Skip to main content

How Lipid-Lowering Agents Work: The Good, the Bad, and the Ugly

  • Chapter
  • First Online:
Book cover Dyslipidemias in Kidney Disease

Abstract

Hyperlipidemia in the general population is strongly associated with atherosclerotic cardiovascular disease. Dyslipidemia is a common finding in patients with chronic kidney disease (CKD) at all stages. Trial results from the general population may not be applicable to all patients with CKD because they have a different lipid profile with increased atherogenic lipid fractions. Lipid-lowering therapies in these patients may have substantial benefit. Statin therapy is recommended in patients with CKD of any stage if they have elevated serum cholesterol levels. Treatment of dyslipidemia in patients with early stage CKD clearly reduces cardiovascular risk; however, available data do not support a strong nephroprotective role for statins in CKD population. In contrast to the predialysis patient population, statins do not seem to have substantial improvement in cardiovascular outcomes in dialysis patients. Although fibrates can be used to treat mixed dyslipidemia, they need to be used carefully in patients with CKD, and limited available data suggest that fibrates may have a place in reducing cardiovascular risk in patients with mild to moderate CKD.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Attman PO, Samuelsson O, Alaupovic P. The effect of decreasing renal function on lipoprotein profiles. Nephrol Dial Transplant. 2011;26(8):2572–5.

    Article  PubMed  CAS  Google Scholar 

  2. Kasiske BL. Hyperlipidemia in patients with chronic renal disease. Am J Kidney Dis. 1998;32(5 Suppl 3):S142–56.

    Article  PubMed  CAS  Google Scholar 

  3. National Cholesterol Education Program (NCEP) Expert Panel on Detection Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). 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.

    Google Scholar 

  4. Contreras G, Hu B, Astor BC, Greene T, Erlinger T, Kusek JW, et al. Malnutrition-inflammation modifies the relationship of cholesterol with cardiovascular disease. J Am Soc Nephrol. 2010;21(12):2131–42.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  5. Kilpatrick RD, McAllister CJ, Kovesdy CP, Derose SF, Kopple JD, Kalantar-Zadeh K. Association between serum lipids and survival in hemodialysis patients and impact of race. J Am Soc Nephrol. 2007;18(1):293–303.

    Article  PubMed  CAS  Google Scholar 

  6. Chawla V, Greene T, Beck GJ, Kusek JW, Collins AJ, Sarnak MJ, et al. Hyperlipidemia and long-term outcomes in nondiabetic chronic kidney disease. Clin J Am Soc Nephrol. 2010;5(9):1582–7.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  7. 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.

    Article  PubMed  CAS  Google Scholar 

  8. Liu Y, Coresh J, Eustace JA, Longenecker JC, Jaar B, Fink NE, et al. Association between cholesterol level and mortality in dialysis patients: role of inflammation and malnutrition. JAMA. 2004;291(4):451–9.

    Article  PubMed  CAS  Google Scholar 

  9. Jellinger PS, Smith DA, Mehta AE, Ganda O, Handelsman Y, Rodbard HW, et al. American Association of Clinical Endocrinologists’ guidelines for management of dyslipidemia and prevention of atherosclerosis. Endocr Pract. 2012;18 Suppl 1:1–78.

    Article  PubMed  Google Scholar 

  10. Jones PH, Davidson MH, Stein EA, Bays HE, McKenney JM, Miller E, et al. Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR* Trial). Am J Cardiol. 2003;92(2):152–60.

    Article  PubMed  CAS  Google Scholar 

  11. Vaughan CJ, Gotto AM, Basson CT. The evolving role of statins in the management of atherosclerosis. J Am Coll Cardiol. 2000;35(1):1–10.

    Article  PubMed  CAS  Google Scholar 

  12. Neuvonen PJ, Backman JT, Niemi M. Pharmacokinetic comparison of the potential over-the-counter statins simvastatin, lovastatin, fluvastatin and pravastatin. Clin Pharmacokinet. 2008;47(7):463–74.

    Article  PubMed  CAS  Google Scholar 

  13. Eidelman RS, Lamas GA, Hennekens CH. The new National Cholesterol Education Program guidelines: clinical challenges for more widespread therapy of lipids to treat and prevent coronary heart disease. Arch Intern Med. 2002;162(18):2033–6.

    Article  PubMed  Google Scholar 

  14. Callister TQ, Raggi P, Cooil B, Lippolis NJ, Russo DJ. Effect of HMG-CoA reductase inhibitors on coronary artery disease as assessed by electron-beam computed tomography. N Engl J Med. 1998;339(27):1972–8.

    Article  PubMed  CAS  Google Scholar 

  15. Brugts JJ, Yetgin T, Hoeks SE, Gotto AM, Shepherd J, Westendorp RG, et al. The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: meta-analysis of randomised controlled trials. BMJ. 2009;338:b2376.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  16. Tonelli M, Isles C, Curhan GC, Tonkin A, Pfeffer MA, Shepherd J, et al. Effect of pravastatin on cardiovascular events in people with chronic kidney disease. Circulation. 2004;110(12):1557–63.

    Article  PubMed  CAS  Google Scholar 

  17. Muhlestein JB, Anderson JL, Horne BD, Carlquist JF, Bair TL, Bunch TJ, et al. Early effects of statins in patients with coronary artery disease and high C-reactive protein. Am J Cardiol. 2004;94(9):1107–12.

    Article  PubMed  CAS  Google Scholar 

  18. Kanat M, Yildiz M, Tunckale A, Ceyhan BO, Karagoz Y, Altuntaş Y, et al. Intensive lipid reduction and proinflammatory markers in the MODEST study. Turk Jem. 2010;14:31–4.

    Google Scholar 

  19. Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994;344(8934):1383–9.

    Google Scholar 

  20. K/DOQI Workgroup. K/DOQI clinical practice guidelines for cardiovascular disease in dialysis patients. Am J Kidney Dis. 2005;45(4 Suppl 3):S1–153.

    Google Scholar 

  21. KDOQIKD Group. K/DOQI clinical practice guidelines for management of dyslipidemias in patients with kidney disease. Am J Kidney Dis. 2003;41(4 Suppl 3):I–IV, S1–91.

    Google Scholar 

  22. Kimura K, Shimano H, Yokote K, Urashima M, Teramoto T. Effects of pitavastatin (LIVALO tablet) on the estimated glomerular filtration rate (eGFR) in hypercholesterolemic patients with chronic kidney disease. Sub-analysis of the LIVALO Effectiveness and Safety (LIVES) study. J Atheroscler Thromb. 2010;17(6):601–9.

    Article  PubMed  CAS  Google Scholar 

  23. Ridker PM, MacFadyen J, Cressman M, Glynn RJ. Efficacy of rosuvastatin among men and women with moderate chronic kidney disease and elevated high-sensitivity C-reactive protein: a secondary analysis from the JUPITER (Justification for the Use of Statins in Prevention-an Intervention Trial Evaluating Rosuvastatin) trial. J Am Coll Cardiol. 2010;55(12):1266–73.

    Article  PubMed  CAS  Google Scholar 

  24. 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.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  25. Ruggenenti P, Perna A, Tonelli M, Loriga G, Motterlini N, Rubis N, et al. Effects of add-on fluvastatin therapy in patients with chronic proteinuric nephropathy on dual renin-angiotensin system blockade: the ESPLANADE trial. Clin J Am Soc Nephrol. 2010;5(11):1928–38.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  26. Douglas K, O’Malley PG, Jackson JL. Meta-analysis: the effect of statins on albuminuria. Ann Intern Med. 2006;145(2):117–24.

    Article  PubMed  CAS  Google Scholar 

  27. Athyros VG, Mikhailidis DP, Papageorgiou AA, Symeonidis AN, Pehlivanidis AN, Bouloukos VI, et al. The effect of statins versus untreated dyslipidaemia on renal function in patients with coronary heart disease. A subgroup analysis of the Greek atorvastatin and coronary heart disease evaluation (GREACE) study. J Clin Pathol. 2004;57(7):728–34.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  28. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360(9326):7–22.

    Article  Google Scholar 

  29. Shepherd J, Kastelein JJ, Bittner V, Deedwania P, Breazna A, Dobson S, et al. Intensive lipid lowering with atorvastatin in patients with coronary heart disease and chronic kidney disease: the TNT (Treating to New Targets) study. J Am Coll Cardiol. 2008;51(15):1448–54.

    Article  PubMed  CAS  Google Scholar 

  30. Navaneethan SD, Pansini F, Perkovic V, Manno C, Pellegrini F, Johnson DW, et al. HMG CoA reductase inhibitors (statins) for people with chronic kidney disease not requiring dialysis. Cochrane Database Syst Rev. 2009(2):CD007784.

    Google Scholar 

  31. Muntner P, Coresh J, Smith JC, Eckfeldt J, Klag MJ. Plasma lipids and risk of developing renal dysfunction: the atherosclerosis risk in communities study. Kidney Int. 2000;58(1):293–301.

    Article  PubMed  CAS  Google Scholar 

  32. Chen J, Muntner P, Hamm LL, Jones DW, Batuman V, Fonseca V, et al. The metabolic syndrome and chronic kidney disease in U.S. adults. Ann Intern Med. 2004;140(3):167–74.

    Article  PubMed  Google Scholar 

  33. de Boer IH, Astor BC, Kramer H, Palmas W, Seliger SL, Shlipak MG, et al. Lipoprotein abnormalities associated with mild impairment of kidney function in the multi-ethnic study of atherosclerosis. Clin J Am Soc Nephrol. 2008;3(1):125–32.

    Article  PubMed Central  PubMed  Google Scholar 

  34. Samuelsson O, Mulec H, Knight-Gibson C, Attman PO, Kron B, Larsson R, et al. Lipoprotein abnormalities are associated with increased rate of progression of human chronic renal insufficiency. Nephrol Dial Transplant. 1997;12(9):1908–15.

    Article  PubMed  CAS  Google Scholar 

  35. Collins R, Armitage J, Parish S, Sleigh P, Peto R, Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet. 2003;361(9374):2005–16.

    Article  PubMed  Google Scholar 

  36. Athyros VG, Papageorgiou AA, Mercouris BR, Athyrou VV, Symeonidis AN, Basayannis EO, et al. Treatment with atorvastatin to the National Cholesterol Educational Program goal versus ‘usual’ care in secondary coronary heart disease prevention. The GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) study. Curr Med Res Opin. 2002;18(4):220–8.

    Article  PubMed  Google Scholar 

  37. Shepherd J, Kastelein JJ, Bittner V, Deedwania P, Breazna A, Dobson S, et al. Effect of intensive lipid lowering with atorvastatin on renal function in patients with coronary heart disease: the Treating to New Targets (TNT) study. Clin J Am Soc Nephrol. 2007;2(6):1131–9.

    Article  PubMed  CAS  Google Scholar 

  38. Atthobari J, Brantsma AH, Gansevoort RT, Visser ST, Asselbergs FW, van Gilst WH, et al. The effect of statins on urinary albumin excretion and glomerular filtration rate: results from both a randomized clinical trial and an observational cohort study. Nephrol Dial Transplant. 2006;21(11):3106–14.

    Article  PubMed  CAS  Google Scholar 

  39. Rahman M, Baimbridge C, Davis BR, Barzilay J, Basile JN, Henriquez MA, et al. Progression of kidney disease in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin versus usual care: a report from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Am J Kidney Dis. 2008;52(3):412–24.

    Article  PubMed Central  PubMed  Google Scholar 

  40. Keller DM. PLANET I and II: atorvastatin beats rosuvastatin for protecting kidneys in diabetic and nondiabetic patients. 2010. http://www.theheart.org/article/1095269.do.

  41. Alsheikh-Ali AA, Ambrose MS, Kuvin JT, Karas RH. The safety of rosuvastatin as used in common clinical practice: a postmarketing analysis. Circulation. 2005;111(23):3051–7.

    Article  PubMed  Google Scholar 

  42. Deslypere JP, Delanghe J, Vermeulen A. Proteinuria as complication of simvastatin treatment. Lancet. 1990;336(8728):1453.

    Article  PubMed  CAS  Google Scholar 

  43. Ozsoy RC, Koopman MG, Kastelein JJ, Arisz L. The acute effect of atorvastatin on proteinuria in patients with chronic glomerulonephritis. Clin Nephrol. 2005;63(4):245–9.

    Article  PubMed  CAS  Google Scholar 

  44. Remuzzi G, Macia M, Ruggenenti P. Prevention and treatment of diabetic renal disease in type 2 diabetes: the BENEDICT study. J Am Soc Nephrol. 2006;17(4 Suppl 2):S90–7.

    Article  PubMed  Google Scholar 

  45. Seliger SL, Weiss NS, Gillen DL, Kestenbaum B, Ball A, Sherrard DJ, et al. HMG-CoA reductase inhibitors are associated with reduced mortality in ESRD patients. Kidney Int. 2002;61(1):297–304.

    Article  PubMed  CAS  Google Scholar 

  46. Andreucci VE, Fissell RB, Bragg-Gresham JL, Ethier J, Greenwood R, Pauly M, et al. Dialysis Outcomes and Practice Patterns Study (DOPPS) data on medications in hemodialysis patients. Am J Kidney Dis. 2004;44(5 Suppl 2):61–7.

    Article  PubMed  Google Scholar 

  47. Wanner C, Krane V, März W, Olschewski M, Mann JF, Ruf G, et al. Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N Engl J Med. 2005;353(3):238–48.

    Article  PubMed  CAS  Google Scholar 

  48. Fellström BC, Jardine AG, Schmieder RE, Holdaas H, Bannister K, Beutler J, et al. Rosuvastatin and cardiovascular events in patients undergoing hemodialysis. N Engl J Med. 2009;360(14):1395–407.

    Article  PubMed  Google Scholar 

  49. Moore R, Thomas D, Morgan E, Wheeler D, Griffin P, Salaman J, et al. Abnormal lipid and lipoprotein profiles following renal transplantation. Transplant Proc. 1993;25(1 Pt 2):1060–1.

    PubMed  CAS  Google Scholar 

  50. Kasiske B, Cosio FG, Beto J, Bolton K, Chavers BM, Grimm 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.

    Article  PubMed  Google Scholar 

  51. Holdaas H, Fellström B, Jardine AG, Holme I, Nyberg G, Fauchald P, et al. Effect of fluvastatin on cardiac outcomes in renal transplant recipients: a multicentre, randomised, placebo-controlled trial. Lancet. 2003;361(9374):2024–31.

    Article  PubMed  CAS  Google Scholar 

  52. Holdaas H, Fellström B, Cole E, Nyberg G, Olsson AG, Pedersen TR, et al. Long-term cardiac outcomes in renal transplant recipients receiving fluvastatin: the ALERT extension study. Am J Transplant. 2005;5(12):2929–36.

    Article  PubMed  CAS  Google Scholar 

  53. Navaneethan SD, Perkovic V, Johnson DW, Nigwekar SU, Craig JC, Strippoli GF. HMG CoA reductase inhibitors (statins) for kidney transplant recipients. Cochrane Database Syst Rev. 2009(2):CD005019.

    Google Scholar 

  54. Palmer SC, Craig JC, Navaneethan SD, Tonelli M, Pellegrini F, Strippoli GF. Benefits and harms of statin therapy for persons with chronic kidney disease: a systematic review and meta-analysis. Ann Intern Med. 2012;157(4):263–75.

    Article  PubMed Central  PubMed  Google Scholar 

  55. Rosenson RS. Current overview of statin-induced myopathy. Am J Med. 2004;116(6):408–16.

    Article  PubMed  CAS  Google Scholar 

  56. Thompson PD, Clarkson PM, Rosenson RS, Panel NLASSTFMSE. An assessment of statin safety by muscle experts. Am J Cardiol. 2006;97(8A):69C–76.

    Article  PubMed  CAS  Google Scholar 

  57. Davidson MH. Safety profiles for the HMG-CoA reductase inhibitors: treatment and trust. Drugs. 2001;61(2):197–206.

    Article  PubMed  CAS  Google Scholar 

  58. Cohen DE, Anania FA, Chalasani N, Panel NLASSTFLE. An assessment of statin safety by hepatologists. Am J Cardiol. 2006;97(8A):77C–81.

    Article  PubMed  CAS  Google Scholar 

  59. Chapman MJ. Pharmacology of fenofibrate. Am J Med. 1987;83(5B):21–5.

    Article  PubMed  CAS  Google Scholar 

  60. Attman PO, Samuelsson O. Dyslipidemia of kidney disease. Curr Opin Lipidol. 2009;20(4):293–9.

    Article  PubMed  CAS  Google Scholar 

  61. 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.

    Article  PubMed  CAS  Google Scholar 

  62. 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.

    Article  PubMed  CAS  Google Scholar 

  63. Tanaka Y, Kume S, Araki S, Isshiki K, Chin-Kanasaki M, Sakaguchi M, et al. Fenofibrate, a PPARα agonist, has renoprotective effects in mice by enhancing renal lipolysis. Kidney Int. 2011;79(8):871–82.

    Article  PubMed  CAS  Google Scholar 

  64. Shin SJ, Lim JH, Chung S, Youn DY, Chung HW, Kim HW, et al. Peroxisome proliferator-activated receptor-alpha activator fenofibrate prevents high-fat diet-induced renal lipotoxicity in spontaneously hypertensive rats. Hypertens Res. 2009;32(10):835–45.

    Article  PubMed  CAS  Google Scholar 

  65. Tonelli M, Collins D, Robins S, Bloomfield H, Curhan GC, Veterans’ Affairs High-Density Lipoprotein Intervention Trial (VA-HIT) Investigators. Gemfibrozil for secondary prevention of cardiovascular events in mild to moderate chronic renal insufficiency. Kidney Int. 2004;66(3):1123–30.

    Article  PubMed  CAS  Google Scholar 

  66. 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.

    Article  PubMed  CAS  Google Scholar 

  67. 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.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  68. Makówka A, Dryja P, Chwatko G, Bald E, Nowicki M. Treatment of chronic hemodialysis patients with low-dose fenofibrate effectively reduces plasma lipids and affects plasma redox status. Lipids Health Dis. 2012;11:47.

    Article  PubMed Central  PubMed  Google Scholar 

  69. 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.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  71. Wu J, Song Y, Li H, Chen J. Rhabdomyolysis associated with fibrate therapy: review of 76 published cases and a new case report. Eur J Clin Pharmacol. 2009;65(12):1169–74.

    Article  PubMed  Google Scholar 

  72. 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(12):1993–9.

    Article  PubMed  CAS  Google Scholar 

  73. 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.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  74. Liang CC, Wang IK, Kuo HL, Yeh HC, Lin HH, Liu YL, et al. Long-term use of fenofibrate is associated with increased prevalence of gallstone disease among patients undergoing maintenance hemodialysis. Ren Fail. 2011;33(5):489–93.

    Article  PubMed  CAS  Google Scholar 

  75. Altmann SW, Davis HR, Zhu LJ, Yao X, Hoos LM, Tetzloff G, et al. Niemann-Pick C1 Like 1 protein is critical for intestinal cholesterol absorption. Science. 2004;303(5661):1201–4.

    Article  PubMed  CAS  Google Scholar 

  76. Dujovne CA, Ettinger MP, McNeer JF, Lipka LJ, LeBeaut AP, Suresh R, et al. Efficacy and safety of a potent new selective cholesterol absorption inhibitor, ezetimibe, in patients with primary hypercholesterolemia. Am J Cardiol. 2002;90(10):1092–7.

    Article  PubMed  CAS  Google Scholar 

  77. Landray M, Baigent C, Leaper C, Adu D, Altmann P, Armitage J, et al. The second United Kingdom Heart and Renal Protection (UK-HARP-II) study: a randomized controlled study of the biochemical safety and efficacy of adding ezetimibe to simvastatin as initial therapy among patients with CKD. Am J Kidney Dis. 2006;47(3):385–95.

    Article  PubMed  CAS  Google Scholar 

  78. Nakamura T, Sato E, Fujiwara N, Kawagoe Y, Ueda Y, Suzuki T, et al. Co-administration of ezetimibe enhances proteinuria-lowering effects of pitavastatin in chronic kidney disease patients partly via a cholesterol-independent manner. Pharmacol Res. 2010;61(1):58–61.

    Article  PubMed  CAS  Google Scholar 

  79. Buchanan C, Smith L, Corbett J, Nelson E, Shihab F. A retrospective analysis of ezetimibe treatment in renal transplant recipients. Am J Transplant. 2006;6(4):770–4.

    Article  PubMed  CAS  Google Scholar 

  80. Rodríguez-Ferrero ML, Anaya F. Ezetimibe in the treatment of uncontrolled hyperlipidemia in kidney transplant patients. Transplant Proc. 2008;40(10):3492–5.

    Article  PubMed  Google Scholar 

  81. Kohnle M, Pietruck F, Kribben A, Philipp T, Heemann U, Witzke O. Ezetimibe for the treatment of uncontrolled hypercholesterolemia in patients with high-dose statin therapy after renal transplantation. Am J Transplant. 2006;6(1):205–8.

    Article  PubMed  CAS  Google Scholar 

  82. Türk TR, Voropaeva E, Kohnle M, Nürnberger J, Philipp T, Kribben A, et al. Ezetimibe treatment in hypercholesterolemic kidney transplant patients is safe and effective and reduces the decline of renal allograft function: a pilot study. Nephrol Dial Transplant. 2008;23(1):369–73.

    Article  PubMed  Google Scholar 

  83. Slim H, Thompson PD. Ezetimibe-related myopathy: a systematic review. J Clin Lipidol. 2008;2(5):328–34.

    Article  PubMed  Google Scholar 

  84. Gille A, Bodor ET, Ahmed K, Offermanns S. Nicotinic acid: pharmacological effects and mechanisms of action. Annu Rev Pharmacol Toxicol. 2008;48:79–106.

    Article  PubMed  CAS  Google Scholar 

  85. Capuzzi DM, Guyton JR, Morgan JM, Goldberg AC, Kreisberg RA, Brusco OA, et al. Efficacy and safety of an extended-release niacin (Niaspan): a long-term study. Am J Cardiol. 1998;82(12A):74U–81U; discussion 5U–6U.

    Google Scholar 

  86. Insull W, McGovern ME, Schrott H, Thompson P, Crouse JR, Zieve F, et al. Efficacy of extended-release niacin with lovastatin for hypercholesterolemia: assessing all reasonable doses with innovative surface graph analysis. Arch Intern Med. 2004;164(10):1121–7.

    Article  PubMed  CAS  Google Scholar 

  87. Cho KH, Kim HJ, Kamanna VS, Vaziri ND. Niacin improves renal lipid metabolism and slows progression in chronic kidney disease. Biochim Biophys Acta. 2010;1800(1):6–15.

    Article  PubMed  CAS  Google Scholar 

  88. Cho KH, Kim HJ, Rodriguez-Iturbe B, Vaziri ND. Niacin ameliorates oxidative stress, inflammation, proteinuria, and hypertension in rats with chronic renal failure. Am J Physiol Renal Physiol. 2009;297(1):F106–13.

    Article  PubMed  CAS  Google Scholar 

  89. Restrepo Valencia CA, Cruz J. [Safety and effectiveness of nicotinic acid in the management of patients with chronic renal disease and hyperlipidemia associated to hyperphosphatemia]. Nefrologia. 2008;28(1):61–6.

    PubMed  CAS  Google Scholar 

  90. Gibbons LW, Gonzalez V, Gordon N, Grundy S. The prevalence of side effects with regular and sustained-release nicotinic acid. Am J Med. 1995;99(4):378–85.

    Article  PubMed  CAS  Google Scholar 

  91. Out C, Groen AK, Brufau G. Bile acid sequestrants: more than simple resins. Curr Opin Lipidol. 2012;23(1):43–55.

    Article  PubMed  CAS  Google Scholar 

  92. Hou R, Goldberg AC. Lowering low-density lipoprotein cholesterol: statins, ezetimibe, bile acid sequestrants, and combinations: comparative efficacy and safety. Endocrinol Metab Clin North Am. 2009;38(1):79–97.

    Article  PubMed  CAS  Google Scholar 

  93. Kshirsagar AV, Shoham DA, Bang H, Hogan SL, Simpson RJ, Colindres RE. The effect of cholesterol reduction with cholestyramine on renal function. Am J Kidney Dis. 2005;46(5):812–9.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Faruk Turgut M.D. .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this chapter

Cite this chapter

Turgut, F., Ustun, I., Gokce, C. (2014). How Lipid-Lowering Agents Work: The Good, the Bad, and the Ugly. 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_4

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-0515-7_4

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4939-0514-0

  • Online ISBN: 978-1-4939-0515-7

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics