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Published in: Pediatric Nephrology 2/2006

01-02-2006 | Original Article

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

Authors: Paul F. Laflam, Eduardo H. Garin

Published in: Pediatric Nephrology | Issue 2/2006

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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.
Literature
1.
go back to reference Shalhoub RJ (1974) Pathogenesis of lipoid nephrosis: a disorder of T-cell function. Lancet II:556–560CrossRef Shalhoub RJ (1974) Pathogenesis of lipoid nephrosis: a disorder of T-cell function. Lancet II:556–560CrossRef
2.
go back to reference Johnson RJ (1996) Role of cytokines and growth factors in glomerulonephritis: a chance for future therapeutic interventions. Nephron 73:506–514PubMed Johnson RJ (1996) Role of cytokines and growth factors in glomerulonephritis: a chance for future therapeutic interventions. Nephron 73:506–514PubMed
3.
go back to reference Schrijvers BF, Flyvbjerg A, De Vriese S (2004) The role of vascular endothelial growth factor (VEGF) in renal pathophysiology. Kidney Int 65:2003–2017CrossRefPubMed Schrijvers BF, Flyvbjerg A, De Vriese S (2004) The role of vascular endothelial growth factor (VEGF) in renal pathophysiology. Kidney Int 65:2003–2017CrossRefPubMed
4.
go back to reference Roberts WG, Palade GE (1995) Increased microvascular permeability and endothelial fenestration induced by vascular endothelial growth factor. J Cell Sci 108:2369–2379PubMed Roberts WG, Palade GE (1995) Increased microvascular permeability and endothelial fenestration induced by vascular endothelial growth factor. J Cell Sci 108:2369–2379PubMed
5.
go back to reference 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 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.
go back to reference 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–F250PubMed 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–F250PubMed
7.
go back to reference 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 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
8.
go back to reference 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 14:263–269PubMed 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 14:263–269PubMed
9.
go back to reference 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 55:1063–1071CrossRefPubMed 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 55:1063–1071CrossRefPubMed
10.
go back to reference Matsumoto K, Kanmatsuse K (2001) Elevated vascular endothelial growth factor levels in the urine of patients with minimal-change nephrotic syndrome. Clin Nephrol 55:269–274PubMed Matsumoto K, Kanmatsuse K (2001) Elevated vascular endothelial growth factor levels in the urine of patients with minimal-change nephrotic syndrome. Clin Nephrol 55:269–274PubMed
11.
go back to reference 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 143:3470–3475PubMed 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 143:3470–3475PubMed
12.
go back to reference 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 74:79–88PubMed 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 74:79–88PubMed
13.
go back to reference 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 79:453–460CrossRefPubMed 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 79:453–460CrossRefPubMed
14.
go back to reference 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 21:251–259PubMed 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 21:251–259PubMed
15.
go back to reference 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:1299–1302CrossRef 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:1299–1302CrossRef
16.
go back to reference 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 52:735–738PubMed 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 52:735–738PubMed
17.
go back to reference 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 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
18.
go back to reference 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 13:875–885CrossRefPubMed 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 13:875–885CrossRefPubMed
19.
go back to reference 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 58:2502–2511CrossRefPubMed 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 58:2502–2511CrossRefPubMed
20.
go back to reference Garin EH (1995) Effect of lipoid nephrosis cytokine on glomerular sulfated compounds and albuminuria. Pediatr Nephrol 9:587–593CrossRefPubMed Garin EH (1995) Effect of lipoid nephrosis cytokine on glomerular sulfated compounds and albuminuria. Pediatr Nephrol 9:587–593CrossRefPubMed
21.
go back to reference 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 19:1115–1121CrossRefPubMed 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 19:1115–1121CrossRefPubMed
22.
go back to reference 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 23:260–266CrossRefPubMed 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 23:260–266CrossRefPubMed
23.
go back to reference 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 47:289–297PubMed 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 47:289–297PubMed
24.
go back to reference 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 24:799–805PubMed 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 24:799–805PubMed
25.
go back to reference 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 67:1812–1820CrossRefPubMed 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 67:1812–1820CrossRefPubMed
26.
go back to reference 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 83:132–138CrossRefPubMed 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 83:132–138CrossRefPubMed
27.
go back to reference 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 39:958–965CrossRefPubMed 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 39:958–965CrossRefPubMed
28.
go back to reference Garin EH, Blanchard DK, Djeu J (1995) Effect of lymphokines on35sulfate uptake by rat glomerular basement membrane. Nephron 9:587–593 Garin EH, Blanchard DK, Djeu J (1995) Effect of lymphokines on35sulfate uptake by rat glomerular basement membrane. Nephron 9:587–593
Metadata
Title
Effect of tumor necrosis factor α and vascular permeability growth factor on albuminuria in rats
Authors
Paul F. Laflam
Eduardo H. Garin
Publication date
01-02-2006
Publisher
Springer-Verlag
Published in
Pediatric Nephrology / Issue 2/2006
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-005-2078-3

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