Table of Contents Author Guidelines Submit a Manuscript
BioMed Research International
Volume 2014, Article ID 482438, 13 pages
http://dx.doi.org/10.1155/2014/482438
Review Article

Biological Pathways and Potential Targets for Prevention and Therapy of Chronic Allograft Nephropathy

Division of Renal Transplantation, Sheffield Kidney Institute, Northern General Hospital, Herries Road, Sheffield S5 7AU, UK

Received 12 February 2014; Accepted 4 May 2014; Published 27 May 2014

Academic Editor: Paul J. Higgins

Copyright © 2014 Badri Man Shrestha and John Haylor. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. A. Shrestha, A. Shrestha, C. Basarab-Horwath, W. McKane, B. Shrestha, and A. Raftery, “Quality of life following live donor renal transplantation: a single centre experience,” Annals of Transplantation, vol. 15, no. 2, pp. 5–10, 2010. View at Google Scholar · View at Scopus
  2. U. Heemann and J. Lutz, “Pathophysiology and treatment options of chronic renal allograft damage,” Nephrology, Dialysis, Transplantation, vol. 28, no. 10, pp. 2438–2446, 2013. View at Google Scholar
  3. L. C. Paul, “Chronic allograft nephropathy: an update,” Kidney International, vol. 56, no. 3, pp. 783–793, 1999. View at Publisher · View at Google Scholar · View at Scopus
  4. L. D. Cornell and R. B. Colvin, “Chronic allograft nephropathy,” Current Opinion in Nephrology and Hypertension, vol. 14, no. 3, pp. 229–234, 2005. View at Google Scholar · View at Scopus
  5. M. Haas, “Chronic allograft nephropathy or interstitial fibrosis and tubular atrophy: what is in a name?” Current Opinion in Nephrology and Hypertension, vol. 23, no. 3, pp. 245–250, 2014. View at Google Scholar
  6. E. J. Schweitzer, A. J. Matas, K. J. Gillingham et al., “Causes of renal allograft loss: progress in the 1980s, challenges for the 1990s,” Annals of Surgery, vol. 214, no. 6, pp. 679–688, 1991. View at Google Scholar · View at Scopus
  7. Y. W. J. Sijpkens, I. I. N. Doxiadis, F. J. van Kemenade et al., “Chronic rejection with or without transplant vasculopathy,” Clinical Transplantation, vol. 17, no. 3, pp. 163–170, 2003. View at Publisher · View at Google Scholar · View at Scopus
  8. M. Naesens, D. R. J. Kuypers, K. De Vusser et al., “Chronic histological damage in early indication biopsies is an independent risk factor for late renal allograft failure,” American Journal of Transplantation, vol. 13, no. 1, pp. 86–99, 2013. View at Publisher · View at Google Scholar · View at Scopus
  9. T. K. Sigdel, L. Li, T. Q. Tran et al., “Non-HLA antibodies to immunogenic epitopes predict the evolution of chronic renal allograft injury,” Journal of the American Society of Nephrology, vol. 23, no. 4, pp. 750–763, 2012. View at Publisher · View at Google Scholar · View at Scopus
  10. J. Pascual, M. J. Pérez-Sáez, M. Mir, and M. Crespo, “Chronic renal allograft injury: early detection, accurate diagnosis and management,” Transplantation Reviews, vol. 26, no. 4, pp. 280–290, 2012. View at Publisher · View at Google Scholar · View at Scopus
  11. L. C. Paul, “Pathogenesis of chronic allograft nephropathy,” Current Opinion in Nephrology and Hypertension, vol. 7, no. 6, pp. 635–637, 1998. View at Publisher · View at Google Scholar · View at Scopus
  12. R. K. Maryniak, M. R. First, and M. A. Weiss, “Transplant glomerulopathy: evolution of morphologically distinct changes,” Kidney International, vol. 27, no. 5, pp. 799–806, 1985. View at Google Scholar · View at Scopus
  13. B. M. Brenner, E. V. Lawler, and H. S. Mackenzie, “The hyperfiltration theory: a paradigm shift in nephrology,” Kidney International, vol. 49, no. 6, pp. 1774–1777, 1996. View at Google Scholar · View at Scopus
  14. B. M. Brenner, T. W. Meyer, and T. H. Hostetter, “Dietary protein intake and the progressive nature of kidney disease: the role of hemodynamically mediated glomerular injury in the pathogenesis of progressive glomerular sclerosis in aging, renal ablation, and intrinsic renal disease,” The New England Journal of Medicine, vol. 307, no. 11, pp. 652–659, 1982. View at Google Scholar · View at Scopus
  15. M. R. Weir and R. K. Wali, “Minimizing the risk of chronic allograft nephropathy,” Transplantation, vol. 87, no. 8, pp. S14–S18, 2009. View at Google Scholar · View at Scopus
  16. S. M. Lal, A. M. Luger, L. K. Saha, and G. Ross Jr., “De novo membranous glomerulopathy in renal allografts with unusual histology,” International Journal of Artificial Organs, vol. 18, no. 2, pp. 78–80, 1995. View at Google Scholar · View at Scopus
  17. D. Y. Tsay, J. D. Lian, K. H. Shu et al., “Glomerular diseases in human renal allograft,” Journal of the Formosan Medical Association, vol. 90, no. 11, pp. 1038–1043, 1991. View at Google Scholar · View at Scopus
  18. F. Ortiz, T. Paavonen, T. Törnroth et al., “Predictors of renal allograft histologic damage progression,” Journal of the American Society of Nephrology, vol. 16, no. 3, pp. 817–824, 2005. View at Publisher · View at Google Scholar · View at Scopus
  19. P. Boor, T. Ostendorf, and J. Floege, “Renal fibrosis: novel insights into mechanisms and therapeutic targets,” Nature Reviews Nephrology, vol. 6, no. 11, pp. 643–656, 2010. View at Publisher · View at Google Scholar · View at Scopus
  20. B. Ivanyi, E. Kemeny, E. Szederkenyi, F. Marofka, and P. Szenohradszky, “The value of electron microscopy in the diagnosis of chronic renal allograft rejection,” Modern Pathology, vol. 14, no. 12, pp. 1200–1208, 2001. View at Publisher · View at Google Scholar · View at Scopus
  21. Z. A. Massy, C. Guijarro, M. R. Wiederkehr, J. Z. Ma, and B. L. Kasiske, “Chronic renal allograft rejection: immunologic and nonimmunologic risk factors,” Kidney International, vol. 49, no. 2, pp. 518–524, 1996. View at Google Scholar · View at Scopus
  22. P. F. Halloran, A. Melk, and C. Barth, “Rethinking chronic allograft nephropathy: the concept of accelerated senescence,” Journal of the American Society of Nephrology, vol. 10, no. 1, pp. 167–181, 1999. View at Google Scholar · View at Scopus
  23. B. J. Nankivell, R. J. Borrows, C. L.-S. Fung, P. J. O'Connell, R. D. M. Allen, and J. R. Chapman, “The natural history of chronic allograft nephropathy,” The New England Journal of Medicine, vol. 349, no. 24, pp. 2326–2333, 2003. View at Publisher · View at Google Scholar · View at Scopus
  24. A. Djamali, “Oxidative stress as a common pathway to chronic tubulointerstitial injury in kidney allografts,” American Journal of Physiology, vol. 293, no. 2, pp. F445–F455, 2007. View at Publisher · View at Google Scholar · View at Scopus
  25. A. Benigni, I. Bruzzi, M. Mister et al., “Nature and mediators of renal lesions in kidney transplant patients given cyclosporine for more than one year,” Kidney International, vol. 55, no. 2, pp. 674–685, 1999. View at Publisher · View at Google Scholar · View at Scopus
  26. A. Hertig, J. Verine, B. Mougenot et al., “Risk factors for early epithelial to mesenchymal transition in renal grafts,” American Journal of Transplantation, vol. 6, no. 12, pp. 2937–2946, 2006. View at Publisher · View at Google Scholar · View at Scopus
  27. A. Djamali, S. Reese, J. Yracheta, T. Oberley, D. Hullett, and B. Becker, “Epithelial-to-mesenchymal transition and oxidative stress in chronic allograft nephropathy,” American Journal of Transplantation, vol. 5, no. 3, pp. 500–509, 2005. View at Publisher · View at Google Scholar · View at Scopus
  28. A. Melk, “Senescence of renal cells: molecular basis and clinical implications,” Nephrology Dialysis Transplantation, vol. 18, no. 12, pp. 2474–2478, 2003. View at Publisher · View at Google Scholar · View at Scopus
  29. M. Siekierka-Harreis, N. Kuhr, R. Willers et al., “Impact of genetic polymorphisms of the renin-angiotensin system and of non-genetic factors on kidney transplant function—a single-center experience,” Clinical Transplantation, vol. 23, no. 5, pp. 606–615, 2009. View at Publisher · View at Google Scholar · View at Scopus
  30. J. Wilczynska, U. Pfeil, A. Zakrzewicz et al., “Acetylcholine and chronic vasculopathy in rat renal allografts,” Transplantation, vol. 91, no. 3, pp. 263–270, 2011. View at Publisher · View at Google Scholar · View at Scopus
  31. H. Abo-Zenah, S. Katsoudas, D. De Takats et al., “Early progressive interstitial fibrosis in human renal allografts,” Clinical Nephrology, vol. 57, no. 1, pp. 9–18, 2002. View at Google Scholar · View at Scopus
  32. D. R. J. Kuypers, J. R. Chapman, P. J. O'Connell, R. D. M. Allen, and B. J. Nankivell, “Predictors of renal transplant histology at three months,” Transplantation, vol. 67, no. 9, pp. 1222–1230, 1999. View at Publisher · View at Google Scholar · View at Scopus
  33. R. B. Mannon, “Therapeutic targets in the treatment of allograft fibrosis,” American Journal of Transplantation, vol. 6, no. 5, pp. 867–875, 2006. View at Publisher · View at Google Scholar · View at Scopus
  34. H. Amer and M. D. Griffin, “Modulating kidney transplant interstitial fibrosis and tubular atrophy: is the RAAS an important target?” Kidney International, vol. 85, no. 2, pp. 240–243, 2014. View at Google Scholar
  35. R. L. Heilman, Y. Devarapalli, H. A. Chakkera et al., “Impact of subclinical inflammation on the development of interstitial fibrosis and tubular atrophy in kidney transplant recipients,” American Journal of Transplantation, vol. 10, no. 3, pp. 563–570, 2010. View at Publisher · View at Google Scholar · View at Scopus
  36. E. P. Böttinger, “TGF-β in renal injury and disease,” Seminars in Nephrology, vol. 27, no. 3, pp. 309–320, 2007. View at Publisher · View at Google Scholar · View at Scopus
  37. J. R. Tyler, H. Robertson, T. A. Booth, A. D. Burt, and J. A. Kirby, “Chronic allograft nephropathy: intraepithelial signals generated by transforming growth factor-β and bone morphogenetic protein-7,” American Journal of Transplantation, vol. 6, no. 6, pp. 1367–1376, 2006. View at Publisher · View at Google Scholar · View at Scopus
  38. J. Zavadil and E. P. Böttinger, “TGF-β and epithelial-to-mesenchymal transitions,” Oncogene, vol. 24, no. 37, pp. 5764–5774, 2005. View at Publisher · View at Google Scholar · View at Scopus
  39. S. Park, T. A. DiMaio, W. Liu, S. Wang, C. M. Sorenson, and N. Sheibani, “Endoglin regulates the activation and quiescence of endothelium by participating in canonical and non-canonical TGF-β signaling pathways,” Journal of Cell Science, vol. 126, no. 6, pp. 1392–1405, 2013. View at Publisher · View at Google Scholar · View at Scopus
  40. J.-M. Fan, N. G. Yee-Yung, P. A. Hill et al., “Transforming growth factor-β regulates tubular epithelial-myofibroblast transdifferentiation in vitro,” Kidney International, vol. 56, no. 4, pp. 1455–1467, 1999. View at Publisher · View at Google Scholar · View at Scopus
  41. T. Hayashida, M. Decaestecker, and H. W. Schnaper, “Cross-talk between ERK MAP kinase and Smad signaling pathways enhances TGF-beta-dependent responses in human mesangial cells,” The FASEB Journal, vol. 17, no. 11, pp. 1576–1578, 2003. View at Google Scholar · View at Scopus
  42. F. Strutz, M. Zeisberg, F. N. Ziyadeh et al., “Role of basic fibroblast growth factor-2 in epithelial-mesenchymal transformation,” Kidney International, vol. 61, no. 5, pp. 1714–1728, 2002. View at Publisher · View at Google Scholar · View at Scopus
  43. I. Z. A. Pawluczyk and K. P. G. Harris, “Macrophages promote prosclerotic responses in cultured rat mesangial cells: a mechanism for the initiation of glomerulosclerosis,” Journal of the American Society of Nephrology, vol. 8, no. 10, pp. 1525–1536, 1997. View at Google Scholar · View at Scopus
  44. W. Kriz, M. Kretzler, M. Nagata et al., “A frequent pathway to glomerulosclerosis: deterioration of tuft architecture—podocyte damage—segmental sclerosis,” Kidney and Blood Pressure Research, vol. 19, no. 5, pp. 245–253, 1996. View at Google Scholar · View at Scopus
  45. A. Ljungquist, “The intrarenal arterial pattern in the normal and deseased human kidney,” Acta Medica Scandinavica, vol. 174, supplement 401, pp. 5–34, 1963. View at Google Scholar
  46. D.-H. Kang, J. Kanellis, C. Hugo et al., “Role of the microvascular endothelium in progressive renal disease,” Journal of the American Society of Nephrology, vol. 13, no. 3, pp. 806–816, 2002. View at Google Scholar · View at Scopus
  47. J. T. Norman, I. M. Clark, and P. L. Garcia, “Hypoxia promotes fibrogenesis in human renal fibroblasts,” Kidney International, vol. 58, no. 6, pp. 2351–2366, 2000. View at Publisher · View at Google Scholar · View at Scopus
  48. L. Renders and U. Heemann, “Chronic renal allograft damage after transplantation: what are the reasons, what can we do?” Current Opinion in Organ Transplantation, vol. 17, no. 6, pp. 634–639, 2012. View at Publisher · View at Google Scholar · View at Scopus
  49. A. Djamali and M. Samaniego, “Fibrogenesis in kidney transplantation: potential targets for prevention and therapy,” Transplantation, vol. 88, no. 10, pp. 1149–1156, 2009. View at Publisher · View at Google Scholar · View at Scopus
  50. E. Song, H. Zou, Y. Yao et al., “Early application of Met-RANTES ameliorates chronic allograft nephropathy,” Kidney International, vol. 61, no. 2, pp. 676–685, 2002. View at Publisher · View at Google Scholar · View at Scopus
  51. J. Bedke, E. Kiss, L. Schaefer et al., “Beneficial effects of CCR1 blockade on the progression of chronic renal allograft damage,” American Journal of Transplantation, vol. 7, no. 3, pp. 527–537, 2007. View at Publisher · View at Google Scholar · View at Scopus
  52. W. Land, H. Schneeberger, S. Schleibner et al., “The beneficial effect of human recombinant superoxide dismutase on acute and chronic rejection events in recipients of cadaveric renal transplants,” Transplantation, vol. 57, no. 2, pp. 211–217, 1994. View at Google Scholar · View at Scopus
  53. R. Pollak, J. H. Andrisevic, M. S. Maddux, S. A. Gruber, and M. S. Paller, “A randomized double-blind trial of the use of human recombinant superoxide dismutase in renal transplantation,” Transplantation, vol. 55, no. 1, pp. 57–60, 1993. View at Google Scholar · View at Scopus
  54. G. Nickenig and D. G. Harrison, “The AT1-type angiotensin receptor in oxidative stress and atherogenesis: part I: oxidative stress and atherogenesis,” Circulation, vol. 105, no. 3, pp. 393–396, 2002. View at Publisher · View at Google Scholar · View at Scopus
  55. T. Chabrashvili, C. Kitiyakara, J. Blau et al., “Effects of ANG II type 1 and 2 receptors on oxidative stress, renal NADPH oxidase, and SOD expression,” American Journal of Physiology, vol. 285, no. 1, pp. R117–R124, 2003. View at Google Scholar · View at Scopus
  56. M. Bhaskaran, K. Reddy, N. Radhakrishanan, N. Franki, G. Ding, and P. C. Singhal, “Angiotensin II induces apoptosis in renal proximal tubular cells,” American Journal of Physiology, vol. 284, no. 5, pp. F955–F965, 2003. View at Google Scholar · View at Scopus
  57. M. Burnier and A. Zanchi, “Blockade of the renin-angiotensin-aldosterone system: a key therapeutic strategy to reduce renal and cardiovascular events in patients with diabetes,” Journal of Hypertension, vol. 24, no. 1, pp. 11–25, 2006. View at Google Scholar · View at Scopus
  58. G. Heinze, C. Mitterbauer, H. Regele et al., “Angiotensin-converting enzyme inhibitor or angiotensin II type 1 receptor antagonist therapy is associated with prolonged patient and graft survival after renal transplantation,” Journal of the American Society of Nephrology, vol. 17, no. 3, pp. 889–899, 2006. View at Publisher · View at Google Scholar · View at Scopus
  59. S. Hiremath, D. Fergusson, S. Doucette, A. V. Mulay, and G. A. Knoll, “Renin angiotensin system blockade in kidney transplantation: a systematic review of the evidence,” American Journal of Transplantation, vol. 7, no. 10, pp. 2350–2360, 2007. View at Publisher · View at Google Scholar · View at Scopus
  60. G. A. Knoll, M. Cantarovitch, E. Cole et al., “The Canadian ACE-inhibitor trial to improve renal outcomes and patient survival in kidney transplantation—study design,” Nephrology Dialysis Transplantation, vol. 23, no. 1, pp. 354–358, 2008. View at Publisher · View at Google Scholar · View at Scopus
  61. R. B. Mannon, J. B. Kopp, P. Ruiz et al., “Chronic rejection of mouse kidney allografts,” Kidney International, vol. 55, no. 5, pp. 1935–1944, 1999. View at Publisher · View at Google Scholar · View at Scopus
  62. A. K. Khanna, V. R. Cairns, C. G. Becker, and J. D. Hosenpud, “Transforming growth factor (TGF)-β mimics and anti-TGF-β antibody abrogates the in vivo effects of cyclosporine demonstration of a direct role of TGF-β in immunosuppression and nephrotoxicity of cyclosporine,” Transplantation, vol. 67, no. 6, pp. 882–889, 1999. View at Google Scholar · View at Scopus
  63. M. M. Shull, I. Ormsby, A. B. Kier et al., “Targeted disruption of the mouse transforming growth factor-β1 gene results in multifocal inflammatory disease,” Nature, vol. 359, no. 6397, pp. 693–699, 1992. View at Publisher · View at Google Scholar · View at Scopus
  64. M. Eikmans, Y. W. J. Sijpkens, H. J. Baelde, E. De Heer, L. C. Paul, and J. A. Bruijn, “High transforming growth factor-β and extracellular matrix mRNA response in renal allografts during early acute rejection is associated with absence of chronic rejection,” Transplantation, vol. 73, no. 4, pp. 573–579, 2002. View at Google Scholar · View at Scopus
  65. F. S. Shihab, W. M. Bennett, H. Yi, and T. F. Andoh, “Pirfenidone treatment decreases transforming growth factor-β1 and matrix proteins and ameliorates fibrosis in chronic cyclosporine nephrotoxicity,” American Journal of Transplantation, vol. 2, no. 2, pp. 111–119, 2002. View at Publisher · View at Google Scholar · View at Scopus
  66. F. S. Shihab, W. M. Bennett, H. Yi, and T. F. Andoh, “Effect of pirfenidone on apoptosis-regulatory genes in chronic cyclosporine nephrotoxicity,” Transplantation, vol. 79, no. 4, pp. 419–426, 2005. View at Publisher · View at Google Scholar · View at Scopus
  67. M. E. Cho, D. C. Smith, M. H. Branton, S. R. Penzak, and J. B. Kopp, “Pirfenidone slows renal function decline in patients with focal segmental glomerulosclerosis,” Clinical Journal of the American Society of Nephrology, vol. 2, no. 5, pp. 906–913, 2007. View at Publisher · View at Google Scholar · View at Scopus
  68. M. H. J. Heeg, M. J. Koziolek, R. Vasko et al., “The antifibrotic effects of relaxin in human renal fibroblasts are mediated in part by inhibition of the Smad2 pathway,” Kidney International, vol. 68, no. 1, pp. 96–109, 2005. View at Publisher · View at Google Scholar · View at Scopus
  69. C. S. Samuel, C. Zhao, R. A. D. Bathgate et al., “The relaxin gene-knockout mouse: a model of progressive fibrosis,” Annals of the New York Academy of Sciences, vol. 1041, pp. 173–181, 2005. View at Publisher · View at Google Scholar · View at Scopus
  70. S. L. Garber, Y. Mirochnik, C. S. Brecklin et al., “Relaxin decreases renal interstitial fibrosis and slows progression of renal disease,” Kidney International, vol. 59, no. 3, pp. 876–882, 2001. View at Publisher · View at Google Scholar · View at Scopus
  71. L. Schaefer, K. Macakova, I. Raslik et al., “Absence of decorin adversely influences tubulointerstitial fibrosis of the obstructed kidney by enhanced apoptosis and increased inflammatory reaction,” American Journal of Pathology, vol. 160, no. 3, pp. 1181–1191, 2002. View at Google Scholar · View at Scopus
  72. W. A. Border, N. A. Noble, T. Yamamoto et al., “Natural inhibitor of transforming growth factor-β protects against scarring in experimental kidney disease,” Nature, vol. 360, no. 6402, pp. 361–364, 1992. View at Publisher · View at Google Scholar · View at Scopus
  73. T. Nakatani, S. Tanabe, Y.-S. Han et al., “Enhanced expression of endothelin-A receptor in human transplant renal arteriosclerosis,” International Journal of Molecular Medicine, vol. 11, no. 2, pp. 153–156, 2003. View at Google Scholar · View at Scopus
  74. S. R. Inman, W. K. Plott, R. A. Pomilee, J. A. Antonelli, and R. M. Lewis, “Endothelin-receptor blockade mitigates the adverse effect of preretrieval warm ischemia on posttransplantation renal function in rats,” Transplantation, vol. 75, no. 10, pp. 1655–1659, 2003. View at Publisher · View at Google Scholar · View at Scopus
  75. J. M. Tikkanen, P. K. Koskinena, and K. B. Lemström, “Role of endogenous endothelin-1 in transplant obliterative airway disease in the rat,” American Journal of Transplantation, vol. 4, no. 5, pp. 713–720, 2004. View at Publisher · View at Google Scholar · View at Scopus
  76. M. Zeisberg, J.-I. Hanai, H. Sugimoto et al., “BMP-7 counteracts TGF-β1-induced epithelial-to-mesenchymal transition and reverses chronic renal injury,” Nature Medicine, vol. 9, no. 7, pp. 964–968, 2003. View at Publisher · View at Google Scholar · View at Scopus
  77. G. R. Grotendorst, “Connective tissue growth factor: a mediator of TGf-β action on fibroblasts,” Cytokine and Growth Factor Reviews, vol. 8, no. 3, pp. 171–179, 1997. View at Publisher · View at Google Scholar · View at Scopus
  78. T. Q. Nguyen, P. Roestenberg, F. A. Van Nieuwenhoven et al., “CTGF inhibits BMP-7 signaling in diabetic nephropathy,” Journal of the American Society of Nephrology, vol. 19, no. 11, pp. 2098–2107, 2008. View at Publisher · View at Google Scholar · View at Scopus
  79. O. Cheng, R. Thuillier, E. Sampson et al., “Connective tissue growth factor is a biomarker and mediator of kidney allograft fibrosis,” American Journal of Transplantation, vol. 6, no. 10, pp. 2292–2306, 2006. View at Publisher · View at Google Scholar · View at Scopus
  80. G. H. Luo, Y. P. Lu, J. Song, L. Yang, Y. J. Shi, and Y. P. Li, “Inhibition of connective tissue growth factor by small interfering RNA prevents renal fibrosis in rats undergoing chronic allograft nephropathy,” Transplantation Proceedings, vol. 40, no. 7, pp. 2365–2369, 2008. View at Publisher · View at Google Scholar · View at Scopus
  81. S. Wakino, T. Kanda, and K. Hayashi, “Rho/Rho kinase as a potential target for the treatment of renal disease,” Drug News and Perspectives, vol. 18, no. 10, pp. 639–643, 2005. View at Publisher · View at Google Scholar · View at Scopus
  82. M. Sato, Y. Muragaki, S. Saika, A. B. Roberts, and A. Ooshima, “Targeted disruption of TGF-β1/Smad3 signaling protects against renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction,” Journal of Clinical Investigation, vol. 112, no. 10, pp. 1486–1494, 2003. View at Publisher · View at Google Scholar · View at Scopus
  83. K. Nagatoya, T. Moriyama, N. Kawada et al., “Y-27632 prevents tubulointerstitial fibrosis in mouse kidneys with unilateral ureteral obstruction,” Kidney International, vol. 61, no. 5, pp. 1684–1695, 2002. View at Publisher · View at Google Scholar · View at Scopus
  84. K. Ishimaru, H. Ueno, S. Kagitani, D. Takabayashi, M. Takata, and H. Inoue, “Fasudil attenuates myocardial fibrosis in association with inhibition of monocyte/macrophage infiltration in the heart of DOCA/salt hypertensive rats,” Journal of Cardiovascular Pharmacology, vol. 50, no. 2, pp. 187–194, 2007. View at Publisher · View at Google Scholar · View at Scopus
  85. T. Nakagawa, “Uncoupling of the VEGF-endothelial nitric oxide axis in diabetic nephropathy: an explanation for the paradoxical effects of VEGF in renal disease,” American Journal of Physiology, vol. 292, no. 6, pp. F1665–F1672, 2007. View at Publisher · View at Google Scholar · View at Scopus
  86. B. H. Özdemir, F. N. Özdemir, N. Haberal, R. Emiroglu, B. Demirhan, and M. Haberal, “Vascular endothelial growth factor expression and cyclosporine toxicity in renal allograft rejection,” American Journal of Transplantation, vol. 5, no. 4, pp. 766–774, 2005. View at Publisher · View at Google Scholar · View at Scopus
  87. S. Mizuno, K. Matsumoto, and T. Nakamura, “HGF as a renotrophic and anti-fibrotic regulator in chronic renal disease,” Frontiers in Bioscience, vol. 13, no. 18, pp. 7072–7086, 2008. View at Publisher · View at Google Scholar · View at Scopus
  88. Y. Liu, “Hepatocyte growth factor in kidney fibrosis: therapeutic potential and mechanisms of action,” American Journal of Physiology, vol. 287, no. 1, p. -F16, 2004. View at Publisher · View at Google Scholar · View at Scopus
  89. H. Azuma, S. Takahara, K. Matsumoto et al., “Hepatocyte growth factor prevents the development of chronic allograft nephropathy in rats,” Journal of the American Society of Nephrology, vol. 12, no. 6, pp. 1280–1292, 2001. View at Google Scholar · View at Scopus
  90. I. Herrero-Fresneda, J. Torras, M. Franquesa et al., “HGF gene therapy attenuates renal allograft scarring by preventing the profibrotic inflammatory-induced mechanisms,” Kidney International, vol. 70, no. 2, pp. 265–274, 2006. View at Publisher · View at Google Scholar · View at Scopus
  91. S. Benvenuti and P. M. Comoglio, “The MET receptor tyrosine kinase in invasion and metastasis,” Journal of Cellular Physiology, vol. 213, no. 2, pp. 316–325, 2007. View at Publisher · View at Google Scholar · View at Scopus
  92. T. Pihlajaniemi, R. Myllyla, and K. I. Kivirikko, “Prolyl 4-hydroxylase and its role in collagen synthesis,” Journal of Hepatology, vol. 13, no. 3, pp. S2–S7, 1991. View at Google Scholar · View at Scopus
  93. N. Franceschini, O. Cheng, X. Zhang, P. Ruiz, and R. B. Mannon, “Inhibition of prolyl-4-hydroxylase ameliorates chronic rejection of mouse kidney allografts,” American Journal of Transplantation, vol. 3, no. 4, pp. 396–402, 2003. View at Publisher · View at Google Scholar · View at Scopus
  94. K. A. Inkinen, A. P. Soots, L. A. Krogerus, I. T. Lautenschlager, and J. P. Ahonen, “Fibrosis and matrix metalloproteinases in rat renal allografts,” Transplant International, vol. 18, no. 5, pp. 506–512, 2005. View at Publisher · View at Google Scholar · View at Scopus
  95. J. Lutz, Y. Yao, E. Song et al., “Inhibition of matrix metalloproteinase during chronic allograft nephropathy in rats,” Transplantation, vol. 79, no. 6, pp. 655–661, 2005. View at Publisher · View at Google Scholar · View at Scopus
  96. M. Kreutz, J. Fritsche, U. Ackermann, S. W. Krause, and R. Andreesen, “Retinoic acid inhibits monocyte to macrophage survival and differentiation,” Blood, vol. 91, no. 12, pp. 4796–4802, 1998. View at Google Scholar · View at Scopus
  97. J. Adams, E. Kiss, A. B. V. Arroyo et al., “13-cis retinoic acid inhibits development and progression of chronic allograft nephropathy,” American Journal of Pathology, vol. 167, no. 1, pp. 285–298, 2005. View at Google Scholar · View at Scopus
  98. C.-H. Heldin, U. Eriksson, and A. Östman, “New members of the platelet-derived growth factor family of mitogens,” Archives of Biochemistry and Biophysics, vol. 398, no. 2, pp. 284–290, 2002. View at Publisher · View at Google Scholar · View at Scopus
  99. F. Eitner, T. Ostendorf, M. Kretzler et al., “PDGF-C expression in the developing and normal adult human kidney and in glomerular diseases,” Journal of the American Society of Nephrology, vol. 14, no. 5, pp. 1145–1153, 2003. View at Publisher · View at Google Scholar · View at Scopus
  100. H. Iida, R. Seifert, C. E. Alpers et al., “Platelet-derived growth factor (PDGF) and PDGF receptor are induced in mesangial proliferative nephritis in the rat,” Proceedings of the National Academy of Sciences of the United States of America, vol. 88, no. 15, pp. 6560–6564, 1991. View at Publisher · View at Google Scholar · View at Scopus
  101. M. Matsuda, K. Shikata, H. Makino et al., “Gene expression of PDGF and PDGF receptor in various forms of glomerulonephritis,” American Journal of Nephrology, vol. 17, no. 1, pp. 25–31, 1997. View at Google Scholar · View at Scopus
  102. G. Liu, S. Changsirikulchai, K. L. Hudkins et al., “Identification of platelet-derived growth factor D in human chronic allograft nephropathy,” Human Pathology, vol. 39, no. 3, pp. 393–402, 2008. View at Publisher · View at Google Scholar · View at Scopus
  103. J. Savikko, E. Taskinen, and E. Von Willebrand, “Chronic allograft nephropathy is prevented by inhibition of platelet-derived growth factor receptor: tyrosine kinase inhibitors as a potential therapy,” Transplantation, vol. 75, no. 8, pp. 1147–1153, 2003. View at Publisher · View at Google Scholar · View at Scopus
  104. J. M. Rintala, J. Savikko, S. E. Rintala, and E. Von Willebrand, “FK778 ameliorates post-transplant expression of fibrogenic growth factors and development of chronic rejection changes in rat kidney allografts,” Nephrology Dialysis Transplantation, vol. 23, no. 11, pp. 3446–3455, 2008. View at Publisher · View at Google Scholar · View at Scopus
  105. D. Gómez-Garre, R. Largo, N. Tejera, J. Fortes, F. Manzarbeitia, and J. Egido, “Activation of NF-κB in tubular epithelial cells of rats with intense proteinuria role of angiotensin II and endothelin-1,” Hypertension, vol. 37, no. 4, pp. 1171–1178, 2001. View at Google Scholar · View at Scopus
  106. N. Sakai, T. Wada, K. Furuichi et al., “Involvement of extracellular signal-regulated kinase and p38 in human diabetic nephropathy,” American Journal of Kidney Diseases, vol. 45, no. 1, pp. 54–65, 2005. View at Publisher · View at Google Scholar · View at Scopus
  107. S. Tamada, T. Nakatani, T. Asai et al., “Inhibition of nuclear factor-κB activation by pyrrolidine dithiocarbamate prevents chronic FK506 nephropathy,” Kidney International, vol. 63, no. 1, pp. 306–314, 2003. View at Publisher · View at Google Scholar · View at Scopus
  108. Y. Yamamoto and R. B. Gaynor, “Therapeutic potential of inhibition of the NF-κB pathway in the treatment of inflammation and cancer,” Journal of Clinical Investigation, vol. 107, no. 2, pp. 135–142, 2001. View at Google Scholar · View at Scopus
  109. K. Tashiro, S. Tamada, N. Kuwabara et al., “Attenuation of renal fibrosis by proteasome inhibition in rat obstructive nephropathy: possible role of nuclear factor kappaB,” International Journal of Molecular Medicine, vol. 12, no. 4, pp. 587–592, 2003. View at Google Scholar · View at Scopus
  110. M. Andreucci, T. Faga, G. Lucisano et al., “Mycophenolic acid inhibits the phosphorylation of NF-κB and JNKs and causes a decrease in IL-8 release in H2O2-treated human renal proximal tubular cells,” Chemico-Biological Interactions, vol. 185, no. 3, pp. 253–262, 2010. View at Publisher · View at Google Scholar · View at Scopus
  111. J. Ashton-Chess, H. L. Mai, V. Jovanovic et al., “Immunoproteasome beta subunit 10 is increased in chronic antibody-mediated rejection,” Kidney International, vol. 77, no. 10, pp. 880–890, 2010. View at Publisher · View at Google Scholar · View at Scopus
  112. N. Lachmann, M. Schütz, K. Budde, C. Schönemann, and J. Waiser, “Antihumoral rejection therapy by proteasome inhibitor bortezomib: a case series,” Clinical Transplants, pp. 351–358, 2009. View at Google Scholar · View at Scopus
  113. J. Ho, D. N. Rush, I. W. Gibson et al., “Early urinary CCL2 is associated with the later development of interstitial fibrosis and tubular atrophy in renal allografts,” Transplantation, vol. 90, no. 4, pp. 394–400, 2010. View at Publisher · View at Google Scholar · View at Scopus
  114. S. M. Kurian, R. Heilman, T. S. Mondala et al., “Biomarkers for early and late stage chronic allograft nephropathy by proteogenomic profiling of peripheral blood,” PLoS ONE, vol. 4, no. 7, Article ID e6212, 2009. View at Publisher · View at Google Scholar · View at Scopus
  115. R. Tetaz, C. Trocmé, M. Roustit et al., “Predictive diagnostic of chronic allograft dysfunction using urinary proteomics analysis,” Annals of Transplantation, vol. 17, no. 3, pp. 52–60, 2012. View at Google Scholar · View at Scopus
  116. A. Scherer, A. Krause, J. R. Walker, A. Korn, D. Niese, and F. Raulf, “Early prognosis of the development of renal chronic allograft rejection by gene expression profiling of human protocol biopsies,” Transplantation, vol. 75, no. 8, pp. 1323–1330, 2003. View at Publisher · View at Google Scholar · View at Scopus
  117. A. Scherer, W. Gwinner, M. Mengel et al., “Transcriptome changes in renal allograft protocol biopsies at 3 months precede the onset of interstitial fibrosistubular atrophy (IFTA) at 6 months,” Nephrology Dialysis Transplantation, vol. 24, no. 8, pp. 2567–2575, 2009. View at Publisher · View at Google Scholar · View at Scopus
  118. G. Einecke, J. Reeve, B. Sis et al., “A molecular classifier for predicting future graft loss in late kidney transplant biopsies,” Journal of Clinical Investigation, vol. 120, no. 6, pp. 1862–1872, 2010. View at Publisher · View at Google Scholar · View at Scopus
  119. W. S. Oetting, W. Guan, D. P. Schladt et al., “Telomere length of recipients and living kidney donors and chronic graft dysfunction in kidney transplants,” Transplantation, vol. 97, no. 3, pp. 325–329, 2014. View at Google Scholar
  120. D. G. Maluf, C. I. Dumur, J. L. Suh et al., “Evaluation of molecular profiles in calcineurin inhibitor toxicity post-kidney transplant: input to chronic allograft dysfunction,” American Journal of Transplantation, vol. 14, no. 5, pp. 1152–1163, 2014. View at Google Scholar
  121. J. K. Walker, R. R. Alloway, P. Roy-Chaudhury et al., “A prospective trial of a steroid-free/calcineurin inhibitor minimization regimen in human leukocyte antigen (HLA)-identical live donor renal transplantation,” Transplantation, vol. 87, no. 3, pp. 408–414, 2009. View at Publisher · View at Google Scholar · View at Scopus
  122. W. Fadili, M. Habib Allah, and I. Laouad, “Chronic renal allograft dysfunction: risk factors, immunology and prevention,” Arab Journal of Nephrology and Transplantation, vol. 6, no. 1, pp. 45–50, 2013. View at Google Scholar · View at Scopus
  123. F. P. Schena, M. D. Pascoe, J. Alberu et al., “Conversion from calcineurin inhibitors to sirolimus maintenance therapy in renal allograft recipients: 24-month efficacy and safety results from the CONVERT trial,” Transplantation, vol. 87, no. 2, pp. 233–242, 2009. View at Publisher · View at Google Scholar · View at Scopus
  124. L. Luo, Z. Sun, and G. Luo, “Rapamycin is less fibrogenic than Cyclosporin A as demonstrated in a rat model of chronic allograft nephropathy,” Journal of Surgical Research, vol. 179, no. 1, pp. E255–E263, 2013. View at Publisher · View at Google Scholar · View at Scopus
  125. G. A. Böhmig, H. Regele, and W. H. Hörl, “Protocol biopsies after kidney transplantation,” Transplant International, vol. 18, no. 2, pp. 131–139, 2005. View at Publisher · View at Google Scholar · View at Scopus
  126. L. C. Paul, “New insights in chronic allograft rejection,” Current Opinion in Urology, vol. 12, no. 2, pp. 89–93, 2002. View at Publisher · View at Google Scholar · View at Scopus
  127. B. M. Shrestha and J. L. Haylor, “Factors influencing long-term outcomes following renal transplantation: a review,” Journal of the Nepal Medical Association, vol. 46, no. 167, pp. 136–142, 2007. View at Google Scholar · View at Scopus
  128. H. Khan, M. Mubarak, T. Aziz et al., “Prevalence and risk factors for early chronic allograft nephropathy in a live related renal transplant program,” Journal of Nephropathology, vol. 3, no. 2, pp. 69–79, 2014. View at Google Scholar