title: Pathogenesis of childhood idiopathic nephrotic syndrome: a paradigm shift from T-cells to podocytes.
abstract: BACKGROUND
  Nephrotic syndrome is the most common cause of kidney disease in children, but its pathogenesis remains unclear. This article reviews the novel aspects of the mechanisms underlying massive proteinuria in minimal-change disease, which is the most common form of childhood nephrotic syndrome.
  
  
  METHODS
  This article integrates the findings of a PubMed database search for English language articles published in the past 40 years (from September 1974 to February 2014) using the key words "pathogenesis", "minimal change nephrotic syndrome" or "idiopathic nephrotic syndrome".
  
  
  RESULTS
  Unknown humoral factors associated with T-cell dysfunction have been thought to play an important role in the pathogenesis of minimal-change disease. However, recent findings are changing this paradigm, i.e., visceral glomerular epithelial cells (podocytes) may be involved via expression of molecules such as CD80 and angiopoietin-like 4.
  
  
  CONCLUSIONS
  Recent evidence suggests that minimal-change disease results from interactions between humoral factors and dysfunctional podocytes. In addition to immunosuppressant drugs that target lymphocytes, a biological agent such as an antibody against the abnormal molecule(s) expressed by podocytes may provide novel drug treatment for minimal-change disease.
authors.affiliation: Department of Pediatrics, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka, 573-1010, Japan, kanekok@hirakata.kmu.ac.jp.
authors.forename: Kazunari
authors.initials: K
authors.lastname: Kaneko
authors.forename: Shoji
authors.initials: S
authors.lastname: Tsuji
authors.forename: Takahisa
authors.initials: T
authors.lastname: Kimata
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kitao
authors.forename: Sohsaku
authors.initials: S
authors.lastname: Yamanouchi
authors.forename: Shogo
authors.initials: S
authors.lastname: Kato
mesh_terms: D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins / Q000378:metabolism; D018122:B7-1 Antigen; D002648:Child; D016207:Cytokines / Q000502:physiology; D006801:Humans; D009402:Nephrosis, Lipoid / Q000378:metabolism / Q000503:physiopathology*; D050199:Podocytes / Q000378:metabolism / Q000502:physiology*; D011507:Proteinuria / Q000503:physiopathology; D013601:T-Lymphocytes / Q000502:physiology*
chemical_list: C474772:ANGPTL4 protein, human; D000075803:Angiopoietin-Like Protein 4; D042682:Angiopoietins; D018122:B7-1 Antigen; D016207:Cytokines
references.citation: Clin J Am Soc Nephrol. 2010 Nov;5(11):2115-21
references.pmid: 20966123
references.citation: Nephrol Dial Transplant. 2003 Jan;18(1):70-6
references.pmid: 12480962
references.citation: Sci Signal. 2010 May 18;3(122):ra39
references.pmid: 20484117
references.citation: Pediatr Nephrol. 1994 Apr;8(2):135-9
references.pmid: 8018488
references.citation: Nephrol Dial Transplant. 2012 Jan;27(1):81-9
references.pmid: 21617192
references.citation: Pediatr Nephrol. 2006 May;21(5):603-10
references.pmid: 16525836
references.citation: Acta Paediatr Taiwan. 2004 Mar-Apr;45(2):77-80
references.pmid: 15335115
references.citation: Int J Nephrol. 2012;2012:481520
references.pmid: 22685655
references.citation: Lancet. 1974 Sep 7;2(7880):556-60
references.pmid: 4140273
references.citation: Pediatr Nephrol. 2000 Aug;14(8-9):779-85
references.pmid: 10955927
references.citation: Nephrol Dial Transplant. 2005 Dec;20(12):2824-6
references.pmid: 16204273
references.citation: Clin Exp Immunol. 1999 Aug;117(2):361-7
references.pmid: 10444271
references.citation: Clin Exp Immunol. 2010 Jul 1;161(1):151-8
references.pmid: 20491793
references.citation: Immunol Rev. 2008 Dec;226:205-18
references.pmid: 19161426
references.citation: Nat Med. 2011 Jan;17(1):117-22
references.pmid: 21151138
references.citation: Clin Sci (Lond). 2004 Aug;107(2):125-36
references.pmid: 15157184
references.citation: Nat Rev Nephrol. 2011 Nov 01;8(1):52-6
references.pmid: 22045242
references.citation: N Engl J Med. 2014 Mar 27;370(13):1263-4
references.pmid: 24670180
references.citation: Curr Opin Nephrol Hypertens. 2001 Jul;10(4):543-9
references.pmid: 11458036
references.citation: J Am Soc Nephrol. 2004 Oct;15(10):2611-8
references.pmid: 15466265
references.citation: Mol Cell. 1998 Mar;1(4):575-82
references.pmid: 9660941
references.citation: Transplantation. 1994 Oct 15;58(7):849-52
references.pmid: 7940721
references.citation: Arch Dis Child. 1981 Jul;56(7):517-24
references.pmid: 7271285
references.citation: Nat Med. 2008 Sep;14(9):931-8
references.pmid: 18724379
references.citation: Am J Pathol. 1992 Sep;141(3):571-8
references.pmid: 1325740
references.citation: Kidney Int. 1999 Mar;55(3):1063-71
references.pmid: 10027945
references.citation: Pediatr Nephrol. 2009 Nov;24(11):2121-8
references.pmid: 17968594
references.citation: J Am Soc Nephrol. 2000 Mar;11(3):403-12
references.pmid: 10703664
references.citation: Clin Nephrol. 2003 Oct;60(4):242-7
references.pmid: 14579938
references.citation: Nephrol Dial Transplant. 2011 Jan;26(1):18-24
references.pmid: 20937691
references.citation: Nephrol Dial Transplant. 2013 Nov;28(11):2800-5
references.pmid: 23975748
references.citation: Lancet. 2003 Aug 23;362(9384):629-39
references.pmid: 12944064
references.citation: Pediatr Nephrol. 2013 Nov;28(11):2079-88
references.pmid: 23250714
references.citation: Am J Kidney Dis. 2012 Feb;59(2):284-92
references.pmid: 21974967
references.citation: Clin Nephrol. 2006 Jun;65(6):423-6
references.pmid: 16792138
references.citation: J Paediatr Child Health. 2004 Jan-Feb;40(1-2):28-32
references.pmid: 14718000
references.citation: Nephron. 1993;65(1):56-61
references.pmid: 8413792
references.citation: Pediatr Nephrol. 2009 Mar;24(3):489-95
references.pmid: 19011907
references.citation: Science. 2008 Oct 10;322(5899):271-5
references.pmid: 18845758
references.citation: Kidney Int. 2010 Aug;78(3):296-302
references.pmid: 20485332
references.citation: Pediatr Nephrol. 2014 Aug;29(8):1363-71
references.pmid: 24263531
references.citation: Pediatr Nephrol. 2009 Sep;24(9):1691-8
references.pmid: 19495805
references.citation: Sci Transl Med. 2011 Jun 1;3(85):85ra46
references.pmid: 21632984
references.citation: Clin Nephrol. 1992 Apr;37(4):177-82
references.pmid: 1582055
references.citation: Eur J Immunol. 1995 Jun;25(6):1497-501
references.pmid: 7614976
references.citation: J Am Soc Nephrol. 2008 Nov;19(11):2140-9
references.pmid: 18753258
references.citation: Am J Nephrol. 2013;38(6):483-8
references.pmid: 24296765
references.citation: Pediatr Nephrol. 1999 Apr;13(3):199-204
references.pmid: 10353405
references.citation: Int J Nephrol. 2011;2011:372304
references.pmid: 21904676
references.citation: Autoimmun Rev. 2013 May;12(7):758-67
references.pmid: 23340277
references.citation: Nephron. 2000 Apr;84(4):342-6
references.pmid: 10754411
references.citation: J Am Soc Nephrol. 2009 Feb;20(2):260-6
references.pmid: 19056875
references.citation: Clin J Am Soc Nephrol. 2010 Nov;5(11):2075-84
references.pmid: 20798252
references.citation: Clin Immunol. 2011 Jun;139(3):314-20
references.pmid: 21450528
references.citation: Pediatr Nephrol. 2009 May;24(5):1033-8
references.pmid: 19153775
references.citation: J Clin Invest. 2004 May;113(10):1390-7
references.pmid: 15146236
references.citation: Am J Nephrol. 2013;37(4):302-9
references.pmid: 23548793
references.citation: J Am Soc Nephrol. 2009 Aug;20(8):1733-43
references.pmid: 19497968
references.citation: J Lipid Res. 2002 Nov;43(11):1770-2
references.pmid: 12401877
references.citation: N Engl J Med. 2007 Jun 28;356(26):2751-2
references.pmid: 17596616
references.citation: J Histochem Cytochem. 1991 Aug;39(8):1047-56
references.pmid: 1856454
references.citation: Clin Exp Immunol. 1985 Sep;61(3):601-7
references.pmid: 3878244
references.citation: Kidney Int Suppl (2011). 2012 Jun;2(2):163-171
references.pmid: 25028636
references.citation: Nephron. 2001 Aug;88(4):334-9
references.pmid: 11474228
references.citation: Nephrol Dial Transplant. 2013 Jun;28(6):1439-46
references.pmid: 23262434
references.citation: Lancet. 1959 Mar 7;1(7071):500-2
references.pmid: 13632065
references.citation: J Am Soc Nephrol. 2007 May;18(5):1476-85
references.pmid: 17429054
references.citation: Pediatr Nephrol. 2011 Mar;26(3):469-71
references.pmid: 21113627
references.citation: Pediatr Nephrol. 2008 Jan;23(1):3-7
references.pmid: 17899207
references.citation: Eur J Clin Invest. 1994 Dec;24(12):799-805
references.pmid: 7705373
references.citation: Kidney Int. 1991 Sep;40(3):453-60
references.pmid: 1787645
references.citation: Pediatr Nephrol. 2013 Sep;28(9):1803-12
references.pmid: 23689904
references.citation: Kidney Int. 2006 Sep;70(6):1038-45
references.pmid: 16837924
references.citation: Front Pharmacol. 2014 Feb 25;5:23
references.pmid: 24611049
references.citation: Am J Kidney Dis. 1993 Mar;21(3):251-9
references.pmid: 8447300
references.citation: Clin Exp Immunol. 1995 Jun;100(3):475-9
references.pmid: 7774059
references.citation: Pediatr Nephrol. 2006 Feb;21(2):177-81
references.pmid: 16211409
references.citation: Lancet. 1970 Mar 14;1(7646):542-3
references.pmid: 4190353
references.citation: Pediatr Nephrol. 2004 Nov;19(11):1281-4
references.pmid: 15338388
references.citation: Am J Nephrol. 2003 Jul-Aug;23(4):260-6
references.pmid: 12840601
references.citation: Pediatr Nephrol. 2004 Mar;19(3):300-5
references.pmid: 14747939
references.citation: Lab Invest. 1988 Nov;59(5):673-82
references.pmid: 3141719
references.citation: N Engl J Med. 2014 Mar 27;370(13):1261-3
references.pmid: 24670179
references.citation: J Am Soc Nephrol. 1999 Mar;10(3):529-37
references.pmid: 10073603
references.citation: J Pediatr. 1979 Aug;95(2):261-4
references.pmid: 376811
references.citation: Biochem Biophys Res Commun. 2010 Jan 22;391(4):1737-41
references.pmid: 20043872
references.citation: Clin Nephrol. 1997 May;47(5):289-97
references.pmid: 9181275
references.citation: Clin Exp Nephrol. 2010 Dec;14(6):578-83
references.pmid: 20686809
references.citation: Pediatr Nephrol. 2011 Apr;26(4):645-9
references.pmid: 21052729
references.citation: Clin Nephrol. 2001 Apr;55(4):269-74
references.pmid: 11334311
references.citation: J Am Soc Nephrol. 2001 Aug;12(8):1648-58
references.pmid: 11461937
references.citation: Nat Clin Pract Rheumatol. 2009 Feb;5(2):80-2
references.pmid: 19092831
references.citation: N Engl J Med. 2013 Dec 19;369(25):2416-23
references.pmid: 24206430
references.citation: Clin Nephrol. 2002 Dec;58(6):393-7
references.pmid: 12508959
references.citation: Am J Clin Pathol. 1989 Jul;92(1):68-72
references.pmid: 2750709
references.citation: Arch Dis Child. 1994 Dec;71(6):522-6
references.pmid: 7726612
references.citation: Nat Med. 2014 Jan;20(1):37-46
references.pmid: 24317117