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Non-statin Therapies for CKD with Dyslipidemia

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Dyslipidemias in Kidney Disease
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Abstract

We will review data from the general population concerning the individual therapeutic interventions and complement that with information specific to chronic kidney disease when available. We will focus on treatment interventions that are specifically targeting lipid disorders, namely therapeutic lifestyle changes, fibrates, nicotinic acid, bile acid sequestrants, omega-3 fatty acids (fish oil), and inhibitors of cholesteryl ester transfer protein. Other, non-specific interventions (optimal treatment of diabetes, reducing proteinuria with the use of ACEI, optimizing medication use) will not be covered here.

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References

  1. Kasiske BL, Wheeler DC. The management of dyslipidemia in CKD: new analyses of an expanding dataset. Am J Kidney Dis. 2013;61(3):371–4. Epub 2012/12/25.

    PubMed  Google Scholar 

  2. Kidney Disease Outcomes Quality Initiative (K/DOQI) Group (2003) K/DOQI clinical practice guidelines for management of dyslipidemias in patients with kidney disease. Am J Kidney Dis. 41(4 Suppl 3):I-IV, S1–91. . Epub 2003/04/03.

    Google Scholar 

  3. Matsushita K, van der Velde M, Astor BC, Woodward M, Levey AS, de Jong PE, et al. Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis. Lancet. 2010;375(9731):2073–81. Epub 2010/05/21.

    PubMed  PubMed Central  Google Scholar 

  4. Kovesdy CP, Anderson JE, Kalantar-Zadeh K. Inverse association between lipid levels and mortality in men with chronic kidney disease who are not yet on dialysis: effects of case mix and the malnutrition-inflammation-cachexia syndrome. J Am Soc Nephrol. 2007;18(1):304–11. Epub 2006/12/15.

    PubMed  CAS  Google Scholar 

  5. Noori N, Caulfield MP, Salameh WA, Reitz RE, Nicholas SB, Molnar MZ, et al. Novel lipoprotein subfraction and size measurements in prediction of mortality in maintenance hemodialysis patients. Clin J Am Soc Nephrol. 2011;6(12):2861–70. Epub 2011/10/29.

    PubMed Central  PubMed  CAS  Google Scholar 

  6. Harper CR, Jacobson TA. Managing dyslipidemia in chronic kidney disease. J Am Coll Cardiol. 2008;51(25):2375–84. Epub 2008/06/21.

    PubMed  CAS  Google Scholar 

  7. Khoueiry G, Abdallah M, Saiful F, Abi Rafeh N, Raza M, Bhat T, et al. High-density lipoprotein in uremic patients: metabolism, impairment, and therapy. International urology and nephrology. 2014;46(1):27–39. Epub 2013/02/28.

    PubMed  CAS  Google Scholar 

  8. Speer T, Rohrer L, Blyszczuk P, Shroff R, Kuschnerus K, Krankel N, et al. Abnormal high-density lipoprotein induces endothelial dysfunction via activation of toll-like receptor-2. Immunity. 2013;38(4):754–68. Epub 2013/03/13.

    PubMed  CAS  Google Scholar 

  9. Kasiske B, Cosio FG, Beto J, Bolton K, Chavers BM, Grimm Jr R, et al. Clinical practice guidelines for managing dyslipidemias in kidney transplant patients: a report from the Managing Dyslipidemias in Chronic Kidney Disease Work Group of the National Kidney Foundation Kidney Disease Outcomes Quality Initiative. Am J Transplant. 2004;4 Suppl 7:13–53. Epub 2004/03/19.

    PubMed  Google Scholar 

  10. 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) final report. Circulation. 2002;106(25):3143–421. Epub 2002/12/18.

    Google Scholar 

  11. Upadhyay A, Earley A, Lamont JL, Haynes S, Wanner C, Balk EM. Lipid-lowering therapy in persons with chronic kidney disease: a systematic review and meta-analysis. Ann Intern Med. 2012;157(4):251–62. Epub 2012/08/23.

    PubMed  Google Scholar 

  12. Jun M, Zhu B, Tonelli M, Jardine MJ, Patel A, Neal B, et al. Effects of fibrates in kidney disease: a systematic review and meta-analysis. J Am Coll Cardiol. 2012;60(20):2061–71. Epub 2012/10/23.

    PubMed  CAS  Google Scholar 

  13. [cited 2013 September 14]. http://www.european-renal-best-practice.org/content/guidelines-topic-ckd-hyperlipidaemia.

    Google Scholar 

  14. Anderson TJ, Gregoire J, Hegele RA, Couture P, Mancini GB, McPherson R, et al. 2012 update of the Canadian Cardiovascular Society guidelines for the diagnosis and treatment of dyslipidemia for the prevention of cardiovascular disease in the adult. Can J Cardiol. 2013;29(2):151–67. Epub 2013/01/29.

    PubMed  Google Scholar 

  15. de Lorgeril M, Salen P, Martin JL, Monjaud I, Delaye J, Mamelle N. Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: final report of the Lyon Diet Heart Study. Circulation. 1999;99(6):779–85. Epub 1999/02/17.

    PubMed  Google Scholar 

  16. Trichopoulou A, Costacou T, Bamia C, Trichopoulos D. Adherence to a Mediterranean diet and survival in a Greek population. N Engl J Med. 2003;348(26):2599–608. Epub 2003/06/27.

    PubMed  Google Scholar 

  17. Pereira MA, O’Reilly E, Augustsson K, Fraser GE, Goldbourt U, Heitmann BL, et al. Dietary fiber and risk of coronary heart disease: a pooled analysis of cohort studies. Arch Intern Med. 2004;164(4):370–6. Epub 2004/02/26.

    PubMed  Google Scholar 

  18. Gaede P, Vedel P, Larsen N, Jensen GV, Parving HH, Pedersen O. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med. 2003;348(5):383–93. Epub 2003/01/31.

    PubMed  Google Scholar 

  19. Greenwood SA, Lindup H, Taylor K, Koufaki P, Rush R, Macdougall IC, et al. Evaluation of a pragmatic exercise rehabilitation programme in chronic kidney disease. Nephrol Dial Transplant. 2012;27 Suppl 3:iii126–34. Epub 2012/07/13.

    PubMed  Google Scholar 

  20. MacLaughlin HL, Sarafidis PA, Greenwood SA, Campbell KL, Hall WL, Macdougall IC. Compliance with a structured weight loss program is associated with reduced systolic blood pressure in obese patients with chronic kidney disease. Am J Hypertens. 2012;25(9):1024–9. Epub 2012/06/22.

    PubMed  Google Scholar 

  21. van Zuilen AD, Bots ML, Dulger A, van der Tweel I, van Buren M, Ten Dam MA, et al. Multifactorial intervention with nurse practitioners does not change cardiovascular outcomes in patients with chronic kidney disease. Kidney Int. 2012;82(6):710–7. Epub 2012/06/29.

    PubMed  Google Scholar 

  22. Mente A, de Koning L, Shannon HS, Anand SS. A systematic review of the evidence supporting a causal link between dietary factors and coronary heart disease. Arch Intern Med. 2009;169(7): 659–69. Epub 2009/04/15.

    PubMed  CAS  Google Scholar 

  23. Keys A. Serum cholesterol response to dietary cholesterol. Am J Clin Nutr. 1984;40(2):351–9. Epub 1984/08/01.

    PubMed  CAS  Google Scholar 

  24. Ordovas JM. Genetic influences on blood lipids and cardiovascular disease risk: tools for primary prevention. Am J Clin Nutr. 2009;89(5):1509S–17. Epub 2009/04/03.

    PubMed Central  PubMed  CAS  Google Scholar 

  25. Mensink RP, Zock PL, Kester AD, Katan MB. Effects of dietary fatty acids and carbohydrates on the ratio of serum total to HDL cholesterol and on serum lipids and apolipoproteins: a meta-analysis of 60 controlled trials. Am J Clin Nutr. 2003;77(5):1146–55. Epub 2003/04/30.

    PubMed  CAS  Google Scholar 

  26. Mozaffarian D, Aro A, Willett WC. Health effects of trans-fatty acids: experimental and observational evidence. Eur J Clin Nutr. 2009;63 Suppl 2:S5–21. Epub 2009/05/09.

    PubMed  CAS  Google Scholar 

  27. Mattar M, Obeid O. Fish oil and the management of hypertriglyceridemia. Nutr Health. 2009;20(1):41–9. Epub 2009/03/31.

    PubMed  CAS  Google Scholar 

  28. Balk EM, Lichtenstein AH, Chung M, Kupelnick B, Chew P, Lau J. Effects of omega-3 fatty acids on serum markers of cardiovascular disease risk: a systematic review. Atherosclerosis. 2006;189(1):19–30. Epub 2006/03/15.

    PubMed  CAS  Google Scholar 

  29. Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, Ishikawa Y, et al. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet. 2007;369(9567):1090–8. Epub 2007/04/03.

    PubMed  CAS  Google Scholar 

  30. Marchioli R, Barzi F, Bomba E, Chieffo C, Di Gregorio D, Di Mascio R, et al. Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico (GISSI)-Prevenzione. Circulation. 2002;105(16):1897–903. Epub 2002/05/09.

    PubMed  CAS  Google Scholar 

  31. Brown L, Rosner B, Willett WW, Sacks FM. Cholesterol-lowering effects of dietary fiber: a meta-analysis. Am J Clin Nutr. 1999;69(1):30–42. Epub 1999/01/30.

    PubMed  CAS  Google Scholar 

  32. Kelly S, Frost G, Whittaker V, Summerbell C. Low glycaemic index diets for coronary heart disease. Cochrane Database Syst Rev. 2004;4, CD004467. Epub 2004/10/21.

    PubMed  Google Scholar 

  33. Rimm EB, Williams P, Fosher K, Criqui M, Stampfer MJ. Moderate alcohol intake and lower risk of coronary heart disease: meta-analysis of effects on lipids and haemostatic factors. BMJ. 1999;319(7224):1523–8. Epub 1999/12/11.

    PubMed Central  PubMed  CAS  Google Scholar 

  34. Mooradian AD, Haas MJ, Wong NC. The effect of select nutrients on serum high-density lipoprotein cholesterol and apolipoprotein A-I levels. Endocr Rev. 2006;27(1):2–16. Epub 2005/10/26.

    PubMed  CAS  Google Scholar 

  35. Dattilo AM, Kris-Etherton PM. Effects of weight reduction on blood lipids and lipoproteins: a meta-analysis. Am J Clin Nutr. 1992;56(2):320–8. Epub 1992/08/01.

    PubMed  CAS  Google Scholar 

  36. Shaw K, Gennat H, O’Rourke P, Del Mar C. Exercise for overweight or obesity. Cochrane Database Syst Rev. 2006;4, CD003817. Epub 2006/10/21.

    PubMed  Google Scholar 

  37. Kraus WE, Houmard JA, Duscha BD, Knetzger KJ, Wharton MB, McCartney JS, et al. Effects of the amount and intensity of exercise on plasma lipoproteins. N Engl J Med. 2002;347(19):1483–92. Epub 2002/11/08.

    PubMed  CAS  Google Scholar 

  38. Axelsson TG, Irving GF, Axelsson J. To eat or not to eat: dietary fat in uremia is the question. Semin Dial. 2010;23(4):383–8. Epub 2010/08/13.

    PubMed  Google Scholar 

  39. Kent PS. Integrating clinical nutrition practice guidelines in chronic kidney disease. Nutr Clin Pract. 2005;20(2):213–7. Epub 2005/10/07.

    PubMed  Google Scholar 

  40. Work Group KDOQI. KDOQI clinical practice guideline for nutrition in children with CKD: 2008 update. Executive summary. Am J Kidney Dis. 2009;53(3 Suppl 2):S11–104.

    Google Scholar 

  41. Kris-Etherton PM, Innis S. Ammerican Dietetic A. Dietitians of C Position of the American Dietetic Association and Dietitians of Canada: dietary fatty acids J Am Diet Assoc. 2007;107(9):1599–611. Epub 2007/10/17.

    CAS  Google Scholar 

  42. Friedman AN. Omega-3 fatty acid supplementation in advanced kidney disease. Semin Dial. 2010;23(4):396–400. Epub 2010/08/13.

    PubMed  Google Scholar 

  43. Kutner NG, Clow PW, Zhang R, Aviles X. Association of fish intake and survival in a cohort of incident dialysis patients. Am J Kidney Dis. 2002;39(5):1018–24. Epub 2002/04/30.

    PubMed  Google Scholar 

  44. Cohen BE, Garg SK, Ali S, Harris WS, Whooley MA. Red blood cell docosahexaenoic acid and eicosapentaenoic acid concentrations are positively associated with socioeconomic status in patients with established coronary artery disease: data from the Heart and Soul Study. J Nutr. 2008;138(6):1135–40. Epub 2008/05/22.

    PubMed Central  PubMed  CAS  Google Scholar 

  45. Saifullah A, Watkins BA, Saha C, Li Y, Moe SM, Friedman AN. Oral fish oil supplementation raises blood omega-3 levels and lowers C-reactive protein in haemodialysis patients—a pilot study. Nephrol Dial Transplant. 2007;22(12):3561–7. Epub 2007/07/12.

    PubMed  CAS  Google Scholar 

  46. Svensson M, Christensen JH, Solling J, Schmidt EB. The effect of n-3 fatty acids on plasma lipids and lipoproteins and blood pressure in patients with CRF. Am J Kidney Dis. 2004;44(1):77–83. Epub 2004/06/24.

    PubMed  CAS  Google Scholar 

  47. Svensson M, Schmidt EB, Jorgensen KA, Christensen JH. N-3 fatty acids as secondary prevention against cardiovascular events in patients who undergo chronic hemodialysis: a randomized, placebo-controlled intervention trial. Clin J Am Soc Nephrol. 2006;1(4):780–6. Epub 2007/08/21.

    PubMed  CAS  Google Scholar 

  48. KDOQI Work Group. K/DOQI clinical practice guidelines for cardiovascular disease in dialysis patients. Am J Kidney Dis. 2005;45(4 Suppl 3):S1–153. Epub 2005/04/05.

    Google Scholar 

  49. Kris-Etherton PM, Harris WS, Appel LJ. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation. 2002;106(21):2747–57. Epub 2002/11/20.

    PubMed  Google Scholar 

  50. Howden EJ, Fassett RG, Isbel NM, Coombes JS. Exercise training in chronic kidney disease patients. Sports Med. 2012;42(6):473–88. Epub 2012/05/17.

    PubMed  Google Scholar 

  51. Leehey DJ, Moinuddin I, Bast JP, Qureshi S, Jelinek CS, Cooper C, et al. Aerobic exercise in obese diabetic patients with chronic kidney disease: a randomized and controlled pilot study. Cardiovasc Diabetol. 2009;8:62. Epub 2009/12/17.

    PubMed Central  PubMed  Google Scholar 

  52. Balakrishnan VS, Rao M, Menon V, Gordon PL, Pilichowska M, Castaneda F, et al. Resistance training increases muscle mitochondrial biogenesis in patients with chronic kidney disease. Clin J Am Soc Nephrol. 2010;5(6):996–1002. Epub 2010/05/26.

    PubMed Central  PubMed  CAS  Google Scholar 

  53. Toyama K, Sugiyama S, Oka H, Sumida H, Ogawa H. Exercise therapy correlates with improving renal function through modifying lipid metabolism in patients with cardiovascular disease and chronic kidney disease. J Cardiol. 2010;56(2):142–6. Epub 2010/08/11.

    PubMed  Google Scholar 

  54. Kovesdy CP, Czira ME, Rudas A, Ujszaszi A, Rosivall L, Novak M, et al. Body mass index, waist circumference and mortality in kidney transplant recipients. Am J Transplant. 2010;10(12):2644–51. Epub 2010/11/20.

    PubMed  CAS  Google Scholar 

  55. Kovesdy CP, Kalantar-Zadeh K. Introduction: the reverse epidemiology controversy. Semin Dial. 2007;20(6):485. Epub 2007/11/10.

    PubMed  Google Scholar 

  56. Zoccali C, Torino C, Tripepi G, Mallamaci F. Assessment of obesity in chronic kidney disease: what is the best measure? Curr Opin Nephrol Hypertens. 2012;21(6):641–6. Epub 2012/09/27.

    PubMed  Google Scholar 

  57. MacLaughlin HL, Cook SA, Kariyawasam D, Roseke M, van Niekerk M, Macdougall IC. Nonrandomized trial of weight loss with orlistat, nutrition education, diet, and exercise in obese patients with CKD: 2-year follow-up. Am J Kidney Dis. 2010;55(1):69–76. Epub 2009/11/21.

    PubMed  Google Scholar 

  58. Navaneethan SD, Yehnert H, Moustarah F, Schreiber MJ, Schauer PR, Beddhu S. Weight loss interventions in chronic kidney disease: a systematic review and meta-analysis. Clin J Am Soc Nephrol. 2009;4(10):1565–74. Epub 2009/10/08.

    PubMed Central  PubMed  Google Scholar 

  59. Morales E, Praga M. The effect of weight loss in obesity and chronic kidney disease. Curr Hypertens Rep. 2012;14(2):170–6. Epub 2012/01/20.

    PubMed  Google Scholar 

  60. Reiner Z, Catapano AL, De Backer G, Graham I, Taskinen MR, Wiklund O, et al. ESC/EAS Guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J. 2011;32(14):1769–818. Epub 2011/06/30.

    PubMed  Google Scholar 

  61. Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C, et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005;366(9493):1267–78. Epub 2005/10/11.

    PubMed  CAS  Google Scholar 

  62. Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376(9753):1670–81. Epub 2010/11/12.

    PubMed  Google Scholar 

  63. Cannon CP, Steinberg BA, Murphy SA, Mega JL, Braunwald E. Meta-analysis of cardiovascular outcomes trials comparing intensive versus moderate statin therapy. J Am Coll Cardiol. 2006;48(3):438–45. Epub 2006/08/01.

    PubMed  CAS  Google Scholar 

  64. Cannon CP, Braunwald E, McCabe CH, Rader DJ, Rouleau JL, Belder R, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004;350(15):1495–504. Epub 2004/03/10.

    PubMed  CAS  Google Scholar 

  65. LaRosa JC, Grundy SM, Waters DD, Shear C, Barter P, Fruchart JC, et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med. 2005;352(14):1425–35. Epub 2005/03/10.

    PubMed  CAS  Google Scholar 

  66. Armitage J, Bowman L, Wallendszus K, Bulbulia R, Rahimi K, Haynes R, et al. Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12,064 survivors of myocardial infarction: a double-blind randomised trial. Lancet. 2010;376(9753):1658–69. Epub 2010/11/12.

    PubMed  Google Scholar 

  67. Rossebo AB, Pedersen TR, Boman K, Brudi P, Chambers JB, Egstrup K, et al. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. N Engl J Med. 2008;359(13):1343–56. Epub 2008/09/04.

    PubMed  Google Scholar 

  68. Toth PP, Morrone D, Weintraub WS, Hanson ME, Lowe RS, Lin J, et al. Safety profile of statins alone or combined with ezetimibe: a pooled analysis of 27 studies including over 22,000 patients treated for 6–24 weeks. Int J Clin Pract. 2012;66(8):800–12. Epub 2012/07/19.

    PubMed  CAS  Google Scholar 

  69. Baigent C, Landray MJ, Reith C, Emberson J, Wheeler DC, Tomson C, et al. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. Lancet. 2011;377(9784):2181–92. Epub 2011/06/15.

    PubMed Central  PubMed  CAS  Google Scholar 

  70. Levy P. Review of studies on the effect of bile acid sequestrants in patients with type 2 diabetes mellitus. Metab Syndr Relat Dis. 2010;8 Suppl 1:S9–13. Epub 2010/10/16.

    CAS  Google Scholar 

  71. Jacobson TA, Armani A, McKenney JM, Guyton JR. Safety considerations with gastrointestinally active lipid-lowering drugs. Am J Cardiol. 2007;99(6A):47C–55. Epub 2007/03/21.

    PubMed  CAS  Google Scholar 

  72. Montague T, Murphy B. Lipid management in chronic kidney disease, hemodialysis, and transplantation. Endocrinol Metab Clin North Am. 2009;38(1):223–34. Epub 2009/02/17.

    PubMed  CAS  Google Scholar 

  73. Yamada K, Fujimoto S, Tokura T, Fukudome K, Ochiai H, Komatsu H, et al. Effect of sevelamer on dyslipidemia and chronic inflammation in maintenance hemodialysis patients. Renal failure. 2005;27(4):361–5. Epub 2005/08/03.

    PubMed  CAS  Google Scholar 

  74. Chertow GM, Burke SK, Raggi P. Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients. Kidney Int. 2002;62(1):245–52. Epub 2002/06/26.

    PubMed  CAS  Google Scholar 

  75. Chertow GM, Burke SK, Dillon MA, Slatopolsky E. Long-term effects of sevelamer hydrochloride on the calcium x phosphate product and lipid profile of haemodialysis patients. Nephrol Dial Transplant. 1999;14(12):2907–14. Epub 1999/11/26.

    PubMed  CAS  Google Scholar 

  76. Block GA, Spiegel DM, Ehrlich J, Mehta R, Lindbergh J, Dreisbach A, et al. Effects of sevelamer and calcium on coronary artery calcification in patients new to hemodialysis. Kidney Int. 2005;68(4):1815–24. Epub 2005/09/17.

    PubMed  CAS  Google Scholar 

  77. Chapman MJ, Redfern JS, McGovern ME, Giral P. Niacin and fibrates in atherogenic dyslipidemia: pharmacotherapy to reduce cardiovascular risk. Pharmacol Ther. 2010;126(3):314–45. Epub 2010/02/16.

    PubMed  CAS  Google Scholar 

  78. Zhao XQ, Krasuski RA, Baer J, Whitney EJ, Neradilek B, Chait A, et al. Effects of combination lipid therapy on coronary stenosis progression and clinical cardiovascular events in coronary disease patients with metabolic syndrome: a combined analysis of the Familial Atherosclerosis Treatment Study (FATS), the HDL-Atherosclerosis Treatment Study (HATS), and the Armed Forces Regression Study (AFREGS). Am J Cardiol. 2009;104(11):1457–64. Epub 2009/11/26.

    PubMed Central  PubMed  CAS  Google Scholar 

  79. Huijgen R, Abbink EJ, Bruckert E, Stalenhoef AF, Imholz BP, Durrington PN, et al. Colesevelam added to combination therapy with a statin and ezetimibe in patients with familial hypercholesterolemia: a 12-week, multicenter, randomized, double-blind, controlled trial. Clin Ther. 2010;32(4):615–25. Epub 2010/05/04.

    PubMed  CAS  Google Scholar 

  80. Ballantyne CM, Weiss R, Moccetti T, Vogt A, Eber B, Sosef F, et al. Efficacy and safety of rosuvastatin 40 mg alone or in combination with ezetimibe in patients at high risk of cardiovascular disease (results from the EXPLORER study). Am J Cardiol. 2007;99(5):673–80. Epub 2007/02/24.

    PubMed  CAS  Google Scholar 

  81. Sarwar N, Sandhu MS, Ricketts SL, Butterworth AS, Di Angelantonio E, Boekholdt SM, et al. Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies. Lancet. 2010;375(9726):1634–9. Epub 2010/05/11.

    PubMed  CAS  Google Scholar 

  82. Frick MH, Elo O, Haapa K, Heinonen OP, Heinsalmi P, Helo P, et al. Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease. N Engl J Med. 1987;317(20):1237–45.

    PubMed  CAS  Google Scholar 

  83. Rubins HB, Robins SJ, Collins D, Fye CL, Anderson JW, Elam MB, et al. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N Engl J Med. 1999;341(6):410–8. Epub 1999/08/07.

    PubMed  CAS  Google Scholar 

  84. Bezafibrate Infarction Prevention (BIP) study. Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coronary artery disease: the Bezafibrate Infarction Prevention (BIP) study. Circulation. 2000;102(1):21–7. Epub 2000/07/06.

    Google Scholar 

  85. Keech A, Simes RJ, Barter P, Best J, Scott R, Taskinen MR, et al. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet. 2005;366(9500):1849–61. Epub 2005/11/29.

    PubMed  CAS  Google Scholar 

  86. Jun M, Foote C, Lv J, Neal B, Patel A, Nicholls SJ, et al. Effects of fibrates on cardiovascular outcomes: a systematic review and meta-analysis. Lancet. 2010;375(9729):1875–84. Epub 2010/05/14.

    PubMed  CAS  Google Scholar 

  87. Davidson MH, Armani A, McKenney JM, Jacobson TA. Safety considerations with fibrate therapy. Am J Cardiol. 2007;99(6A):3C–18. Epub 2007/03/21.

    PubMed  CAS  Google Scholar 

  88. Taskinen MR, Sullivan DR, Ehnholm C, Whiting M, Zannino D, Simes RJ, et al. Relationships of HDL cholesterol, ApoA-I, and ApoA-II with homocysteine and creatinine in patients with type 2 diabetes treated with fenofibrate. Arterioscler Thromb Vasc Biol. 2009;29(6):950–5. Epub 2009/03/28.

    PubMed  CAS  Google Scholar 

  89. McCullough PA, Ahmed AB, Zughaib MT, Glanz ED, Di Loreto MJ. Treatment of hypertriglyceridemia with fibric acid derivatives: impact on lipid subfractions and translation into a reduction in cardiovascular events. Rev Cardiovasc Med. 2011;12(4):173–85. Epub 2012/01/18.

    PubMed  Google Scholar 

  90. Ginsberg HN, Elam MB, Lovato LC, Crouse III JR, Leiter LA, Linz P, et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med. 2010;362(17):1563–74. Epub 2010/03/17.

    PubMed  Google Scholar 

  91. Boden WE, Probstfield JL, Anderson T, Chaitman BR, Desvignes-Nickens P, Koprowicz K, et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011;365(24):2255–67. Epub 2011/11/17.

    PubMed  Google Scholar 

  92. Keane WF, Tomassini JE, Neff DR. Lipid abnormalities in patients with chronic kidney disease: implications for the pathophysiology of atherosclerosis. J Atheroscler Thromb. 2013;20(2):123–33. Epub 2012/10/26.

    PubMed  CAS  Google Scholar 

  93. Tonelli M, Collins D, Robins S, Bloomfield H, Curhan GC. Gemfibrozil for secondary prevention of cardiovascular events in mild to moderate chronic renal insufficiency. Kidney Int. 2004;66(3):1123–30. Epub 2004/08/26.

    PubMed  CAS  Google Scholar 

  94. Ting RD, Keech AC, Drury PL, Donoghoe MW, Hedley J, Jenkins AJ, et al. Benefits and safety of long-term fenofibrate therapy in people with type 2 diabetes and renal impairment: the FIELD Study. Diabetes Care. 2012;35(2):218–25. Epub 2012/01/03.

    PubMed Central  PubMed  CAS  Google Scholar 

  95. Slinin Y, Ishani A, Rector T, Fitzgerald P, MacDonald R, Tacklind J, et al. Management of hyperglycemia, dyslipidemia, and albuminuria in patients with diabetes and CKD: a systematic review for a KDOQI clinical practice guideline. Am J Kidney Dis. 2012;60(5):747–69. Epub 2012/09/25.

    PubMed  Google Scholar 

  96. Lee MS, Kim SM, Kim SB, Lee SK, Park JS, Yang WS. Effects of gemfibrozil on lipid and hemostatic factors in CAPD patients. Perit Dial Int. 1999;19(3):280–3. Epub 1999/08/05.

    PubMed  CAS  Google Scholar 

  97. Lucatello A, Sturani A, Di Nardo AM, Cocchi R, Fusaroli M. Safe use of gemfibrozil in uremic patients on continuous ambulatory peritoneal dialysis. Nephron. 1998;78(3):338. Epub 1998/04/18.

    PubMed  CAS  Google Scholar 

  98. Clouatre Y, Leblanc M, Ouimet D, Pichette V. Fenofibrate-induced rhabdomyolysis in two dialysis patients with hypothyroidism. Nephrol Dial Transplant. 1999;14(4):1047–8. Epub 1999/05/18.

    PubMed  CAS  Google Scholar 

  99. Hottelart C, El Esper N, Rose F, Achard JM, Fournier A. Fenofibrate increases creatininemia by increasing metabolic production of creatinine. Nephron. 2002;92(3):536–41. Epub 2002/10/10.

    PubMed  CAS  Google Scholar 

  100. Brown WV. Expert commentary: the safety of fibrates in lipid-lowering therapy. Am J Cardiol. 2007;99(6A):19C–21. Epub 2007/03/21.

    PubMed  CAS  Google Scholar 

  101. Ansquer JC, Dalton RN, Causse E, Crimet D, Le Malicot K, Foucher C. Effect of fenofibrate on kidney function: a 6-week randomized crossover trial in healthy people. Am J Kidney Dis. 2008;51(6):904–13. Epub 2008/05/27.

    PubMed  CAS  Google Scholar 

  102. Hottelart C, el Esper N, Achard JM, Pruna A, Fournier A. [Fenofibrate increases blood creatinine, but does not change the glomerular filtration rate in patients with mild renal insufficiency]. Nephrologie. 1999;20(1):41–4. Epub 1999/03/19. Le fenofibrate augmente la creatininemie mais n’altere pas le debit de filtration glomerulaire chez les patients presentant une insuffisance renale moderee.

    Google Scholar 

  103. Devuyst O, Goffin E, Pirson Y, van Ypersele de Strihou C. Creatinine rise after fibrate therapy in renal graft recipients. Lancet. 1993;341(8848):840.

    PubMed  CAS  Google Scholar 

  104. Zhao YY, Weir MA, Manno M, Cordy P, Gomes T, Hackam DG, et al. New fibrate use and acute renal outcomes in elderly adults: a population-based study. Ann Intern Med. 2012;156(8):560–9. Epub 2012/04/18.

    PubMed  Google Scholar 

  105. Davis TM, Ting R, Best JD, Donoghoe MW, Drury PL, Sullivan DR, et al. Effects of fenofibrate on renal function in patients with type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study. Diabetologia. 2011;54(2):280–90. Epub 2010/11/06.

    PubMed  CAS  Google Scholar 

  106. Tonelli M, Collins D, Robins S, Bloomfield H, Curhan GC. Effect of gemfibrozil on change in renal function in men with moderate chronic renal insufficiency and coronary disease. Am J Kidney Dis. 2004;44(5):832–9. Epub 2004/10/20.

    PubMed  CAS  Google Scholar 

  107. Mychaleckyj JC, Craven T, Nayak U, Buse J, Crouse JR, Elam M, et al. Reversibility of fenofibrate therapy-induced renal function impairment in ACCORD type 2 diabetic participants. Diabetes Care. 2012;35(5):1008–14. Epub 2012/03/21.

    PubMed Central  PubMed  CAS  Google Scholar 

  108. Lipscombe J, Lewis GF, Cattran D, Bargman JM. Deterioration in renal function associated with fibrate therapy. Clin Nephrol. 2001;55(1):39–44. Epub 2001/02/24.

    PubMed  CAS  Google Scholar 

  109. Kamanna VS, Kashyap ML. Mechanism of action of niacin. Am J Cardiol. 2008;101(8A):20B–6. Epub 2008/06/14.

    PubMed  CAS  Google Scholar 

  110. Canner PL, Berge KG, Wenger NK, Stamler J, Friedman L, Prineas RJ, et al. Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin. J Am Coll Cardiol. 1986;8(6):1245–55. Epub 1986/12/01.

    PubMed  CAS  Google Scholar 

  111. Bruckert E, Labreuche J, Amarenco P. Meta-analysis of the effect of nicotinic acid alone or in combination on cardiovascular events and atherosclerosis. Atherosclerosis. 2010;210(2):353–61. Epub 2010/01/19.

    PubMed  CAS  Google Scholar 

  112. Lee JM, Robson MD, Yu LM, Shirodaria CC, Cunnington C, Kylintireas I, et al. Effects of high-dose modified-release nicotinic acid on atherosclerosis and vascular function: a randomized, placebo-controlled, magnetic resonance imaging study. J Am Coll Cardiol. 2009;54(19):1787–94. Epub 2009/10/31.

    PubMed  CAS  Google Scholar 

  113. Villines TC, Stanek EJ, Devine PJ, Turco M, Miller M, Weissman NJ, et al. The ARBITER 6-HALTS Trial (Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol 6-HDL and LDL Treatment Strategies in Atherosclerosis): final results and the impact of medication adherence, dose, and treatment duration. J Am Coll Cardiol. 2010;55(24):2721–6. Epub 2010/04/20.

    PubMed  Google Scholar 

  114. Lavigne PM, Karas RH. The current state of niacin in cardiovascular disease prevention: a systematic review and meta-regression. J Am Coll Cardiol. 2013;61(4):440–6. Epub 2012/12/26.

    PubMed  CAS  Google Scholar 

  115. Niacin causes serious unexpected side-effects, but no worthwhile benefits, for patients who are at increased risk of heart attacks and strokes; 2013 [April 17, 2013]. http://www.thrivestudy.org/press_release.htm.

  116. HPS2-THRIVE Collaborative Group. HPS2-THRIVE randomized placebo-controlled trial in 25 673 high-risk patients of ER niacin/laropiprant: trial design, pre-specified muscle and liver outcomes, and reasons for stopping study treatment. Eur Heart J. 2013;34(17):1279–91.

    PubMed Central  Google Scholar 

  117. Lai E, De Lepeleire I, Crumley TM, Liu F, Wenning LA, Michiels N, et al. Suppression of niacin-induced vasodilation with an antagonist to prostaglandin D2 receptor subtype 1. Clin Pharmacol Ther. 2007;81(6):849–57. Epub 2007/03/30.

    PubMed  CAS  Google Scholar 

  118. Alsheikh-Ali AA, Karas RH. The safety of niacin in the US Food and Drug Administration adverse event reporting database. Am J Cardiol. 2008;101(8A):9B–13. Epub 2008/06/14.

    PubMed  CAS  Google Scholar 

  119. Ballantyne CM, Davidson MH, McKenney J, Keller LH, Bajorunas DR, Karas RH. Comparison of the safety and efficacy of a combination tablet of niacin extended release and simvastatin vs simvastatin monotherapy in patients with increased non-HDL cholesterol (from the SEACOAST I study). Am J Cardiol. 2008;101(10):1428–36. Epub 2008/05/13.

    PubMed  CAS  Google Scholar 

  120. Grundy SM, Vega GL, Yuan Z, Battisti WP, Brady WE, Palmisano J. Effectiveness and tolerability of simvastatin plus fenofibrate for combined hyperlipidemia (the SAFARI trial). Am J Cardiol. 2005;95(4):462–8. Epub 2005/02/08.

    PubMed  CAS  Google Scholar 

  121. McKenney JM, Jones PH, Bays HE, Knopp RH, Kashyap ML, Ruoff GE, et al. Comparative effects on lipid levels of combination therapy with a statin and extended-release niacin or ezetimibe versus a statin alone (the COMPELL study). Atherosclerosis. 2007;192(2):432–7. Epub 2007/01/24.

    PubMed  CAS  Google Scholar 

  122. Guyton JR, Brown BG, Fazio S, Polis A, Tomassini JE, Tershakovec AM. Lipid-altering efficacy and safety of ezetimibe/simvastatin coadministered with extended-release niacin in patients with type IIa or type IIb hyperlipidemia. J Am Coll Cardiol. 2008;51(16):1564–72. Epub 2008/04/19.

    PubMed  CAS  Google Scholar 

  123. Davidson MH, Stein EA, Bays HE, Maki KC, Doyle RT, Shalwitz RA, et al. Efficacy and tolerability of adding prescription omega-3 fatty acids 4 g/d to simvastatin 40 mg/d in hypertriglyceridemic patients: an 8-week, randomized, double-blind, placebo-controlled study. Clin Ther. 2007;29(7):1354–67. Epub 2007/09/11.

    PubMed  CAS  Google Scholar 

  124. Castelli WP, Garrison RJ, Wilson PW, Abbott RD, Kalousdian S, Kannel WB. Incidence of coronary heart disease and lipoprotein cholesterol levels. The Framingham Study. JAMA. 1986;256(20):2835–8. Epub 1986/11/28.

    PubMed  CAS  Google Scholar 

  125. Gordon DJ, Probstfield JL, Garrison RJ, Neaton JD, Castelli WP, Knoke JD, et al. High-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies. Circulation. 1989;79(1):8–15. Epub 1989/01/01.

    PubMed  CAS  Google Scholar 

  126. Cooney MT, Dudina A, De Bacquer D, Wilhelmsen L, Sans S, Menotti A, et al. HDL cholesterol protects against cardiovascular disease in both genders, at all ages and at all levels of risk. Atherosclerosis. 2009;206(2):611–6. Epub 2009/04/21.

    PubMed  CAS  Google Scholar 

  127. Jafri H, Alsheikh-Ali AA, Karas RH. Meta-analysis: statin therapy does not alter the association between low levels of high-density lipoprotein cholesterol and increased cardiovascular risk. Ann Intern Med. 2010;153(12):800–8. Epub 2010/12/22.

    PubMed  Google Scholar 

  128. Chapman MJ, Ginsberg HN, Amarenco P, Andreotti F, Boren J, Catapano AL, et al. Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management. Eur Heart J. 2011;32(11):1345–61. Epub 2011/05/03.

    PubMed Central  PubMed  CAS  Google Scholar 

  129. Rahilly-Tierney C, Sesso HD, Djousse L, Gaziano JM. Lifestyle changes and 14-year change in high-density lipoprotein cholesterol in a cohort of male physicians. Am Heart J. 2011;161(4):712–8. Epub 2011/04/09.

    PubMed Central  PubMed  Google Scholar 

  130. Wing RR. Long-term effects of a lifestyle intervention on weight and cardiovascular risk factors in individuals with type 2 diabetes mellitus: four-year results of the Look AHEAD trial. Arch Intern Med. 2010;170(17):1566–75. Epub 2010/09/30.

    PubMed  CAS  Google Scholar 

  131. Toth PP. High-density lipoprotein as a therapeutic target: clinical evidence and treatment strategies. Am J Cardiol. 2005;96(9A):50K–8; discussion 34K–5K. Epub 2005/11/18.

    PubMed  CAS  Google Scholar 

  132. Kuvin JT, Dave DM, Sliney KA, Mooney P, Patel AR, Kimmelstiel CD, et al. Effects of extended-release niacin on lipoprotein particle size, distribution, and inflammatory markers in patients with coronary artery disease. Am J Cardiol. 2006;98(6):743–5. Epub 2006/09/05.

    PubMed  CAS  Google Scholar 

  133. Schaefer EJ, Asztalos BF. Increasing high-density lipoprotein cholesterol, inhibition of cholesteryl ester transfer protein, and heart disease risk reduction. Am J Cardiol. 2007;100(11 A):n25–31. Epub 2007/12/06.

    PubMed  Google Scholar 

  134. Barter PJ, Kastelein JJ. Targeting cholesteryl ester transfer protein for the prevention and management of cardiovascular disease. J Am Coll Cardiol. 2006;47(3):492–9. Epub 2006/02/07.

    PubMed  CAS  Google Scholar 

  135. Forrester JS, Makkar R, Shah PK. Increasing high-density lipoprotein cholesterol in dyslipidemia by cholesteryl ester transfer protein inhibition: an update for clinicians. Circulation. 2005;111(14):1847–54. Epub 2005/04/13.

    PubMed  CAS  Google Scholar 

  136. Natarajan P, Ray KK, Cannon CP. High-density lipoprotein and coronary heart disease: current and future therapies. J Am Coll Cardiol. 2010;55(13):1283–99. Epub 2010/03/27.

    PubMed  CAS  Google Scholar 

  137. Barter PJ, Caulfield M, Eriksson M, Grundy SM, Kastelein JJ, Komajda M, et al. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med. 2007;357(21):2109–22. Epub 2007/11/07.

    PubMed  CAS  Google Scholar 

  138. Schwartz GG, Olsson AG, Abt M, Ballantyne CM, Barter PJ, Brumm J, et al. Effects of dalcetrapib in patients with a recent acute coronary syndrome. N Engl J Med. 2012;367(22):2089–99. Epub 2012/11/07.

    PubMed  CAS  Google Scholar 

  139. Voight BF, Peloso GM, Orho-Melander M, Frikke-Schmidt R, Barbalic M, Jensen MK, et al. Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study. Lancet. 2012;380(9841):572–80. Epub 2012/05/23.

    PubMed Central  PubMed  CAS  Google Scholar 

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Mucsi, I. (2014). Non-statin Therapies for CKD with Dyslipidemia. In: Covic, A., Kanbay, M., Lerma, E. (eds) Dyslipidemias in Kidney Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-0515-7_9

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