Journal of General Internal Medicine

, Volume 19, Issue 10, pp 1045–1052 | Cite as

Managing dyslipidemia in chronic kidney disease

  • Daniel E. Weiner
  • Mark J. Sarnak


OBJECTIVE: Patients with chronic kidney disease (CKD) are at higher risk for cardiovascular disease (CVD) than patients in the general population. One potentially modifiable risk factor for CVD in patients with CKD is dyslipidemia. In the current manuscript we review observational and trial data assessing dyslipidemia and its treatment in this patient population.

RESULTS: Observational studies have noted a “reverse epidemiology” in patients with CKD such that low total cholesterol levels are associated with a higher mortality rate. The complex lipid profile of patients with CKD also raises questions as to whether lipid-lowering therapy will be beneficial in this patient population. Although there are only a few trials assessing the relationship between lipid-lowering therapy and CVD outcomes in CKD patients, many lipid-lowering medications are both safe and effective. In addition, there is suggestive evidence that statin therapy, in particular, also may reduce inflammation and slow the decline in glomerular filtration rate (GFR) in patients during the earlier stages of CKD.

CONCLUSION: Because of the high rate of CVD in patients with CKD and the overall safety of most medical therapies for dyslipidemia in CKD, current guidelines from the National Kidney Foundation Kidney Disease Outcomes Quality Initiative recommend aggressive therapy of dyslipidemia. These guidelines do, however, acknowledge the paucity of trial data in this patient population. There are 3 ongoing randomized controlled trials that are assessing the effect of statin therapy on CVD outcomes. These studies will hopefully provide definitive answers as to the appropriate treatment of dyslipidemia in CKD.

Key words

cardiovascular disease dyslipidemia hydroxymethylglutaryl-CoA reductase inhibitors chronic kidney disease dialysis 


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  1. 1.
    Levey AS, Coresh J, Balk E, et al. National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann Intern Med. 2003;139:137–47.PubMedGoogle Scholar
  2. 2.
    Prichard S. Risk factors for coronary artery disease in patients with renal failure. Am J Med Sci. 2003;325:209–13.PubMedCrossRefGoogle Scholar
  3. 3.
    National Kidney Foundation. K/DOQI clinical practice guidelines for managing dyslipidemias in chronic kidney disease. Am J Kidney Dis. 2003;41(suppl 3):S1-S92.Google Scholar
  4. 4.
    National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002;39(suppl 1):S1-S237.Google Scholar
  5. 5.
    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). JAMA. 2001;285:2486–97.Google Scholar
  6. 6.
    Sarnak MJ, Levey AS. Cardiovascular disease and chronic renal disease: a new paradigm. Am J Kidney Dis. 2000;35(4 suppl 1):S117-S131.PubMedGoogle Scholar
  7. 7.
    Weiner DE, Tighiouart H, Amin MG, et al. Chronic kidney disease as a risk factor for cardiovascular disease and all-cause mortality: a pooled analysis of community-based studies. J Am Soc Nephrol. 2004;15:1307–15.PubMedCrossRefGoogle Scholar
  8. 8.
    Stehouwer CD, Gall MA, Twisk JW, Knudsen E, Emeis JJ, Parving HH. Increased urinary albumin excretion, endothelial dysfunction, and chronic low-grade inflammation in type 2 diabetes: progressive, interrelated, and independently associated with risk of death. Diabetes. 2002;51:1157–65.PubMedCrossRefGoogle Scholar
  9. 9.
    Clausen P, Jensen JS, Jensen G, Borch-Johnsen K, Feldt-Rasmussen B. Elevated urinary albumin excretion is associated with impaired arterial dilatory capacity in clinically healthy subjects. Circulation. 2001;103:1869–74.PubMedGoogle Scholar
  10. 10.
    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.PubMedCrossRefGoogle Scholar
  11. 11.
    McKenney JM. Lipid management: tools for getting to the goal. Am J Manag Care. 2001;7(9 suppl):S299-S306.PubMedGoogle Scholar
  12. 12.
    Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. N Engl J Med. 1998;339:1349–57.CrossRefGoogle Scholar
  13. 13.
    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.PubMedCrossRefGoogle Scholar
  14. 14.
    Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994;344:1383–9.Google Scholar
  15. 15.
    MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360:7–22.CrossRefGoogle Scholar
  16. 16.
    Attman PO, Knight-Gibson C, Tavella M, Samuelsson O, Alaupovic P. The compositional abnormalities of lipoproteins in diabetic renal failure. Nephrol Dial. Transplant. 1998;13:2833–41.PubMedCrossRefGoogle Scholar
  17. 17.
    Attman PO, Samuelsson O, Johansson AC, Moberly JB, Alaupovic P. Dialysis modalities and dyslipidemia. Kidney Int Suppl. 2003;84:S110-S112.PubMedCrossRefGoogle Scholar
  18. 18.
    Quaschning T, Krane V, Metzger T, Wanner C. Abnormalities in uremic lipoprotein metabolism and its impact on cardiovascular disease. Am J Kidney Dis. 2001;38(4 suppl 1):S14-S19.PubMedGoogle Scholar
  19. 19.
    Attman PO, Samuelsson O, Alaupovic P. Lipoprotein metabolism and renal failure. Am J Kidney Dis. 1993;21:573–92.PubMedGoogle Scholar
  20. 20.
    Kasiske BL. Hyperlipidemia in patients with chronic renal disease. Am J Kidney Dis. 1998;32(5 suppl 3):S142-S156.PubMedGoogle Scholar
  21. 21.
    Aakhus S, Dahl K, Wideroe TE. Hyperlipidaemia in renal transplant patients. J Intern Med. 1996;239:407–15.PubMedCrossRefGoogle Scholar
  22. 22.
    Gonyea JE, Anderson CF. Weight change and serum lipoproteins in recipients of renal allografts. Mayo Clin Proc. 1992;67:653–7.PubMedGoogle Scholar
  23. 23.
    Moore R, Thomas D, Morgan E, et al. Abnormal lipid and lipoprotein profiles following renal transplantation. Transplant Proc. 1993;25(1 pt 2):1060–1.PubMedGoogle Scholar
  24. 24.
    Lowrie EG, Lew NL. Death risk in hemodialysis patients: the predictive value of commonly measured variables and an evaluation of death rate differences between facilities. Am J Kidney Dis. 1990;15:458–82.PubMedGoogle Scholar
  25. 25.
    Iseki K, Yamazato M, Tozawa M, Takishita S. Hypocholesterolemia is a significant predictor of death in a cohort of chronic hemodialysis patients. Kidney Int. 2002;61:1887–93.PubMedCrossRefGoogle Scholar
  26. 26.
    Liu Y, Coresh J, Eustace JA, et al. Association between cholesterol level and mortality in dialysis patients: role of inflammation and malnutrition. JAMA. 2004;291:451–9.PubMedCrossRefGoogle Scholar
  27. 27.
    Harris KP, Wheeler DC, Chong CC. A placebo-controlled trial examining atorvastatin in dyslipidemic patients undergoing CAPD. Kidney Int. 2002;61:1469–74.PubMedCrossRefGoogle Scholar
  28. 28.
    Hufnagel G, Michel C, Vrtovsnik F, Queffeulou G, Kossari N, Mignon F. Effects of atorvastatin on dyslipidaemia in uraemic patients on peritoneal dialysis. Nephrol Dial Transplant. 2000;15:684–8.PubMedCrossRefGoogle Scholar
  29. 29.
    Saltissi D, Morgan C, Rigby RJ, Westhuyzen J. Safety and efficacy of simvastatin in hypercholesterolemic patients undergoing chronic renal dialysis. Am J Kidney Dis. 2002;39:283–90.PubMedGoogle Scholar
  30. 30.
    Chang JW, Yang WS, Min WK, Lee SK, Park JS, Kim SB. Effects of simvastatin on high-sensitivity C-reactive protein and serum albumin in hemodialysis patients. Am J Kidney Dis. 2002;39:1213–7.PubMedCrossRefGoogle Scholar
  31. 31.
    Nishikawa O, Mune M, Miyano M, et al. Effect of simvastatin on the lipid profile of hemodialysis patients. Kidney Int Suppl. 1999;71:S219-S221.PubMedCrossRefGoogle Scholar
  32. 32.
    van den Akker JM, Bredie SJ, Diepenveen SH, van Tits LJ, Stalenhoef AF, van Leusen R. Atorvastatin and simvastatin in patients on hemodialysis: effects on lipoproteins, C-reactive protein and in vivo oxidized LDL. J Nephrol. 2003;16:238–44.PubMedCrossRefGoogle Scholar
  33. 33.
    Holdaas H, Jardine AG, Wheeler DC, et al. Effect of fluvastatin on acute renal allograft rejection: a randomized multicenter trial. Kidney Int. 2001;60:1990–7.PubMedCrossRefGoogle Scholar
  34. 34.
    Kasiske BL, Heim-Duthoy KL, Singer GG, Watschinger B, Germain MJ, Bastani B. The effects of lipid-lowering agents on acute renal allograft rejection. Transplantation. 2001;72:223–7.PubMedCrossRefGoogle Scholar
  35. 35.
    Sahu K, Sharma R, Gupta A, et al. Effect of lovastatin, an HMG CoA reductase inhibitor, on acute renal allograft rejection. Clin Transplant. 2001;15:173–5.PubMedCrossRefGoogle Scholar
  36. 36.
    Holdaas H, Fellstrom B, Jardine AG, et al. Effect of fluvastatin on cardiac outcomes in renal transplant recipients: a multicentre, randomised, placebo-controlled trial. Lancet. 2003;361:2024–31.PubMedCrossRefGoogle Scholar
  37. 37.
    Tonelli M, Moye L, Sacks FM, Kiberd B, Curhan G. Pravastatin for secondary prevention of cardiovascular events in persons with mild chronic renal insufficiency. Ann Intern Med. 2003;138:98–104.PubMedGoogle Scholar
  38. 38.
    Seliger SL, Weiss NS, Gillen DL, et al. HMG-CoA reductase inhibitors are associated with reduced mortality in ESRD patients. Kidney Int. 2002;61:297–304.PubMedCrossRefGoogle Scholar
  39. 39.
    Balk EM, Lau J, Goudas LC, et al. Effects of statins on nonlipid serum markers associated with cardiovascular disease: a systematic review. Ann Intern Med. 2003;139:670–82.PubMedGoogle Scholar
  40. 40.
    Fried LF, Orchard TJ, Kasiske BL. Effect of lipid reduction on the progression of renal disease: a meta-analysis. Kidney Int. 2001;59:260–9.PubMedCrossRefGoogle Scholar
  41. 41.
    Tonelli M, Moye L, Sacks FM, Cole T, Curhan GC. Effect of pravastatin on loss of renal function in people with moderate chronic renal insufficiency and cardiovascular disease. J Am Soc Nephrol. 2003;14:1605–13.PubMedCrossRefGoogle Scholar
  42. 42.
    Bianchi S, Bigazzi R, Caiazza A, Campese VM. A controlled, prospective study of the effects of atorvastatin on proteinuria and progression of kidney disease. Am J Kidney Dis. 2003;41:565–70.PubMedCrossRefGoogle Scholar
  43. 43.
    Broeders N, Knoop C, Antoine M, Tielemans C, Abramowicz D. Fibrate-induced increase in blood urea and creatinine: is gemfibrozil the only innocuous agent? Nephrol Dial Transplant. 2000;15:1993–9.PubMedCrossRefGoogle Scholar
  44. 44.
    Dierkes J, Westphal S, Luley C. Serum homocysteine increases after therapy with fenofibrate or bezafibrate. Lancet. 1999;354:219–20.PubMedCrossRefGoogle Scholar
  45. 45.
    Hottelart C, El Esper N, Rose F, Achard JM, Fournier A. Fenofibrate increases creatininemia by increasing metabolic production of creatinine. Nephron. 2002;92:536–41.PubMedCrossRefGoogle Scholar
  46. 46.
    Westphal S, Dierkes J, Luley C. Effects of fenofibrate and gemfibrozil on plasma homocysteine. Lancet. 2001;358:39–40.PubMedCrossRefGoogle Scholar
  47. 47.
    Miller M. Niacin as a component of combination therapy for dyslipidemia. Mayo Clin Proc. 2003;78:735–42.PubMedCrossRefGoogle Scholar
  48. 48.
    Hiatt JG, Shamsie SG, Schectman G. Discontinuation rates of cholesterol-lowering medications: implications for primary care. Am J Manag Care. 1999;5:437–44.PubMedGoogle Scholar
  49. 49.
    Grundy SM, Vega GL, McGovern ME, et al. Efficacy, safety, and tolerability of once-daily niacin for the tratment of dyslipidemia associated with type 2 diabetes: results of the assessment of diabetes control and evaluation of the efficacy of niaspan trial. Arch Intern Med. 2002;162:1568–76.PubMedCrossRefGoogle Scholar
  50. 50.
    Lins RL, Matthys KE, Verpooten GA, et al. Pharmacokinetics of atorvastatin and its metabolites after single and multiple dosing in hypercholesterolaemic haemodialysis patients. Nephrol Dial Transplant. 2003;18:967–76.PubMedCrossRefGoogle Scholar
  51. 51.
    Baigent C, Landry M. Study of Heart and Renal Protection (SHARP). Kidney Int Suppl. 2003;84:S207-S210.PubMedCrossRefGoogle Scholar
  52. 52.
    Fellstrom BC, Holdaas H, Jardine AG. Why do we need a statin trial in hemodialysis patients? Kidney Int Suppl. 2003;84:S204-S206.PubMedCrossRefGoogle Scholar
  53. 53.
    Wanner C, Krane V, Ruf G, Marz W, Ritz E. Rationale and design of a trial improving outcome of type 2 diabetics on hemodialysis. Die Deutsche Diabetes Dialyse Studie Investigators. Kidney Int Suppl. 1999;71:S222-S226.PubMedCrossRefGoogle Scholar
  54. 54.
    Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. The Expert Panel. Arch Intern Med. 1988;148:36–69.Google Scholar
  55. 55.
    Schaefer EJ, Lamon-Fava S, Cohn SD, et al. Effects of age, gender, and menopausal status on plasma low density lipoprotein cholesterol and apolipoprotein B levels in the Framingham Offspring Study. J Lipid Res. 1994;35:779–92.PubMedGoogle Scholar

Copyright information

© Society of General Internal Medicine 2004

Authors and Affiliations

  • Daniel E. Weiner
    • 1
  • Mark J. Sarnak
    • 1
  1. 1.Tufts-New England Medical CenterBoston

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