Abstract
Dyslipidemia is a well-known risk factor for cardiovascular disease in the general population, and the cardioprotective role of statins is well established. However, although cardiovascular disease is the major cause of morbidity and mortality in chronic kidney disease (CKD), the role of statin therapy is still under investigation. In CKD the atherosclerotic burden is high and pathophysiology of dyslipidemia is complex; however, the majority of large-scale statin trials excluded patients with CKD. Statins could have different effects in the different stages of CKD. Two large trials involving haemodialysis patients showed unfavourable results, whereas in renal transplant subjects as well as in early CKD subjects, statins reduced cardiovascular risk. The studies involving early CKD patients are post-hoc analyses of large trials and they showed that statins are more effective in secondary than in primary prevention. The aim of this study was to evaluate the effectiveness of statins for prevention of cardiovascular events by calculating the number of patients needed to be treated in different interventional trials. We conclude that dyslipidemia is a modifiable cardiovascular risk and statins appear to be an effective treatment especially in the early stages of CKD. Patients on renal replacement therapy could obtain an advantage from this treatment; however, the patient’s clinical prognosis should be taken into account when evaluating treatment.
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References
Lindner A, Charra B, Sherrard DJ, Scribner BH. Accelerated atherosclerosis in prolonged maintenance hemodialysis. N Engl J Med. 1974;290:697–701.
Collins AJ, Li S, Ma JS, Herzog C. Cardiovascular disease in end stage renal disease patients. Am J Kidney Dis. 2001;38(Suppl 1):26–9.
Foley RN, Parfrey PS, Sarnak MJ. Epidemiology of cardiovascular disease in chronic renal disease. J Am Soc Nephrol. 1998;9(Suppl 12):16–23.
Muntner P, He J, Astor BC, Folsom AR, Coresh J. Traditional and non-traditional risk factors predict coronary heart disease in chronic kidney disease: results from the atherosclerosis risk in communities study. J Am Soc Nephrol. 2005;16:529–38.
Thvendiranathen P, Bagai A, Brookhart MA, Chudhry NK. Primary prevention of cardiovascular diseases with statin therapy: a meta-analysis of randomized controlled trials. Arch Intern Med. 2006;166:2307–13.
Kaysen GA, de sain-van der Veldem MG. New insights into lipid metabolism in the nephritic syndrome. Kidney Int 1999;71 (Suppl):S18–21.
Coka SG, Krumholz HM, Garg AX, Parikh CR. Under-representation of renal disease in randomized controlled trials of cardiovascular disease. JAMA. 2006;296:1377–84.
Cholesterol Treatment Trialists’ (CTT) Collaborators. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90056 participants in 14 randomised trials of statins. Lancet 2005;366:1267–78.
Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM Jr, Kastelein JJ, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359:2195–207.
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;94:1107–12.
Dautin G, Soltani Z, Duclox D, Gautier T, de Pais Barros JP, Gambert P, et al. Hemodialysis reduces plasma apolipoprotein C-I concentration making VLDL a better substrate for lipoprotein lipase. Kidney Int. 2007;72:871–8.
Kasiske BL. Hyperlipidemia in patients with chronic renal disease. Am J Kidney Dis. 1998;32(Suppl 3):S142–56.
Chmielewski M, Carrero JJ, Nordfors L, Lindholm B, Stenvinkel P. Lipid disorders in chronic kidney disease: reverse epidemiology and therapeutic approach. J Nephrol. 2008;21:635–44.
Ikewaki K, Schaefer JR, Frischmann ME, Okubo K, Hosoya T, Mochizuki S, et al. Delayed in vivo catabolism of intermediate-density lipoprotein and low-density lipoprotein in hemodialysis patients as potential cause of premature atherosclerosis. Arterioscler Thromb Vasc Biol. 2005;25:2615–22.
Weintraub M, Burstein A, Rassin T, Liron M, Ringel Y, Cabili S, et al. Severe deficit in clearing post-prandial chylomicron remnants in dialysis patients. Kidney Int. 1992;42:1247–52.
O’Neal D, Lee P, Murphy B, Best J. Low-density lipoprotein particle size distribution in end-stage renal disease treated with hemodialysis or peritoneal dialysis. Am J Kidney Dis. 1996;27:84–91.
Kronenberg F, Kuen E, Ritz E, Junker R, König P, Kraatz G, et al. Lipoprotein(a) serum concentration and apolipoprotein(a) phenotypes in mild and moderate renal failure. J Am Soc Nephrol. 2000;11:105–15.
Kronenberg F, Neyer U, Lhotta K, Trenkwalder E, Auinger M, Pribasnig A, et al. The low molecular weight apo(a) phenotype is an independent predictor for coronary artery disease in hemodialysis patients. A prospective follow-up. J Am Soc Nephrol. 1999;10:1027–36.
Frishmann ME, Kronenberg F, Trenkwalder E, Shaefer JR, Schweer H, Dieplinger B, et al. In vivo turnover study demonstrates diminished clearance of lipoprotein(a) in hemodialysis patients. Kidney Int. 2007;71:1036–43.
Degoulet P, Legrain M, Réach I, Aimé F, Derriés C, Rojas P, et al. Mortality risk factors in patients treated by chronic hemodialysis. Report of the Diaphane Collaborative Study. Nephron. 1982;31:103–10.
Keith DS, Nicholas GA, Gullion CM, Brown JB, Smith DH. Longitudinal follow-up and outcomes among a population with chronic kidney disease in a large managed care organization. Arch Intern Med. 2004;164:659–63.
Wanner C, Krane V, März W, Olschewski M, Mann JF, Ruf G, et al. German diabetes and dialysis study investigators Atorvastatin in patients with type 2 diabetes mellitus undergoing dialysis. N Engl J Med. 2005;353:238–48.
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;360:1395–407.
Chan KE, Thadhani R, Lazarus JM, Hakim RM. Modeling the 4D Study: statins and cardiovascular outcomes in long-term hemodialysis patients with diabetes. Clin J Am Soc Nephrol. 2010;5:856–66.
Navaneethan SD, Nigwekar SU, Perkovic V, Johnson DW, Craig JC, Strippoli GFM. HMG CoA reductase inhibitors (statins) for dialysis patients (review). Cochrane Database Syst Rev. 2009;3:CD004289.
Kanbay M, Yildirir A, Akcay A, Colak T, Ozdemir FN, Muderrisoglu H, et al. Effects of immunosuppressive drugs on serum lipid levels in renal transplant recipients. Transplant Proc. 2006;38:502–5.
Kasiske BL, Guijarro C, Massy ZA, Wiederkehr MR, Ma JZ. Cardiovascular disease after renal transplantation. J Am Soc Nephrol. 1996;7:158–65.
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, randomized placebo-controlled trial. Lancet. 2003;361:2024–31.
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;5:2929–36.
Soveri I, Abedini S, Holdaas H, Jardine A, Eriksson N, Fellström B. Metabolic syndrome and cardiovascular risk in renal transplant recipients: effect of statin treatment. Clin Transplant. 2009;23:914–20.
Navaneethan SD, Perkovic V, Johnson DW, Nigwekar SU, Craig JC, Strippoli GFM. HMG CoA reductase inhibitors (statins) for kidney transplant recipients (review). Cochrane Database Syst Rev. 2009;2:CD005019.
Davies JB, Crook MA, Wierzbicki AS, Goldsmith DJ. The incidence of low eGFR and proteinuria in a large tertiary referral lipid clinic. Int Urol Nephrol. 2010. doi:https://doi.org/10.1007/s11255-010-9819-3.
Navaneethan SD, Pansini F, Perkovic V, Manno C, Pellegrini F, Johnson DW. HMG CoA reductase inhibitors (statins) for people with chronic kidney disease not requiring dialysis (review). Cochrane Database Syst Rev. 2009;2:CD007784.
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. J Am Coll Cardiol. 2010;55:1266–73.
Holme I, Fayyad R, Faergeman O, Kastelein JJP, Olsson AG, Tikkanen MJ, et al. Cardiovascular outcomes and their relationship to lipoprotein components in patients with and without chronic kidney disease: results from the IDEAL trial. J Intern Med. 2010;267:567–75.
Shepherd J, Kastelein JJP, 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. J Am Coll Cardiol. 2008;51:1448–54.
Tonelli M, Keech A, Shepherd J, Sacks F, Tonkin A, Packard C, et al. Effect of pravastatin in people with diabetes and chronic kidney disease. J Am Soc Nephrol. 2005;16:3748–54.
Kanbay M, Turgut F, Covic A, Gldsmith D. Statin treatment for dyslipidemia in chronic kidney disease and renal transplantation: a review of the evidence. J Nephrol. 2009;22:598–609.
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The study was in adherence with the declaration of Helsinki.
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Fabbian, F., De Giorgi, A., Pala, M. et al. Evidence-based statin prescription for cardiovascular protection in renal impairment. Clin Exp Nephrol 15, 456–463 (2011). https://doi.org/10.1007/s10157-011-0454-9
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DOI: https://doi.org/10.1007/s10157-011-0454-9