Free Access
Kidney Blood Press Res 2010;33:100–110
(DOI:10.1159/000302712)

Alterations of Lipid Metabolism in Chronic Nephropathies: Mechanisms, Diagnosis and Treatment

Lacquaniti A. · Bolignano D. · Donato V. · Bono C. · Fazio M.R. · Buemi M.
Section of Nephrology, Department of Internal Medicine, University of Messina, Messina, Italy
email Corresponding Author


 goto top of outline Key Words

  • Lipid metabolism
  • Nephropathy
  • Cardiovascular disease
  • Atherosclerosis
  • Dyslipidemia

 goto top of outline Abstract

Nephropathic subjects show an increased tendency to develop cardiovascular diseases, mainly as the consequence of several risk factors including increased oxidative stress, inflammation, physical inactivity, anemia, vascular calcification, and endothelial dysfunction. The alterations in lipid metabolism represent a relatively lesser important cause of genesis and progression of atherosclerosis. Unfortunately, in these patients the atherogenic potential of dyslipidemia may depend more on apolipoproteins than on lipid abnormalities, and may not always be recognized by measurement of plasma lipids alone. The aim of this review was therefore to analyze the main lipid alterations that can occur in nephropathic patients, as well as their causes and their effects on the cardiovascular system. The clinical evidence and recommendations for the use of lipid-regulating drugs in patients with chronic kidney disease, nephrotic syndrome, in patients undergoing hemo- and peritoneal dialysis and in transplanted patients was also reviewed. Moreover, we analyzed the link between dyslipidemia and kidney disease onset and progression and the role of statins in preventing it.

Copyright © 2010 S. Karger AG, Basel


 goto top of outline References
  1. Attman PO, Alaupovic P: Lipid and apolipoprotein profiles of uremic dyslipoproteinemia: relation to renal function and dialysis. Nephron 1991;57:401–410.
  2. Kronenberg F, Kuen E, Ritz E, et al: Apolipoprotein A-IV serum concentrations are elevated in mild and moderate renal failure. J Am Soc Nephrol 2002;13:461–469.
  3. Keith DS, Nichols GA, Gullion CM, et al: Longitudinal follow-up and outcomes among a population with chronic kidney disease in a large managed care organization. Arch Intern Med 2004;164:659–663.
  4. Vaziri ND, Moradi H: Mechanisms of dyslipidemia of chronic renal failure. Hemodial Int 2006;10:1–7.
  5. Vaziri ND: Dyslipidemia of chronic renal failure: the nature, mechanisms, and potential consequences. Am J Physiol Renal Physiol 2006;290:F262–F272.
  6. Prinsen BH, de Sain-van der Velden MG, de Koning EJ et al: Hypertriglyceridemia in patients with chronic renal failure: possible mechanisms. Kidney Int Suppl 2003;84:S121–S124.
  7. Mori Y, Hirano T, Nagashima M, et al: Decreased peroxisome proliferator-activated receptor alpha gene expression is associated with dyslipidemia in a rat model of chronic renal failure. Metabolism 2007;56:1714–1718.
  8. Vaziri ND, Deng G, Liang K: Hepatic HDL receptor, SR-B1 and Apo A-I expression in chronic renal failure. Nephrol Dial Transplant 1999;14:1462–1466.
  9. Guarnieri GF, Moracchiello M, Campanacci L, et al: Lecithin-cholesterol acyltransferase (LCAT) activity in chronic uremia. Kidney Int Suppl 1978;8:S26–S30.

    External Resources

  10. Kimura H, Miyazaki R, Imura T, et al: Hepatic lipase mutation may reduce vascular disease prevalence in hemodialysis patients with high CETP levels. Kidney Int 2003;64:1829–1837.
  11. 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 Quebec Cardiovascular Study. Arterioscler Thromb Vasc Biol 2005;25:553–559.
  12. Danesh J, Collins R, Peto R: Lipoprotein(a) and coronary heart disease: meta-analysis of prospective studies. Circulation 2000;102:1082–1085.
  13. Kronenberg F, Kuen E, Ritz E, et al: Lipoprotein(a) serum concentrations and apolipoprotein(a) phenotypes in mild and moderate renal failure. J Am Soc Nephrol 2000;11:105–115.
  14. National Kidney Foundation: K/DOQI Clinical Practice Guidelines for Managing Dyslipidemias in Chronic Kidney Disease. Guideline 4. New York, National Kidney Foundation, 2002.
  15. Expert Panel on Detection Evaluation and Treatment of High Blood Cholesterol in Adults: Executive Summary of the 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). JAMA 2001;285:2486–2497.
  16. Rubins HB, Robins SJ, Collins D, et al: Diabetes, plasma insulin, and cardiovascular disease: subgroup analysis from the Department of Veterans Affairs High-Density Lipoprotein Intervention Trial (VA-HIT). Arch Intern Med 2002;162:2597–2604.
  17. Deighan CJ, Caslake MJ, McConnell M, et al: The atherogenic lipoprotein phenotype: small dense LDL and lipoprotein remnants in nephrotic range proteinuria. Atherosclerosis 2001;157:211–220.
  18. Vaziri ND, Sato T, Liang K: Molecular mechanism of altered cholesterol metabolism in focal glomerulosclerosis. Kidney Int 2003;63:1756–1763.
  19. Vaziri ND: Molecular mechanisms of lipid disorders in nephrotic syndrome. Kidney Int 2003;63:1964–1976.
  20. Vaziri ND, Liang K, Park JS: Acquired lecithin: cholesterol acyltransferase (LCAT) deficiency in nephrotic syndrome. Am J Physiol 2001;49:F823–F829.
  21. Vaziri ND, Kim CH, Phan D, et al: Up-regulation of hepatic Acyl CoA: diacylglycerol acyltransferase-1 (DGAT-1) expression in nephrotic syndrome. Kidney Int 2004;66:262–267.
  22. Tsimihodimos V, Dounousi E, Siamopoulos KC: Dyslipidemia in chronic kidney disease: an approach to pathogenesis and treatment. Am J Nephrol 2008;28:958–973.
  23. Ordonez JD, Hiatt RA, Killebrew EJ, Fireman BH: The increased risk of coronary heart disease associated with nephrotic syndrome. Kidney Int 1993;44:638–642.
  24. Lechner BL, Bockenhauer D, Iragorri S, et al: The risk of cardiovascular disease in adults who have had childhood nephrotic syndrome. Pediatr Nephrol 2004;19:744–748.
  25. Fried LF, Orchard TJ, Kasiske BL; for the Lipids and Renal Disease Progression Meta-analysis Study Group: Effect of lipid reduction on the progression of renal disease: a meta-analysis. Kidney Int 2001;59:260–269.
  26. Gheit OA, Sobh MA, Mohamed Kel-S, et al: Impact of treatment of dyslipidemia on renal function, fat deposits and scarring in patients with persistent nephrotic syndrome. Nephron 2002;91:612–619.
  27. Valdivesio P, Moliz M, Valera A, et al: Atorvastatin in dislipidemia of the nephrotic syndrome. Nephrology 2003;8:61–64.
  28. Rayner BL, Byrne MJ, van Zyl Smit R: A prospective clinical trial comparing the treatment of idiopathic membranous nephropathy and nephrotic syndrome with simvastatin and diet, versus diet alone. Clin Nephrol 1996;46:219–224.
  29. Dalrymple LS, Kaysen GA: The effect of lipoproteins on the development and progression of renal disease. Am J Nephrol 2008;28:723–731.
  30. Brunskill NJ: Albumin signals the coming of age of proteinuric nephropathy. J Am Soc Nephrol 2004;15:504–505.
  31. Vaziri ND: Dyslipidemia of chronic renal failure: the nature, mechanisms, and potential consequences. Am J Physiol Renal Physiol 2006;290:F262–F272.
  32. Muntner P, Coresh J, Smith JC, et al: Plasma lipids and risk of developing renal dysfunction: the Atherosclerosis Risk in Communities Study. Kidney Int 2000;58:293–301.
  33. Samuelsson O, Attman PO, Knight-Gibson C et al: Complex apolipoprotein B-containing lipoprotein particles are associated with a higher rate of progression of human chronic renal insufficiency. J Am Soc Nephrol 1998;9:1482–1488.
  34. Ozsoy RC, van der Steeg WA, Kastelein JJ, et al: Dyslipidaemia as predictor of progressive renal failure and the impact of treatment with atorvastatin. Nephrol Dial Transplant 2007;22:1578–1586.
  35. Schaeffner ES, Kurth T, Curhan GC, et al: Cholesterol and the risk of renal dysfunction in apparently healthy men. J Am Soc Nephrol 2003;14:2084–2091.
  36. Scheuer H, Gwinner W, Hohbach J, et al: Oxidant stress in hyperlipidemia-induced renal damage. Am J Physiol Renal Physiol 2000;78:F63–F74.
  37. Buemi M, Senatore M, Corica F, et al: Are there potential non-lipid-lowering uses of statins in the kidney? Nephron 2001;89:363–368.
  38. Buemi M, Senatore M, Corica F, et al: Statins and progressive renal disease. Med Res Rev 2002;22:76–84.
  39. Buemi M, Corica F, Marino D, et al: Cardiovascular remodelling, apoptosis and drugs. Am J Hyperten 2000;13:450–454.
  40. Buemi M, Allegra A, Senatore M, et al: Pro-apoptotic effect of fluvastatin on human smooth muscle cells. Eur J Pharmacol 1999;370:201–203.
  41. Buemi M, Nostro L, Crascì E, et al: Statins in nephrotic syndrome: a new weapon against tissue injury. Med Res Rev 2005; 25:587–609.
  42. Zhou MS, Jaimes EA, Raij L: Atorvastatin prevents end-organ injury in salt-sensitive hypertension: role of eNOS and oxidant stress. Hypertension 2004;44:186–190.
  43. Tonelli M, Isles C, Curhan GC, et al: Effect of pravastatin on cardiovascular events in people with chronic kidney disease. Circulation 2004;110:1557–1563.
  44. Agarwal R: Effects of statins on renal function. Am J Cardiol 2006;97:748–755.
  45. Abbate M, Zoja C, Corna D, et al: In progressive nephropathies, overload of tubular cells with filtered proteins translates glomerular permeability dysfunction into cellular signals of interstitial inflammation. J Am Soc Nephrol 1998;9:1213–1224.
  46. Sandhu S, Wiebe N, Fried LF, Tonelli M: Statins for improving renal outcomes: a meta-analysis. J Am Soc Nephrol 2006;17:2006–2016.
  47. Kilpatrick RD, McAllister CJ, Kalantar-Zadeh K: Comparing mortality-predictability of serum total cholesterol and low density lipoprotein (LDL) cholesterol in hemodialysis patients. J Am Soc Nephrol 2005;16:728A.
  48. Liu Y, Coresh J, Eustace JA, et al: Association between cholesterol level and mortality in dialysis patients: role of inflammation and malnutrition. JAMA 2004;291:451–459.
  49. Iseki K, Yamazato M, Tozawa M, Takishita S: Hypocholesterolemia is a significant predictor of death in a cohort of chronic hemodialysis patients. Kidney Int 2002;61:1887–1893.
  50. Kwan BC, Kronenberg F, Beddhu S, Cheung AK: Lipoprotein metabolism and lipid management in chronic kidney disease. J Am Soc Nephrol 2007;18:1246–1261.
  51. National Kidney Foundation: K/DOQI clinical practice guidelines for managing dyslipidemias in chronic kidney disease. Am J Kidney Dis 2003;41(suppl 3):S1–S92.
  52. Attman PO, Samuelsson OG, Moberly J, et al: Apolipoprotein B-containing lipoproteins in renal failure: the relation to mode of dialysis. Kidney Int 1999;55:1536–1542.
  53. Okubo K, Ikewaki K, Sakai S, et al: Abnormal HDL apolipoprotein A-I and A-II kinetics in hemodialysis patients: a stable isotope study. J Am Soc Nephrol 2004;15:1008–1015.
  54. Blankestijn PJ, Vos PF, Rabelink TJ, et al: High-flux dialysis membranes improve lipid profile in chronic hemodialysis patients. J Am Soc Nephrol 1995;5:1703–1708.
  55. Näsström B, Stegmayr B, Gupta J et al: A single bolus of a low molecular weight heparin to patients on haemodialysis depletes lipoprotein lipase stores and retards triglyceride clearing. Nephrol Dial Transplant 2005;20:1172–1179.
  56. Kidney Disease Outcomes Quality Initiative (K/DOQI) Group: K/DOQI clinical practice guidelines for management of dyslipidemias in patients with kidney disease. Am J Kidney Dis 2003;41(suppl 3):I–IV, S1–S91.
  57. Navaneethan SD, Shrivastava R: HMG CoA reductase inhibitors (statins) for dialysis patients. Cochrane Database Syst Rev 2004;4:CD004289.
  58. Launay-Vacher V, Izzedine H, Deray G: Statins’ dosage in patients with renal failure and cyclosporine drug-drug interactions in transplant recipient patients. Int J Cardiol 2005;101:9–17.
  59. Tonelli M, Isles C, Craven T, et al: Effect of pravastatin on rate of kidney function loss in people with or at risk for coronary disease. Circulation 2005;112:171–178.
  60. Kosoglou T, Statkevich P, Johnson-Levonas AO, et al: Ezetimibe: a review of its metabolism, pharmacokinetics and drug interactions. Clin Pharmacokinet 2005;44:467–494.
  61. Davidson MH, Armani A, McKenney JM, Jacobson TA: Safety considerations with fibrate therapy. Am J Cardiol 2007;99:3C–18C.
  62. Wanner C, Krane V, März W, et al; for the German Diabetes and Dialysis Study Investigators: Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N Engl J Med 2005;353:238–248.
  63. Fathi R, Isbel N, Short L, et al: The effect of long-term aggressive lipid lowering on ischemic and atherosclerotic burden in patients with chronic kidney disease. Am J Kidney Dis 2004;43:45–52.
  64. Schwarz U, Buzello M, Ritz E, Stein G, et al: Morphology of coronary atherosclerotic lesions in patients with end-stage renal failure. Nephrol Dial Transplant 2000;15:218–223.
  65. Fellström BC, Jardine AG, Schmieder RE: Rosuvastatin and cardiovascular events in patients undergoing hemodialysis. N Engl J Med 2009;360:1395–1407.
  66. Baigent C, Landry M: Study of Heart and Renal Protection (SHARP). Kidney Int 2003;63(suppl):S207–S210.

    External Resources

  67. Molitch ME: Management of dyslipidemias in patients with diabetes and chronic kidney disease. Clin J Am Soc Nephrol 2006;1:1090–1099.
  68. Prinsen BH, Rabelink TJ, Romijn JA, et al: A broad-based metabolic approach to study VLDL apoB100 metabolism in patients with ESRD and patients treated with peritoneal dialysis. Kidney Int 2004;65:1064–1075.
  69. Babazono T, Nakamoto H, Kasai K, et al: Effects of icodextrin on glycemic and lipid profiles in diabetic patients undergoing peritoneal dialysis. Am J Nephrol 2007;27:409–415.
  70. Paraskevas KI: Statin therapy in peritoneal dialysis patients: effects beyond lipid lowering. Int Urol Nephrol 2008;40:165–170.
  71. Calabrò P, Yeh ET: The pleiotropic effects of statins. Curr Opin Cardiol 2005;20:541–546.
  72. Haslinger B, Goedde MF, Toet KH, et al: Simvastatin increases fibrinolytic activity in human peritoneal mesothelial cells independent of cholesterol lowering. Kidney Int 2002;62:1611–1619.
  73. Trence DL: Management of patients on chronic glucocorticoidi therapy: an endocrine perspective. Prim Care 2003;30:593–605.
  74. Artz MA, Boots JM, Ligtenberg G, et al: Improved cardiovascular risk profile and renal function in renal transplant patients after randomized conversion from cyclosporine to tacrolimus. J Am Soc Nephrol 2003;14:1880–1888.
  75. 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.
  76. Kasiske BL, Vazquez MA, Harmon WE, et al: Recommendations for the outpatient surveillance of renal transplant recipients. J Am Soc Nephrol 2000;11:S1.
  77. Holdaas H, Fellström B, Jardine A, et al: Effect of fluvastatin on cardiac outcomes in renal transplant recipients: a multicentre, randomised, placebo-controlled trial. Lancet 2003;361:2024–2031.
  78. 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.
  79. Cosio FG, Pesavento TE, Pelletier RP, et al: Patient survival after renal transplantation: the effects of statins. Am J Kidney Dis 2002;40:638–643.
  80. 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.
  81. Puthenparumpil J, Keough-Ryan T, Kibed M, et al: Treatment of hypercholesterolemia with ezetimibe in the kidney transplant population. Transplant Proc 2005;37:1033.
  82. Buchanan C, Smith L, Corbett J, et al: A retrospective analysis of ezetimibe treatment in renal transplant recipients. Am J Transplant 2006;6:770–774.
  83. López V, Gutiérrez C, Gutiérrez E, et al: Treatment with ezetimibe in kidney transplant recipients with uncontrolled dyslipidemia. Transplant Proc 2008;40:2925–2926.

 goto top of outline Author Contacts

Prof. Michele Buemi
Via Salita Villa Contino, 30
IT–98100 Messina (Italy)
Tel. +39 090 221 2265, Fax +39 090 293 5162
E-Mail buemim@unime.it


 goto top of outline Article Information

Published online: March 27, 2010
Number of Print Pages : 11
Number of Figures : 3, Number of Tables : 1, Number of References : 83


 goto top of outline Publication Details

Kidney and Blood Pressure Research

Vol. 33, No. 2, Year 2010 (Cover Date: June 2010)

Journal Editor: Tesar V. (Prague)
ISSN: 1420-4096 (Print), eISSN: 1423-0143 (Online)

For additional information: http://www.karger.com/KBR


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.