Monocyte chemoattractant protein-1 and transforming growth factor-beta1 urinary excretion as a marker of renal fibrosis in chronic glomerulonephritis


Cite item

Full Text

Abstract

Purpose: Estimation the content of fibrogenic mediators - monocytic chemotactic protein-1 (MCP-1) and transforming growth factor-β1 (TGF-β1) in the urine and kidney tissue in patients with CGN, and specification their significance for the evaluation of inflammation and fibrosis in the kidney and as prediction criteria.
Materials and Methods: The study enrolled 83 patients with active CGN (Group I - with moderate urinary syndrome, Group II - with nephrotic syndrome (NS), Group III - with severe proteinuria, arterial hypertension and progressive renal failure). Urinary MCP-1 and TGF-β excretion was analyzed by ELISA method. The control group included 12 healthy individuals. Morphometry of 25 biopsy materials of kidney with measurement of interstitial area, the degree of cellular inflammatory infiltration of the interstitium, as well as the degree of interstitial expression of α-SMA, main myofibroblastic marker, were performed.
Results: The level of urinary MCP-1 excretion was higher in all groups of patients with active CGN as compared with healthy controls, and in patients with NS (Group II) was significantly higher than in patients with moderate urinary syndrome (Group I). In particular, high level of urinary MCP-1 excretion was in Group III. The level of TGF β was also higher in CGN patients as compared with healthy controls. The TGF-β excretion was depend mainly on the level of creatininemia, and high level of TGF-β excretion was observed in patients with severe progressive course of nephritis with persistent renal dysfunction (Group III). There was a direct correlation between levels of urinary MCP-1 excretion and the severity of inflammatory cell infiltration of interstitium (RS = 0.8, P<0.001). Levels of urinary MCP-1 and TGF-β excretion were correlated with the value of TIF, estimated by interstitium area (RS = 0.78, P<0.001 and RS = 0.5, P<0.05, respectively), and with the number of major producers of TIF - interstitial myofibroblasts expressing α-SMA (RS = 0.64, P<0.05 and RS = 0.65, P<0.05, respectively).
Conclusion: The results demonstrate the important role of MCP-1 and TGF-β1 in the remodeling of tubulointerstitium. The studied parameters are markers of TIF, and the definition of urinary MCP-1 and TGF-β1 excretion is a helpful noninvasive method that allows monitoring disease activity and fibrosis stages, and assesses the prognosis of CGN

References

  1. Magil A.B. Tubulointerstitial lesions in human membranous glomerulonephritis: Relationship to proteinuria. Am J Kidney Dis. 1995; 25:375-379.
  2. Bohle A, Muller G.A., Wehrmann W et al. Pathogenesis of chronic renal failure in the primary glomerulopathies, renal vasculopathies and chronic interstitial nephritides. 1996. Kidney Int ; 54: 2-9
  3. Bottinger E.P., Bitzer M. TGF-β signaling in renal disease. J Am Soc Nephrol. 2002; 13:2600-2610
  4. Wada T., Yokoyama H., Kobayashi K. Chemokines: new target molecules in renal diseases. Clin Exp Nephrol. 2000; 4:273-280
  5. Okuda S., Languino L.R., Ruoslahti E., Border W.A. Elevated expression of transforming growth factor β and proteoglycan production in experimental glomerulonephritis: possible role in expansion of the mesangial extracellular matrix. J Clin Invest. 1990; 86:453-462.
  6. Schena F.P. Cytokine network and resident renal cells in glomerular diseases// Nephrol Dial Transplant.1999; 14 (1): 22-26.
  7. Wada T., Yokoyama H., Su S., Mukaida N., Iwano M., Dohi K., Takahashi Y., Sasaki T., Furuichi K.,Segawa C., Hisada Y., Ohta S., Takasawa K., Kobayashi K., Matsushima K. Monitoring urinary levels of Monocyte chemotactic and activating factor reflects disease activity of lupus nephritis. Kidney Int. 1996;49:761-767.
  8. Honkanen E, Teppo A, Tornroth T, Groop P., Gronhagen-Riska C. Urinary transforming growth factor-beta 1 in membranous glomerulonephritis. Nephrol Dials Transplant.1997;12 (12): 2562-2568.
  9. Wada T., Furuichi K., Sakai N. et al. Up-regulation of monocyte chemoattractant protein-1 in tubulointerstitial lesions of human diabetic nephropathy. Kidney Int. 2000; 58:1492-1499.
  10. Tesch G.H., Schwarting A., Kinoshita K., Lan H.Y.,Rollins B.J.,Kelley V.R. Monocyte chemoattractant protein-1 promotes macrophage-mediated tubular injury, but not glomerular injury, in nephrotoxic serum nephritis. J Clin Invest. 1999; 103, 1: 73-80
  11. Remuzzi G., Bertani T. Pathophysiology of progressive nephropathies. New Eng J Med. 1998; 20 (339):1448-1456
  12. Wang Y., Rangan G.K., Tay Y.C. et al. Induction of monocyte chemoattractant protein-1 by albumin is mediated by nuclear factor kB in proximal tubule cells. J am Soc Nephrol 1999; 10: 1204-1213
  13. Rovin B.H., Doe N., Tan L.C. Monocyte chemoattractant protein-1 levels in patients with glomerular disease. Am J Kidney Dis. 1996;27:640-646
  14. Schneider A., Panzer U., Zahner G. et al. Monocyte chemoattractant protein-1 mediates collagen deposition in experimental glomerulonephritis by transforming growth factor-beta. Kidney Int. 1999; 56 (1):135-144.
  15. Yamamoto T., Noble N.A., Cohen A.H., Nast C.C., Hishida A., Gold L.I., Border W.A. Expression of transforming growth factor β isoforms in human glomerular diseases. Kidney Int. 1996; 49:461-469
  16. Ando T., Okuda S., Yanagida T et al. Localization of TGFβ and its receptors in the kidney. Miner Electrolyte Metab. 1998; 24 (2-3): 149-153
  17. Fan J.M., Ng Y.Y., Hill P.A. et al. Transforming growth factor beta regulates tubular epithelial-myofibroblasts transdifferentiation in vitro. Kidney Int. 1999; 56(4): 1455-1467.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies