Eardley, Kevin S., Kubal, Chandrashekhar, Zehnder, Daniel, Quinkler, Marcus, Lepenies, Julia, Savage, Caroline O. S., Howie, Alexander J., Kaur, Kirrenjit, Cooper, Mark S., Adu, Dwomoa and Cockwell, Paul. (2008) The role of capillary density, macrophage infiltration and interstitial scarring in the pathogenesis of human chronic kidney disease. Kidney International, Volume 74 (Number 4). pp. 495-504. ISSN 0085-2538

Full text not available from this repository.

Abstract

To assess the relationship between interstitial capillary density and interstitial macrophages we prospectively measured these factors in situ in 110 patients with chronic kidney disease. Macrophage numbers and urinary MCP-1/CCL2 levels significantly correlated inversely with capillary density which itself significantly correlated inversely with chronic damage and predicted disease progression. In 54 patients with less than 20% chronic damage, there was a significant correlation between the urinary albumin to creatinine ratio and MCP-1/CCL2, and MCP-1/CCL2 and macrophages but not between MCP-1/CCL2 and capillary density. Conversely, in 56 patients with over 20% chronic damage there was no correlation between MCP-1/CCL2 and macrophages but there were significant inverse correlations between capillary density and both macrophages and chronic damage. The expression of VEGF mRNA significantly correlated with macrophage infiltration, capillary density and chronic scarring. In an ischemic-hypertensive subgroup there was upregulation of the hypoxia marker carbonic anhydrase IX and with over 20% chronic damage an increased macrophage to CCR2 ratio. Our study shows that proteinuria and MCP-1/CCL2 are important for macrophage recruitment in early disease. As renal scarring evolves, alternative pathways relating to progressive tissue ischemia secondary to obliteration of the interstitial capillary bed predominate.

Item Type:	Journal Article
Subjects:	Q Science > QP Physiology Q Science > QR Microbiology > QR180 Immunology R Medicine > RC Internal medicine
Divisions:	Faculty of Medicine > Warwick Medical School > Metabolic and Vascular Health Faculty of Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Capillaries, Macrophages, Anoxemia, Kidneys -- Diseases, Vascular endothelial growth factors, Chemokines -- Immunology
Journal or Publication Title:	Kidney International
Publisher:	Nature Publishing Group
ISSN:	0085-2538
Date:	August 2008
Volume:	Volume 74
Number:	Number 4
Number of Pages:	10
Page Range:	pp. 495-504
Identification Number:	10.1038/ki.2008.183
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
References:	1. Sean Eardley K, Cockwell P. Macrophages and progressive tubulointerstitial disease. Kidney Int 2005; 68: 437–455. 2. Eardley KS, Zehnder D, Quinkler M et al. The relationship between albuminuria, MCP-1/CCL2, and interstitial macrophages in chronic kidney disease. Kidney Int 2006; 69: 1189–1197. 3. Grandaliano G, Gesualdo L, Ranieri E et al. Monocyte chemotactic peptide-1 expression in acute and chronic human nephritides: a pathogenetic role in interstitial monocytes recruitment. J Am Soc Nephrol 1996; 7: 906–913. 4. Kitagawa K, Wada T, Furuichi K et al. Blockade of CCR2 ameliorates progressive fibrosis in kidney. Am J Pathol 2004; 165: 237–246. 5. Prodjosudjadi W, Gerritsma JS, van Es LA et al. Monocyte chemoattractant protein-1 in normal and diseased human kidneys: an immunohistochemical analysis. Clin Nephrol 1995; 44: 148–155. 6. Segerer S, Cui Y, Hudkins KL et al. Expression of the chemokine monocyte chemoattractant protein-1 and its receptor chemokine receptor 2 in human crescentic glomerulonephritis. J Am Soc Nephrol 2000; 11: 2231–2242. 7. Shimizu H, Maruyama S, Yuzawa Y et al. Anti-monocyte chemoattractant protein-1 gene therapy attenuates renal injury induced by proteinoverload proteinuria. J Am Soc Nephrol 2003; 14: 1496–1505. 8. Tang WW, Qi M, Warren JS et al. Chemokine expression in experimental tubulointerstitial nephritis. J Immunol 1997; 159: 870–876. 9. Wada T, Furuichi K, Sakai N et al. Gene therapy via blockade of monocyte chemoattractant protein-1 for renal fibrosis. J Am Soc Nephrol 2004; 15: 940–948. 10. Yoshimoto K, Wada T, Furuichi K et al. CD68 and MCP-1/CCR2 expression of initial biopsies reflect the outcomes of membranous nephropathy. Nephron Clin Pract 2004; 98: c25–c34. 11. Bohle A, Mackensen-Haen S, Wehrmann M. Significance of postglomerular capillaries in the pathogenesis of chronic renal failure. Kidney Blood Press Res 1996; 19: 191–195. 12. Choi YJ, Chakraborty S, Nguyen V et al. Peritubular capillary loss is associated with chronic tubulointerstitial injury in human kidney: altered expression of vascular endothelial growth factor. Hum Pathol 2000; 31: 1491–1497. 13. Futrakul P, Yenrudi S, Sensirivatana R et al. Renal perfusion and nephronal structure. Nephron 1999; 82: 79–80. 14. Seron D, Alexopoulos E, Raftery MJ et al. Number of interstitial capillary cross-sections assessed by monoclonal antibodies: relation to interstitial damage. Nephrol Dial Transplant 1990; 5: 889–893. 15. Fine LG, Bandyopadhay D, Norman JT. Is there a common mechanism for the progression of different types of renal diseases other than proteinuria? Towards the unifying theme of chronic hypoxia. Kidney Int Suppl 2000; 75: S22–S26. 16. Nangaku M. Chronic hypoxia and tubulointerstitial injury: a final common pathway to end-stage renal failure. J Am Soc Nephrol 2006; 17: 17–25. 17. Shweiki D, Itin A, Soffer D et al. Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature 1992; 359: 843–845. 18. Namikoshi T, Satoh M, Horike H et al. Implication of peritubular capillary loss and altered expression of vascular endothelial growth factor in IgA nephropathy. Nephron Physiol 2006; 102: 9–16. 19. Combe C, Burton CJ, Dufourco P et al. Hypoxia induces intercellular adhesion molecule-1 on cultured human tubular cells. Kidney Int 1997; 51: 1703–1709. 20. Lewis JS, Lee JA, Underwood JC et al. Macrophage responses to hypoxia: relevance to disease mechanisms. J Leukoc Biol 1999; 66: 889–900. 21. Manotham K, Tanaka T, Matsumoto M et al. Evidence of tubular hypoxia in the early phase in the remnant kidney model. J Am Soc Nephrol 2004; 15: 1277–1288. 22. Matsumoto M, Tanaka T, Yamamoto T et al. Hypoperfusion of peritubular capillaries induces chronic hypoxia before progression of tubulointerstitial injury in a progressive model of rat glomerulonephritis. J Am Soc Nephrol 2004; 15: 1574–1581. 23. Futrakul N, Yenrudi S, Sensirivatana R et al. Peritubular capillary flow determines tubulointerstitial disease in idiopathic nephrotic syndrome. Ren Fail 2000; 22: 329–335. 24. Manotham K, Tanaka T, Matsumoto M et al. Transdifferentiation of cultured tubular cells induced by hypoxia. Kidney Int 2004; 65: 871–880. 25. Norman JT, Orphanides C, Garcia P et al. Hypoxia-induced changes in extracellular matrix metabolism in renal cells. Exp Nephrol 1999; 7: 463–469.26. Jubb AM, Pham TQ, Hanby AM et al. Expression of vascular endothelial growth factor, hypoxia inducible factor 1alpha, and carbonic anhydrase IX in human tumours. J Clin Pathol 2004; 57: 504–512. 27. Wykoff CC, Beasley NJ, Watson PH et al. Hypoxia-inducible expression of tumor-associated carbonic anhydrases. Cancer Res 2000; 60: 7075–7083. 28. Loncaster JA, Harris AL, Davidson SE et al. Carbonic anhydrase (CA IX) expression, a potential new intrinsic marker of hypoxia: correlations with tumor oxygen measurements and prognosis in locally advanced carcinoma of the cervix. Cancer Res 2001; 61: 6394–6399. 29. Hui EP, Chan AT, Pezzella F et al. Coexpression of hypoxia-inducible factors 1alpha and 2alpha, carbonic anhydrase IX, and vascular endothelial growth factor in nasopharyngeal carcinoma and relationship to survival. Clin Cancer Res 2002; 8: 2595–2604. 30. Li X, Kimura H, Hirota K et al. Hypoxia reduces constitutive and TNF-alpha-induced expression of monocyte chemoattractant protein-1 in human proximal renal tubular cells. Biochem Biophys Res Commun 2005; 335: 1026–1034. 31. Segerer S, Alpers CE. Chemokines and chemokine receptors in renal pathology. Curr Opin Nephrol Hypertens 2003; 12: 243–249. 32. Segerer S, Hughes E, Hudkins KL et al. Expression of the fractalkine receptor (CX3CR1) in human kidney diseases. Kidney Int 2002; 62: 488–495. 33. Green SR, Han KH, Chen Y et al. The CC chemokine MCP-1 stimulates surface expression of CX3CR1 and enhances the adhesion of monocytes to fractalkine/CX3CL1 via p38 MAPK. J Immunol 2006; 176: 7412–7420. 34. Barlic J, Zhang Y, Foley JF et al. Oxidized lipid-driven chemokine receptor switch, CCR2 to CX3CR1, mediates adhesion of human macrophages to coronary artery smooth muscle cells through a peroxisome proliferatoractivated receptor gamma-dependent pathway. Circulation 2006; 114: 807–819. 35. Howie AJ, Ferreira MA, Adu D. Prognostic value of simple measurement of chronic damage in renal biopsy specimens. Nephrol Dial Transplant 2001; 16: 1163–1169. 36. Quinkler M, Zehnder D, Eardley KS et al. Increased expression of mineralocorticoid effector mechanisms in kidney biopsies of patients with heavy proteinuria. Circulation 2005; 112: 1435–1443.
URI:	http://wrap.warwick.ac.uk/id/eprint/29621

Data sourced from Thomson Reuters' Web of Knowledge

Request changes to a record

Actions (login required)

View Item