UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Lipoprotein glomerulopathy

Author
Takao Saito, MD, PhD
Section Editors
Richard J Glassock, MD, MACP
Brad H Rovin, MD
Deputy Editor
Albert Q Lam, MD

INTRODUCTION

Lipoprotein glomerulopathy (LPG) is a unique and rare disorder of renal lipidosis that was first reported in a Japanese patient in 1989 [1]. It is characterized by lipoprotein thrombi in glomeruli, an abnormal plasma lipoprotein profile that resembles type III hyperlipoproteinemia, and a marked increase in serum apolipoprotein E (apo E) concentrations. LPG was subsequently found to be due to mutations of the APOE gene [2]. However, intrinsic renal factors are also involved in the pathogenesis of LPG because of the incomplete penetrance based upon many asymptomatic carriers of APOE variants [3-5].

A review of the clinical features of LPG is presented in this topic review.

PATHOGENESIS

Initial reports of familial cases as well as recurrence in transplanted kidneys suggested that a systemically acting genetic factor may underlie lipoprotein glomerulopathy (LPG). It was also observed that the serum apo E isoform was inconsistent with the APOE genotype among affected individuals.

These findings predicted that an uncharacterized variant(s) of the APOE gene may underlie the pathogenesis of this disorder [6]. This was subsequently confirmed as mutations in the APOE gene have been found in all reported cases of LPG in which DNA sequencing has been performed (algorithm 1).

APOE variants — Apolipoprotein E (apo E), an essential apolipoprotein, is a major constituent of various plasma lipoproteins. Plasma lipoprotein levels are determined in part by the binding activities of apo E to the LDL receptor, LDL receptor-related protein, and VLDL receptor. Apo E is composed of 299 amino acids and has a relative molecular mass of 34kDa.

                   

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Nov 2016. | This topic last updated: Tue Nov 10 00:00:00 GMT+00:00 2015.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
References
Top
  1. Saito T, Sato H, Kudo K, et al. Lipoprotein glomerulopathy: glomerular lipoprotein thrombi in a patient with hyperlipoproteinemia. Am J Kidney Dis 1989; 13:148.
  2. Saito T, Matsunaga A, Oikawa S. Impact of lipoprotein glomerulopathy on the relationship between lipids and renal diseases. Am J Kidney Dis 2006; 47:199.
  3. Saito T, Oikawa S, Sato H, Sasaki J. Lipoprotein glomerulopathy: renal lipidosis induced by novel apolipoprotein E variants. Nephron 1999; 83:193.
  4. Toyota K, Hashimoto T, Ogino D, et al. A founder haplotype of APOE-Sendai mutation associated with lipoprotein glomerulopathy. J Hum Genet 2013; 58:254.
  5. Hu Z, Huang S, Wu Y, et al. Hereditary features, treatment, and prognosis of the lipoprotein glomerulopathy in patients with the APOE Kyoto mutation. Kidney Int 2014; 85:416.
  6. Oikawa S, Matsunaga A, Saito T, et al. Apolipoprotein E Sendai (arginine 145-->proline): a new variant associated with lipoprotein glomerulopathy. J Am Soc Nephrol 1997; 8:820.
  7. Amatruda JM, Margolis S, Hutchins GM. Type 3 hyperlipoproteinemia with mesangial foam cells in renal glomeruli. Arch Pathol 1974; 98:51.
  8. Suzaki K, Kobori S, Ueno S, et al. Effects of plasmapheresis on familial type III hyperlipoproteinemia associated with glomerular lipidosis, nephrotic syndrome and diabetes mellitus. Atherosclerosis 1990; 80:181.
  9. Ellis D, Orchard TJ, Lombardozzi S, et al. Atypical hyperlipidemia and nephropathy associated with apolipoprotein E homozygosity. J Am Soc Nephrol 1995; 6:1170.
  10. Saito T, Ishigaki Y, Oikawa S, Yamamoto TT. Etiological significance of apolipoprotein E mutations in lipoprotein glomerulopathy. Trends Cardiovasc Med 2002; 12:67.
  11. Chen S, Liu ZH, Zheng JM, et al. A complete genomic analysis of the apolipoprotein E gene in Chinese patients with lipoprotein glomerulopathy. J Nephrol 2007; 20:568.
  12. Matsunaga A, Sasaki J, Komatsu T, et al. A novel apolipoprotein E mutation, E2 (Arg25Cys), in lipoprotein glomerulopathy. Kidney Int 1999; 56:421.
  13. Rovin BH, Roncone D, McKinley A, et al. APOE Kyoto mutation in European Americans with lipoprotein glomerulopathy. N Engl J Med 2007; 357:2522.
  14. Murano T, Matsumura R, Misawa Y, et al. Interaction of endothelial cells and triglyceride-rich lipoproteins with apolipoprotein E (Arg-->Cys) from a patient with lipoprotein glomerulopathy. Metabolism 2002; 51:201.
  15. Foster K, Matsunaga A, Matalon R, et al. A rare cause of posttransplantation nephrotic syndrome. Am J Kidney Dis 2005; 45:1132.
  16. Cheung CY, Chan AO, Chan YH, et al. A rare cause of nephrotic syndrome: lipoprotein glomerulopathy. Hong Kong Med J 2009; 15:57.
  17. Han J, Pan Y, Chen Y, et al. Common apolipoprotein E gene mutations contribute to lipoprotein glomerulopathy in China. Nephron Clin Pract 2010; 114:c260.
  18. Hagiwara M, Yamagata K, Matsunaga T, et al. A novel apolipoprotein E mutation, ApoE Tsukuba (Arg 114 Cys), in lipoprotein glomerulopathy. Nephrol Dial Transplant 2008; 23:381.
  19. Kinomura M, Sugiyama H, Saito T, et al. A novel variant apolipoprotein E Okayama in a patient with lipoprotein glomerulopathy. Nephrol Dial Transplant 2008; 23:751.
  20. Luo B, Huang F, Liu Q, et al. Identification of apolipoprotein E Guangzhou (arginine 150 proline), a new variant associated with lipoprotein glomerulopathy. Am J Nephrol 2008; 28:347.
  21. Bomback AS, Song H, D'Agati VD, et al. A new apolipoprotein E mutation, apoE Las Vegas, in a European-American with lipoprotein glomerulopathy. Nephrol Dial Transplant 2010; 25:3442.
  22. Magistroni R, Bertolotti M, Furci L, et al. Lipoprotein glomerulopathy associated with a mutation in apolipoprotein e. Clin Med Insights Case Rep 2013; 6:189.
  23. Konishi K, Saruta T, Kuramochi S, et al. Association of a novel 3-amino acid deletion mutation of apolipoprotein E (Apo E Tokyo) with lipoprotein glomerulopathy. Nephron 1999; 83:214.
  24. Ando M, Sasaki J, Hua H, et al. A novel 18-amino acid deletion in apolipoprotein E associated with lipoprotein glomerulopathy. Kidney Int 1999; 56:1317.
  25. Ogawa T, Maruyama K, Hattori H, et al. A new variant of apolipoprotein E (apo E Maebashi) in lipoprotein glomerulopathy. Pediatr Nephrol 2000; 14:149.
  26. Matsunaga A, Saito T. Apolipoprotein E mutations: a comparison between lipoprotein glomerulopathy and type III hyperlipoproteinemia. Clin Exp Nephrol 2014; 18:220.
  27. Sam R, Wu H, Yue L, et al. Lipoprotein glomerulopathy: a new apolipoprotein E mutation with enhanced glomerular binding. Am J Kidney Dis 2006; 47:539.
  28. Mitani A, Ishigami M, Watase K, et al. A novel apolipoprotein E mutation, ApoE Osaka (Arg158 Pro), in a dyslipidemic patient with lipoprotein glomerulopathy. J Atheroscler Thromb 2011; 18:531.
  29. Tokura T, Itano S, Kobayashi S, et al. A novel mutation ApoE2 Kurashiki (R158P) in a patient with lipoprotein glomerulopathy. J Atheroscler Thromb 2011; 18:536.
  30. Ishigaki Y, Oikawa S, Suzuki T, et al. Virus-mediated transduction of apolipoprotein E (ApoE)-sendai develops lipoprotein glomerulopathy in ApoE-deficient mice. J Biol Chem 2000; 275:31269.
  31. Ishimura A, Watanabe M, Nakashima H, et al. Lipoprotein glomerulopathy induced by ApoE-Sendai is different from glomerular lesions in aged apoE-deficient mice. Clin Exp Nephrol 2009; 13:430.
  32. Hoffmann M, Scharnagl H, Panagiotou E, et al. Diminished LDL receptor and high heparin binding of apolipoprotein E2 Sendai associated with lipoprotein glomerulopathy. J Am Soc Nephrol 2001; 12:524.
  33. Janus ED, Grant S, Lintott CJ, Wardell MR. Apolipoprotein E phenotypes in hyperlipidaemic patients and their implications for treatment. Atherosclerosis 1985; 57:249.
  34. Innerarity TL, Hui DY, Bersot TP, Mahley RW. Type III hyperlipoproteinemia: a focus on lipoprotein receptor-apolipoprotein E2 interactions. Adv Exp Med Biol 1986; 201:273.
  35. Ghiselli G, Gregg RE, Zech LA, et al. Phenotype study of apolipoprotein E isoforms in hyperlipoproteinaemic patients. Lancet 1982; 2:405.
  36. Wen M, Segerer S, Dantas M, et al. Renal injury in apolipoprotein E-deficient mice. Lab Invest 2002; 82:999.
  37. Langheinrich AC, Kampschulte M, Scheiter F, et al. Atherosclerosis, inflammation and lipoprotein glomerulopathy in kidneys of apoE-/-/LDL-/- double knockout mice. BMC Nephrol 2010; 11:18.
  38. Kiener PA, Rankin BM, Davis PM, et al. Immune complexes of LDL induce atherogenic responses in human monocytic cells. Arterioscler Thromb Vasc Biol 1995; 15:990.
  39. Huang Y, Jaffa A, Koskinen S, et al. Oxidized LDL-containing immune complexes induce Fc gamma receptor I-mediated mitogen-activated protein kinase activation in THP-1 macrophages. Arterioscler Thromb Vasc Biol 1999; 19:1600.
  40. Zwaka TP, Hombach V, Torzewski J. C-reactive protein-mediated low density lipoprotein uptake by macrophages: implications for atherosclerosis. Circulation 2001; 103:1194.
  41. Kanamaru Y, Nakao A, Shirato I, et al. Chronic graft-versus-host autoimmune disease in Fc receptor gamma chain-deficient mice results in lipoprotein glomerulopathy. J Am Soc Nephrol 2002; 13:1527.
  42. Miyahara Y, Nishimura S, Watanabe M, et al. Scavenger receptor expressions in the kidneys of mice with lipoprotein glomerulopathy. Clin Exp Nephrol 2012; 16:115.
  43. Ito K, Nakashima H, Watanabe M, et al. Macrophage impairment produced by Fc receptor gamma deficiency plays a principal role in the development of lipoprotein glomerulopathy in concert with apoE abnormalities. Nephrol Dial Transplant 2012; 27:3899.
  44. Tavori H, Fan D, Giunzioni I, et al. Macrophage-derived apoESendai suppresses atherosclerosis while causing lipoprotein glomerulopathy in hyperlipidemic mice. J Lipid Res 2014; 55:2073.
  45. Saito T, Matsunaga A. Lipoprotein glomerulopathy may provide a key to unlock the puzzles of renal lipidosis. Kidney Int 2014; 85:243.
  46. Zhang P, Matalon R, Kaplan L, et al. Lipoprotein glomerulopathy: first report in a Chinese male. Am J Kidney Dis 1994; 24:942.
  47. Meyrier A, Dairou F, Callard P, Mougenot B. Lipoprotein glomerulopathy: first case in a white European. Nephrol Dial Transplant 1995; 10:546.
  48. Mourad G, Djamali A, Turc-Baron C, Cristol JP. Lipoprotein glomerulopathy: a new cause of nephrotic syndrome after renal transplantation. Nephrol Dial Transplant 1998; 13:1292.
  49. Boumendjel R, Papari M, Gonzalez M. A rare case of lipoprotein glomerulopathy in a white man: an emerging entity in Asia, rare in the white population. Arch Pathol Lab Med 2010; 134:279.
  50. Sethi S. Renal failure with intracapillary thrombi. Lipoprotein glomerulopathy. Kidney Int 2008; 73:1097.
  51. Pasquariello A, Pasquariello G, Innocenti M, et al. Lipoprotein glomerulopathy: first report of 2 not consanguineous Italian men from the same town. J Nephrol 2011; 24:381.
  52. Chang CF, Lin CC, Chen JY, et al. Lipoprotein glomerulopathy associated with psoriasis vulgaris: report of 2 cases with apolipoprotein E3/3. Am J Kidney Dis 2003; 42:E18.
  53. Oikawa S, Suzuki N, Sakuma E, et al. Abnormal lipoprotein and apolipoprotein pattern in lipoprotein glomerulopathy. Am J Kidney Dis 1991; 18:553.
  54. Hazzard WR, Porte D Jr, Bierman EL. Abnormal lipid composition of very low density lipoproteins in diagnosis of broad-beta disease (type 3 hyperlipoproteinemia). Metabolism 1972; 21:1009.
  55. Fredrickson DS, Morganroth J, Levy RI. Type III hyperlipoproteinemia: an analysis of two contemporary definitions. Ann Intern Med 1975; 82:150.
  56. Saito T, Sato H, Oikawa S, et al. Lipoprotein glomerulopathy. Report of a normolipidemic case and review of the literature. Am J Nephrol 1993; 13:64.
  57. Saito T, Oikawa S, Sato H, et al. Lipoprotein glomerulopathy: significance of lipoprotein and ultrastructural features. Kidney Int Suppl 1999; 71:S37.
  58. Kawanishi K, Sawada A, Ochi A, et al. Glomerulopathy with homozygous apolipoprotein e2: a report of three cases and review of the literature. Case Rep Nephrol Urol 2013; 3:128.
  59. Amenomori M, Haneda M, Morikawa J, et al. A case of lipoprotein glomerulopathy successfully treated with probucol. Nephron 1994; 67:109.
  60. Sakatsume M, Kadomura M, Sakata I, et al. Novel glomerular lipoprotein deposits associated with apolipoprotein E2 homozygosity. Kidney Int 2001; 59:1911.
  61. Ieiri N, Hotta O, Taguma Y. Resolution of typical lipoprotein glomerulopathy by intensive lipid-lowering therapy. Am J Kidney Dis 2003; 41:244.
  62. Arai T, Yamashita S, Yamane M, et al. Disappearance of intraglomerular lipoprotein thrombi and marked improvement of nephrotic syndrome by bezafibrate treatment in a patient with lipoprotein glomerulopathy. Atherosclerosis 2003; 169:293.
  63. Matsunaga A, Furuyama M, Hashimoto T, et al. Improvement of nephrotic syndrome by intensive lipid-lowering therapy in a patient with lipoprotein glomerulopathy. Clin Exp Nephrol 2009; 13:659.
  64. Xin Z, Zhihong L, Shijun L, et al. Successful treatment of patients with lipoprotein glomerulopathy by protein A immunoadsorption: a pilot study. Nephrol Dial Transplant 2009; 24:864.
  65. Atkins KL, Burman JD, Chamberlain ES, et al. S. aureus IgG-binding proteins SpA and Sbi: host specificity and mechanisms of immune complex formation. Mol Immunol 2008; 45:1600.
  66. Russi G, Furci L, Leonelli M, et al. Lipoprotein glomerulopathy treated with LDL-apheresis (Heparin-induced Extracorporeal Lipoprotein Precipitation system): a case report. J Med Case Rep 2009; 3:9311.
  67. Miyata T, Sugiyama S, Nangaku M, et al. Apolipoprotein E2/E5 variants in lipoprotein glomerulopathy recurred in transplanted kidney. J Am Soc Nephrol 1999; 10:1590.