Skip to main content

Advertisement

Log in

Effect of tumor necrosis factor α and vascular permeability growth factor on albuminuria in rats

  • Original Article
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

The purposes of this study were to measure the serum levels of vascular permeability growth factor (VPGF) and tumor necrosis factor α (TNFα) in minimal lesion nephrotic syndrome (MLNS) patients and to assess their effect on albuminuria in rats. Serum for VPGF and TNFα was obtained during relapse and remission from 18 MLNS patients. Tumor necrosis factor α was infused at the rate of 10 and 20 ng/h and VPGF at the rate of 20 and 40 ng/h for 5 days into the left renal artery of rats. Urinary albumin (24-h collection) was measured prior to infusion and on days 2, 4 and 5. Rats infused with 1% bovine serum albumin served as controls. Serum VPGF and TNFα levels in MLNS patients in relapse were not different from those seen during remission. A significant increase in albuminuria was observed on day 4 and 5 only when rats were infused with TNFα at the rate of 20 ng/h as compared to the excretion seen in same animals prior to the infusion of cytokine and on days 4 and 5 of normal controls. Neither VPGF nor TNFα seems to be the circulating pathogenic cytokine for proteinuria in MLNS. However, TNFα may contribute to the increased albuminuria via a paracrine effect at the glomerulus.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Shalhoub RJ (1974) Pathogenesis of lipoid nephrosis: a disorder of T-cell function. Lancet II:556–560

    Article  Google Scholar 

  2. Johnson RJ (1996) Role of cytokines and growth factors in glomerulonephritis: a chance for future therapeutic interventions. Nephron 73:506–514

    PubMed  Google Scholar 

  3. Schrijvers BF, Flyvbjerg A, De Vriese S (2004) The role of vascular endothelial growth factor (VEGF) in renal pathophysiology. Kidney Int 65:2003–2017

    Article  PubMed  Google Scholar 

  4. Roberts WG, Palade GE (1995) Increased microvascular permeability and endothelial fenestration induced by vascular endothelial growth factor. J Cell Sci 108:2369–2379

    PubMed  Google Scholar 

  5. Kretzler M, Schroppel B, Merkle M, Huber S, Mundel P, Horster M, Schlondorff D (1998) Detection of multiple vascular endothelial growth factor splice isoforms in single glomerular podocytes. Kidney Int 41 [Suppl 67]:S159–S161

  6. Simon M, Grone HJ, Johren O, Kullmer J, Plate KH, Risau W, Fuchs E (1995) Expression of vascular endothelial growth factor and its receptors in human renal ontogenesis and in adult kidney. Am J Physiol 268:F240–F250

    PubMed  Google Scholar 

  7. Webb NJA, Postlethwaite RJ, Lewis MA, Brenchley PEC (1994) Increased expression of vascular permeability factor (VPF) during relapse of childhood steroid sensitive nephrotic syndrome (SSNS) (abstract). J Am Soc Nephrol 5:845

    Google Scholar 

  8. Cheong H, Lee JH, Hahn H, Park HW, Ha IIS, Choi Y (2001) Circulating VEGF and TGF-β1 in children with idiopathic nephrotic syndrome. J Nephrol 14:263–269

    PubMed  Google Scholar 

  9. Webb NJ, Watson CJ, Roberts IS, Bottomley MJ, Jones CA, Lewis MA, Postlethwaite RJ, Brenchley PE (1999) Circulating vascular endothelial growth factor is not increased during relapses of steroid-sensitive nephrotic syndrome. Kidney Int 55:1063–1071

    Article  PubMed  Google Scholar 

  10. Matsumoto K, Kanmatsuse K (2001) Elevated vascular endothelial growth factor levels in the urine of patients with minimal-change nephrotic syndrome. Clin Nephrol 55:269–274

    PubMed  Google Scholar 

  11. Brennan DC, Yui MA, Wuthrich RP, Kelley VE (1989) Tumor necrosis factor and IL-1 New Zealand black/white mice. Enhanced gene expression and acceleration of renal injury. J Immunol 143:3470–3475

    PubMed  Google Scholar 

  12. Wu TH, Wu SC, Huang TP, Yu CL, Tsai CY (1996) Increased expression of tumor necrosis factor alpha and interleukin 1 beta in urine from patients with IgA nephropathy and Scholein-Henoch purpura. Nephron 74:79–88

    PubMed  Google Scholar 

  13. Ryffel B, Eugster H, Haas C, Lee HM (1998) Failure to induce anti-glomerular basement membrane glomerulonephritis in TNF alpha/beta deficient mice. Int J Exp Pathol 79:453–460

    Article  PubMed  Google Scholar 

  14. Suranyi MG, Guasch A, Hall BM, Myers BD (1993) Elevated levels of tumor necrosis factor-a in the nephrotic syndrome in humans. Am J Kidney Dis 21:251–259

    PubMed  Google Scholar 

  15. Churg J, Habib R, White HRH (1970) Pathology of the nephrotic syndrome in children: a report for the International Study of Kidney Disease in Children. Lancet I:1299–1302

    Article  Google Scholar 

  16. Bailey E, Bottomley MJ, Westwell S, Pringle JH, Furness PN, Feehally J, Brenchley PE, Harper SJ (1999) Vascular endothelial growth factor mRNA expression in minimal change, membranous, and diabetic nephropathy demonstrated by non-isotopic in situ hybridization. J Clin Pathol 52:735–738

    PubMed  Google Scholar 

  17. Horita Y, Myazaki M, Koji T, Kobayashi N, Shibuya M, Razzaque MS, Cheng M, Ozono Y, Kohno S, Taguchi T (1998) Expression of vascular endothelial growth factor and its receptors in rats with protein-overload nephrosis Nephrol Dial Transplant 13:2519–2528

    Google Scholar 

  18. Klanke B, Simon M, Rockl W, Weich HA, Stole H, Grone HJ (1998) Effects of vascular endothelial growth factor (VEGF)/vascular permeability factor ( VPF) on haemodynamics and permselectivity of the isolated perfused rat kidney. Nephrol Dial Transplant 13:875–885

    Article  PubMed  Google Scholar 

  19. Le Berre L, Godfrin Y, Lafond-Puyet L, Perretto S, Le Carrer D, Bouhours JF, Soulillou JP, Dantal J (2000) Effect of plasma fractions from patients with focal segmental glomerulosclerosis on rat proteinuria. Kidney Int 58:2502–2511

    Article  PubMed  Google Scholar 

  20. Garin EH (1995) Effect of lipoid nephrosis cytokine on glomerular sulfated compounds and albuminuria. Pediatr Nephrol 9:587–593

    Article  PubMed  Google Scholar 

  21. Shimoyama H, Nakajima M, Naka H, Maruhashi Y, Akazawa H, Ueda T, Nishiguchi M, Yamoto Y, Kamitsuji H, Yoshioka A (2004) Up-regulation of interleukin-2 mRNA in children with idiopathic nephrotic syndrome. Pediatr Nephrol 19:1115–1121

    Article  PubMed  Google Scholar 

  22. 22, Cho MH, Lee HS, Choe BH, Kwon SH, Chung KY, Koo JH, Ko CW (2003) Interleukin-8 and tumor necrosis factor-alpha are increased in minimal change disease but do not alter albumin permeability. Am J Nephrol 23:260–266

    Article  PubMed  Google Scholar 

  23. Daniel V, Trautman, Konrad M, Nayir A, Scharer K (1997) T-lymphocyte populations, cytokines and other growth factors in serum and urine of children with idiopathic nephrotic syndrome. Clin Nephrol 47:289–297

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  25. Khan SB, Cook HT, Bhangal G, Smith J, Tam FW, Pusey CD (2005) Antibody blockade of TNF-alpha reduces inflammation and scarring in experimental crescentic glomerulonephritis. Kidney Int 67:1812–1820

    Article  PubMed  Google Scholar 

  26. Nakajima M, Kawahara S, Sakagami Y, Takagawa K, Akazawa H, Kamitsuji H, Yoshioka A (1999) Immunogold labeling of cytokines in glomeruli in children with various renal diseases. Nephron 83:132–138

    Article  PubMed  Google Scholar 

  27. Lama G, Luongo I, Tirino G, Borriello A, Carangio C, Salsano ME (2002) T-lymphocyte populations and cytokines in childhood nephrotic syndrome. Am J Kidney Dis 39:958–965

    Article  PubMed  Google Scholar 

  28. Garin EH, Blanchard DK, Djeu J (1995) Effect of lymphokines on35sulfate uptake by rat glomerular basement membrane. Nephron 9:587–593

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Eduardo H. Garin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Laflam, P.F., Garin, E.H. Effect of tumor necrosis factor α and vascular permeability growth factor on albuminuria in rats. Pediatr Nephrol 21, 177–181 (2006). https://doi.org/10.1007/s00467-005-2078-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-005-2078-3

Keywords

Navigation