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Role of dyslipidemia in impairment of energy metabolism, oxidative stress, inflammation and cardiovascular disease in chronic kidney disease

  • Review Article
  • WCN 2013 Satellite Symposium “Kidney and Lipids”
  • Published:
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Abstract

Advanced chronic kidney disease (CKD) results in a constellation of dysregulation of lipid metabolism, oxidative stress, and inflammation which are causally interconnected and participate in a vicious cycle. The CKD-associated lipid disorders are marked by impaired clearance of very low density lipoprotein and chylomicrons, hypertriglyceridemia, formation of small dense low-density lipoprotein (LDL), oxidative modification of LDL, intermediate density lipoprotein and chylomicron remnants, and high-density lipoprotein deficiency and dysfunction. This review provides a brief overview of the role of CKD-induced lipid disorders in the pathogenesis of oxidative stress, inflammation, cardiovascular disease, impaired exercise capacity, cachexia and wasting syndrome.

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References

  1. Vaziri ND, Norris K. Lipid disorders and their relevance to outcomes in chronic kidney disease. Blood Purif. 2011;31:189–96.

    Article  CAS  PubMed  Google Scholar 

  2. Vaziri ND. Dyslipidemia of chronic renal failure: the nature, mechanisms and potential consequences. Am J Physiol, Renal Physiol. 2006;290:262–72.

    Article  Google Scholar 

  3. Vaziri ND, Moradi H. Mechanism of dyslipidemia of chronic renal failure. Hemodial Int. 2006;10:1–7.

    Article  PubMed  Google Scholar 

  4. Kaysen GA. New insights into lipid metabolism in chronic kidney disease. J Ren Nutr. 2011;21(1):120–3.

    Article  CAS  PubMed  Google Scholar 

  5. Rajman I, Harper L, McPake D, et al. Low-density lipoprotein subfraction profiles in chronic renal failure. Nephrol Dial Transplant. 1998;13:2281–7.

    Article  CAS  PubMed  Google Scholar 

  6. Deighan CJ, Caslake MJ, McConnell M, Boulton-Jones JM, Packard CJ. Atherogenic lipoprotein phenotype in end-stage renal failure: origin and extent of small dense low-density lipoprotein formation. Am J Kidney Dis. 2000;35:852–62.

    Article  CAS  PubMed  Google Scholar 

  7. Kronenberg F, Neyer U, Lhotta K, 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.

    CAS  PubMed  Google Scholar 

  8. Vaziri ND, Navab M, Fogelman AM. HDL metabolism and activity in chronic kidney disease. Nat Rev Nephrol. 2010;6(5):287–96.

    Article  CAS  PubMed  Google Scholar 

  9. Akmal M, Kasim SE, Soliman AR, Massry SG. Excess parathyroid hormone adversely affects lipid metabolism in chronic renal failure. Kidney Int. 1990;37:854–8.

    Article  CAS  PubMed  Google Scholar 

  10. Vaziri ND, Liang K. Down-regulation of tissue lipoprotein lipase expression in experimental chronic renal failure. Kidney Int. 1996;50:1928–35.

    Article  CAS  PubMed  Google Scholar 

  11. Vaziri ND, Wang XQ, Liang K. Secondary hyperparathyroidism downregulates lipoprotein lipase expression in chronic renal failure. Am J Physiol. 1997;273:F925–30.

    CAS  PubMed  Google Scholar 

  12. Vaziri ND, Yuan J, Ni Z, Nicholas SB, Norris KC. Lipoprotein lipase deficiency in chronic kidney disease is compounded by downregulation of endothelial GPIHBP1 expression. Clin Exp Nephrol. 2012;16:238–43.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Herz J, Strickland DK. LRP: a multifunctional scavenger and signaling receptor. J Clin Invest. 2001;108:779–84.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Kim C, Vaziri ND. Downregulation of hepatic LDL receptor-related protein (LRP) in chronic renal failure. Kidney Int. 2005;67:1028–32.

    Article  CAS  PubMed  Google Scholar 

  15. Pahl MV, Ni Z, Sepassi L, Vaziri ND. Plasma phospholipid transfer protein, cholesterol ester transfer protein and lecithin: cholesterol acyltransferase in end-stage renal disease. Nephrol Dial Transplant. 2009;24(8):2541–6.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Klin M, Smogorzewski M, Ni Z, Zhang G, Massry SG. Abnormalities in hepatic lipase in chronic renal failure: role of excess parathyroid hormone. J Clin Invest. 1996;97:2167–73.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Liang K, Vaziri ND. Downregulation of hepatic lipase expression in experimental nephrotic syndrome. Kidney Int. 1997;51:1933–7.

    Article  CAS  PubMed  Google Scholar 

  18. Sato T, Liang K, Vaziri ND. Protein restriction and AST-120 improve lipoprotein lipase, hepatic lipase and VLDL receptor deficiencies in focal glomerulosclerosis. Kidney Int. 2003;64:1780–6.

    Article  CAS  PubMed  Google Scholar 

  19. Takahashi S, Kawarabayasi Y, Nakai T, et al. Rabbit very low density lipoprotein receptor: a low density lipoprotein receptor-like protein with distinct ligand specificity. Proc Natl Acad Sci USA. 1992;89:9252–6.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Liang K, Vaziri ND. Acquired VLDL receptor deficiency in experimental nephrosis. Kidney Int. 1997;51:1761–5.

    Article  CAS  PubMed  Google Scholar 

  21. Sato T, Liang K. VaziriND: downregulation of lipoprotein lipase and VLDL receptor in rats with focal glomerulosclerosis. Kidney Int. 2002;61:157–62.

    Article  CAS  PubMed  Google Scholar 

  22. Yamamoto S, Yancey PG, Ikizler TA, Jerome WG, Kaseda R, Cox B, Bian A, Shintani A, Fogo AB, Linton MF, Fazio S, Kon V. Dysfunctional high-density lipoprotein in patients on chronic hemodialysis. J Am Coll Cardiol (2012) pii: S0735-1097(12)04651-7.

  23. Vaziri ND, Moradi H, Pahl MV, Fogelman AM, Navab M. In vitro stimulation of HDL anti-inflammatory activity and inhibition of LDL pro-inflammatory activity in the plasma of patients with end-stage renal disease by an apoA-1 mimetic peptide. Kidney Int. 2009;76(4):437–44.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Moradi H, Said HM, Vaziri ND Post-transcriptional nature of uremia-induced down-regulation of hepatic apolipoprotein A-I production. Transl Res PMID: 23219399, (2012).

  25. Shao B, Oda MN, Oram JF, Heinecke JW. Myeloperoxidase: an inflammatory enzyme for generating dysfunctional high density lipoprotein. Curr Opin Cardiol. 2006;21:322–8.

    Article  PubMed  Google Scholar 

  26. Liang K, Vaziri ND. Upregulation of Acyl-CoA: cholesterol acyltransferase (ACAT) in chronic renal failure. Am J Physiol Endocrinol Metab. 2002;283:E676–81.

    CAS  PubMed  Google Scholar 

  27. Kim HJ, Moradi H, Vaziri ND. Renal mass reduction results in accumulation of lipids and dysregulation of lipid regulatory proteins in the remnant kidney. Am J Physiol Renal Physiol. 2009;296(6):F1297–306.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Moradi H, Yuan J, Ni Z, Norris K, Vaziri ND. Reverse cholesterol transport pathway in experimental chronic kidney disease. Am J Nephrol. 2009;30:147–54.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Vaziri ND, Bai Y, Yuan J, Said H, Sigala W, Ni Z. ApoA-1 mimetic peptide reverses uremia-induced up-regulation of pro-atherogenic pathways in the aorta. Am J Nephrol. 2010;32(3):201–11.

    Article  CAS  PubMed  Google Scholar 

  30. Vaziri ND, Liang K, Parks JS. Downregulation of hepatic lecithin: cholesterol acyltransferase gene expression in chronic renal failure. Kidney Int. 2001;59:2192–6.

    Article  CAS  PubMed  Google Scholar 

  31. Martinez LO, Jacquet S, Esteve JP, Rolland C, Cabezón E, Champagne E, Pineau T, Georgeaud V, Walker JE, Tercé F, Collet X, Perret B, Barbaras R. Ectopic beta-chain of ATP synthase is an apolipoprotein A-I receptor in hepatic HDL endocytosis. Nature. 2003;421:75–9.

    Article  CAS  PubMed  Google Scholar 

  32. Adams G, Vaziri ND. Skeletal muscle dysfunction in chronic renal failure: effect of exercise. Am J Physiol Renal Physiol. 2006;290:783–91.

    Google Scholar 

  33. Glass CK, Witztum JL. Atherosclerosis: the road ahead. Cell. 2001;104:503–16.

    Article  CAS  PubMed  Google Scholar 

  34. Li D, Mehta JL. Antisense to LOX-1 inhibits oxidized LDL-mediated upregulation of monocyte chemoattractant protein-1 and monocyte adhesion to human coronary artery endothelial cells. Circulation. 2000;101:2889–95.

    Article  CAS  PubMed  Google Scholar 

  35. Go AS, Chertow GM, Fan D, et al. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004;351:1296–305.

    Article  CAS  PubMed  Google Scholar 

  36. Collins AJ, Foley R, Herzog C, et al. Excerpts from the US renal data system 2007 annual data report. Am J Kidney Dis. 2008;51:S1–320.

    Google Scholar 

  37. Zoccali C, Mallamaci F, Tripepi G. Novel cardiovascular risk factors in end-stage renal disease. J Am Soc Nephrol. 2004;15(Suppl. 1):S77–80.

    Article  PubMed  Google Scholar 

  38. Drüeke TB, Massy ZA. Atherosclerosis in CKD: differences from the general population. Nat Rev Nephrol. 2010;6:723–35.

    Article  PubMed  Google Scholar 

  39. Schwarz U, Buzello M, Ritz E, Stein G, Raabe G, Wiest G, et al. Morphology of coronary atherosclerotic lesions in patients with end-stage renal failure. Nephrol Dial Transplant. 2000;15(2):218–23.

    Article  CAS  PubMed  Google Scholar 

  40. Pecoits-Filho R, Lindholm B, Stenvinkel P. The malnutrition, inflammation, and atherosclerosis (MIA) syndrome––the heart of the matter. Nephrol Dial Transplant. 2002;17(Suppl 11):28–31.

    Article  CAS  PubMed  Google Scholar 

  41. 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.

    Article  CAS  PubMed  Google Scholar 

  42. Kilpatrick RD, McAllister CJ, Kovesdy CP, et al. Association between serum lipids and survival in hemodialysis patients and impact of race. J Am Soc Nephrol. 2007;18:293–303.

    Article  CAS  PubMed  Google Scholar 

  43. Wanner C, Krane V, Marz W, et al. Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N Engl J Med. 2005;353:238–48.

    Article  CAS  PubMed  Google Scholar 

  44. Fellstrom BC, Jardine AG, Schmieder RE, et al. Rosuvastatin and cardiovascular events in patients undergoing hemodialysis. N Engl J Med. 2009;360:1395–407.

    Article  CAS  PubMed  Google Scholar 

  45. Baigent C, Landray MJ, Reith 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 randomized placebo-controlled trial. Lancet. 2011;377:2181–92.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Nephrology and Hypertension, University of California Irvine Medical Center, Suite 400, City Tower, 101 City Drive, Orange, CA, 92868, USA

    Nosratola D. Vaziri

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Correspondence to Nosratola D. Vaziri.

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Vaziri, N.D. Role of dyslipidemia in impairment of energy metabolism, oxidative stress, inflammation and cardiovascular disease in chronic kidney disease . Clin Exp Nephrol 18, 265–268 (2014). https://doi.org/10.1007/s10157-013-0847-z

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  • DOI: https://doi.org/10.1007/s10157-013-0847-z

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