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Dyslipidemia following kidney transplantation: Diagnosis and treatment

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Abstract

Lipid abnormalities are a common complication of kidney transplantation, occurring in up to 60% of patients. In fact, impairment of lipid metabolism is often present before renal transplantation due to the uremic state. After transplantation and recovery of renal function, lipid disturbances usually persist but show a different profile due to the various effects of immunosuppressive drugs on lipid metabolism. Actually, steroids, calcineurin inhibitors, and mammalian target of rapamycin inhibitors usually lead to quantitative and qualitative abnormalities of very low-density, low-density, and high-density lipoproteins. As cardiovascular diseases remain the leading cause of death in renal transplant recipients, management of dyslipidemia and other traditional risk factors, such as smoking, arterial hypertension, diabetes mellitus, and obesity, is of great importance to prevent cardiovascular complications and chronic allograft dysfunction. This review addresses the causes of dyslipidemia, the role of immunosuppressive drugs, and current recommendations to manage lipid disorders in renal transplant recipients.

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References and Recommended Reading

  1. National Kidney Foundation: Survival, mortality, and causes of death. Am J Kidney Dis 2003, 41(Suppl 4):151–164.

    Google Scholar 

  2. Del Castillo D, Cruzado JM, Manel Diaz J, et al.: The effects of hyperlipidaemia on graft and patient outcome in renal transplantation. Nephrol Dial Transplant 2004, 19(Suppl 3):67–71.

    Google Scholar 

  3. Quaschning T, Mainka T, Nauck M, et al.: Immunosuppression enhances atherogenicity of lipid profile after transplantation. Kidney Int Suppl 1999, 71(Suppl):S235–S237.

    Article  PubMed  CAS  Google Scholar 

  4. Badiou S, Garrigue V, Dupuy AM, et al.: Small dense low-density lipoprotein in renal transplant recipients: a potential target for prevention of cardiovascular complications? Transplant Proc 2006, 38:2314–2316.

    Article  PubMed  CAS  Google Scholar 

  5. Rostaing L, Cantarovich D, Mourad G, et al.: Corticosteroid-free immunosuppression with tacrolimus, mycophenolate mofetil, and daclizumab induction in renal transplantation. Transplantation 2005, 79:807–814.

    Article  PubMed  CAS  Google Scholar 

  6. Woodle ES, Alloway R, Rike A, et al.: Corticosteroid elimination: the Cincinnati experience. Clin Transpl 2007, 47:51–60.

    Google Scholar 

  7. Deleuze S, Garrigue V, Delmas S, et al.: New onset dyslipidemia after renal transplantation: is there a difference between tacrolimus and cyclosporine? Transplant Proc 2006, 38:2311–2313.

    Article  PubMed  CAS  Google Scholar 

  8. Akman B, Uyar M, Afsar B, et al.: Lipid profile during azathioprine or mycophenolate mofetil combinations with cyclosporine and steroids. Transplant Proc 2007, 39:135–137.

    Article  PubMed  CAS  Google Scholar 

  9. Gueguen Y, Ferrari L, Souidi M, et al.: Compared effect of immunosuppressive drugs cyclosporine A and rapamycin on cholesterol homeostasis key enzymes CYP27A1 and HMG-CoA reductase. Basic Clin Pharmacol Toxicol 2007, 100:392–397.

    Article  PubMed  CAS  Google Scholar 

  10. Tory R, Sachs-Barrable K, Hill JS, Wasan KM: Cyclosporine A and rapamycin induce in vitro cholesteryl ester transfer protein activity, and suppress lipoprotein lipase activity in human plasma. Int J Pharm 2008, 358:219–223.

    Article  PubMed  CAS  Google Scholar 

  11. Demirag A, Moray G, Ozdemir N, et al.: Comparison of serum lipids, lipoproteins, and fibrinogen in patients with kidney transplantation and hemodialysis. Transplant Proc 1998, 30:2052–2053.

    Article  PubMed  CAS  Google Scholar 

  12. Artz MA, Boots JM, Ligtenberg G, et al.: Conversion from cyclosporine to tacrolimus improves quality-of-life indices, renal graft function and cardiovascular risk profile. Am J Transplant 2004, 4:937–945.

    Article  PubMed  CAS  Google Scholar 

  13. Marcén R, Chahin J, Alarcón A, Bravo J: Conversion from cyclosporine microemulsion to tacrolimus in stable kidney transplant patients with hypercholesterolemia is related to an improvement in cardiovascular risk profile: a prospective study. Transplant Proc 2006, 38:2427–2430.

    Article  PubMed  Google Scholar 

  14. Porrini E, Delgado P, Bigo C, et al.: Impact of metabolic syndrome on graft function and survival after cadaveric renal transplantation. Am J Kidney Dis 2006, 48:134–142.

    Article  PubMed  Google Scholar 

  15. Bellinghieri G, Bernardi A, Piva M, et al.: Metabolic syndrome after kidney transplantation. J Ren Nutr 2009, 19:105–110.

    Article  PubMed  Google Scholar 

  16. Vincenti F, Friman S, Scheuermann E, et al.: Results of an international, randomized trial comparing glucose metabolism disorders and outcome with cyclosporine versus tacrolimus. Am J Transplant 2007, 7:1506–1514.

    Article  PubMed  CAS  Google Scholar 

  17. Porrini E, Delgado P, Alvarez A, et al.: The combined effect of pre-transplant triglyceride levels and the type of calcineurin inhibitor in predicting the risk of new onset diabetes after renal transplantation. Nephrol Dial Transplant 2008, 23:1436–1441.

    Article  PubMed  CAS  Google Scholar 

  18. Nashan B, Curtis J, Ponticelli C, et al.: on behalf of the 156 Study Group: Everolimus and reduced exposure cyclosporine in de novo renal-transplant recipients: a three-year phase II, randomized, multicenter, open-label study. Transplantation 2004, 78:1332–1340.

    Article  PubMed  CAS  Google Scholar 

  19. Ekberg H, Tedesco-Silva H, Demirbas A, et al.: ELITESymphony Study: Reduced exposure to calcineurin inhibitors in renal transplantation. N Engl J Med 2007, 357:2562–2575.

    Article  PubMed  CAS  Google Scholar 

  20. Carmellini M, Collini A, Ruggieri G, et al.: Excellent long-term results in de novo renal transplant recipients treated with proliferation signal inhibitors and reduced calcineurin inhibitors exposure. Transplant Proc 2008, 40:1858–1861.

    Article  PubMed  CAS  Google Scholar 

  21. Vítko S, Margreiter R, Weimar W, et al.: Three-year efficacy and safety results from a study of everolimus versus mycophenolate mofetil in de novo renal transplant patients. Am J Transplant 2005, 5:2521–2530.

    Article  PubMed  Google Scholar 

  22. Büchler M, Caillard S, Barbier S, et al.: Sirolimus versus cyclosporine in kidney recipients receiving thymoglobulin, mycophenolate mofetil and a 6-month course of steroids. Am J Transplant 2007, 7:2522–2531.

    Article  PubMed  Google Scholar 

  23. Morrisett JD, Abdel-Fattah G, Kahan BD: Sirolimus changes lipid concentrations and lipoprotein metabolism in kidney transplant recipients. Transplant Proc 2003, 35:143S–150S.

    Article  PubMed  CAS  Google Scholar 

  24. Ma KL, Ruan XZ, Powis SH, et al.: Sirolimus modifies cholesterol homeostasis in hepatic cells: a potential molecular mechanism for sirolimus-associated dyslipidemia. Transplantation 2007, 84:1029–1036.

    Article  PubMed  CAS  Google Scholar 

  25. Elloso MM, Azrolan N, Sehgal SN, et al.: Protective effect of the immunosuppressant sirolimus against aortic atherosclerosis in apo E-deficient mice. Am J Transplant 2003, 3:562–569.

    Article  PubMed  CAS  Google Scholar 

  26. Miller LW: Cardiovascular toxicities of immunosuppressive agents. Am J Transplant 2002, 2:807–818.

    Article  PubMed  CAS  Google Scholar 

  27. Ferraris JR, Pasqualini T, Alonso G, et al.: Effects of deflazacort vs. methylprednisone: a randomized study in kidney transplant patients. Pediatr Nephrol 2007, 22:734–741.

    Article  PubMed  Google Scholar 

  28. Vincenti F, Schena FP, Paraskevas S, et al.; FREEDOM Study Group: A randomized, multicenter study of steroid avoidance, early steroid withdrawal or standard steroid therapy in kidney transplant recipients. Am J Transplant 2008, 8:307–316.

    PubMed  CAS  Google Scholar 

  29. Rike AH, Mogilishetty G, Alloway RR, et al.: Cardiovascular risk, cardiovascular events, and metabolic syndrome in renal transplantation: comparison of early steroid withdrawal and chronic steroids. Clin Transplant 2008, 22:229–235.

    PubMed  Google Scholar 

  30. Kasiske B, Cosio FG, Beto J, 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 

  31. National Kidney Foundation: K/DOQI clinical practice guidelines for managing dyslipidemias in chronic kidney disease. Am J Kidney Dis 2003, 41(Suppl 3):1–91.

    Google Scholar 

  32. 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, 106:3143–3421.

    Google Scholar 

  33. Lopes iM, Martín M, Errasti P, Martínez JA: Benefits of a dietary intervention on weight loss, body composition, and lipid profile after renal transplantation. Nutrition 1999, 15:7–10.

    Article  PubMed  CAS  Google Scholar 

  34. Guida B, Trio R, Laccetti R, et al.: Role of dietary intervention on metabolic abnormalities and nutritional status after renal transplantation. Nephrol Dial Transplant 2007, 22:3304–3310.

    Article  PubMed  CAS  Google Scholar 

  35. 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, 361:2024–2031.

    Article  PubMed  CAS  Google Scholar 

  36. Holdaas H, Fellström B, Cole E, et al.: Long-term cardiac outcomes in renal transplant recipients receiving fluvastatin: the ALERT extension study. Am J Transplant 2005, 5:2929–2936.

    Article  PubMed  CAS  Google Scholar 

  37. Cosio FG, Pesavento TE, Pelletier RP, et al.: Patient survival after renal transplantation III: the effects of statins. Am J Kidney Dis 2002, 40:638–643.

    Article  PubMed  CAS  Google Scholar 

  38. Wiesbauer F, Heinze G, Mitterbauer C, et al.: Statin use is associated with prolonged survival of renal transplant recipients. J Am Soc Nephrol 2008, 19:2211–2218.

    Article  PubMed  Google Scholar 

  39. Asberg A, Hartmann A, Fjeldsa E, et al.: Bilateral pharmacokinetic interaction between cyclosporine A and atorvastatin in renal transplant recipients. Am J Transplant 2001, 1:382–386.

    Article  PubMed  CAS  Google Scholar 

  40. Ichimaru N, Takahara S, Kokado Y, et al.: Changes in lipid metabolism and effect of simvastatin in renal transplant recipients induced by cyclosporine or tacrolimus. Atherosclerosis 2001, 158:417–423.

    Article  PubMed  CAS  Google Scholar 

  41. Türk TR, Voropaeva E, Kohnle M, 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, 23:369–373.

    Article  PubMed  Google Scholar 

  42. Shihab FS, Waid TH, Conti DJ, et al.: Conversion from cyclosporine to tacrolimus in patients at risk for chronic renal allograft failure: 60-month results of the CRAF Study. Transplantation 2008, 85:1261–1269.

    Article  PubMed  CAS  Google Scholar 

  43. Angeles C, Lane BP, Miller F, Nord EP: Fenofibrate-associated reversible acute allograft dysfunction in 3 renal transplant recipients: biopsy evidence of tubular toxicity. Am J Kidney Dis 2004, 44:543–550.

    Article  PubMed  Google Scholar 

  44. Boizel R, Benhamou PY, Lardy B, et al.: Ratio of triglycerides to HDL cholesterol is an indicator of LDL particle size in patients with type 2 diabetes and normal HDL cholesterol levels. Diabetes Care 2000, 23:1679–1685.

    Article  PubMed  CAS  Google Scholar 

  45. Badiou S, Thiebaut R, Aurillac-Lavignolle V, et al.: Association of non-HDL cholesterol with subclinical atherosclerosis in HIV-positive patients. J Infect 2008, 57:47–54.

    Article  PubMed  CAS  Google Scholar 

  46. St-Pierre AC, Cantin B, Dagenais GR, et al.: Low-density lipoprotein subfractions and the long-term risk of ischemic heart disease in men: 13-year follow-up data from the Québec Cardiovascular Study. Arterioscler Thromb Vasc Biol 2005, 25:553–559.

    Article  PubMed  CAS  Google Scholar 

  47. Tribble DL, Farnier M, Macdonell G, et al.: Effects of fenofibrate and ezetimibe, both as monotherapy and in coadministration, on cholesterol mass within lipoprotein subfractions and low-density lipoprotein peak particle size in patients with mixed hyperlipidemia. Metabolism 2008, 57:796–801.

    Article  PubMed  CAS  Google Scholar 

  48. Wissing KM, Unger P, Ghisdal L, et al.: Effect of atorvastatin therapy and conversion to tacrolimus on hypercholesterolemia and endothelial dysfunction after renal transplantation. Transplantation 2006, 82:771–778.

    Article  PubMed  CAS  Google Scholar 

  49. Cui Y, Blumenthal RS, Flaws JA, et al.: Non-high-density lipoprotein cholesterol level as a predictor of cardiovascular disease mortality. Arch Intern Med 2001, 161:1413–1419.

    Article  PubMed  CAS  Google Scholar 

  50. Orakzai SH, Nasir K, Blaha M, et al.: Non-HDL cholesterol is strongly associated with coronary artery calcification in asymptomatic individuals. Atherosclerosis 2009, 202:289–295.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Nephrology and Transplantation, University of Montpellier, Höpital Lapeyronie, 371 Avenue du Doyen Gaston Giraud, 34295, Montpellier 05, France

    Georges Mourad

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  1. Stéphanie Badiou
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  2. Jean-Paul Cristol
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  3. Georges Mourad
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Correspondence to Georges Mourad.

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Badiou, S., Cristol, JP. & Mourad, G. Dyslipidemia following kidney transplantation: Diagnosis and treatment. Curr Diab Rep 9, 305–311 (2009). https://doi.org/10.1007/s11892-009-0047-0

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