Molecular and cellular mechanisms for proteinuria in minimal change disease

Frontiers in Medicine

Volumn 5, Issue JUN, 2018, Pages

  Bertelli, Roberta ^a   Bonanni, Alice ^a   Caridi, Gianluca ^a   Canepa, Alberto ^b   Ghiggeri, G M ^a,b  

^a Laboratory of Molecular Nephrology   (Italy)

^b G GASLINI INSTITUTE   (Italy)

Author keywords

Experimental models; Focal segmental glomerulosclerosis; Minimal change disease; Nephrotic syndrome; Proteinuria

Indexed keywords

EID: 85050116648     PISSN: None     EISSN: 2296858X     Source Type: Journal    
DOI: 10.3389/fmed.2018.00170     Document Type: Review

References (119)

1. Hayslett JP, Krassner LS, Bensch KG, Kashgarian M, Epstein FH. Progression of "lipoid nephrosis" to renal insufficiency. N Engl J Med. (1969) 281:181-7
2. Tejani A, Phadke K, Nicastri A, Adamson O, Chen CK, Trachtman H, et al. Efficacy of cyclophosphamide in steroid-sensitive childhood nephrotic syndrome with different morphological lesions. Nephron (1985) 41:170-3
3. Maas RJ, Deegens JK, Smeets B, Moeller MJ, Wetzels JF. Minimal change disease and idiopathic FSGS: manifestations of the same disease. Nat Rev Nephrol. (2016) 12:768-76. doi: 10.1038/nrneph.2016.147
4. Fogo AB. Causes and pathogenesis of focal segmental glomerulosclerosis. Nat Rev Nephrol. (2015) 11:76-87. doi: 10.1038/nrneph.2014.216
5. Motoyama O, Sugawara H, Hatano M, Fujisawa T, Iitaka K. Steroid-sensitive nephrotic syndrome in two families. Clin Exp Nephrol. (2009) 13:170-3. doi: 10.1007/s10157-008-0117-7
6. Konrad M, Mytilineos J, Bonissou F, Scherer S, Gulli MP, Meissner I. HLA class II associations with idiopathic nephrotic syndrome in children. Tissue Antigens (1994) 43:275-80
7. Clark AG, Vaughan RW, Stephens HA, Chantler C, Williams DG, Welsh KI. Genes encoding the beta-chains of HLA-DR7 and HLA-DQw2 define major susceptibility determinants for idiopathic nephrotic syndrome. Clin Sci. (1990) 78:391-7
8. Lagueruela CC, Buettner TL, Cole BR, Kissane JM, Robson AM. HLA extended haplotypes in steroid-sensitive nephrotic syndrome of childhood. Kidney Int. (1990) 38:145-50
9. Abe KK, Michinaga I, Hiratsuka T, Ogahara S, Naito S, Arakawa K, et al. Association of DQB1*0302 alloantigens in Japanese pediatric patients with steroid-sensitive nephrotic syndrome. Nephron (1995) 70:28-34
10. Feehally J, Kendell NP, Swift PG, Walls J. High incidence of minimal change nephrotic syndrome in Asians. Arch Dis Child (1985) 60:1018-20
11. Hinkes B, Wiggins RC, Gbadegesins RA, Vlangos CN, Seelow D, Nürberg G. Positional cloning uncovers mutations in PLCE1 responsible for a nephrotic syndrome variant that may be reversible. Nat Genet. (2006) 38:1397-405. doi: 10.1038/ng1918
12. Gbadegesin RA, Adeyamo A, Webb NJ, Greenbaum LA, Abeyagunawardena A, Thalgahagada S. HLA-DQA1 and PLCG2 are candidate risk loci for childhood-onset steroid-sensitive nephrotic syndrome. J Am Soc Nephrol. (2015) 26:1701-10. doi: 10.1681/ASN.2014030247
13. Kiryluk K, Li Y, Scolari F, Sanna-Cherchi S, Choi M, Verbitsky M. Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens. Nat Genet. (2014) 46:1187-96. doi: 10.1038/ng.3118
14. Roberts IS, Gleadle JM. Familial nephropathy and multiple exostoses with exostosin-1 (EXT1) gene mutation. J Am Soc Nephrol. (2008) 19:450-3. doi: 10.1681/ASN.2007080842
15. Gee HY, Ashraf S, Wan X, Vega-Warner V, Esteve-Rudd J, Lovric S. Mutations in EMP2 cause childhood-onset nephrotic syndrome. Am J Hum Genet. (2014) 94:884-90. doi: 10.1016/j.ajhg.2014.04.010
16. Gee HY, Zhang F, Ashraf S, Kohl S, Sadowski CE, Vega-Warner V. KANK deficiency leads to podocyte dysfunction and nephrotic syndrome. J Clin Invest. (2015) 125:2375-84. doi: 10.1172/JCI79504
17. Lahdenkari AT, Kestila M, Holmberg C, Koskimies O, Jalanko H. Nephrin gene (NPHS1) in patients with minimal change nephrotic syndrome (MCNS). Kidney Int. (2004) 65:1856-63. doi: 10.1111/j.1523-1755.2004.00583.x
18. Cambier JF, Ronco P. Onco-nephrology: glomerular diseases with cancer. Clin J Am Soc Nephrol. (2012) 7:1701-12. doi: 10.2215/CJN.03770412
19. Lien YH, Lai LW. Pathogenesis, diagnosis and management of paraneoplastic glomerulonephritis. Nat Rev Nephrol. (2011) 7:85-95. doi: 10.1038/nrneph.2010.171
20. Cohen LJ, Rennke HG, Laubach JP, Humphreys BD. The spectrum of kidney involvement in lymphoma: a case report and review of the literature. Am J Kidney Dis. (2010) 56:1191-6. doi: 10.1053/j.ajkd.2010.07.009
21. Ronco PM. Paraneoplastic glomerulopathies: new insights into an old entity. Kidney Int. (1999) 56:355-77
22. Kofman T, Zhang SY, Copie-Bergman C, Moktefi A, Rainbourg Q, Francois H. Minimal change nephrotic syndrome associated with non-Hodgkin lymphoid disorders: a retrospective study of 18 cases. Medicine (2014) 93:350-8. doi: 10.1097/MD.0000000000000206
23. Karras A, de Montpreville V, Fakhouri F, Grünfeld JP, Lesavre P. Group d'Etudes des nephropaties associees aux thymomes renal and thymic pathology in thymoma-associated nephropathy: report of 21 cases and review of the literature. Nephrol Dial Transplant. (2005) 20:1075-82. doi: 10.1093/ndt/gfh615
24. Audard V, Larousserie F, Grimbert P, Abtahi M, Sotto JI, Delmer A. Minimal change nephrotic syndrome and classical Hodgkin's lymphoma: report of 21 cases and review of the literature. Kidney Int. (2006) 69:2251-60. doi: 10.1038/sj.ki.5000341
25. Audard V, Zhang SY, Copie-Bergman C, Rucker-Martin C, Ory V, Candelier M. Occurrence of minimal change nephrotic syndrome in classical Hodgkin lymphoma is closely related to the induction of c-mip in Hodgkin-Reed Sternberg cells and podocytes. Blood (2010) 115:3756-62. doi: 10.1182/blood-2009-11-251132
26. Brenner BM, Hostetter TH, Humes HD. Molecular basis of proteinuria of glomerular origin. N Engl J Med. (1978) 298:826-33
27. Ghiggeri GM, Ginevri F, Candiano G, Oleggini R, Perfumo F, Queirolo C, et al. Characterization of cationic albumin in minimal change nephropathy. Kidney Int. (1987) 32:547-53
28. Meyrier A. Treatment of focal segmental glomerulosclerosis. Expert Opin Pharmacother. (2005) 6:1539-49. doi: 10.1517/14656566.6.9.1539
29. Faul C, Donnelly M, Merscher-Gomez S, Chang YH, Franz S, Delfgaauw J. The actin cytoskeleton of kidney podocytes is a direct target of the antiproteinuric effect of cyclosporine A. Nat Med. (2008) 14:931-8. doi: 10.1038/nm.1857
30. Sanna-Cherchi S, Somenzi D, Carnevali ML, Pilato FP, Carraro M, Ghiggeri GM, et al. Recurrent autosomal-dominant focal segmental glomerulosclerosis. Kidney Int. (2006) 70:1664-5. doi: 10.1038/sj.ki.5001796
31. Koyama A, Fujisaki M, Kobayashi M, Igarashi M, Narita M. A glomerular permeability factor produced by human T cell hybridomas. Kidney Int. (1991) 40:453-60
32. Frank C, Herrmann M, Fernandez M, Dirnecker S, Böswald M, Kolowos W. Dominant T cells in idiopathic nephrotic syndrome of childhood. Kidney Int. (2000) 57:510-7. doi: 10.1046/j.1523-1755.2000.00870.x
33. Fiser RT, Arnold WC, Charlton RK, Steele RW, Childress SH, Shirkey B. T-lymphocyte subsets in nephrotic syndrome. Kidney Int. (1991) 40:913-6
34. Yap HK, Cheung W, Murugasu B, Sim SK, Seah CC, Jordan SC. Th1 and Th2 cytokine mRNA profiles in childhood nephrotic syndrome: evidence for increased IL-13 mRNA expression in relapse. J Am Soc Nephrol. (1999) 10:529-37
35. Liu LL, Qin V, Cai JF, Wang HY, Tao JL, Li H. Th17/Treg imbalance in adult patients with minimal change nephrotic syndrome. Clin Immunol. (2011) 139:314-20. doi: 10.1016/j.clim.2011.02.018
36. Lama G, Luongo I, Tirino G, Borriello A, Carangio C, Salsamo ME. T-lymphocyte populations and cytokines in childhood nephrotic syndrome. Am J Kidney Dis. (2002) 39:958-65. doi: 10.1053/ajkd.2002.32769
37. Araya C, Diaz L, Wasserfall C, Atkinson M, Mu W, Johnson R, et al. T regulatory cell function in idiopathic minimal lesion nephrotic syndrome. Pediatr Nephrol. (2009) 24:1691-8. doi: 10.1007/s00467-009-1214-x
38. Cho BS, Yoon SR, Jang JY, Pyun KH, Lee CE. Up-regulation of interleukin-4 and CD23/FcepsilonRII in minimal change nephrotic syndrome. Pediatr Nephrol. (1999) 13:199-204
39. Le Berre L, Hervè C, Buzelin F, Usai C, Soulillou JP, Dantal J. Renal macrophage activation and Th2 polarization precedes the development of nephrotic syndrome in Buffalo/Mna rats. Kidney Int. (2005) 68:2079-90. doi: 10.1111/j.1523-1755.2005.00664.x
40. Le Berre L, Bruneau S, Naulet J, Renaudin K, Buzelin F, Usai C. Induction of T regulatory cells attenuates idiopathic nephrotic syndrome. J Am Soc Nephrol. (2009) 20:57-67. doi: 10.1681/ASN.2007111244
41. Lai KW, Wei CL, Tan LK, Tan PH, Chiang GS, Lee CG. Overexpression of interleukin-13 induces minimal-change-like nephropathy in rats. J Am Soc Nephrol. (2007) 18:1476-85. doi: 10.1681/ASN.2006070710
42. Couser WG. Basic and translational concepts of immune-mediated glomerular diseases. J Am Soc Nephrol. (2012) 23:381-99. doi: 10.1681/ASN.2011030304
43. Josefowicz SZ, Lu LF, Rudensky AY. Regulatory T cells: mechanisms of differentiation and function. Annu Rev Immunol. (2012) 30:531-64. doi: 10.1146/annurev.immunol.25.022106.141623
44. Bertelli R, Bonanni A, Di Donato A, Cioni M, Ravani PG, Ghiggeri M. Regulatory T cells and minimal change nephropathy: in the midst of a complex network. Clin Exp Immunol. (2016) 183:166-74. doi: 10.1111/cei.12675
45. Wang YM, Zhang GY, Hu M, Polhill T, Sawyer A, Zhou JJ. CD8+ regulatory T cells induced by T cell vaccination protect against autoimmune nephritis. J Am Soc Nephrol. (2012) 23:1058-67. doi: 10.1681/ASN.2011090914
46. Polhill T, Zhang GY, Hu M, Sawyer A, Zhou JJ, Saito M. IL-2/IL-2Ab complexes induce regulatory T cell expansion and protect against proteinuric CKD. J Am Soc Nephrol. (2012) 23:1303-8. doi: 10.1681/ASN.2011111130
47. Bertelli R, Di Donato A, Cioni M, Grassi F, Ikehata M, Bonanni A, et al. LPS nephropathy in mice is ameliorated by IL-2 independently of regulatory T cells activity. PLoS ONE (2014) 9:e111285. doi: 10.1371/journal.pone.0111285
48. Bertelli R, Trivelli A, Magnasco A, Cioni M, Bodria M, Carrea A. Failure of regulation results in an amplified oxidation burst by neutrophils in children with primary nephrotic syndrome. Clin Exp Immunol. (2010) 161:151-8. doi: 10.1111/j.1365-2249.2010.04160.x
49. Bertelli R, Bodria M, Nobile M, Alloisio S, Barbieri R, Montobbio G, et al. Regulation of innate immunity by the nucleotide pathway in children with idiopathic nephrotic syndrome. Clin Exp Immunol. (2011) 166:55-63. doi: 10.1111/j.1365-2249.2011.04441.x
50. Saadoun D, Rosenzwajg M, Joly F, Six A, Carrat F, Thibault V. Regulatory T-cell responses to low-dose interleukin-2 in HCV-induced vasculitis. N Engl J Med. (2011) 365:2067-77. doi: 10.1056/NEJMoa1105143
51. Koreth J, Matsuoka K, Kim HT, McDonough SM, Bindra B, Alyea EP III. Interleukin-2 and regulatory T cells in graft-versus-host disease. N Engl J Med. (2011) 365:2055-66. doi: 10.1056/NEJMoa1108188
52. Bonanni A, Bertelli R, Rossi R, Bruschi M, Di Donato A, Ravani P, et al. A pilot study of IL2 in drug-resistant idiopathic nephrotic syndrome. PLoS ONE (2015) 10:e0138343. doi: 10.1371/journal.pone.0138343
53. Ravani P, Bonanni A, Rossi R, Caridi G, Ghiggeri GM. Anti-CD20 antibodies for idiopathic nephrotic syndrome in children. Clin J Am Soc Nephrol. (2016) 11:710-20. doi: 10.2215/CJN.08500815
54. Ravani P, Rossi R, Bonanni A, Quinn RR, Sica F, Bodria M. Rituximab in children with steroid-dependent nephrotic syndrome: a multicenter, open-label, noninferiority, randomized controlled trial. J Am Soc Nephrol. (2015) 26:2259-66. doi: 10.1681/ASN.2014080799
55. Fornoni A, Sageshima J, Wei C, Merscher-Gomez S, Aguillon-Prada R, Jauregui AN. Rituximab targets podocytes in recurrent focal segmental glomerulosclerosis. Sci Transl Med. (2011) 3:85ra46. doi: 10.1126/scitranslmed.3002231
56. Yoo TH, Pedigo CE, Guzman J, Correa-Medina M, Wei C, Villareal R. Sphingomyelinase-like phosphodiesterase 3b expression levels determine podocyte injury phenotypes in glomerular disease. J Am Soc Nephrol. (2015) 26:133-47. doi: 10.1681/ASN.2013111213
57. Alunno A, Carubbi F, Bistoni O, Caterbi S, Bartoloni E, Di Benedetto P. Interleukin (IL)-17-producing pathogenic T lymphocytes co-express CD20 and are depleted by rituximab in primary Sjogren's syndrome: a pilot study. Clin Exp Immunol. (2016) 184:284-92. doi: 10.1111/cei.12771
58. van de Veerdonk FL, Lauwerys B, Marijnissen RJ, Timmermans K, Di Padova F, Koenders MI. The anti-CD20 antibody rituximab reduces the Th17 cell response. Arthritis Rheum. (2011) 63:1507-16. doi: 10.1002/art.30314
59. Frenk S, Antonowicz I, Craig JM, Metcoff J. Experimental nephrotic syndrome induced in rats by aminonucleoside; renal lesions and body electrolyte composition. Proc Soc Exp Biol Med. (1955) 89:424-7
60. Ghiggeri GM, Cercignani G, Ginevri F, Bertelli R, Zetta L, Greco F. Puromycin aminonucleoside metabolism by glomeruli and glomerular epithelial cells in vitro. Kidney Int. (1991) 40:35-42
61. Ginevri F, Gusmano R, Oleggini R, Acerbo S, Bertelli R, Perfumo F. Renal purine efflux and xanthine oxidase activity during experimental nephrosis in rats: difference between puromycin aminonucleoside and adriamycin nephrosis. Clin Sci. (1990) 78:283-93
62. Fukuda F, Kitada M, Horie T, Awazu S. Evaluation of adriamycin-induced lipid peroxidation. Biochem Pharmacol. (1992) 44:755-60
63. Coers W, Huitema S, van der Horst ML, Weening JJ. Puromycin aminonucleoside and adriamycin disturb cytoskeletal and extracellular matrix protein organization, but not protein synthesis of cultured glomerular epithelial cells. Exp Nephrol. (1994) 2:40-50
64. Adachi K, Fujiura Y, Mayumi F, Nozuhara A, Sugiu Y, Sakanashi T. A deletion of mitochondrial DNA in murine doxorubicin-induced cardiotoxicity. Biochem Biophys Res Commun. (1993) 195:945-51
65. Bertani T, Poggi A, Pozzoni R, Delaini F, Sacchi G, Thoua Y. Adriamycin-induced nephrotic syndrome in rats: sequence of pathologic events. Lab Invest. (1982) 46:16-23
66. Papeta N, Zheng Z, Schon EA, Brosel S, Altintas MM, Nasr SH. Prkdc participates in mitochondrial genome maintenance and prevents Adriamycin-induced nephropathy in mice. J Clin Invest. (2010) 120:4055-64. doi: 10.1172/JCI43721
67. Morgan WA, Kaler B, Bach PH. The role of reactive oxygen species in adriamycin and menadione-induced glomerular toxicity. Toxicol Lett. (1998) 94:209-15
68. Reiser J, von Gersdorff G, Loos M, Oh J, Asanuma K, Giardino L. Induction of B7-1 in podocytes is associated with nephrotic syndrome. J Clin Invest. (2004) 113:1390-7. doi: 10.1172/JCI20402
69. Matsuyama M, Yamada C, Hiai H. A single dominant susceptible gene determines spontaneous development of thymoma in BUF/Mna rat. Jpn J Cancer Res. (1986) 77:1066-8
70. Iwasa K, Komai K, Takamori M. Spontaneous thymoma rat as a model for myasthenic weakness caused by anti-ryanodine receptor antibodies. Muscle Nerve (1998) 21:1655-60
71. Matsuyama M, Ogiu T, Kontani K, Yamada C, Kawai M, Hiai H. Genetic regulation of the development of glomerular sclerotic lesions in the BUF/Mna rat. Nephron (1990) 54:334-7
72. Murayama S, Yagyu S, Higo K, Ye C, Mizuno T, Oyabu A. A genetic locus susceptible to the overt proteinuria in BUF/Mna rat. Mamm Genome (1998) 9:886-8
73. Le Berre L, Godfrin Y, Günther E, Buzelin F, Perretto S, Smit H. Extrarenal effects on the pathogenesis and relapse of idiopathic nephrotic syndrome in Buffalo/Mna rats. J Clin Invest. (2002) 109:491-8. doi: 10.1172/JCI12858
74. Musante L, Candiano G, Petretto A, Bruschi M, Dimasi N, Caridi G. Active focal segmental glomerulosclerosis is associated with massive oxidation of plasma albumin. J Am Soc Nephrol. (2007) 18:799-810. doi: 10.1681/ASN.2006090965
75. Ishidoh K, Kominami E. Procathepsin L degrades extracellular matrix proteins in the presence of glycosaminoglycans in vitro. Biochem Biophys Res Commun. (1995) 217:624-31
76. Sever S, Altintas MM, Nankoe SR, Möller CC, Ko D, Wei C. Proteolytic processing of dynamin by cytoplasmic cathepsin L is a mechanism for proteinuric kidney disease. J Clin Invest. (2007) 117:2095-104. doi: 10.1172/JCI32022
77. Bagnasco D, Ferrando M, Varricchi G, Passalacqua G, Canonica GW. A critical evaluation of anti-IL-13 and anti-IL-4 strategies in severe asthma. Int Arch Allergy Immunol. (2016) 170:122-31. doi: 10.1159/000447692
78. Matsunaga MC, Yamauchi PS. IL-4 and IL-13 inhibition in atopic dermatitis. J Drugs Dermatol. (2016) 15:925-9
79. Chung KF. Targeting the interleukin pathway in the treatment of asthma. Lancet (2015) 386:1086-96. doi: 10.1016/S0140-6736(15)00157-9
80. Luo J, Liu D, Liu CT. The efficacy and safety of antiinterleukin 13, a monoclonal antibody, in adult patients with asthma: a systematic review and meta-analysis. Medicine (2016) 95:e2556. doi: 10.1097/MD.0000000000002556
81. Shimada M, Ishimoto T, Lee PY, Lanaspa MA, Rivard CJ, Roncal-Jimenez CA. Toll-like receptor 3 ligands induce CD80 expression in human podocytes via an NF-kappaB-dependent pathway. Nephrol Dial Transplant. (2012) 27:81-9. doi: 10.1093/ndt/gfr271
82. Abbas AK, Sharpe AH. T-cell stimulation: an abundance of B7s. Nat Med. (1999) 5:1345-6
83. Chambers CA, Allison JP. Costimulatory regulation of T cell function. Curr Opin Cell Biol. (1999) 11:203-10
84. Garin EH, Diaz LN, Mu W, Wasserfall C, Araya C, Segal M, et al. Urinary CD80 excretion increases in idiopathic minimal-change disease. J Am Soc Nephrol. (2009) 20:260-6. doi: 10.1681/ASN.2007080836
85. Garin EH, Mu W, Arthur JM, Rivard CJ, Araya CE, Shimada M, et al. Urinary CD80 is elevated in minimal change disease but not in focal segmental glomerulosclerosis. Kidney Int. (2010) 78:296-302. doi: 10.1038/ki.2010.143
86. Mishra OP, Kumar R, Narayan G, Srivastava P, Abhinay A, Prasad R. Toll-like receptor 3 (TLR-3), TLR-4 and CD80 expression in peripheral blood mononuclear cells and urinary CD80 levels in children with idiopathic nephrotic syndrome. Pediatr Nephrol. (2017) 32:1355-61. doi: 10.1007/s00467-017-3613-8
87. Fiorina P, Vergani A, Bassi R, Niewczas MA, Altintas MM, Pezzolesi MG. Role of podocyte B7-1 in diabetic nephropathy. J Am Soc Nephrol. (2014) 25:1415-29. doi: 10.1681/ASN.2013050518
88. Yu CC, Fornoni A, Weins A, Hakroush S, Maiquel D, Sageshima J. Abatacept in B7-1-positive proteinuric kidney disease. N Engl J Med. (2013) 369:2416-23. doi: 10.1056/NEJMoa1304572
89. Delville M, Baye E, Durrbach A, Audard V, Kofman T, Braun L. B7-1 blockade does not improve post-transplant nephrotic syndrome caused by recurrent FSGS. J Am Soc Nephrol. (2016) 27:2520-7. doi: 10.1681/ASN.2015091002
90. Quezada SA, Jarvinen LZ, Lind EF, Noelle RJ. CD40/CD154 interactions at the interface of tolerance and immunity. Annu Rev Immunol. (2004) 22:307-28. doi: 10.1146/annurev.immunol.22.012703.104533
91. Hassan GS, Merhi Y, Mourad W. CD40 ligand: a neo-inflammatory molecule in vascular diseases. Immunobiology (2012) 217:521-32. doi: 10.1016/j.imbio.2011.03.010
92. Kairaitis L, Wang Y, Zheng L, Tay YC, wang YD, Harris C. Blockade of CD40-CD40 ligand protects against renal injury in chronic proteinuric renal disease. Kidney Int. (2003) 64:1265-72. doi: 10.1046/j.1523-1755.2003.00223.x
93. Doublier S, Zennaro C, Musante L, Spatola T, Candiano G, Bruschi M. Soluble CD40 ligand directly alters glomerular permeability and may act as a circulating permeability factor in FSGS. PLoS ONE (2017) 12:e0188045. doi: 10.1371/journal.pone.0188045
94. Ruth AJ, Kitching AR, Semple TJ, Tipping PG, Holdsworth SR. Intrinsic renal cell expression of CD40 directs Th1 effectors inducing experimental crescentic glomerulonephritis. J Am Soc Nephrol. (2003) 14:2813-22. doi: 10.1097/01.ASN.0000091381.60059.FB
95. Reynolds J, Khan SB, Allen AR, Benjamin CD, Pusey CD. Blockade of the CD154-CD40 costimulatory pathway prevents the development of experimental autoimmune glomerulonephritis. Kidney Int. (2004) 66:1444-52. doi: 10.1111/j.1523-1755.2004.00907.x
96. Lee VW, Qin X, Wang Y, Zheng G, Wang Y, Wang Y. The CD40-CD154 co-stimulation pathway mediates innate immune injury in adriamycin nephrosis. Nephrol Dial Transplant. (2010) 25:717-30. doi: 10.1093/ndt/gfp569
97. Delville M, Sigdel TK, Wei C, Li J, Hsieh SC, Fornoni A. A circulating antibody panel for pretransplant prediction of FSGS recurrence after kidney transplantation. Sci Transl Med. (2014) 6:256ra136. doi: 10.1126/scitranslmed.3008538
98. Sahali D, Sendeyo k, Mangier M, Audard V, Zhang SY, Lang P. Immunopathogenesis of idiopathic nephrotic syndrome with relapse. Semin Immunopathol. (2014) 36:421-9. doi: 10.1007/s00281-013-0415-3
99. Zhang SY, Kamal M, Dahan K, Pawlak A, Ory VD. Desvaux c-mip impairs podocyte proximal signaling and induces heavy proteinuria. Sci Signal. (2010) 3:ra39. doi: 10.1126/scisignal.2000678
100. Ivy SP, Wick JY, Kaufman BM. An overview of small-molecule inhibitors of VEGFR signaling. Nat Rev Clin Oncol. (2009) 6:569-79. doi: 10.1038/nrclinonc.2009.130
101. Izzedine H, Massard C, Spano JP, Goldwasser F, Khayat D, Soria JC. VEGF signalling inhibition-induced proteinuria: mechanisms, significance and management. Eur J Cancer (2010) 46:439-48. doi: 10.1016/j.ejca.2009.11.00
102. Echeverria V, Burgess S, Gamble-George J, Zeitlin R, Lin X, Cao CG, et al. Sorafenib inhibits nuclear factor kappa B, decreases inducible nitric oxide synthase and cyclooxygenase-2 expression, and restores working memory in APPswe mice. Neuroscience (2009) 162:1220-31. doi: 10.1016/j.neuroscience.2009.05.019
103. Kamal M, Valanciute A, Dahan K, Ory V, Pawlak A, Lang P. C-mip interacts physically with RelA and inhibits nuclear factor kappa B activity. Mol Immunol. (2009) 46:991-8. doi: 10.1016/j.molimm.2008.09.034
104. Sendeyo K, Audard V, Zhang SY, Fan Q, Bouachi K, Ollero M. Upregulation of c-mip is closely related to podocyte dysfunction in membranous nephropathy. Kidney Int. (2013) 83:414-25. doi: 10.1038/ki.2012.426
105. Patrakka J, Tryggvason K. Nephrin-a unique structural and signaling protein of the kidney filter. Trends Mol Med. (2007) 13:396-403. doi: 10.1016/j.molmed.2007.06.006
106. Ossowski L, Aguirre-Ghiso JA. Urokinase receptor and integrin partnership: coordination of signaling for cell adhesion, migration and growth. Curr Opin Cell Biol. (2000) 12:613-20. doi: 10.1016/S0955-0674(00)00140-X
107. Wei C, El Hindi S, Li J, Fornoni A, Goes N, Sageshima J. Circulating urokinase receptor as a cause of focal segmental glomerulosclerosis. Nat Med. (2011) 17:952-60. doi: 10.1038/nm.2411
108. Wei C, Möller CC, Altintas MM, Li J, Schwarz K, Zacchigna S. Modification of kidney barrier function by the urokinase receptor. Nat Med. (2008) 14:55-63. doi: 10.1038/nm1696
109. Hayek SS, Sever S, Ko YA, Trachtman H, Awad M, Wadhwani S. Soluble urokinase receptor and chronic kidney disease. N Engl J Med. (2015) 373:1916-25. doi: 10.1056/NEJMoa1506362
110. Hayek SS, Koh KH, Grams ME, Wei C, Ko YA, Li J. A tripartite complex of suPAR, APOL1 risk variants and alphavbeta3 integrin on podocytes mediates chronic kidney disease. Nat Med. (2017) 23:945-53. doi: 10.1038/nm.4362
111. Kopp JB, Nelson GW, Sampath K, Johnson RC, Genovese G, An P. APOL1 genetic variants in focal segmental glomerulosclerosis and HIV-associated nephropathy. J Am Soc Nephrol. (2011) 22:2129-37. doi: 10.1681/ASN.2011040388
112. Chugh SS, Clement LC, Mace C. New insights into human minimal change disease: lessons from animal models. Am J Kidney Dis. (2012) 59:284-92. doi: 10.1053/j.ajkd.2011.07.024
113. Clement LC, Avila-Casado C, Macé C, Soria E, Bakker WW, Kersten S, et al. Podocyte-secreted angiopoietin-like-4 mediates proteinuria in glucocorticoid-sensitive nephrotic syndrome. Nat Med. (2011) 17:117-22. doi: 10.1038/nm.2261
114. Immenschuh S, Song DX, Satoh H, Muller-Eberhard U. The type II hemopexin interleukin-6 response element predominates the transcriptional regulation of the hemopexin acute phase responsiveness. Biochem Biophys Res Commun. (1995) 207:202-8
115. Gutteridge JM. Lipid peroxidation and antioxidants as biomarkers of tissue damage. Clin Chem. (1995) 41:1819-28
116. Lennon R, Singh A, Welsh GI, Coward RJ, Satchell S, Ni L. Hemopexin induces nephrin-dependent reorganization of the actin cytoskeleton in podocytes. J Am Soc Nephrol. (2008) 19, 2140-9. doi: 10.1681/ASN.2007080940
117. Bakker WW, van Dael CM, Pierik LJ, van Wijk JA, Nauta J, Borghuis T, et al. Altered activity of plasma hemopexin in patients with minimal change disease in relapse. Pediatr Nephrol. (2005) 20:1410-5. doi: 10.1007/s00467-005-1936-3
118. Ravani P, Magnasco A, Edefonti A, Murer L, Rossi R, Ghio L. Short-term effects of rituximab in children with steroid-and calcineurin-dependent nephrotic syndrome: a randomized controlled trial. Clin J Am Soc Nephrol. (2011) 6:1308-15. doi: 10.2215/CJN.09421010
119. Ravani P, Ponticelli A, Siciliano C, Fornoni A, Magnasco A, Sica F. Rituximab is a safe and effective long-term treatment for children with steroid and calcineurin inhibitor-dependent idiopathic nephrotic syndrome. Kidney Int. (2013) 84:1025-33. doi: 10.1038/ki.2013.211