Skip to main content
SpringerLink
Log in

Cytokines as Active Factors in Minimal Change Nephrotic Syndrome

  • Chapter
Molecular Mechanisms in the Pathogenesis of Idiopathic Nephrotic Syndrome

  • 633 Accesses

Abstract

The pathogenesis of proteinuria in minimal change disease (MCD) is unknown. Shalhoub in 1974 proposed that the increased glomerular permeability to plasma proteins was due to a circulating factor released by T cells.

Up to this date, the search for the circulating cytokine has been unsuccessful. Published studies have reported contrasting results, and only in a few cases, proteinuria has been elicited in the experimental animal by specific cytokine.

Among a myriad of cytokines, two of them (IL-13 and IL-8) have been suggested as the elusive circulating factor. However, not all MCD patients present with elevated serum levels of these cytokines during relapse. While circulating IL-13 has been associated with podocyte CD80 expression and proteinuria in animal models, no correlation with proteinuria has been demonstrated. In addition, serum IL-13 is increased in other clinical conditions not associated with proteinuria. IL-8 seems to play a role in proteinuria by increasing the catabolism of glomerular basement membrane heparan sulfate, a non-CD80-mediated mechanism.

MCD is considered a podocytopathy. Recent animal and in vitro studies suggest that viral molecules rather than cytokine(s) may be the circulating factors triggering proteinuria in MCD. These findings are consistent with the clinical observation that relapses in 80 % of MCD patients are associated with viral illness.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 159.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. The primary nephrotic syndrome in children. Identification of patients with minimal change nephrotic syndrome from initial response to prednisone. A report of the International Study of Kidney Disease in Children. J Pediatr. 1981;98:561–4.

    Google Scholar 

  2. Churg J, Habib R, White RH. Pathology of the nephrotic syndrome in children: a report for the International Study of Kidney Disease in Children. Lancet. 1970;760:1299–302.

    Article  CAS  PubMed  Google Scholar 

  3. Shalhoub RJ. Pathogenesis of lipoid nephrosis: a disorder of T-cell function. Lancet. 1974;2:556–60.

    Article  CAS  PubMed  Google Scholar 

  4. 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.

    Article  CAS  PubMed  Google Scholar 

  5. Ali AA, Wilson E, Moorhead JF, Amlot P, Abdulla A, Fernando ON, et al. Minimal-change glomerular nephritis. Normal kidneys in an abnormal environment? Transplantation. 1994;58:849–52.

    Article  CAS  PubMed  Google Scholar 

  6. Kestila M, Lenkkeri U, Mannikko M, Lamerdin J, McCready P, Putaala H, et al. Positionally cloned gene for a novel glomerular protein – nephrin – is mutated in congenital nephrotic syndrome. Mol Cell. 1998;1:575–82.

    Article  CAS  PubMed  Google Scholar 

  7. Boute N, Gribouval O, Roselli S, Benessy F, Lee H, Fuchshuber A, et al. NPHS2, encoding the glomerular protein podocin, is mutated in autosomal recessive steroid-resistant nephrotic syndrome. Nat Genet. 2000;24:349–54.

    Article  CAS  PubMed  Google Scholar 

  8. Barisoni L, Schnaper HW, Kopp JB. A proposed taxonomy for the podocytopathies: a reassessment of the primary nephrotic diseases. Clin J Am Soc Nephrol. 2007;2:529–42.

    Article  PubMed  Google Scholar 

  9. Karnovsky MJ, Ryan GB. Substructure of the glomerular slit diaphragm in freeze-fractured normal rat kidney. J Cell Biol. 1975;65:233–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Ryan GB, Rodewald R, Karnovsky MJ. An ultrastructural study of the glomerular slit diaphragm in aminonucleoside nephrosis. Lab Invest. 1975;33:461–8.

    CAS  PubMed  Google Scholar 

  11. Kaplan JM, Kim SH, North KN, Rennke H, Correia LA, Tong HQ, et al. Mutations in ACTN4, encoding alpha-actinin-4, cause familial focal segmental glomerulosclerosis. Nat Genet. 2000;24:251–6.

    Article  CAS  PubMed  Google Scholar 

  12. Reiser J, Polu KR, Moller CC, Kenlan P, Altintas MM, Wei C, et al. TRPC6 is a glomerular slit diaphragm-associated channel required for normal renal function. Nat Genet. 2005;37:739–44.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Winn MP, Conlon PJ, Lynn KL, Farrington MK, Creazzo T, Hawkins AF, et al. A mutation in the TRPC6 cation channel causes familial focal segmental glomerulosclerosis. Science. 2005;308:1801–4.

    Article  CAS  PubMed  Google Scholar 

  14. Reiser J, von Gersdorff G, Loos M, Oh J, Asanuma K, Giardino L, et al. Induction of B7-1 in podocytes is associated with nephrotic syndrome. J Clin Invest. 2004;113:1390–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Ishimoto T, Shimada M, Gabriela G, Kosugi T, Sato W, Lee PY, et al. Toll-like receptor 3 ligand, polyIC, induces proteinuria and glomerular CD80, and increases urinary CD80 in mice. Nephrol Dial Transplant. 2013;28:1439–46. doi:10.1093/ndt/gfs543.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Shimada M, Ishimoto T, Lee PY, Lanaspa MA, Rivard CJ, Roncal-Jimenez CA, et al. 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.

    Article  CAS  PubMed  Google Scholar 

  17. Ishimoto T, Cara-Fuentes G, Wang H, Shimada M, Wasserfall CH, Winter WE, et al. Serum from minimal change patients in relapse increases CD80 expression in cultured podocytes. Pediatr Nephrol. 2013;28:1803–12. doi:10.1007/s00467-013-2498-4.

    Article  PubMed Central  PubMed  Google Scholar 

  18. 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.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. 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.

    Article  CAS  PubMed  Google Scholar 

  20. Garin EH, Reiser J, Cara-Fuentes G, Wei C, Matar D, Wang H, et al. Case series: CTLA4-IgG1 therapy in minimal change disease and focal segmental glomerulosclerosis. Pediatr Nephrol. 2015;30:469–77. doi:10.1007/s00467-014-2957-6.

    Article  PubMed  Google Scholar 

  21. Cara-Fuentes G, Wei C, Segarra A, Ishimoto T, Rivard C, Johnson RJ, et al. CD80 and suPAR in patients with minimal change disease and focal segmental glomerulosclerosis: diagnostic and pathogenic significance. Pediatr Nephrol. 2014;29:1363–71. doi:10.1007/s00467-013-2679-1.

    Article  PubMed Central  PubMed  Google Scholar 

  22. Cara-Fuentes G, Wasserfall CH, Wang H, Johnson RJ, Garin EH. Minimal change disease: a dysregulation of the podocyte CD80-CTLA-4 axis? Pediatr Nephrol. 2014;29:2333–40. doi:10.1007/s00467-014-2874-8.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Tejani AT, Butt K, Trachtman H, Suthanthiran M, Rosenthal CJ, Khawar MR. Cyclosporine A induced remission of relapsing nephrotic syndrome in children. Kidney Int. 1988;33:729–34.

    Article  CAS  PubMed  Google Scholar 

  24. Uchida K, Suzuki K, Iwamoto M, Kawachi H, Ohno M, Horita S, et al. Decreased tyrosine phosphorylation of nephrin in rat and human nephrosis. Kidney Int. 2008;73:926–32. doi:10.1038/ki.2008.19.

    Article  CAS  PubMed  Google Scholar 

  25. Ohashi T, Uchida K, Uchida S, Sasaki S, Nitta K. Dexamethasone increases the phosphorylation of nephrin in cultured podocytes. Clin Exp Nephrol. 2011;15:688–93. doi:10.1007/s10157-011-0479-0.

    Article  CAS  PubMed  Google Scholar 

  26. Faul C, Donnelly M, Merscher-Gomez S, Chang YH, Franz S, Delfgaauw J, et al. 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.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Eagen JW. Glomerulopathies of neoplasia. Kidney Int. 1977;11:297–303.

    Article  CAS  PubMed  Google Scholar 

  28. Alpers CE, Cotran RS. Neoplasia and glomerular injury. Kidney Int. 1986;30:465–73.

    Article  CAS  PubMed  Google Scholar 

  29. Ronco PM. Paraneoplastic glomerulopathies: new insights into an old entity. Kidney Int. 1999;56:355–77.

    Article  CAS  PubMed  Google Scholar 

  30. Kramer P, Sizoo W, Twiss EE. Nephrotic syndrome in Hodgkin’s disease. Report of five cases and review of the literature. Neth J Med. 1981;24:114–9.

    CAS  PubMed  Google Scholar 

  31. Plager J, Stutzman L. Acute nephrotic syndrome as a manifestation of active Hodgkin’s disease. Report of four cases and review of the literature. Am J Med. 1971;50:56–66.

    Article  CAS  PubMed  Google Scholar 

  32. Audard V, Zhang SY, Copie-Bergman C, Rucker-Martin C, Ory V, Candelier M, et al. 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.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  33. Zhang SY, Kamal M, Dahan K, Pawlak A, Ory V, Desvaux D, et al. c-mip impairs podocyte proximal signaling and induces heavy proteinuria. Sci Signal. 2010;3:39. doi:10.1126/scisignal.2000678.

    Google Scholar 

  34. Pippin JW, Brinkkoetter PT, Cormack-Aboud FC, Durvasula RV, Hauser PV, Kowalewska J, et al. Inducible rodent models of acquired podocyte diseases. Am J Physiol Renal Physiol. 2009;296:F213–29. doi:10.1152/ajprenal.90421.

    Article  CAS  PubMed  Google Scholar 

  35. Sternberg SS. Cross-striated fibrils and other ultrastructural alterations in glomeruli of rats with daunomycin nephrosis. Lab Invest. 1970;23:39–51.

    CAS  PubMed  Google Scholar 

  36. Bertani T, Poggi A, Pozzoni R, Delaini F, Sacchi G, Thoua Y, et al. Adriamycin-induced nephrotic syndrome in rats: sequence of pathologic events. Lab Invest. 1982;46:16–23.

    CAS  PubMed  Google Scholar 

  37. Okuda S, Oh Y, Tsuruda H, Onoyama K, Fujimi S, Fujishima M. Adriamycin-induced nephropathy as a model of chronic progressive glomerular disease. Kidney Int. 1986;29:502–10.

    Article  CAS  PubMed  Google Scholar 

  38. Olson JL, Rennke HG, Venkatachalam MA. Alterations in the charge and size selectivity barrier of the glomerular filter in aminonucleoside nephrosis in rats. Lab Invest. 1981;44:271–9.

    CAS  PubMed  Google Scholar 

  39. Shiiki H, Sasaki Y, Nishino T, Kimura T, Kurioka H, Fujimoto S, et al. Cell proliferation and apoptosis of the glomerular epithelial cells in rats with puromycin aminonucleoside nephrosis. Pathobiology. 1998;66:221–9.

    Article  CAS  PubMed  Google Scholar 

  40. Kim YH, Goyal M, Kurnit D, Wharram B, Wiggins J, Holzman L, et al. Podocyte depletion and glomerulosclerosis have a direct relationship in the PAN-treated rat. Kidney Int. 2001;60:957–68.

    Article  CAS  PubMed  Google Scholar 

  41. Chen CA, Hwang JC, Guh JY, Chang JM, Lai YH, Chen HC. Reduced podocyte expression of alpha3beta1 integrins and podocyte depletion in patients with primary focal segmental glomerulosclerosis and chronic PAN-treated rats. J Lab Clin Med. 2006;147:74–82.

    Article  CAS  PubMed  Google Scholar 

  42. Marshall CB, Pippin JW, Krofft RD, Shankland SJ. Puromycin aminonucleoside induces oxidant-dependent DNA damage in podocytes in vitro and in vivo. Kidney Int. 2006;70:1962–73.

    Article  CAS  PubMed  Google Scholar 

  43. Diamond JR, Bonventre JV, Karnovsky MJ. A role for oxygen free radicals in aminonucleoside nephrosis. Kidney Int. 1986;29:478–83.

    Article  CAS  PubMed  Google Scholar 

  44. Bondeva T, Roger T, Wolf G. Differential regulation of toll-like receptor 4 gene expression in renal cells by angiotensin II: dependency on AP1 and PU.1 transcriptional sites. Am J Nephrol. 2007;27:308–14.

    Article  CAS  PubMed  Google Scholar 

  45. Doi K, Leelahavanichkul A, Yuen PS, Star RA. Animal models of sepsis and sepsis-induced kidney injury. J Clin Invest. 2009;119:2868–78. doi:10.1172/JCI39421.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  46. Xu C, Chang A, Hack BK, Eadon MT, Alper SL, Cunningham PN. TNF-mediated damage to glomerular endothelium is an important determinant of acute kidney injury in sepsis. Kidney Int. 2014;85:72–81. doi:10.1038/ki.2013.286.

    Article  CAS  PubMed  Google Scholar 

  47. Ling C, Liu X, Shen Y, Chen Z, Fan J, Jiang Y, et al. Urinary CD80 levels as a diagnostic biomarker of minimal change disease. Pediatr Nephrol. 2015;30:309–16. doi:10.1007/s00467-014-2915-3.

    Article  PubMed  Google Scholar 

  48. Alwadhi RK, Mathew JL, Rath B. Clinical profile of children with nephrotic syndrome not on glucocorticoid therapy, but presenting with infection. J Paediatr Child Health. 2004;40:28–32.

    Article  CAS  PubMed  Google Scholar 

  49. Marks MI, McLaine PN, Drummond KN. Proteinuria in children with febrile illnesses. Arch Dis Child. 1970;45:250–3.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  50. Randolph MF, Greenfield M. Proteinuria. A six-year study of normal infants, preschool, and school-age populations previously screened for urinary tract disease. Am J Dis Child. 1967;114:631–8.

    Article  CAS  PubMed  Google Scholar 

  51. Ishimoto T, Shimada M, Araya CE, Huskey J, Garin EH, Johnson RJ. Minimal change disease: a CD80 podocytopathy? Semin Nephrol. 2011;31:320–5. doi:10.1016/j.semnephrol.2011.06.002.

    Article  CAS  PubMed  Google Scholar 

  52. Shimada M, Araya C, Rivard C, Ishimoto T, Johnson RJ, Garin EH. Minimal change disease: a “two-hit” podocyte immune disorder? Pediatr Nephrol. 2011;26:645–9. doi:10.1007/s00467-010-1676-x.

    Article  PubMed  Google Scholar 

  53. Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol. 1986;136:2348–57.

    CAS  PubMed  Google Scholar 

  54. Mosmann TR, Coffman RL. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol. 1989;7:145–73.

    Article  CAS  PubMed  Google Scholar 

  55. Mosmann TR, Sad S. The expanding universe of T-cell subsets: Th1, Th2 and more. Immunol Today. 1996;17:138–46.

    Article  CAS  PubMed  Google Scholar 

  56. Rebien W, Muller-Wiefel DE, Wahn U, Scharer K. IgE mediated hypersensitivity in children with idiopathic nephrotic syndrome. Int J Pediatr Nephrol. 1981;2:23–8.

    CAS  PubMed  Google Scholar 

  57. Abdel-Hafez M, Shimada M, Lee PY, Johnson RJ, Garin EH. Idiopathic nephrotic syndrome and atopy: is there a common link? Am J Kidney Dis. 2009;54:945–53.

    Article  PubMed Central  PubMed  Google Scholar 

  58. Daniel V, Trautmann Y, Konrad M, Nayir A, Scharer K. T-lymphocyte populations, cytokines and other growth factors in serum and urine of children with idiopathic nephrotic syndrome. Clin Nephrol. 1997;47:289–97.

    CAS  PubMed  Google Scholar 

  59. Neuhaus TJ, Wadhwa M, Callard R, Barratt TM. Increased IL-2, IL-4 and interferon-gamma (IFN-gamma) in steroid-sensitive nephrotic syndrome. Clin Exp Immunol. 1995;100:475–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  60. Hulton SA, Shah V, Byrne MR, Morgan G, Barratt TM, Dillon MJ. Lymphocyte subpopulations, interleukin-2 and interleukin-2 receptor expression in childhood nephrotic syndrome. Pediatr Nephrol. 1994;8:135–9.

    Article  CAS  PubMed  Google Scholar 

  61. Lama G, Luongo I, Tirino G, Borriello A, Carangio C, Salsano ME. T-lymphocyte populations and cytokines in childhood nephrotic syndrome. Am J Kidney Dis. 2002;39:958–65.

    Article  CAS  PubMed  Google Scholar 

  62. Printza N, Papachristou F, Tzimouli V, Taparkou A, Kanakoudi-Tsakalidou F. IL-18 is correlated with type-2 immune response in children with steroid sensitive nephrotic syndrome. Cytokine. 2008;44:262–8. doi:10.1016/j.cyto.2008.08.012.

    Article  CAS  PubMed  Google Scholar 

  63. Suranyi MG, Guasch A, Hall BM, Myers BD. Elevated levels of tumor necrosis factor-alpha in the nephrotic syndrome in humans. Am J Kidney Dis. 1993;21:251–9.

    Article  CAS  PubMed  Google Scholar 

  64. Shimoyama H, Nakajima M, Naka H, Maruhashi Y, Akazawa H, Ueda T, et al. Up-regulation of interleukin-2 mRNA in children with idiopathic nephrotic syndrome. Pediatr Nephrol. 2004;19:1115–21.

    Article  PubMed  Google Scholar 

  65. Stefanovic V, Golubovic E, Mitic-Zlatkovic M, Vlahovic P, Jovanovic O, Bogdanovic R. Interleukin-12 and interferon-gamma production in childhood idiopathic nephrotic syndrome. Pediatr Nephrol. 1998;12:463–6.

    Article  CAS  PubMed  Google Scholar 

  66. Kanai T, Shiraishi H, Yamagata T, Ito T, Odaka J, Saito T, et al. Th2 cells predominate in idiopathic steroid-sensitive nephrotic syndrome. Clin Exp Nephrol. 2010;14:578–83. doi:10.1007/s10157-010-0330-z.

    Article  CAS  PubMed  Google Scholar 

  67. Hayden FG, Fritz R, Lobo MC, Alvord W, Strober W, Straus SE. Local and systemic cytokine responses during experimental human influenza A virus infection. Relation to symptom formation and host defense. J Clin Invest. 1998;101:643–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  68. Kaiser L, Fritz RS, Straus SE, Gubareva L, Hayden FG. Symptom pathogenesis during acute influenza: interleukin-6 and other cytokine responses. J Med Virol. 2001;64:262–8.

    Article  CAS  PubMed  Google Scholar 

  69. Youn YS, Lim HH, Lee JH. The clinical characteristics of steroid responsive nephrotic syndrome of children according to the serum immunoglobulin E levels and cytokines. Yonsei Med J. 2012;53:715–22. doi:10.3349/ymj.2012.53.4.715.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  70. Lee YC, Lee KH, Lee HB, Rhee YK. Serum levels of interleukins (IL)-4, IL-5, IL-13, and interferon-gamma in acute asthma. J Asthma. 2001;38:665–71.

    Article  CAS  PubMed  Google Scholar 

  71. Do Park S, Youn YH. Clinical significance of serum interleukin-18 concentration in the patients with atopic dermatitis. Korean J Lab Med. 2007;27:128–32.

    Article  CAS  Google Scholar 

  72. Tamagawa-Mineoka R, Okuzawa Y, Masuda K, Katoh N. Increased serum levels of interleukin 33 in patients with atopic dermatitis. J Am Acad Dermatol. 2014;70:882–8. doi:10.1016/j.jaad.2014.01.867.

    Article  CAS  PubMed  Google Scholar 

  73. Kanai T, Shiraishi H, Yamagata T, Ito T, Odaka J, Saito T, et al. Elevated serum interleukin-7 level in idiopathic steroid-sensitive nephrotic syndrome. Pediatr Int. 2011;53:906–9. doi:10.1111/j.1442-200X.2011.03380.x.

    Article  CAS  PubMed  Google Scholar 

  74. Wasilewska A, Zoch-Zwierz WM, Tomaszewska B, Zelazowska B. Relationship of serum interleukin-7 concentration and the coagulation state in children with nephrotic syndrome. Pediatr Int. 2005;47:424–9.

    Article  CAS  PubMed  Google Scholar 

  75. Bustos C, Gonzalez E, Muley R, Alonso JL, Egido J. Increase of tumour necrosis factor alpha synthesis and gene expression in peripheral blood mononuclear cells of children with idiopathic nephrotic syndrome. Eur J Clin Invest. 1994;24:799–805.

    Article  CAS  PubMed  Google Scholar 

  76. Cho MH, Lee HS, Choe BH, Kwon SH, Chung KY, Koo JH, et al. Interleukin-8 and tumor necrosis factor-alpha are increased in minimal change disease but do not alter albumin permeability. Am J Nephrol. 2003;23:260–6.

    Article  CAS  PubMed  Google Scholar 

  77. Matsumoto K, Kanmatsuse K. Increased IL-12 release by monocytes in nephrotic patients. Clin Exp Immunol. 1999;117:361–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  78. Matsumoto K, Kanmatsuse K. Augmented interleukin-18 production by peripheral blood monocytes in patients with minimal-change nephrotic syndrome. Am J Nephrol. 2001;21:20–7.

    Article  CAS  PubMed  Google Scholar 

  79. Matsumoto K. Decreased release of IL-10 by monocytes from patients with lipod nephrosis. Clin Exp Immunol. 1995;102:603–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  80. Matsumoto K. IL-8 release from cultured peripheral blood monocytes of patients with glomerulonephritis. Clin Exp Immunol. 1995;99:106–11.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  81. Saxena S, Mittal A, Andal A. Pattern of interleukins in minimal-change nephrotic syndrome of childhood. Nephron. 1993;65:56–61.

    Article  CAS  PubMed  Google Scholar 

  82. Hinoshita F, Noma T, Tomura S, Shiigai T, Yata J. Decreased production and responsiveness of interleukin 2 in lymphocytes of patients with nephrotic syndrome. Nephron. 1990;54:122–6.

    Article  CAS  PubMed  Google Scholar 

  83. Stachowski J, Barth C, Michalkiewicz J, Krynicki T, Jarmolinski T, Runowski D, et al. Th1/Th2 balance and CD45-positive T cell subsets in primary nephrotic syndrome. Pediatr Nephrol. 2000;14:779–85.

    Article  CAS  PubMed  Google Scholar 

  84. Kang J, Bai KM, Wang BL, Yao Z, Pang XW, Chen WF. Increased production of interleukin 4 in children with simple idiopathic nephrotic syndrome. Chin Med J (Engl). 1994;107:347–50.

    CAS  Google Scholar 

  85. Cho BS, Yoon SR, Jang JY, Pyun KH, Lee CE. Up-regulation of interleukin-4 and CD23/Fcepsilon RII in minimal change nephrotic syndrome. Pediatr Nephrol. 1999;13:199–204.

    Article  CAS  PubMed  Google Scholar 

  86. Bakr A, Shokeir M, El-Chenawi F, El-Husseni F, Abdel-Rahman A, El-Ashry R. Tumor necrosis factor-alpha production from mononuclear cells in nephrotic syndrome. Pediatr Nephrol. 2003;18:516–20.

    PubMed  Google Scholar 

  87. 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.

    CAS  PubMed  Google Scholar 

  88. Laflam PF, Haraguchi S, Garin EH. Cytokine mRNA profile in lipoid nephrosis: evidence for increased IL-8 mRNA stability. Nephron. 2002;91:620–6.

    Article  CAS  PubMed  Google Scholar 

  89. Garin EH, Blanchard DK, Matsushima K, Djeu JY. IL-8 production by peripheral blood mononuclear cells in nephrotic patients. Kidney Int. 1994;45:1311–7.

    Article  CAS  PubMed  Google Scholar 

  90. Cheung W, Wei CL, Seah CC, Jordan SC, Yap HK. Atopy, serum IgE, and interleukin-13 in steroid-responsive nephrotic syndrome. Pediatr Nephrol. 2004;19:627–32.

    Article  PubMed  Google Scholar 

  91. Zachwieja J, Bobkowski W, Dobrowolska-Zachwieja A, Lewandowska-Stachowiak M, Zaniew M, Maciejewski J. Intracellular cytokines of peripheral blood lymphocytes in nephrotic syndrome. Pediatr Nephrol. 2002;17:733–40.

    Article  CAS  PubMed  Google Scholar 

  92. Kaneko K, Tuchiya K, Fujinaga S, Kawamura R, Ohtomo Y, Shimizu T, et al. Th1/Th2 balance in childhood idiopathic nephrotic syndrome. Clin Nephrol. 2002;58:393–7.

    Article  CAS  PubMed  Google Scholar 

  93. Wynn TA. IL-13 effector functions. Annu Rev Immunol. 2003;21:425–56.

    Article  CAS  PubMed  Google Scholar 

  94. Lai KW, Wei CL, Tan LK, Tan PH, Chiang GS, Lee CG, et al. Overexpression of interleukin-13 induces minimal-change-like nephropathy in rats. J Am Soc Nephrol. 2007;18:1476–85.

    Article  CAS  PubMed  Google Scholar 

  95. Mishra OP, Teli AS, Singh U, Abhinay A, Prasad R. Serum immunoglobulin E and interleukin-13 levels in children with idiopathic nephrotic syndrome. J Trop Pediatr. 2014;60:467–71. doi:10.1093/tropej/fmu040.

    Article  PubMed  Google Scholar 

  96. Tain YL, Chen TY, Yang KD. Implications of serum TNF-beta and IL-13 in the treatment response of childhood nephrotic syndrome. Cytokine. 2003;21:155–9.

    Article  CAS  PubMed  Google Scholar 

  97. Huber TB, Reinhardt HC, Exner M, Burger JA, Kerjaschki D, Saleem MA, et al. Expression of functional CCR and CXCR chemokine receptors in podocytes. J Immunol. 2002;168:6244–52.

    Article  CAS  PubMed  Google Scholar 

  98. Baggiolini M, Clark-Lewis I. Interleukin-8, a chemotactic and inflammatory cytokine. FEBS Lett. 1992;307:97–101.

    Article  CAS  PubMed  Google Scholar 

  99. Kaneko S, Satoh T, Chiba J, Ju C, Inoue K, Kagawa J. Interleukin-6 and interleukin-8 levels in serum and synovial fluid of patients with osteoarthritis. Cytokines Cell Mol Ther. 2000;6:71–9.

    Article  CAS  PubMed  Google Scholar 

  100. Ashitani J, Mukae H, Ihiboshi H, Taniguchi H, Mashimoto H, Matsukura S. Adult respiratory distress syndrome with increased serum and bronchoalveolar lavage fluid levels of squamous cell carcinoma-related antigen. Intern Med. 1996;35:497–501.

    Article  CAS  PubMed  Google Scholar 

  101. Bont L, Heijnen CJ, Kavelaars A, van Aalderen WM, Brus F, Draaisma JT, et al. Peripheral blood cytokine responses and disease severity in respiratory syncytial virus bronchiolitis. Eur Respir J. 1999;14:144–9.

    Article  CAS  PubMed  Google Scholar 

  102. Sheu JN, Chen SM, Meng MH, Lue KH. The role of serum and urine interleukin-8 on acute pyelonephritis and subsequent renal scarring in children. Pediatr Infect Dis J. 2009;28:885–90. doi:10.1097/INF.0b013e3181a39e23.

    Article  PubMed  Google Scholar 

  103. Besbas N, Ozaltin F, Catal F, Ozen S, Topaloglu R, Bakkaloglu A. Monocyte chemoattractant protein-1 and interleukin-8 levels in children with acute poststreptococcal glomerulonephritis. Pediatr Nephrol. 2004;19:864–8.

    Article  PubMed  Google Scholar 

  104. Garin EH, Laflam P, Chandler L. Anti-interleukin 8 antibody abolishes effects of lipoid nephrosis cytokine. Pediatr Nephrol. 1998;12:381–5.

    Article  CAS  PubMed  Google Scholar 

  105. Garin EH, West L, Zheng W. Effect of interleukin-8 on glomerular sulfated compounds and albuminuria. Pediatr Nephrol. 1997;11:274–9.

    Article  CAS  PubMed  Google Scholar 

  106. Garin EH, West L, Zheng W. Interleukin-8 alters glomerular heparan sulfate glycosaminoglycan chain size and charge in rats. Pediatr Nephrol. 2000;14:284–7.

    Article  CAS  PubMed  Google Scholar 

  107. Garin EH. Effect of lipoid nephrosis cytokine on glomerular sulfated compounds and albuminuria. Pediatr Nephrol. 1995;9:587–93.

    Article  CAS  PubMed  Google Scholar 

  108. Garin EH, West L, Blanchard K, Matsushima K, Djeu JY. Effect of lymphokines on 35sulfate uptake by the glomerular basement membrane. Nephron. 1995;71:442–7.

    Article  CAS  PubMed  Google Scholar 

  109. Kanai T, Yamagata T, Momoi MY. Macrophage inflammatory protein-1beta and interleukin-8 associated with idiopathic steroid-sensitive nephrotic syndrome. Pediatr Int. 2009;51:443–7. doi:10.1111/j.1442-200X.2008.02759.x.

    Article  CAS  PubMed  Google Scholar 

  110. Wada T, Yokoyama H, Tomosugi N, Hisada Y, Ohta S, Naito T, et al. Detection of urinary interleukin-8 in glomerular diseases. Kidney Int. 1994;46:455–60.

    Article  CAS  PubMed  Google Scholar 

  111. Niemir ZI, Stein H, Ciechanowicz A, Olejniczak P, Dworacki G, Ritz E, et al. The in situ expression of interleukin-8 in the normal human kidney and in different morphological forms of glomerulonephritis. Am J Kidney Dis. 2004;43:983–98.

    Article  CAS  PubMed  Google Scholar 

  112. Strehlau J, Schachter AD, Pavlakis M, Singh A, Tejani A, Strom TB. Activated intrarenal transcription of CTL-effectors and TGF-beta1 in children with focal segmental glomerulosclerosis. Kidney Int. 2002;61:90–5.

    Article  CAS  PubMed  Google Scholar 

  113. Cockwell P, Brooks CJ, Adu D, Savage CO. Interleukin-8: a pathogenetic role in antineutrophil cytoplasmic autoantibody-associated glomerulonephritis. Kidney Int. 1999;55:852–63.

    Article  CAS  PubMed  Google Scholar 

  114. Laflam PF, Garin EH. Effect of tumor necrosis factor alpha and vascular permeability growth factor on albuminuria in rats. Pediatr Nephrol. 2006;21:177–81.

    Article  PubMed  Google Scholar 

  115. Klanke B, Simon M, Rockl W, Weich HA, Stolte H, Grone HJ. Effects of vascular endothelial growth factor (VEGF)/vascular permeability factor (VPF) on haemodynamics and permselectivity of the isolated perfused rat kidney. Nephrol Dial Transplant. 1998;13:875–85.

    Article  CAS  PubMed  Google Scholar 

  116. Webb NJ, Watson CJ, Roberts IS, Bottomley MJ, Jones CA, Lewis MA, et al. Circulating vascular endothelial growth factor is not increased during relapses of steroid-sensitive nephrotic syndrome. Kidney Int. 1999;55:1063–71.

    Article  CAS  PubMed  Google Scholar 

  117. Veron D, Reidy KJ, Bertuccio C, Teichman J, Villegas G, Jimenez J, et al. Overexpression of VEGF-A in podocytes of adult mice causes glomerular disease. Kidney Int. 2010;77:989–99. doi:10.1038/ki.2010.64.

    Article  CAS  PubMed  Google Scholar 

  118. Eremina V, Sood M, Haigh J, Nagy A, Lajoie G, Ferrara N, et al. Glomerular-specific alterations of VEGF-A expression lead to distinct congenital and acquired renal diseases. J Clin Invest. 2003;111:707–16.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  119. Cheong HI, Lee JH, Hahn H, Park HW, Ha IS, Choi Y. Circulating VEGF and TGF-beta1 in children with idiopathic nephrotic syndrome. J Nephrol. 2001;14:263–9.

    CAS  PubMed  Google Scholar 

  120. Bailey E, Bottomley MJ, Westwell S, Pringle JH, Furness PN, Feehally J, et al. Vascular endothelial growth factor mRNA expression in minimal change, membranous, and diabetic nephropathy demonstrated by non-isotopic in situ hybridisation. J Clin Pathol. 1999;52:735–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  121. Noguchi K, Yoshikawa N, Ito-Kariya S, Inoue Y, Hayashi Y, Ito H, et al. Activated mesangial cells produce vascular permeability factor in early-stage mesangial proliferative glomerulonephritis. J Am Soc Nephrol. 1998;9:1815–25.

    CAS  PubMed  Google Scholar 

  122. Shulman K, Rosen S, Tognazzi K, Manseau EJ, Brown LF. Expression of vascular permeability factor (VPF/VEGF) is altered in many glomerular diseases. J Am Soc Nephrol. 1996;7:661–6.

    CAS  PubMed  Google Scholar 

  123. Platanias LC. Mechanisms of type-I- and type-II-interferon-mediated signalling. Nat Rev Immunol. 2005;5:375–86.

    Article  CAS  PubMed  Google Scholar 

  124. Gonzalez-Navajas JM, Lee J, David M, Raz E. Immunomodulatory functions of type I interferons. Nat Rev Immunol. 2012;12:125–35. doi:10.1038/nri3133.

    PubMed Central  CAS  PubMed  Google Scholar 

  125. Gurkan S, Cabinian A, Lopez V, Bhaumik M, Chang JM, Rabson AB, et al. Inhibition of type I interferon signalling prevents TLR ligand-mediated proteinuria. J Pathol. 2013;231:248–56.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Pediatric Nephrology, Department of Pediatrics, University of Florida, 1600 SW Archer Road, HD214, Gainesville, FL, 32607, USA

    Gabriel M. Cara-Fuentes & Eduardo H. Garin

  2. Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado, Denver, CO, USA

    Richard J. Johnson

Authors
  1. Gabriel M. Cara-Fuentes
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Richard J. Johnson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eduardo H. Garin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eduardo H. Garin .

Editor information

Editors and Affiliations

  1. Department of Pediatrics, Kansai Medical University, Hirakata, Osaka, Osaka, Japan

    Kazunari Kaneko

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer Japan

About this chapter

Cite this chapter

Cara-Fuentes, G.M., Johnson, R.J., Garin, E.H. (2016). Cytokines as Active Factors in Minimal Change Nephrotic Syndrome. In: Kaneko, K. (eds) Molecular Mechanisms in the Pathogenesis of Idiopathic Nephrotic Syndrome. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55270-3_8

Download citation

  • DOI: https://doi.org/10.1007/978-4-431-55270-3_8

  • Publisher Name: Springer, Tokyo

  • Print ISBN: 978-4-431-55269-7

  • Online ISBN: 978-4-431-55270-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation