigs JB, et al. Low-grade albuminuria and incidence of cardiovascular disease events in nonhypertensive and nondiabetic individuals: the Framingham Heart Study. Circulation 2005; 112: 969–75

    Article  PubMed  Google Scholar 

  42. Jager A, Kostense PJ, Ruhe HG, et al. 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

    Article  PubMed  CAS  Google Scholar 

  43. Gerstein HC, Mann JF, Yi Q, et al. Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals. JAMA 2001; 286: 421–6

    Article  PubMed  CAS  Google Scholar 

  44. Wachtell K, Ibsen H, Olsen MH, et al. Albuminuria and cardiovascular risk in hypertensive patients with left ventricular hypertrophy: the LIFE study. Ann Intern Med 2003; 139: 901–6

    PubMed  Google Scholar 

  45. Roest M, Banga JD, Janssen WM, et al. Excessive urinary albumin levels are associated with future cardiovascular mortality in postmenopausal women. Circulation 2001; 103: 3057–61

    Article  PubMed  CAS  Google Scholar 

  46. Olsen MH, Wachtell K, Ibsen H, et al. Reductions in albuminuria and in electrocardiographic left ventricular hypertrophy independently improve prognosis in hypertension: the LIFE study. J Hypertens 2006; 24: 775–81

    Article  PubMed  CAS  Google Scholar 

  47. Wang TJ, Evans JC, Meigs JB, et al. Low-grade albuminuria and the risks of hypertension and blood pressure progression. Circulation 2005; 111: 1370–6

    Article  PubMed  CAS  Google Scholar 

  48. Ruggenenti P, Remuzzi G. Time to abandon microalbuminuria? Kidney Int 2006; 70: 1214–22

    Article  PubMed  CAS  Google Scholar 

  49. Mehrotra R. Disordered mineral metabolism and vascular calcification in nondialyzed chronic kidney disease patients. J Ren Nutr 2006; 16: 100–18

    Article  PubMed  Google Scholar 

  50. Mehrotra R, Budoff MJ, Christenson P, et al. Determinants of coronary artery calcification in diabetics with and without nephropathy. Kidney Int 2004; 66(5): 2022–31

    Article  PubMed  Google Scholar 

  51. Stehouwer CD, Nauta JJ, Zeldenrust GC, et al. Urinary albumin excretion, cardiovascular disease, and endothelial dysfunction in non-insulin-dependent diabetes mellitus. Lancet 1992; 340(8815): 319–23

    Article  PubMed  CAS  Google Scholar 

  52. Stehouwer CD, Smulders YM. Microalbuminuria and risk for cardiovascular disease: analysis of potential mechanisms. J Am Soc Nephrol 2006; 17: 2106–11

    Article  PubMed  CAS  Google Scholar 

  53. Stehouwer CD, Henry RM, Dekker JM, et al. Microalbuminuria is associated with impaired brachial artery, flow-mediated vasodilation in elderly individuals without and with diabetes: further evidence for a link between microalbuminuria and endothelial dysfunction. The HOORN study. Kidney Int Suppl 2004; 92: s42–4

    Article  PubMed  Google Scholar 

  54. Rakhit DJ, Marwick TH, Armstrong KA, et al. Effect of aggressive risk factor modification on cardiac events and myocardial ischaemia in patients with chronic kidney disease. Heart 2006; 92: 1402–8

    Article  PubMed  CAS  Google Scholar 

  55. Sarnak MJ, Greene T, Wang X, et al. The effect of a lower target blood pressure on the progression of kidney disease: long-term follow-up of the modification of diet in renal disease study. Ann Intern Med 2005; 142: 342–51

    PubMed  Google Scholar 

  56. Norris K, Bourgoigne J, Gassman J, et al. Cardiovascular outcomes in the African American Study of Kidney Disease and Hypertension (AASK) trial. Am J Kidney Dis 2006; 48: 739–51

    Article  PubMed  CAS  Google Scholar 

  57. Asselbergs FW, Diercks GF, Hillege HL, et al. Effects of fosinopril and pravastatin on cardiovascular events in subjects with microalbuminuria. Circulation 2004 Nov 2; 110(18): 2809–16

    Article  PubMed  CAS  Google Scholar 

  58. Brenner BM, Cooper ME, de Zeeuw D, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001; 345: 861–9

    Article  PubMed  CAS  Google Scholar 

  59. Lewis EJ, Hunsicker LG, Clarke WR, et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 2001; 345(12): 851–60

    Article  PubMed  CAS  Google Scholar 

  60. Sever PS, Dahlof B, Poulter NR, et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet 2003; 361: 1149–58

    Article  PubMed  CAS  Google Scholar 

  61. Tonelli M, Moye L, Sacks FM, et al. Pravastatin for secondary prevention of cardiovascular events in persons with mild chronic renal insufficiency. Ann Intern Med 2003; 138: 98–104

    PubMed  CAS  Google Scholar 

  62. 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: 2071–84

    Article  PubMed  CAS  Google Scholar 

  63. Singh AK, Szczech L, Tang KL, et al. Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med 2006; 355: 2085–98

    Article  PubMed  CAS  Google Scholar 

  64. Toole JF, Malinow MR, Chambless LE, et al. Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial. JAMA 2004; 291: 565–75

    Article  PubMed  CAS  Google Scholar 

  65. Bonaa KH, Njolstad I, Ueland PM, et al. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med 2006 Apr 13; 354(15): 1578–88

    Article  PubMed  CAS  Google Scholar 

  66. Lonn E, Yusuf S, Arnold MJ, et al. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med 2006 Apr 13; 354(15): 1567–77

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

Rajnish Mehrotra is supported by a grant from the US National Institutes of Health (RR81298), Satellite Health and DaVita Research Grant. The funding source had no role in the preparation or review of the manuscript. Rajnish Mehrotra serves as a consultant for Novartis and Shire, and has received research grants from Amgen, Genzyme, Shire and Baxter Healthcare and honoraria from Shire, Genzyme and Baxter Healthcare. The other authors have no conflicts of interest that are directly relevant to the content of this review. We thank Dr Richard Glassock for critically reviewing this manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Rajnish Mehrotra.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dukkipati, R., Adler, S. & Mehrotra, R. Cardiovascular Implications of Chronic Kidney Disease in Older Adults. Drugs Aging 25, 241–253 (2008). https://doi.org/10.2165/00002512-200825030-00006

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00002512-200825030-00006

Keywords

Navigation