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Cytokines as Active Factors in Focal Segmental Glomerulosclerosis

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Molecular Mechanisms in the Pathogenesis of Idiopathic Nephrotic Syndrome

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Abstract

Cytokines may play important roles in primary focal segmental sclerosis. One or more may be the elusive circulating factor(s) that induces proteinuria in this condition, and their local renal tissue production may be crucial to the development of glomerular and interstitial fibrosis.

To this date, the data on a specific laboratory test that will allow us to detect the presence of a circulating factor are controversial. Moreover, only three cytokines (CLC-1, VEGF, and TGF alpha) have been suggested as putative circulating factor. However, there is no conclusive evidence of the presence of these cytokines in the serum of focal segmental glomerulosclerosis patients, and no proteinuria has been consistently observed when the experimental animal has been infused with these cytokines.

There is more compelling evidence for the role of an increased production of TGF beta in the development of glomerular and interstitial fibrosis in this condition. The increased TGF beta observed is produced at the level of the glomerulus and interstitium triggered by an unknown mechanism.

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References

  1. D’Agati VD, Fogo AB, Bruijn JA, Jennette JC. Pathologic classification of focal segmental glomerulosclerosis: a working proposal. Am J Kidney Dis. 2004;43:368–82.

    Article  PubMed  Google Scholar 

  2. 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 

  3. Benfield MR, McDonald R, Sullivan EK, Stablein DM, Tejani A. The 1997 annual renal transplantation in children report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS). Pediatr Transplant. 1999;3:152–67.

    Article  CAS  PubMed  Google Scholar 

  4. D’Agati VD, Kaskel FJ, Falk RJ. Focal segmental glomerulosclerosis. N Engl J Med. 2011;365:2398–411. doi:10.1056/NEJMra1106556.

    Article  PubMed  Google Scholar 

  5. Hoyer JR, Vernier RL, Najarian JS, Raij L, Simmons RL, Michael AF. Recurrence of idiopathic nephrotic syndrome after renal transplantation. Lancet. 1972;2:343–8.

    Article  CAS  PubMed  Google Scholar 

  6. Hoyer JR, Vernier RL, Najarian JS, Raij L, Simmons RL, Michael AF. Recurrence of idiopathic nephrotic syndrome after renal transplantation. 1972. J Am Soc Nephrol. 2001;12:1994–2002.

    CAS  PubMed  Google Scholar 

  7. Artero M, Biava C, Amend W, Tomlanovich S, Vincenti F. Recurrent focal glomerulosclerosis: natural history and response to therapy. Am J Med. 1992;92:375–83.

    Article  CAS  PubMed  Google Scholar 

  8. Artero ML, Sharma R, Savin VJ, Vincenti F. Plasmapheresis reduces proteinuria and serum capacity to injure glomeruli in patients with recurrent focal glomerulosclerosis. Am J Kidney Dis. 1994;23:574–81.

    Article  CAS  PubMed  Google Scholar 

  9. Savin VJ, Sharma R, Sharma M, McCarthy ET, Swan SK, Ellis E, et al. Circulating factor associated with increased glomerular permeability to albumin in recurrent focal segmental glomerulosclerosis. N Engl J Med. 1996;334:878–83.

    Article  CAS  PubMed  Google Scholar 

  10. Haffner K, Zimmerhackl LB, von Schnakenburg C, Brandis M, Pohl M. Complete remission of post-transplant FSGS recurrence by long-term plasmapheresis. Pediatr Nephrol. 2005;20:994–7.

    Article  PubMed  Google Scholar 

  11. Canaud G, Zuber J, Sberro R, Royale V, Anglicheau D, Snanoudj R, et al. Intensive and prolonged treatment of focal and segmental glomerulosclerosis recurrence in adult kidney transplant recipients: a pilot study. Am J Transplant. 2009;9:1081–6. doi:10.1111/j.1600-6143.2009.02580.x.

    Article  CAS  PubMed  Google Scholar 

  12. Cochat P, Kassir A, Colon S, Glastre C, Tourniaire B, Parchoux B, et al. Recurrent nephrotic syndrome after transplantation: early treatment with plasmapheresis and cyclophosphamide. Pediatr Nephrol. 1993;7:50–4.

    Article  CAS  PubMed  Google Scholar 

  13. Pradhan M, Petro J, Palmer J, Meyers K, Baluarte HJ. Early use of plasmapheresis for recurrent post-transplant FSGS. Pediatr Nephrol. 2003;18:934–8.

    Article  PubMed  Google Scholar 

  14. Dantal J, Testa A, Bigot E, Soulillou JP. Disappearance of proteinuria after immunoadsorption in a patient with focal glomerulosclerosis. Lancet. 1990;336:190.

    Article  CAS  PubMed  Google Scholar 

  15. Dantal J, Testa A, Bigot E, Soulillou JP. Effects of plasma-protein A immunoadsorption on idiopathic nephrotic syndrome recurring after renal transplantation. Ann Med Interne (Paris). 1992;143 Suppl 1:48–51.

    Google Scholar 

  16. Dantal J, Godfrin Y, Koll R, Perretto S, Naulet J, Bouhours JF, et al. Antihuman immunoglobulin affinity immunoadsorption strongly decreases proteinuria in patients with relapsing nephrotic syndrome. J Am Soc Nephrol. 1998;9:1709–15.

    CAS  PubMed  Google Scholar 

  17. Dantal J, Bigot E, Bogers W, Testa A, Kriaa F, Jacques Y, et al. Effect of plasma protein adsorption on protein excretion in kidney-transplant recipients with recurrent nephrotic syndrome. N Engl J Med. 1994;330:7–14.

    Article  CAS  PubMed  Google Scholar 

  18. Kemper MJ, Wolf G, Muller-Wiefel DE. Transmission of glomerular permeability factor from a mother to her child. N Engl J Med. 2001;344:386–7.

    Article  CAS  PubMed  Google Scholar 

  19. Gallon L, Leventhal J, Skaro A, Kanwar Y, Alvarado A. Resolution of recurrent focal segmental glomerulosclerosis after retransplantation. N Engl J Med. 2012;366:1648–9. doi:10.1056/NEJMc1202500.

    Article  CAS  PubMed  Google Scholar 

  20. Kato F, Watanabe M. Biochemical study on spontaneous thymoma rats with motor dysfunction. J Pharmacobiodyn. 1983;6:275–9.

    Article  CAS  PubMed  Google Scholar 

  21. Le Berre L, Godfrin Y, Gunther E, Buzelin F, Perretto S, Smit H, et al. Extrarenal effects on the pathogenesis and relapse of idiopathic nephrotic syndrome in Buffalo/Mna rats. J Clin Invest. 2002;109:491–8.

    Article  PubMed Central  PubMed  Google Scholar 

  22. Zimmerman SW. Increased urinary protein excretion in the rat produced by serum from a patient with recurrent focal glomerular sclerosis after renal transplantation. Clin Nephrol. 1984;22:32–8.

    CAS  PubMed  Google Scholar 

  23. Avila-Casado Mdel C, Perez-Torres I, Auron A, Soto V, Fortoul TI, Herrera-Acosta J. Proteinuria in rats induced by serum from patients with collapsing glomerulopathy. Kidney Int. 2004;66:133–43.

    Article  PubMed  Google Scholar 

  24. Sharma M, Sharma R, McCarthy ET, Savin VJ. “The FSGS factor:” enrichment and in vivo effect of activity from focal segmental glomerulosclerosis plasma. J Am Soc Nephrol. 1999;10:552–61.

    CAS  PubMed  Google Scholar 

  25. Sharma M, Sharma R, Reddy SR, McCarthy ET, Savin VJ. Proteinuria after injection of human focal segmental glomerulosclerosis factor. Transplantation. 2002;73:366–72.

    Article  PubMed  Google Scholar 

  26. Le Berre L, Godfrin Y, Lafond-Puyet L, Perretto S, Le Carrer D, Bouhours JF, et al. Effect of plasma fractions from patients with focal and segmental glomerulosclerosis on rat proteinuria. Kidney Int. 2000;58:2502–11.

    Article  PubMed  Google Scholar 

  27. Savin VJ, Sharma R, Lovell HB, Welling DJ. Measurement of albumin reflection coefficient with isolated rat glomeruli. J Am Soc Nephrol. 1992;3:1260–9.

    CAS  PubMed  Google Scholar 

  28. Dall’Amico R, Ghiggeri G, Carraro M, Artero M, Ghio L, Zamorani E, et al. Prediction and treatment of recurrent focal segmental glomerulosclerosis after renal transplantation in children. Am J Kidney Dis. 1999;34:1048–55.

    Article  PubMed  Google Scholar 

  29. Trachtman H, Greenbaum LA, McCarthy ET, Sharma M, Gauthier BG, Frank R, et al. Glomerular permeability activity: prevalence and prognostic value in pediatric patients with idiopathic nephrotic syndrome. Am J Kidney Dis. 2004;44:604–10.

    Article  PubMed  Google Scholar 

  30. Cattran D, Neogi T, Sharma R, McCarthy ET, Savin VJ. Serial estimates of serum permeability activity and clinical correlates in patients with native kidney focal segmental glomerulosclerosis. J Am Soc Nephrol. 2003;14:448–53.

    Article  CAS  PubMed  Google Scholar 

  31. Godfrin Y, Dantal J, Bouhours JF, Heslan JM, Soulillou JP. A new method of measuring albumin permeability in isolated glomeruli. Kidney Int. 1996;50:1352–7.

    Article  CAS  PubMed  Google Scholar 

  32. Godfrin Y, Dantal J, Perretto S, Hristea D, Legendre C, Kreis H, et al. Study of the in vitro effect on glomerular albumin permselectivity of serum before and after renal transplantation in focal segmental glomerulosclerosis. Transplantation. 1997;64:1711–5.

    Article  CAS  PubMed  Google Scholar 

  33. McCarthy ET, Sharma M, Savin VJ. Circulating permeability factors in idiopathic nephrotic syndrome and focal segmental glomerulosclerosis. Clin J Am Soc Nephrol. 2010;5:2115–21. doi:10.2215/CJN.03800609.

    Article  PubMed  Google Scholar 

  34. Sharma M, Sharma R, McCarthy ET, Savin VJ. The focal segmental glomerulosclerosis permeability factor: biochemical characteristics and biological effects. Exp Biol Med (Maywood). 2004;229:85–98.

    CAS  Google Scholar 

  35. Savin VJ, McCarthy ET, Sharma R, Charba D, Sharma M. Galactose binds to focal segmental glomerulosclerosis permeability factor and inhibits its activity. Transl Res. 2008;151:288–92. doi:10.1016/j.trsl.2008.04.001.

    Article  CAS  PubMed  Google Scholar 

  36. McCarthy ET, Sharma R, Sharma M, Li JZ, Ge XL, Dileepan KN, et al. TNF-alpha increases albumin permeability of isolated rat glomeruli through the generation of superoxide. J Am Soc Nephrol. 1998;9:433–8.

    CAS  PubMed  Google Scholar 

  37. Dileepan KN, Sharma R, Stechschulte DJ, Savin VJ. Effect of superoxide exposure on albumin permeability of isolated rat glomeruli. J Lab Clin Med. 1993;121:797–804.

    CAS  PubMed  Google Scholar 

  38. Charba DS, Wiggins RC, Goyal M, Wharram BL, Wiggins JE, McCarthy ET, et al. Antibodies to protein tyrosine phosphatase receptor type O (PTPro) increase glomerular albumin permeability (P(alb)). Am J Physiol Renal Physiol. 2009;297:F138–44. doi:10.1152/ajprenal.00122.2008.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Adler S, Sharma R, Savin VJ, Abbi R, Eng B. Alteration of glomerular permeability to macromolecules induced by cross-linking of beta 1 integrin receptors. Am J Pathol. 1996;149:987–96.

    PubMed Central  CAS  PubMed  Google Scholar 

  40. Aggarwal N, Batwara R, McCarthy ET, Sharma R, Sharma M, Savin VJ. Serum permeability activity in steroid-resistant minimal change nephrotic syndrome is abolished by treatment of Hodgkin disease. Am J Kidney Dis. 2007;50:826–9.

    Article  CAS  PubMed  Google Scholar 

  41. Carraro M, Caridi G, Bruschi M, Artero M, Bertelli R, Zennaro C, et al. Serum glomerular permeability activity in patients with podocin mutations (NPHS2) and steroid-resistant nephrotic syndrome. J Am Soc Nephrol. 2002;13:1946–52.

    Article  CAS  PubMed  Google Scholar 

  42. Srivastava T, Garola RE, Kestila M, Tryggvason K, Ruotsalainen V, Sharma M, et al. Recurrence of proteinuria following renal transplantation in congenital nephrotic syndrome of the Finnish type. Pediatr Nephrol. 2006;21:711–8.

    Article  PubMed  Google Scholar 

  43. Sgambat K, Banks M, Moudgil A. Effect of galactose on glomerular permeability and proteinuria in steroid-resistant nephrotic syndrome. Pediatr Nephrol. 2013;28:2131–5. doi:10.1007/s00467-013-2539-z.

    Article  PubMed  Google Scholar 

  44. De Smet E, Rioux JP, Ammann H, Deziel C, Querin S. FSGS permeability factor-associated nephrotic syndrome: remission after oral galactose therapy. Nephrol Dial Transplant. 2009;24:2938–40. doi:10.1093/ndt/gfp278.

    Article  PubMed  CAS  Google Scholar 

  45. Kopac M, Meglic A, Rus RR. Partial remission of resistant nephrotic syndrome after oral galactose therapy. Ther Apher Dial. 2011;15:269–72. doi:10.1111/j.1744-9987.2011.00949.x.

    Article  PubMed  Google Scholar 

  46. Jhaveri KD, Naber TH, Wang X, Molmenti E, Bhaskaran M, Boctor FN, et al. Treatment of recurrent focal segmental glomerular sclerosis posttransplant with a multimodal approach including high-galactose diet and oral galactose supplementation. Transplantation. 2011;91:e35–6. doi:10.1097/TP.0b013e3182088b67.

    Article  PubMed  Google Scholar 

  47. Mishra OP, Singh AK. Galactose treatment in focal and segmental glomerulosclerosis. Pediatr Nephrol. 2014;29:935. doi:10.1007/s00467-013-2731-1.

    Article  PubMed  Google Scholar 

  48. Olsson AK, Dimberg A, Kreuger J, Claesson-Welsh L. VEGF receptor signalling – in control of vascular function. Nat Rev Mol Cell Biol. 2006;7:359–71.

    Article  CAS  PubMed  Google Scholar 

  49. Schrijvers BF, Flyvbjerg A, De Vriese AS. The role of vascular endothelial growth factor (VEGF) in renal pathophysiology. Kidney Int. 2004;65:2003–17.

    Article  CAS  PubMed  Google Scholar 

  50. Brown LF, Berse B, Tognazzi K, Manseau EJ, Van de Water L, Senger DR, et al. Vascular permeability factor mRNA and protein expression in human kidney. Kidney Int. 1992;42:1457–61.

    Article  CAS  PubMed  Google Scholar 

  51. Foster RR, Hole R, Anderson K, Satchell SC, Coward RJ, Mathieson PW, et al. Functional evidence that vascular endothelial growth factor may act as an autocrine factor on human podocytes. Am J Physiol Renal Physiol. 2003;284:F1263–73.

    Article  CAS  PubMed  Google Scholar 

  52. Simon M, Grone HJ, Johren O, Kullmer J, Plate KH, Risau W, et al. Expression of vascular endothelial growth factor and its receptors in human renal ontogenesis and in adult kidney. Am J Physiol. 1995;268:F240–50.

    CAS  PubMed  Google Scholar 

  53. 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 

  54. 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 

  55. 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 

  56. 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 

  57. Liu E, Morimoto M, Kitajima S, Koike T, Yu Y, Shiiki H, et al. Increased expression of vascular endothelial growth factor in kidney leads to progressive impairment of glomerular functions. J Am Soc Nephrol. 2007;18:2094–104.

    Article  CAS  PubMed  Google Scholar 

  58. 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 

  59. Ostalska-Nowicka D, Zachwieja J, Nowicki M, Kaczmarek E, Siwinska A, Witt M. Vascular endothelial growth factor (VEGF-C1)-dependent inflammatory response of podocytes in nephrotic syndrome glomerulopathies in children: an immunohistochemical approach. Histopathology. 2005;46:176–83.

    Article  CAS  PubMed  Google Scholar 

  60. 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 

  61. 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 

  62. Baud L, Fouqueray B, Philippe C, Amrani A. Tumor necrosis factor alpha and mesangial cells. Kidney Int. 1992;41:600–3.

    Article  CAS  PubMed  Google Scholar 

  63. Gray PW, Aggarwal BB, Benton CV, Bringman TS, Henzel WJ, Jarrett JA, et al. Cloning and expression of cDNA for human lymphotoxin, a lymphokine with tumour necrosis activity. Nature. 1984;312:721–4.

    Article  CAS  PubMed  Google Scholar 

  64. Robak T, Gladalska A, Stepien H. The tumour necrosis factor family of receptors/ligands in the serum of patients with rheumatoid arthritis. Eur Cytokine Netw. 1998;9:145–54.

    CAS  PubMed  Google Scholar 

  65. Fang N, Li Y, Xu YS, Ma D, Fu P, Gao HQ, et al. Serum concentrations of IL-2 and TNF-alpha in patients with painful bone metastases: correlation with responses to 89SrCl2 therapy. J Nucl Med. 2006;47:242–6.

    CAS  PubMed  Google Scholar 

  66. Damas P, Reuter A, Gysen P, Demonty J, Lamy M, Franchimont P. Tumor necrosis factor and interleukin-1 serum levels during severe sepsis in humans. Crit Care Med. 1989;17:975–8.

    Article  CAS  PubMed  Google Scholar 

  67. Brennan DC, Yui MA, Wuthrich RP, Kelley VE. Tumor necrosis factor and IL-1 in New Zealand Black/White mice. Enhanced gene expression and acceleration of renal injury. J Immunol. 1989;143:3470–5.

    CAS  PubMed  Google Scholar 

  68. Ryffel B, Eugster H, Haas C, Le Hir M. Failure to induce anti-glomerular basement membrane glomerulonephritis in TNF alpha/beta deficient mice. Int J Exp Pathol. 1998;79:453–60.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  69. 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 

  70. Le Berre L, Herve C, Buzelin F, Usal 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.

    Article  PubMed  Google Scholar 

  71. Bertani T, Abbate M, Zoja C, Corna D, Perico N, Ghezzi P, et al. Tumor necrosis factor induces glomerular damage in the rabbit. Am J Pathol. 1989;134:419–30.

    PubMed Central  CAS  PubMed  Google Scholar 

  72. 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 

  73. Drewe E, McDermott EM, Powell RJ. Treatment of the nephrotic syndrome with etanercept in patients with the tumor necrosis factor receptor-associated periodic syndrome. N Engl J Med. 2000;343:1044–5.

    Article  CAS  PubMed  Google Scholar 

  74. Raveh D, Shemesh O, Ashkenazi YJ, Winkler R, Barak V. Tumor necrosis factor-alpha blocking agent as a treatment for nephrotic syndrome. Pediatr Nephrol. 2004;19:1281–4.

    Article  PubMed  Google Scholar 

  75. Verschueren P, Lensen F, Lerut E, Claes K, De Vos R, Van Damme B, et al. Benefit of anti-TNFalpha treatment for nephrotic syndrome in a patient with juvenile inflammatory bowel disease associated spondyloarthropathy complicated with amyloidosis and glomerulonephritis. Ann Rheum Dis. 2003;62:368–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  76. Leroy S, Guigonis V, Bruckner D, Emal-Aglae V, Deschenes G, Bensman A, et al. Successful anti-TNFalpha treatment in a child with posttransplant recurrent focal segmental glomerulosclerosis. Am J Transplant. 2009;9:858–61. doi:10.1111/j.1600-6143.2009.02550.x.

    Article  CAS  PubMed  Google Scholar 

  77. Joy MS, Gipson DS, Powell L, MacHardy J, Jennette JC, Vento S, et al. Phase 1 trial of adalimumab in Focal Segmental Glomerulosclerosis (FSGS): II. Report of the FONT (Novel Therapies for Resistant FSGS) study group. Am J Kidney Dis. 2010;55:50–60. doi:10.1053/j.ajkd.2009.08.019.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  78. Kopp JB, Factor VM, Mozes M, Nagy P, Sanderson N, Bottinger EP, et al. Transgenic mice with increased plasma levels of TGF-beta 1 develop progressive renal disease. Lab Invest. 1996;74:991–1003.

    CAS  PubMed  Google Scholar 

  79. 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 

  80. Goumenos DS, Tsakas S, El Nahas AM, Alexandri S, Oldroyd S, Kalliakmani P, et al. Transforming growth factor-beta(1) in the kidney and urine of patients with glomerular disease and proteinuria. Nephrol Dial Transplant. 2002;17:2145–52.

    Article  CAS  PubMed  Google Scholar 

  81. Kanai H, Mitsuhashi H, Ono K, Yano S, Naruse T. Increased excretion of urinary transforming growth factor beta in patients with focal glomerular sclerosis. Nephron. 1994;66:391–5.

    Article  CAS  PubMed  Google Scholar 

  82. Murakami K, Takemura T, Hino S, Yoshioka K. Urinary transforming growth factor-beta in patients with glomerular diseases. Pediatr Nephrol. 1997;11:334–6.

    Article  CAS  PubMed  Google Scholar 

  83. Wasilewska AM, Zoch-Zwierz WM. Transforming growth factor-beta1 in nephrotic syndrome treated with cyclosporine and ACE inhibitors. Pediatr Nephrol. 2004;19:1349–53.

    Article  PubMed  Google Scholar 

  84. 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 

  85. Kriz W, Gretz N, Lemley KV. Progression of glomerular diseases: is the podocyte the culprit? Kidney Int. 1998;54:687–97.

    Article  CAS  PubMed  Google Scholar 

  86. Kriz W, Lemley KV. The role of the podocyte in glomerulosclerosis. Curr Opin Nephrol Hypertens. 1999;8:489–97.

    Article  CAS  PubMed  Google Scholar 

  87. Kriz W. Progression of chronic renal failure in focal segmental glomerulosclerosis: consequence of podocyte damage or of tubulointerstitial fibrosis? Pediatr Nephrol. 2003;18:617–22.

    Article  PubMed  Google Scholar 

  88. Dennler S, Goumans MJ, ten Dijke P. Transforming growth factor beta signal transduction. J Leukoc Biol. 2002;71:731–40.

    CAS  PubMed  Google Scholar 

  89. Border WA, Noble NA. Transforming growth factor beta in tissue fibrosis. N Engl J Med. 1994;331:1286–92.

    Article  CAS  PubMed  Google Scholar 

  90. Jones CL, Buch S, Post M, McCulloch L, Liu E, Eddy AA. Pathogenesis of interstitial fibrosis in chronic purine aminonucleoside nephrosis. Kidney Int. 1991;40:1020–31.

    Article  CAS  PubMed  Google Scholar 

  91. Border WA, Okuda S, Languino LR, Sporn MB, Ruoslahti E. Suppression of experimental glomerulonephritis by antiserum against transforming growth factor beta 1. Nature. 1990;346:371–4.

    Article  CAS  PubMed  Google Scholar 

  92. Anscher MS, Peters WP, Reisenbichler H, Petros WP, Jirtle RL. Transforming growth factor beta as a predictor of liver and lung fibrosis after autologous bone marrow transplantation for advanced breast cancer. N Engl J Med. 1993;328:1592–8.

    Article  CAS  PubMed  Google Scholar 

  93. Nakamura T, Ebihara I, Fukui M, Osada S, Nagaoka I, Horikoshi S, et al. Messenger RNA expression for growth factors in glomeruli from focal glomerular sclerosis. Clin Immunol Immunopathol. 1993;66:33–42.

    Article  CAS  PubMed  Google Scholar 

  94. Connor Jr TB, Roberts AB, Sporn MB, Danielpour D, Dart LL, Michels RG, et al. Correlation of fibrosis and transforming growth factor-beta type 2 levels in the eye. J Clin Invest. 1989;83:1661–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  95. Yamamoto T, Nakamura T, Noble NA, Ruoslahti E, Border WA. Expression of transforming growth factor beta is elevated in human and experimental diabetic nephropathy. Proc Natl Acad Sci U S A. 1993;90:1814–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  96. Kopp JB, Klotman ME, Adler SH, Bruggeman LA, Dickie P, Marinos NJ, et al. Progressive glomerulosclerosis and enhanced renal accumulation of basement membrane components in mice transgenic for human immunodeficiency virus type 1 genes. Proc Natl Acad Sci U S A. 1992;89:1577–81.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  97. Kaneto H, Morrissey J, Klahr S. Increased expression of TGF-beta 1 mRNA in the obstructed kidney of rats with unilateral ureteral ligation. Kidney Int. 1993;44:313–21.

    Article  CAS  PubMed  Google Scholar 

  98. Yamamoto T, Noble NA, Miller DE, Border WA. Sustained expression of TGF-beta 1 underlies development of progressive kidney fibrosis. Kidney Int. 1994;45:916–27.

    Article  CAS  PubMed  Google Scholar 

  99. Isaka Y, Fujiwara Y, Ueda N, Kaneda Y, Kamada T, Imai E. Glomerulosclerosis induced by in vivo transfection of transforming growth factor-beta or platelet-derived growth factor gene into the rat kidney. J Clin Invest. 1993;92:2597–601.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  100. Border WA, Noble NA, Yamamoto T, Harper JR, Yamaguchi Y, Pierschbacher MD, et al. Natural inhibitor of transforming growth factor-beta protects against scarring in experimental kidney disease. Nature. 1992;360:361–4.

    Article  CAS  PubMed  Google Scholar 

  101. Yamamoto T, Noble NA, Cohen AH, Nast CC, Hishida A, Gold LI, et al. Expression of transforming growth factor-beta isoforms in human glomerular diseases. Kidney Int. 1996;49:461–9.

    Article  CAS  PubMed  Google Scholar 

  102. 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 

  103. Kim JH, Kim BK, Moon KC, Hong HK, Lee HS. Activation of the TGF-beta/Smad signaling pathway in focal segmental glomerulosclerosis. Kidney Int. 2003;64:1715–21.

    Article  CAS  PubMed  Google Scholar 

  104. Trachtman H, Fervenza FC, Gipson DS, Heering P, Jayne DR, Peters H, et al. A phase 1, single-dose study of fresolimumab, an anti-TGF-beta antibody, in treatment-resistant primary focal segmental glomerulosclerosis. Kidney Int. 2011;79:1236–43. doi:10.1038/ki.2011.33.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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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
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  2. Richard J. Johnson
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  3. Eduardo H. Garin
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Correspondence to Eduardo H. Garin .

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Editors and Affiliations

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

    Kazunari Kaneko

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Cara-Fuentes, G.M., Johnson, R.J., Garin, E.H. (2016). Cytokines as Active Factors in Focal Segmental Glomerulosclerosis. 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_10

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  • DOI: https://doi.org/10.1007/978-4-431-55270-3_10

  • Publisher Name: Springer, Tokyo

  • Print ISBN: 978-4-431-55269-7

  • Online ISBN: 978-4-431-55270-3

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