Seminars in Immunopathology

, Volume 36, Issue 4, pp 381–397 | Cite as

Immunopathogenesis of membranous nephropathy: an update

  • Hanna Debiec
  • Pierre Ronco


Membranous nephropathy (MN) is a non-inflammatory organ-specific autoimmune disease which affects the kidney glomerulus, resulting in the formation of immune deposits on the outer aspect of the glomerular basement membrane, complement-mediated proteinuria, and severe renal failure in 30 % of patients. In the last 10 years, substantial advances have been made in the understanding of the molecular bases of MN, with the identification of several antigens and predisposing genes in children and adults. These ground-breaking findings already have a major impact on diagnosis and monitoring and to some extent on therapies. However, there is evidence that the disease is more complex and involves a variety of antigen–antibody systems and genes involved in immune response, progression, recovery, and protective mechanisms. We herein review these recent findings which open new perspectives of research. Understanding the complex pathogenesis of MN will offer many opportunities for future therapeutic interventions and will hopefully have a major impact on patient care. New insights into the molecular mechanisms of MN may also enlighten the pathogenesis of organ-specific autoimmune diseases.


Membranous nephropathy Podocyte Antigens Complement Autoimmunity Stress response 



Research is supported by European Research Council Grant ERC-2012-ADG_20120314 (Grant Agreement 322947), Agence Nationale pour la Recherche Programme Blanc SVSE1 (2012) Decision ANR-12-BSE1-0002-01, Fondation pour la Recherche Médicale Equipe FRM 2012 grant, and 7th Framework Programme of the European Community Contract 2012-305608 (European Consortium for High-Throughput Research in Rare Kidney Diseases).


  1. 1.
    Kerjaschki D (2000) Pathogenetic concepts of membranous glomerulopathy (MGN). J Nephrol 13:S96–S100PubMedGoogle Scholar
  2. 2.
    Glassock RJ (2010) The pathogenesis of idiopathic membranous nephropathy: a 50-year odyssey. Am J Kidney Dis 56:157–167PubMedGoogle Scholar
  3. 3.
    Ronco P, Debiec H (2010) Antigen identification in membranous nephropathy moves toward targeted monitoring and new therapy. J Am Soc Nephrol 21:564–569PubMedGoogle Scholar
  4. 4.
    Simon P, Ramée MP, Autuly V, Laruelle E, Charasse C, Cam G, Ang KS (1994) Epidemiology of primary glomerular diseases in a French region. Variations according to period and age. Kidney Int 46:1192–1198PubMedGoogle Scholar
  5. 5.
    Maisonneuve P, Agodoa L, Gellert R, Stewart JH, Buccianti G, Lowenfels AB, Wolfe RA, Jones E, Disney AP, Briggs D, McCredie M, Boyle P (2000) Distribution of primary renal diseases leading to end-stage renal failure in the United States, Europe, and Australia/New Zealand: results from an international comparative study. Am J Kidney Dis 35:157–165PubMedGoogle Scholar
  6. 6.
    Eddy AA, Symons JM (2003) Nephrotic syndrome in childhood. Lancet 362:629–639PubMedGoogle Scholar
  7. 7.
    Chen A, Frank R, Vento S, Crosby V, Chandra M, Gauthier B, Valderrama E, Trachtman H (2007) Idiopathic membranous nephropathy in pediatric patients: presentation, response to therapy, and long-term outcome. BMC Nephrol 6:8–11Google Scholar
  8. 8.
    Polanco N, Gutiérrez E, Covarsí A, Ariza F, Carreño A, Vigil A, Baltar J, Fernández-Fresnedo G, Martín C, Pons S, Lorenzo D, Bernis C, Arrizabalaga P, Fernández-Juárez G, Barrio V, Sierra M, Castellanos I, Espinosa M, Rivera F, Oliet A, Fernández-Vega F, Praga M (2010) Spontaneous remission of nephrotic syndrome in idiopathic membranous nephropathy. J Am Soc Nephrol 21:697–704PubMedCentralPubMedGoogle Scholar
  9. 9.
    Polanco N, Gutiérrez E, Rivera F, Castellanos I, Baltar J, Lorenzo D, Praga M (2012) Spontaneous remission of nephrotic syndrome in membranous nephropathy with chronic renal impairment. Nephrol Dial Transplant 27:231–234PubMedGoogle Scholar
  10. 10.
    Glassock RJ (2003) Diagnosis and natural course of membranous nephropathy. Semin Nephrol 23:324–332PubMedGoogle Scholar
  11. 11.
    Glassock RJ (2004) The treatment of idiopathic membranous nephropathy: a dilemma or a conundrum? Am J Kidney Dis 44:562–566PubMedGoogle Scholar
  12. 12.
    Hofstra JM, Fervenza FC, Wetzels JF (2013) Treatment of idiopathic membranous nephropathy. Nat Rev Nephrol 9:443–458PubMedGoogle Scholar
  13. 13.
    Waldman M, Austin HA III (2009) Controversies in the treatment of idiopathic membranous nephropathy. Nat Rev Nephrol 5:469–479PubMedCentralPubMedGoogle Scholar
  14. 14.
    Heymann W, Hackel DB, Harwood S, Wilson SGF, Hunter JL (1959) Production of nephrotic syndrome in rats by Freund’s adjuvants and rat kidney suspension. Proc Soc Exp Biol Med 100:660–664PubMedGoogle Scholar
  15. 15.
    Van Damme BJ, Fleuren GJ, Bakker WW, Vernier RL, Hoedemaeker PJ (1978) Experimental glomerulonephritis in the rat induced by antibodies directed against tubular antigens. V. Fixed glomerular antigens in the pathogenesis of heterologous immune complex glomerulonephritis. Lab Investig 38:502–510PubMedGoogle Scholar
  16. 16.
    Couser WG, Steinmuller DR, Stilmant MM, Salant DJ, Lowenstein LM (1978) Experimental glomerulonephritis in the isolated perfused rat kidney. J Clin Invest 62:1275–1287PubMedCentralPubMedGoogle Scholar
  17. 17.
    Kerjaschki D, Farquhar MG (1982) The pathogenic antigen of Heymann nephritis is a membrane glycoprotein of the renal proximal tubule brush border. Proc Natl Acad Sci 79:5557–5561PubMedCentralPubMedGoogle Scholar
  18. 18.
    Kerjaschki D, Farquhar MG (1983) Immunocytochemical localization of the Heymann nephritis antigen (gp330) in glomerular epithelial cells of normal Lewis rats. J Exp Med 157:667–686PubMedCentralPubMedGoogle Scholar
  19. 19.
    Shah P, Tramontano A, Makker SP (2007) Intramolecular spreading in Heymann nephritis. J Am Soc Nephrol 18:3060–3066PubMedGoogle Scholar
  20. 20.
    Prabakaran T, Nielsen R, Larsen JV, Sørensen SS, Feldt-Rasmussen U, Saleem MA, Petersen CM, Verroust PJ, Christensen EI (2011) Receptor-mediated endocytosis of α-galactosidase A in human podocytes in Fabry disease. PLoS One 6:e25065PubMedCentralPubMedGoogle Scholar
  21. 21.
    Border WA, Ward HJ, Kamil ES, Cohen AH (1982) Induction of membranous nephropathy in rabbits by administration of an exogenous cationic antigen. J Clin Invest 69:451–461PubMedCentralPubMedGoogle Scholar
  22. 22.
    Adler SG, Wang H, Ward HJ, Cohen AH, Border WA (1983) Electrical charge. Its role in the pathogenesis and prevention of experimental membranous nephropathy in the rabbit. J Clin Invest 71:487–499PubMedCentralPubMedGoogle Scholar
  23. 23.
    Koyama A, Inage H, Kobayashi M, Nakamura H, Narita M, Tojo S (1986) Effect of chemical cationization of antigen on glomerular localization of immune complexes in active models of serum sickness nephritis in rabbits. Immunology 58:529–534PubMedCentralPubMedGoogle Scholar
  24. 24.
    Bass PS, Drake AF, Wang Y, Thomas JH, Davies DR (1990) Cationization of bovine serum albumin alters its conformation as well as its charge. Lab Investig 62:185–188PubMedGoogle Scholar
  25. 25.
    Wright NG, Mohammed NA, Eckersall PD, Nash AS (1985) Experimental immune complex glomerulonephritis in dogs receiving cationized bovine serum albumin. Res Vet Sci 38:322–328PubMedGoogle Scholar
  26. 26.
    Koyama A, Inage H, Kobayashi M, Ohta Y, Narita M, Tojo S, Cameron JS (1986) Role of antigenic charge and antibody avidity on the glomerular immune complex localization in serum sickness of mice. Clin Exp Immunol 64:606–614Google Scholar
  27. 27.
    Kobayashi M, Muro K, Yoh K, Kondoh M, Iwabuchi S, Hirayama K, Ishizu (1998) Effects of FK506 on experimental membranous glomerulonephritis induced by cationized bovine serum albumin in rats. Nephrol Dial Transplant 13:2501–2508PubMedGoogle Scholar
  28. 28.
    Debiec H, Guigonis V, Mougenot B, Decobert F, Haymann JP, Bensman A, Deschênes G, Ronco PM (2002) Antenatal membranous glomerulonephritis due to anti-neutral endopeptidase antibodies. N Engl J Med 346:2053–2060PubMedGoogle Scholar
  29. 29.
    Ronco P, Debiec H, Guigonis V (2006) Mechanisms of disease: alloimmunization in renal diseases. Nat Clin Pract Nephrol 2:388–397PubMedGoogle Scholar
  30. 30.
    Platt JL, Tucker WL, Michael AF (1983) Stages of renal ontogenesis identified by monoclonal antibodies reactive with lymphohematopoietic differentiation antigens. J Exp Med 157:155–172PubMedGoogle Scholar
  31. 31.
    Appay MD, Mounier F, Gubler MC, Rouchon M, Beziau A, Kazatchkine MD (1985) Ontogenesis of the glomerular C3b receptor (CR1) in fetal human kidney. Clin Immunol Immunopathol 37:103–113PubMedGoogle Scholar
  32. 32.
    Debiec H, Nauta J, Coulet F, van der Burg M, Guigonis V, Schurmans T, de Heer E, Soubrier F, Janssen F, Ronco P (2004) Role of truncating mutations in MME gene in feto-maternal allo-immunization and neonatal glomerulopathies. Lancet 364:1252–1259PubMedGoogle Scholar
  33. 33.
    Ronco P, Debiec H (2005) Molecular pathomechanisms of membranous nephropathy: from Heymann nephritis to alloimmunization. J Am Soc Nephrol 16:1205–1213PubMedGoogle Scholar
  34. 34.
    Vivarelli M, Gerken C, Pelle T, Pedicelli S, Diomedi F, Klaus G, Waldegger S, Emma F, Ronco P, Debiec H (2013) Alloimmune membranous nephropathy with anti-neutral endopeptidase antibodies: genetic homogeneity but IgG subclass-dependent clinical variability. Nephrol Dial Transplant 28 (suppl 1). ERA-EDTA congress in Istanbul 2013.Google Scholar
  35. 35.
    Nortier JL, Debiec H, Tournay Y, Mougenot B, Nöel JC, Deschodt-Lanckman MM, Janssen F, Ronco P (2006) Neonatal disease in neutral endopeptidase alloimmunization: lessons for immunological monitoring. Pediatr Nephrol 1:1399–1405Google Scholar
  36. 36.
    Beck LH Jr, Bonegio RG, Lambeau G, Beck DM, Powell DW, Cummins TD, Klein JB, Salant DJ (2009) M-type phospholipase A2 receptor as target antigen in idiopathic MN. N Engl J Med 361:11–21PubMedCentralPubMedGoogle Scholar
  37. 37.
    Stahl R, Hoxha E, Fechner K (2010) PLA2R autoantibodies and recurrent membranous nephropathy after transplantation. N Engl J Med 363:496–498PubMedGoogle Scholar
  38. 38.
    Blosser CD, Ayalon R, Nair R, Thomas C, Beck LH Jr (2012) Very early recurrence of anti-phospholipase A2 receptor-positive membranous nephropathy after transplantation. Am J Transplant 12:1637–1642PubMedGoogle Scholar
  39. 39.
    Debiec H, Martin L, Jouanneau C, Dautin G, Mesnard L, Rondeau E, Mousson C, Ronco P (2011) Autoantibodies specific for the phospholipase A(2) receptor in recurrent and de novo membranous nephropathy. Am J Transplant 11:2144–2152PubMedGoogle Scholar
  40. 40.
    Debiec H, Hanoy M, Francois A, Guerrot D, Ferlicot S, Johanet C, Aucouturier P, Godin M, Ronco P (2012) Recurrent membranous nephropathy in an allograft caused by IgG3κ targeting the PLA2 receptor. J Am Soc Nephrol 23:1949–1954PubMedCentralPubMedGoogle Scholar
  41. 41.
    East L, Isacke CM (2002) The mannose receptor family. Biochim Biophys Acta 1572:364–386PubMedGoogle Scholar
  42. 42.
    Llorca O (2008) Extended and bent conformations of the mannose receptor family. Cell Mol Life Sci 65:1302–1310PubMedGoogle Scholar
  43. 43.
    Behnert A, Fritzler MJ, Teng B, Zhang M, Bollig F, Haller H, Skoberne A, Mahler M, Schiffer M (2013) An anti-phospholipase A2 receptor quantitative immunoassay and epitope analysis in membranous nephropathy reveals different antigenic domains of the receptor. PLoS One 8(4):e61669PubMedCentralPubMedGoogle Scholar
  44. 44.
    Vangelista A, Tazzari R, Bonomini V (1988) Idiopathic membranous nephropathy in twin brothers. Nephron 50:79–80PubMedGoogle Scholar
  45. 45.
    Bockenhauer D, Debiec H, Sebire N, Barratt M, Warwicker P, Ronco P, Kleta R (2008) Familial membranous nephropathy: an X-linked genetic susceptibility? Nephron Clin Pract 108:10–15Google Scholar
  46. 46.
    Short CD, Feehally J, Gokal R, Mallick NP (1984) Familial membranous nephropathy. Br Med J (Clin Res Ed) 289:1500Google Scholar
  47. 47.
    Vasmant D, Murnaghan K, Bensman A, Muller JY, Mougenot B (1984) Familial idiopathic membranous glomerulonephritis. Int J Pediatr Nephrol 5:193–196PubMedGoogle Scholar
  48. 48.
    Sato K, Oguchi H, Hora K, Furukawa T, Furuta S, Shigematsu H, Yoshizawa S (1987) Idiopathic membranous nephropathy in two brothers. Nephron 46:174–178PubMedGoogle Scholar
  49. 49.
    Elshihabi I, Kaye CI, Brzowski A (1993) Membranous nephropathy in two human leukocyte antigen-identical brothers. J Pediatr 123:940–942PubMedGoogle Scholar
  50. 50.
    Chen JS, Chen A, Chang LC, Chang WS, Lee HS, Lin SH, Lin YF (2004) Mouse model of membranous nephropathy induced by cationic bovine serum albumin: antigen dose–response relations and strain differences. Nephrol Dial Transplant 19:2721–2728PubMedGoogle Scholar
  51. 51.
    Bagchus WM, Hoedemaeker PJ, Vos JT, Bakker WW (1989) Thymocytes reacting with heterologous antibodies against GP 330 in autologous immune complex glomerulopathy (AICG) in the rat. The relation between susceptibility for AICG and anti-GP 330-binding thymocytes. Immunobiology 179:432–444PubMedGoogle Scholar
  52. 52.
    Klouda PT, Manos J, Acheson EJ, Dyer PA, Goldby FS, Harris R, Lawler W, Mallick NP, Williams G (1979) Strong association between idiopathic membranous nephropathy and HLA-DRW3. Lancet 2:770–771PubMedGoogle Scholar
  53. 53.
    Le Petit JC, Laurent B, Berthoux FC (1982) HLA-DR3 and idiopathic membranous nephritis (IMN) association. Tissue Antigens 20:227–228PubMedGoogle Scholar
  54. 54.
    Berthoux FC, Alamartine E, Laurent B, Berthoux P, Vacherot C, Lambert C, Le Petit JC (1984) Immunogenetics and immunopathology of human primary membranous glomerulonephritis: HLA-A, B, DR antigens functional activity of splenic macrophage Fc-receptors and peripheral blood T-lymphocyte subpopulations. Clin Nephrol 22:15–20PubMedGoogle Scholar
  55. 55.
    Vaughan RW, Demaine AG, Welsh KI (1989) A DQA1 allele is strongly associated with idiopathic membranous nephropathy. Tissue Antigens 34:261–269PubMedGoogle Scholar
  56. 56.
    Dyer PA, Short CD, Clarke EA, Mallick NP (1992) HLA antigen and gene polymorphisms and haplotypes established by family studies in membranous nephropathy. Nephrol Dial Transplant 7(Suppl 1):42–47PubMedGoogle Scholar
  57. 57.
    Sacks SH, Warner C, Campbell RD, Dunham I (1993) Molecular mapping of the HLA class II region in HLA-DR3 associated idiopathic membranous nephropathy. Kidney Int Suppl 39:S13–S19PubMedGoogle Scholar
  58. 58.
    Chevrier D, Giral M, Perrichot R, Latinne D, Coville P, Muller JY, Soulillou JP, Bignon JD (1997) Idiopathic and secondary membranous nephropathy and polymorphism at TAP1 and HLA-DMA loci. Tissue Antigens 50:164–169PubMedGoogle Scholar
  59. 59.
    Stanescu HC, Arcos-Burgos M, Medlar A, Bockenhauer D, Kottgen A, Dragomirescu L, Voinescu C, Patel N, Pearce K, Hubank M, Stephens HA, Laundy V, Padmanabhan S, Zawadzka A, Hofstra JM, Coenen MJ, den Heijer M, Kiemeney LA, Bacq-Daian D, Stengel B, Powis SH, Brenchley P, Feehally J, Rees AJ, Debiec H, Wetzels JF, Ronco P, Mathieson PW, Kleta R (2011) Risk HLA-DQA1 and PLA(2)R1 alleles in idiopathic membranous nephropathy. N Engl J Med 364:616–626PubMedGoogle Scholar
  60. 60.
    Kanigicherla D, Gummadova J, McKenzie EA, Roberts SA, Harris S, Nikam M, Poulton K, McWilliam L, Short CD, Venning M, Brenchley PE (2013) Anti-PLA2R antibodies measured by ELISA predict long-term outcome in a prevalent population of patients with idiopathic membranous nephropathy. Kidney Int 83:940–948PubMedGoogle Scholar
  61. 61.
    Bullich G, Ballarín J, Oliver A, Ayasreh N, Silva I, Santín S, Díaz-Encarnación MM, Torra R, Ars E (2014) HLA-DQA1 and PLA2R1 polymorphisms and risk of idiopathic membranous nephropathy. Clin J Am Soc Nephrol 9:335–343PubMedGoogle Scholar
  62. 62.
    Liu YH, Chen CH, Chen SY, Lin YJ, Liao WL, Tsai CH, Wan L, Tsai FJ (2010) Association of phospholipase A2 receptor 1 polymorphisms with idiopathic membranous nephropathy in Chinese patients in Taiwan. J Biomed Sci 17:81–88PubMedCentralPubMedGoogle Scholar
  63. 63.
    Kim S, Chin HJ, Na KY, Kim S, Oh J, Chung W, Noh JW, Lee YK, Cho JT, Lee EK, Chae DW (2011) Single nucleotide polymorphisms in the phospholipase A2 receptor gene are associated with genetic susceptibility to idiopathic membranous nephropathy. Nephron Clin Pract 117:c253–c258PubMedGoogle Scholar
  64. 64.
    Lv J, Hou W, Zhou X, Liu G, Zhou F, Zhao N, Hou P, Zhao M, Zhang H (2013) Interaction between PLA2R1 and HLA-DQA1 variants associates with anti-PLA2R antibodies and membranous nephropathy. J Am Soc Nephrol 24:1323–1329PubMedCentralPubMedGoogle Scholar
  65. 65.
    Coenen MJ, Hofstra JM, Debiec H, Stanescu HC, Medlar AJ, Stengel B, Boland-Augé A, Groothuismink JM, Bockenhauer D, Powis SH, Mathieson PW, Brenchley PE, Kleta R, Wetzels JF, Ronco P (2013) Phospholipase A2 receptor (PLA2R1) sequence variants in idiopathic membranous nephropathy. J Am Soc Nephrol 24:677–683PubMedCentralPubMedGoogle Scholar
  66. 66.
    Bantis C, Heering PJ, Aker S, Siekierka M, Kuhr N, Grabensee B, Ivens K (2006) Tumor necrosis factor-alpha gene G-308A polymorphism is a risk factor for the development of membranous glomerulonephritis. Am Nephrol 26:12–15Google Scholar
  67. 67.
    Thibaudin D, Thibaudin L, Berthoux P, Mariat C, Filippis JP, Laurent B, Alamartine E, Berthoux F (2007) TNFA2 and d2 alleles of the tumor necrosis factor alpha gene polymorphism are associated with onset/occurrence of idiopathic membranous nephropathy. Kidney Int 71:431–437PubMedGoogle Scholar
  68. 68.
    Honkanen E, von Willebrand E, Teppo AM, Törnroth T, Grönhagen-Riska C (1998) Adhesion molecules and urinary tumor necrosis factor-alpha in idiopathic membranous glomerulonephritis. Kidney Int 53:909–917PubMedGoogle Scholar
  69. 69.
    Neale TJ, Rüger BM, Macaulay H, Dunbar PR, Hasan Q, Bourke A, Murray-McIntosh RP, Kitching AR (1995) Tumor necrosis factor-alpha is expressed by glomerular visceral epithelial cells in human membranous nephropathy. Am J Pathol 146:1444–1454PubMedCentralPubMedGoogle Scholar
  70. 70.
    Tabibzadeh S, Kong QF, Kapur S et al (1995) TNF-alpha induces dyscohesion of epithelial cells-association with disassembly of actin filaments. Endocrine 3:549–556PubMedGoogle Scholar
  71. 71.
    Huber TB, Benzing T (2005) The slit diaphragm: a signaling platform to regulate podocyte function. Curr Opin Nephrol Hypertens 14:211–216PubMedGoogle Scholar
  72. 72.
    Lo WY, Chen SY, Wang HJ, Shih HC, Chen CH, Tsai CH, Tsai FJ (2010) Association between genetic polymorphisms of the NPHS1 gene and membranous in the Taiwanese population. Clin Chim Acta 411:714–718PubMedGoogle Scholar
  73. 73.
    Chen CH, Shu KH, Wen MC, Chen KJ, Cheng CH, Lian JD, Wu MJ, Yu TM, Tsai FJ (2008) Impact of plasminogen activator inhibitor-1 gene polymorphisms on primary membranous nephropathy. Nephrol Dial Transplant 23:3166–3173PubMedGoogle Scholar
  74. 74.
    Luo Y, Wang C, Tu H (2014) Impact of the 4G/5G polymorphism in the plasminogen activator inhibitor-1 gene on primary nephrotic syndrome. Mol Med Rep 9:894–898PubMedGoogle Scholar
  75. 75.
    Chen SY, Chen CH, Huang YC, Chuang HM, Lo MM, Tsai FJ (2010) Effect of IL-6C-572G polymorphism on idiopathic membranous nephropathy risk in a Han Chinese population. Ren Fail 32:1172–1176PubMedGoogle Scholar
  76. 76.
    Chen SY, Chen CH, Huang YC, Chan CJ, Hsieh YY, Yu MC, Tsai CH, Tsai FJ (2011) Association of STAT4 polymorphisms with susceptibility to primary membranous glomerulonephritis and renal failure. Clin Chim Acta 412:1899–1904PubMedGoogle Scholar
  77. 77.
    Chen YT, Wei CC, Ng KL, Chen CH, Chan CJ, Chen XX, Chang YY, Chen SY, Tsai FJ (2013) Toll-like receptor 9 SNPs are susceptible to the development and progression of membranous glomerulonephritis: 27 years follow-up in Taiwan. Ren Fail 35:1370–1375PubMedGoogle Scholar
  78. 78.
    Debiec H, Ronco P (2011) Nephrotic syndrome: a new specific test for idiopathic membranous nephropathy. Nat Rev Nephrol 7:496–498PubMedGoogle Scholar
  79. 79.
    Hoxha E, Harendza S, Zahner G, Panzer U, Steinmetz O, Fechner K, Helmchen U, Stahl RA (2011) An immunofluorescence test for phospholipase-A2-receptor antibodies and its clinical usefulness in patients with membranous glomerulonephritis. Nephrol Dial Transplant 26:2526–2532PubMedGoogle Scholar
  80. 80.
    Dähnrich C, Komorowski L, Probst C, Seitz-Polski B, Esnault V, Wetzels JF, Hofstra JM, Hoxha E, Stahl RA, Lambeau G, Stöcker W, Schlumberger W (2013) Development of a standardized ELISA for the determination of autoantibodies against human M-type phospholipase A2 receptor in primary membranous nephropathy. Clin Chim Acta 421:213–218PubMedGoogle Scholar
  81. 81.
    Qin W, Beck LH Jr, Zeng C, Chen Z, Li S, Zuo K, Salant DJ, Liu Z (2011) Anti-phospholipase A2 receptor antibody in membranous nephropathy. J Am Soc Nephrol 22:1137–1143PubMedCentralPubMedGoogle Scholar
  82. 82.
    Knehtl M, Debiec H, Kamgang P, Callard P, Cadranel J, Ronco P, Boffa JJ (2011) A case of phospholipase A2 receptor-positive membranous nephropathy preceding sarcoid-associated granulomatous tubulointerstitial nephritis. Am J Kidney Dis 57:140–143PubMedGoogle Scholar
  83. 83.
    Nawaz FA, Larsen CP, Troxell ML (2013) Membranous nephropathy and nonsteroidal anti-inflammatory agents. Am J Kidney Dis 62:1012–1017PubMedGoogle Scholar
  84. 84.
    Huang X, Qin W, Zhang M, Zheng C, Zeng C, Liu Z (2013) Detection of anti-PLA2R autoantibodies and IgG subclasses in post-allogeneic hematopoietic stem cell transplantation membranous nephropathy. Am J Med Sci 346:32–37PubMedGoogle Scholar
  85. 85.
    Svobodova B, Honsova E, Ronco P, Tesar V, Debiec H (2013) Kidney biopsy is a sensitive tool for retrospective diagnosis of PLA2R-related membranous nephropathy. Nephrol Dial Transplant 28:1839–1844PubMedGoogle Scholar
  86. 86.
    Larsen CP, Messias NC, Silva FG, Messias E, Walker PD (2013) Determination of primary versus secondary membranous glomerulopathy utilizing phospholipase A2 receptor staining in renal biopsies. Mod Pathol 26:709–715PubMedGoogle Scholar
  87. 87.
    Debiec H, Ronco P (2011) PLA2R autoantibodies and PLA2R glomerular deposits in membranous nephropathy. N Engl J Med 364:689–690PubMedGoogle Scholar
  88. 88.
    Hoxha E, Kneißler U, Stege G, Zahner G, Thiele I, Panzer U, Harendza S, Helmchen UM, Stahl RA (2012) Enhanced expression of the M-type phospholipase A2 receptor in glomeruli correlates with serum receptor antibodies in primary membranous nephropathy. Kidney Int 82:797–804PubMedGoogle Scholar
  89. 89.
    Kuroki A, Shibata T, Honda H, Totsuka D, Kobayashi K, Sugisaki T (2002) Glomerular and serum IgG subclasses in diffuse proliferative lupus nephritis, membranous lupus nephritis, and idiopathic membranous nephropathy. Intern Med 41:936–942PubMedGoogle Scholar
  90. 90.
    Ohtani H, Wakui H, Komatsuda A, Okuyama S, Masai R, Maki N, Kigawa A, Sawada K, Imai H (2004) Distribution of glomerular IgG subclass deposits in malignancy-associated membranous nephropathy. Nephrol Dial Transplant 19:574–579PubMedGoogle Scholar
  91. 91.
    Segawa Y, Hisano S, Matsushita M, Fujita T, Hirose S, Takeshita M, Iwasaki H (2010) IgG subclasses and complement pathway in segmental and global membranous nephropathy. Pediatr Nephrol 25:1091–1099PubMedGoogle Scholar
  92. 92.
    Qu Z, Liu G, Li J, Wu LH, Tan Y, Zheng X, Ao J, Zhao MH (2012) Absence of glomerular IgG4 deposition in patients with membranous nephropathy may indicate malignancy. Nephrol Dial Transplant 27:1931–1937PubMedGoogle Scholar
  93. 93.
    Hofstra JM, Beck LH Jr, Beck DM, Wetzels JF, Salant DJ (2011) Anti-phospholipase A2 receptor antibodies correlate with clinical status in idiopathic membranous nephropathy. Clin J Am Soc Nephrol 6:1286–1291PubMedCentralPubMedGoogle Scholar
  94. 94.
    Beck LH Jr, Fervenza FC, Beck DM, Bonegio RG, Malik FA, Erickson SB, Cosio FG, Cattran DC, Salant DJ (2011) Rituximab-induced depletion of anti-PLA2R autoantibodies predicts response in membranous nephropathy. J Am Soc Nephrol 22:1543–1550PubMedCentralPubMedGoogle Scholar
  95. 95.
    Hofstra JM, Debiec H, Short CD, Pellé T, Kleta R, Mathieson PW, Ronco P, Brenchley PE, Wetzels JF (2012) Antiphospholipase A2 receptor antibody titer and subclass in idiopathic membranous nephropathy. J Am Soc Nephrol 23:1735–1743PubMedCentralPubMedGoogle Scholar
  96. 96.
    Oh YJ, Yang SH, Kim DK, Kang SW, Kim YS (2013) Autoantibodies against phospholipase A2 receptor in Korean patients with membranous nephropathy. PLoS One 8:e62151PubMedCentralPubMedGoogle Scholar
  97. 97.
    Hofstra J, Bech A, Brenchley P, Wetzels J (2013) Measurement of anti PLA2R antibodies predicts relapse rate after immunosuppressive therapy in patients with idiopathic membranous nephropathy, abstract [OR049] ASN meeting Atlanta 2013Google Scholar
  98. 98.
    Hu SL, Wang D, Gou WJ, Lei QF, Ma TA, Cheng JZ (2014) Diagnostic value of phospholipase A(2) receptor in idiopathic membranous nephropathy: a systematic review and meta-analysis. J Nephrol 27:111–116PubMedGoogle Scholar
  99. 99.
    Briganti EM, Russ GR, McNeil JJ, Atkins RC, Chadban SJ (2002) Risk of renal allograft loss from recurrent glomerulonephritis. N Engl J Med 347:103–109PubMedGoogle Scholar
  100. 100.
    Dabade TS, Grande JP, Norby SM, Fervenza FC, Cosio FG (2008) Recurrent idiopathic membranous nephropathy after kidney transplantation: a surveillance biopsy study. Am J Transplant 8:1318–1322PubMedGoogle Scholar
  101. 101.
    Larsen CP, Walker PD (2013) Phospholipase A2 receptor (PLA2R) staining is useful in the determination of de novo versus recurrent membranous glomerulopathy. Transplantation 95:1259–1262PubMedGoogle Scholar
  102. 102.
    Takahashi S, Hiromura K, Tsukida M, Ohishi Y, Hamatani H, Sakurai N, Sakairi T, Ikeuchi H, Kaneko Y, Maeshima A, Kuroiwa T, Yokoo H, Aoki T, Nagata M, Nojima Y (2013) Nephrotic syndrome caused by immune-mediated acquired LCAT deficiency. J Am Soc Nephrol 24:1305–1312PubMedCentralPubMedGoogle Scholar
  103. 103.
    Prunotto M, Carnevali ML, Candiano G, Murtas C, Bruschi M, Corradini E, Trivelli A, Magnasco A, Petretto A, Santucci L, Mattei S, Gatti R, Scolari F, Kador P, Allegri L, Ghiggeri GM (2010) Autoimmunity in membranous nephropathy targets aldose reductase and SOD2. J Am Soc Nephrol 21:507–519PubMedCentralPubMedGoogle Scholar
  104. 104.
    Bruschi M, Carnevali ML, Murtas C, Candiano G, Petretto A, Prunotto M, Gatti R, Argentiero L, Magistroni R, Garibotto G, Scolari F, Ravani P, Gesualdo L, Allegri L, Ghiggeri GM (2011) Direct characterization of target podocyte antigens and auto-antibodies in human membranous glomerulonephritis: alfa-enolase and borderline antigens. J Proteomics 74:2008–2017PubMedGoogle Scholar
  105. 105.
    Murtas C, Bruschi M, Candiano G, Moroni G, Magistroni R, Magnano A, Bruno F, Radice A, Furci L, Argentiero L, Carnevali ML, Messa P, Scolari F, Sinico RA, Gesualdo L, Fervenza FC, Allegri L, Ravani P, Ghiggeri GM (2012) Coexistence of different circulating anti-podocyte antibodies in membranous nephropathy. Clin J Am Soc Nephrol 7:1394–1400PubMedCentralPubMedGoogle Scholar
  106. 106.
    Ronco P, Debiec H, Imai H (2013) Circulating antipodocyte antibodies in membranous nephropathy: pathophysiologic and clinical relevance. Am J Kidney Dis 62:16–19PubMedGoogle Scholar
  107. 107.
    Debiec H, Lefeu F, Kemper MJ, Niaudet P, Deschênes G, Remuzzi G, Ulinski T, Ronco P (2011) Early childhood membranous nephropathy due to cationic bovine serum albumin. N Engl J Med 364:2101–2110PubMedGoogle Scholar
  108. 108.
    Sathe SK, Teuber SS, Roux KH (2005) Effects of food processing on the stability of food allergens. Biotechnol Adv 23:423–429PubMedGoogle Scholar
  109. 109.
    Sanchez C, Fremont S (2003) Consequences of heat treatment and processing of food on the structure and allergenicity of component proteins. Rev Fr Allergol Immunol Clin 43:13–20Google Scholar
  110. 110.
    van Elburg RM, Fetter WP, Bunkers CM, Heymans HS (2003) Intestinal permeability in relation to birth weight and gestational and postnatal age. Arch Dis Child Fetal Neonatal Ed 88:F52–F55PubMedCentralPubMedGoogle Scholar
  111. 111.
    Sreedharan R, Mehta DI (2004) Gastrointestinal tract. Pediatrics 113:1044–1050PubMedGoogle Scholar
  112. 112.
    Torente F, Murch S (2004) Food allergic enteropathy. In: Walker AW, Goulet O, Kleinman RE et al (eds) Pediatric gastrointestinal disease, 4th edn. BC Decker, Hamilton, pp 944–958Google Scholar
  113. 113.
    Richards SM (2002) Immunologic considerations for enzyme replacement therapy in the treatment of lysosomal storage disorders. Clin Appl Immunol Rev 2:241–253Google Scholar
  114. 114.
    Brooks DA (1999) Immune response to enzyme replacement therapy in lysosomal storage disorder patients and animal models. Mol Genet Metab 68:268–275PubMedGoogle Scholar
  115. 115.
    Koren E, Zuckerman LA, Mire-Sluis AR (2002) Immune responses to therapeutic proteins in humans—clinical significance, assessment and prediction. Curr Pharm Biotechnol 3:349–360PubMedGoogle Scholar
  116. 116.
    Hunley TE, Corzo D, Dudek M, Kishnani P, Amalfitano A, Chen YT, Richards SM, Phillips JA 3rd, Fogo AB, Tiller GE (2004) Nephrotic syndrome complicating alpha-glucosidase replacement therapy for Pompe disease. Pediatrics 114:e532–e535PubMedGoogle Scholar
  117. 117.
    Debiec H, Valayannopoulos V, Boyer O, Nöel LH, Callard P, Sarda H, de Lonlay P, Niaudet P, Ronco P (2013) Allo-immune membranous nephropathy and recombinant aryl sulfatase replacement therapy: a need for tolerance induction therapy. J Am Soc Nephrol 25:675–680Google Scholar
  118. 118.
    Jordan SC, Buckingham B, Sakai R, Olson D (1981) Studies of immune-complex glomerulonephritis mediated by human thyroglobulin. N Engl J Med 304:1212–1215PubMedGoogle Scholar
  119. 119.
    Hörl WH, Kerjaschki D (2000) Membranous glomerulonephritis (MGN). J Nephrol 13:291–316PubMedGoogle Scholar
  120. 120.
    Bhimma R, Coovadia HM (2004) Hepatitis B virus-associated nephropathy. Am J Nephrol 24:198–211PubMedGoogle Scholar
  121. 121.
    Nakahara K, Takahashi H, Okuse C, Shigefuku R, Yamada N, Murao M, Matsunaga K, Koike J, Yotsuyanagi H, Suzuki M, Kimura K, Itoh F (2010) Membranous nephropathy associated with chronic hepatitis B occurring in a short period after acute hepatitis B virus infection. Intern Med 49:383–388PubMedGoogle Scholar
  122. 122.
    Guiard E, Karras A, Plaisier E, Duong Van Huyen JP, Fakhouri F, Rougier JP, Noel LH, Callard P, Delahousse M, Ronco P (2011) Patterns of noncryoglobulinemic glomerulonephritis with monoclonal Ig deposits: correlation with IgG subclass and response to rituximab. Clin J Am Soc Nephrol 6:1609–1616PubMedGoogle Scholar
  123. 123.
    de Seigneux S, Bindi P, Debiec H, Alyanakian MA, Aymard B, Callard P, Ronco P, Aucouturier P (2010) Immunoglobulin deposition disease with a membranous pattern and a circulating monoclonal immunoglobulin G with charge-dependent aggregation properties. Am J Kidney Dis 56:117–121PubMedGoogle Scholar
  124. 124.
    Lundberg K, Venables PJ (2008) Epitope spreading in animal models: array of hope in rheumatoid arthritis and multiple sclerosis. Arthritis Res Ther 10:122PubMedCentralPubMedGoogle Scholar
  125. 125.
    Chen L, Hellmark T, Pedchenko V, Hudson BG, Pusey CD, Fox JW, Bolton WK (2006) A nephritogenic peptide induces intermolecular epitope spreading on collagen IV in experimental autoimmune glomerulonephritis. J Am Soc Nephrol 17:3076–3081PubMedGoogle Scholar
  126. 126.
    Adler S, Chen X (1992) Anti-Fx1A antibody recognizes a beta 1-integrin on glomerular epithelial cells and inhibits adhesion and growth. Am J Physiol 262:F770–F776PubMedGoogle Scholar
  127. 127.
    Binstadt BA, Patel PR, Alencar H, Nigrovic PA, Lee DM, Mahmood U, Weissleder R, Mathis D, Benoist C (2006) Particularities of the vasculature can promote the organ specificity of autoimmune attack. Nat Immunol 7:284–292PubMedGoogle Scholar
  128. 128.
    Spicer ST, Tran GT, Killingsworth MC, Carter N, Power DA, Paizis K, Boyd R, Hodgkinson SJ, Hall BM (2007) Induction of passive Heymann nephritis in complement component 6-deficient PVG rats. J Immunol 179:172–178PubMedGoogle Scholar
  129. 129.
    Leenaerts PL, Hall BM, Van Damme BJ, Daha MR, Vanrenterghem YF (1995) Active Heymann nephritis in complement component C6 deficient rats. Kidney Int 47:1604–1614PubMedGoogle Scholar
  130. 130.
    Kerjaschki D, Exner M, Ullrich R, Susani M, Curtiss LK, Witztum JL, Farquhar MG, Orlando RA (1997) Pathogenic antibodies inhibit the binding of apolipoproteins to megalin/gp330 in passive Heymann nephritis. J Clin Invest 100:2303–2309PubMedCentralPubMedGoogle Scholar
  131. 131.
    Turner AJ, Isaac RE, Coates D (2001) The neprilysin (NEP) family of zinc metalloendopeptidases: genomics and function. Bioessays 23:261–269PubMedGoogle Scholar
  132. 132.
    Ancian P, Lambeau G, Lazdunski M (1995) Multifunctional activity of the extracellular domain of the M-type (180 kDa) membrane receptor for secretory phospholipases A2. Biochemistry 34:13146–13151PubMedGoogle Scholar
  133. 133.
    Zvaritch E, Lambeau G, Lazdunski M (1996) Endocytic properties of the M-type 180-kDa receptor for secretory phospholipases A2. J Biol Chem 271:250–257PubMedGoogle Scholar
  134. 134.
    Hanasaki K, Arita H (2002) Phospholipase A2 receptor: a regulator of biological functions of secretory phospholipase A2. Prostaglandins Other Lipid Mediat 69:71–82Google Scholar
  135. 135.
    Lambeau G, Gelb MH (2008) Biochemistry and physiology of mammalian secreted phospholipases A2. Annu Rev Biochem 77:495–520PubMedGoogle Scholar
  136. 136.
    Augert A, Payré C, de Launoit Y, Gil J, Lambeau G, Bernard D (2009) The M-type receptor PLA2R regulates senescence through the p53 pathway. EMBO Rep 10:271–217PubMedCentralPubMedGoogle Scholar
  137. 137.
    Sis B, Tasanarong A, Khoshjou F, Dadras F, Solez K, Halloran PF (2007) Accelerated expression of senescence associated cell cycle inhibitor p16INK4A in kidneys with glomerular disease. Kidney Int 71:218–226PubMedGoogle Scholar
  138. 138.
    Cybulsky AV, Quigg RJ, Salant DJ (2005) Experimental membranous nephropathy redux. Am J Physiol Renal Physiol 289:F660–F671PubMedCentralPubMedGoogle Scholar
  139. 139.
    Sarma JV, Ward PA (2011) The complement system. Cell Tissue Res 343:227–235PubMedCentralPubMedGoogle Scholar
  140. 140.
    Morgan BP, Haris CL (1999) Regulation in the activation pathways. In: Complement regulatory proteins. Academic, San Diego, pp 41–136Google Scholar
  141. 141.
    Naik A, Sharma S, Quigg RJ (2013) Complement regulation in renal disease models. Semin Nephrol 33:575–585PubMedGoogle Scholar
  142. 142.
    Loirat C, Frémeaux-Bacchi V (2011) Atypical hemolytic uremic syndrome. Orphanet J Rare Dis 6:60–90PubMedCentralPubMedGoogle Scholar
  143. 143.
    Hughes AE, Orr N, Esfandiary H, Diaz-Torres M, Goodship T, Chakravarthy U (2006) A common CFH haplotype, with deletion of CFHR1 and CFHR3, is associated with lower risk of age-related macular degeneration. Nat Genet 38:1173–1177PubMedGoogle Scholar
  144. 144.
    Gold B, Merriam JE, Zernant J, Hancox LS, Taiber AJ, Gehrs K, Cramer K, Neel J, Bergeron J, Barile GR, Smith RT, AMD Genetics Clinical Study Group, Hageman GS, Dean M, Allikmets R (2006) Variation in factor B (BF) and complement component 2 (C2) genes is associated with age-related macular degeneration. Nat Genet 38:458–462PubMedCentralPubMedGoogle Scholar
  145. 145.
    van der Zee JS, van Swieten P, Aalberse RC (1986) Inhibition of complement activation by IgG4 antibodies. Clin Exp Immunol 64:415–422PubMedCentralPubMedGoogle Scholar
  146. 146.
    Aalberse RC, Schuurman J (2002) IgG4 breaking the rules. Immunology 105:9–19PubMedCentralPubMedGoogle Scholar
  147. 147.
    Huang CC, Lehman A, Albawardi A, Satoskar A, Brodsky S, Nadasdy G, Hebert L, Rovin B, Nadasdy T (2013) IgG subclass staining in renal biopsies with membranous glomerulonephritis indicates subclass switch during disease progression. Mod Pathol 26:799–805PubMedGoogle Scholar
  148. 148.
    Lhotta K, Würzner R, König P (1999) Glomerular deposition of mannose-binding lectin in human glomerulonephritis. Nephrol Dial Transplant 14:881–886PubMedGoogle Scholar
  149. 149.
    Espinosa-Hernández M, Ortega-Salas R, López-Andreu M, Gómez-Carrasco JM, Pérez-Sáez MJ, Pérez-Seoane C, Aljama-García P (2012) C4d as a diagnostic tool in membranous nephropathy. Nefrologia 32:295–299PubMedGoogle Scholar
  150. 150.
    Thiel S, Gadjeva M (2009) Humoral pattern recognition molecules: mannan-binding lectin and ficolins. Adv Exp Med Biol 653:58–73PubMedGoogle Scholar
  151. 151.
    Malhotra R, Wormald MR, Rudd PM, Fischer PB, Dwek RA, Sim RB (1995) Glycosylation changes of IgG associated with rheumatoid arthritis can activate complement via the mannose-binding protein. Nat Med 1:237–243PubMedGoogle Scholar
  152. 152.
    Bond A, Alavi A, Axford JS, Bourke BE, Bruckner FE, Kerr MA, Maxwell JD, Tweed KJ, Weldon MJ, Youinou P, Hay FC (1997) A detailed lectin analysis of IgG glycosylation, demonstrating disease specific changes in terminal galactose and N-acetylglucosamine. J Autoimmun 10:77–85PubMedGoogle Scholar
  153. 153.
    Parekh R, Isenberg D, Rook G, Roitt I, Dwek R, Rademacher T (1989) A comparative analysis of disease-associated changes in the galactosylation of serum IgG. J Autoimmun 2:101–114PubMedGoogle Scholar
  154. 154.
    Ma H, Beck LH Jr, Salant D (2011) J Am Soc Nephrol 22:62A, abstr. ASN congress in 2013.Google Scholar
  155. 155.
    Rispens T, Ooievaar-De Heer P, Vermeulen E, Schuurman J, van der Neut Kolfschoten M, Aalberse RC (2009) Human IgG4 binds to IgG4 and conformationally altered IgG1 via Fc-Fc interactions. J Immunol 182:4275–4281PubMedGoogle Scholar
  156. 156.
    Ito T, Kitahara K, Umemura T, Ota M, Shimozuru Y, Kawa S, Bahram S (2010) A novel heterophilic antibody interaction involves IgG4. Scand J Immunol 71:109–114PubMedGoogle Scholar
  157. 157.
    Nangaku M, Shankland SJ, Couser WG (2005) Cellular response to injury in membranous nephropathy. J Am Soc Nephrol 16:1195–1204PubMedGoogle Scholar
  158. 158.
    Cunningham PN, Quigg RJ (2005) Contrasting roles of complement activation and its regulation in membranous nephropathy. J Am Soc Nephrol 16:1214–1222PubMedGoogle Scholar
  159. 159.
    Tegla CA, Cudrici C, Patel S, Trippe R 3rd, Rus V, Niculescu F, Rus H (2011) Membrane attack by complement: the assembly and biology of terminal complement complexes. Immunol Res 51:45–60PubMedCentralPubMedGoogle Scholar
  160. 160.
    Bohana-Kashtan O, Ziporen L, Donin N, Kraus S, Fishelson Z (2004) Cell signals transduced by complement. Mol Immunol 41:583–597PubMedGoogle Scholar
  161. 161.
    Moskovich O, Fishelson Z (2000) Live cell imaging of outward and inward vesiculation induced by the complement c5b-9 complex. J Biol Chem 28:29977–29986Google Scholar
  162. 162.
    Kerjaschki D, Schulze M, Binder S, Kain R, Ojha PP, Susani M, Horvat R, Baker PJ, Couser WG (1989) Transcellular transport and membrane insertion of the C5b-9 membrane attack complex of complement by glomerular epithelial cells in experimental membranous nephropathy. J Immunol 143:546–552PubMedGoogle Scholar
  163. 163.
    Kon SP, Coupes B, Short CD, Solomon LR, Raftery MJ, Mallick NP, Brenchley PE (1995) Urinary C5b-9 excretion and clinical course in idiopathic human membranous nephropathy. Kidney Int 48:1953–1958PubMedGoogle Scholar
  164. 164.
    Cybulsky AV (2010) Endoplasmic reticulum stress in proteinuric kidney disease. Kidney Int 7:187–193Google Scholar
  165. 165.
    Cybulsky AV (2013) The intersecting roles of endoplasmic reticulum stress, ubiquitin- proteasome system, and autophagy in the pathogenesis of proteinuric kidney disease. Kidney Int 84:25–33PubMedGoogle Scholar
  166. 166.
    Wang L, Hong Q, Lv Y, Feng Z, Zhang X, Wu L, Cui S, Hou K, Su H, Huang Z, Wu D, Chen X (2012) Autophagy can repair endoplasmic reticulum stress damage of the passive Heymann nephritis model as revealed by proteomics analysis. J Proteomics 75:3866–3876PubMedGoogle Scholar
  167. 167.
    Meyer-Schwesinger C, Meyer TN, Sievert H, Hoxha E, Sachs M, Klupp EM, Münster S, Balabanov S, Carrier L, Helmchen U, Thaiss F, Stahl RA (2011) Ubiquitin C-terminal hydrolase-l1 activity induces polyubiquitin accumulation in podocytes and increases proteinuria in rat membranous nephropathy. Am J Pathol 178:2044–2057PubMedCentralPubMedGoogle Scholar
  168. 168.
    Meyer-Schwesinger C, Meyer TN, Münster S, Klug P, Saleem M, Helmchen U, Stahl RA (2009) A new role for the neuronal ubiquitin C-terminal hydrolase-L1 (UCH-L1) in podocyte process formation and podocyte injury in human glomerulopathies. J Pathol 217:452–464PubMedGoogle Scholar
  169. 169.
    Hetz C (2012) The unfolded protein response: controlling cell fate decisions under ER stress and beyond. Nat Rev Mol Cell Biol 13:89–102PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Sorbonne UniversitésParisFrance
  2. 2.INSERMParisFrance
  3. 3.AP-HP, Hôpital TenonNéphrologie et DialysesParisFrance
  4. 4.INSERM UMR_S 1155, Hôpital TenonParisFrance

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