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BioMed Research International
Volume 2014, Article ID 638732, 9 pages
http://dx.doi.org/10.1155/2014/638732
Review Article

The Role of Uric Acid in Kidney Fibrosis: Experimental Evidences for the Causal Relationship

1Division of Nephrology, Department of Internal Medicine, Pusan National University School of Medicine, Yangsan 626-770, Republic of Korea
2Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 626-770, Republic of Korea
3Medical Research Institute, Pusan National University Hospital, Busan 602-739, Republic of Korea

Received 27 February 2014; Revised 5 April 2014; Accepted 21 April 2014; Published 5 May 2014

Academic Editor: Keizo Kanasaki

Copyright © 2014 Il Young Kim et al. 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. S. B. Lee and R. Kalluri, “Mechanistic connection between inflammation and fibrosis,” Kidney International, vol. 78, no. 119, pp. S22–S26, 2010. View at Publisher · View at Google Scholar · View at Scopus
  2. L. H. Beck, “Requiem for gouty nephropathy,” Kidney International, vol. 30, no. 2, pp. 280–287, 1986. View at Google Scholar · View at Scopus
  3. V. Filiopoulos, D. Hadjiyannakos, and D. Vlassopoulos, “New insights into uric acid effects on the progression and prognosis of chronic kidney disease,” Renal Failure, vol. 34, no. 4, pp. 510–520, 2012. View at Publisher · View at Google Scholar · View at Scopus
  4. D.-H. Kang and W. Chen, “Uric acid and chronic kidney disease: new understanding of an old problem,” Seminars in Nephrology, vol. 31, no. 5, pp. 447–452, 2011. View at Publisher · View at Google Scholar · View at Scopus
  5. S. V. Badve, F. Brown, C. M. Hawley et al., “Challenges of conducting a trial of uric-acid-lowering therapy in CKD,” Nature Reviews Nephrology, vol. 7, no. 5, pp. 295–300, 2011. View at Publisher · View at Google Scholar · View at Scopus
  6. D. I. Jalal, M. Chonchol, W. Chen, and G. Targher, “Uric acid as a target of therapy in CKD,” The American Journal of Kidney Diseases, vol. 61, no. 1, pp. 134–146, 2013. View at Publisher · View at Google Scholar
  7. R. J. Johnson, T. Nakagawa, D. Jalal, L. G. Sánchez-Lozada, D. H. Kang, and E. Ritz, “Uric acid and chronic kidney disease: which is chasing which?” Nephrology Dialysis Transplantation, vol. 28, no. 9, pp. 2221–2228, 2013. View at Publisher · View at Google Scholar
  8. G. Bellomo, “Uric acid and chronic kidney disease: a time to act?” World Journal of Nephrology, vol. 2, no. 2, pp. 17–25, 2013. View at Google Scholar
  9. D. Gustafsson and R. Unwin, “The pathophysiology of hyperuricaemia and its possible relationship to cardiovascular disease, morbidity and mortality,” BMC Nephrology, vol. 14, article 164, 2013. View at Publisher · View at Google Scholar
  10. C. E. Berry and J. M. Hare, “Xanthine oxidoreductase and cardiovascular disease: molecular mechanisms and pathophysiological implications,” Journal of Physiology, vol. 555, part 3, pp. 589–606, 2004. View at Publisher · View at Google Scholar · View at Scopus
  11. H. K. Choi, D. B. Mount, and A. M. Reginato, “Pathogenesis of gout,” Annals of Internal Medicine, vol. 143, no. 7, pp. 499–516, 2005. View at Google Scholar · View at Scopus
  12. S. Watanabe, D.-H. Kang, L. Feng et al., “Uric acid, hominoid evolution, and the pathogenesis of salt-sensitivity,” Hypertension, vol. 40, no. 3, pp. 355–360, 2002. View at Publisher · View at Google Scholar · View at Scopus
  13. N. L. Edwards, “The role of hyperuricemia and gout in kidney and cardiovascular disease,” Cleveland Clinic Journal of Medicine, vol. 75, supplement 5, pp. S13–S16, 2008. View at Google Scholar · View at Scopus
  14. D. J. Levinson and L. B. Sorensen, “Renal handling of uric acid in normal and gouty subjects: evidence for a 4-component system,” Annals of the Rheumatic Diseases, vol. 39, no. 2, pp. 173–179, 1980. View at Google Scholar · View at Scopus
  15. A. Taniguchi and N. Kamatani, “Control of renal uric acid excretion and gout,” Current Opinion in Rheumatology, vol. 20, no. 2, pp. 192–197, 2008. View at Publisher · View at Google Scholar · View at Scopus
  16. Y. Takano, K. Hase-Aoki, H. Horiuchi et al., “Selectivity of febuxostat, a novel non-purine inhibitor of xanthine oxidase/xanthine dehydrogenase,” Life Sciences, vol. 76, no. 16, pp. 1835–1847, 2005. View at Publisher · View at Google Scholar · View at Scopus
  17. T. Hosoya, K. Kimura, S. Itoh et al., “The effect of febuxostat to prevent a further reduction in renal function of patients with hyperuricemia who have never had gout and are complicated by chronic kidney disease stage 3: study protocol for a multicenter randomized controlled study,” Trials, vol. 15, no. 1, p. 26, 2014. View at Publisher · View at Google Scholar
  18. B. A. Grabowski, R. Khosravan, L. Vernillet, and D. J. Mulford, “Metabolism and excretion of [14C] febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase, in healthy male subjects,” Journal of Clinical Pharmacology, vol. 51, no. 2, pp. 189–201, 2011. View at Publisher · View at Google Scholar · View at Scopus
  19. I. Garcia-Valladares, T. Khan, and L. R. Espinoza, “Efficacy and safety of febuxostat in patients with hyperuricemia and gout,” Therapeutic Advances in Musculoskeletal Disease, vol. 3, no. 5, pp. 245–253, 2011. View at Publisher · View at Google Scholar · View at Scopus
  20. K. Komoriya, S. Hoshide, K. Takeda et al., “Pharmacokinetics and pharmacodynamics of febuxostat (TMX-67), a non-purine selective inhibitor of xanthine oxidase/xanthine dehydrogenase (NPSIXO) in patients with gout and/or hyperuricemia,” Nucleosides, Nucleotides and Nucleic Acids, vol. 23, no. 8-9, pp. 1119–1122, 2004. View at Publisher · View at Google Scholar · View at Scopus
  21. Y. Osada, M. Tsuchimoto, H. Fukushima et al., “Hypouricemic effect of the novel xanthine oxidase inhibitor, TEI-6720, in rodents,” European Journal of Pharmacology, vol. 241, no. 2-3, pp. 183–188, 1993. View at Google Scholar · View at Scopus
  22. S. P. Bruce, “Febuxostat: a selective xanthine oxidase inhibitor for the treatment of hyperuricemia and gout,” Annals of Pharmacotherapy, vol. 40, no. 12, pp. 2187–2194, 2006. View at Publisher · View at Google Scholar · View at Scopus
  23. C. L. Gray and N. E. Walters-Smith, “Febuxostat for treatment of chronic gout,” The American Journal of Health-System Pharmacy, vol. 68, no. 5, pp. 389–398, 2011. View at Publisher · View at Google Scholar · View at Scopus
  24. R. J. Johnson, S. D. Kivlighn, Y.-G. Kim, S. Suga, and A. B. Fogo, “Reappraisal of the pathogenesis and consequences of hyperuricemia in hypertension, cardiovascular disease, and renal disease,” The American Journal of Kidney Diseases, vol. 33, no. 2, pp. 225–234, 1999. View at Google Scholar · View at Scopus
  25. X. Wu, M. Wakamiya, S. Vaishnav et al., “Hyperuricemia and urate nephropathy in urate oxidase-deficient mice,” Proceedings of the National Academy of Sciences of the United States of America, vol. 91, no. 2, pp. 742–746, 1994. View at Google Scholar · View at Scopus
  26. M. Mazzali, J. Hughes, Y.-G. Kim et al., “Elevated uric acid increases blood pressure in the rat by a novel crystal-independent mechanism,” Hypertension, vol. 38, no. 5, pp. 1101–1106, 2001. View at Google Scholar · View at Scopus
  27. M. Mazzali, J. Kanellis, L. Han et al., “Hyperuricemia induces a primary renal arteriolopathy in rats by a blood pressure-independent mechanism,” The American Journal of Physiology—Renal Physiology, vol. 282, no. 6, pp. F991–F997, 2002. View at Google Scholar · View at Scopus
  28. L. G. Sánchez-Lozada, E. Tapia, J. Santamaría et al., “Mild hyperuricemia induces vasoconstriction and maintains glomerular hypertension in normal and remnant kidney rats,” Kidney International, vol. 67, no. 1, pp. 237–247, 2005. View at Publisher · View at Google Scholar · View at Scopus
  29. D.-H. Kang, T. Nakagawa, L. Feng et al., “A role for uric acid in the progression of renal disease,” Journal of the American Society of Nephrology, vol. 13, no. 12, pp. 2888–2897, 2002. View at Publisher · View at Google Scholar · View at Scopus
  30. V. Diwan, A. Mistry, G. Gobe, and L. Brown, “Adenine-induced chronic kidney and cardiovascular damage in rats,” Journal of Pharmacological and Toxicological Methods, vol. 68, no. 2, pp. 197–207, 2013. View at Publisher · View at Google Scholar
  31. M. Correa-Costa, T. T. Braga, P. Semedo et al., “Pivotal role of toll-like receptors 2 and 4, its adaptor molecule MyD88, and inflammasome complex in experimental tubule-interstitial nephritis,” PLoS ONE, vol. 6, no. 12, Article ID e29004, 2011. View at Publisher · View at Google Scholar · View at Scopus
  32. L. G. Sánchez-Lozada, E. Tapia, V. Soto et al., “Treatment with the xanthine oxidase inhibitor febuxostat lowers uric acid and alleviates systemic and glomerular hypertension in experimental hyperuricaemia,” Nephrology Dialysis Transplantation, vol. 23, no. 4, pp. 1179–1185, 2008. View at Publisher · View at Google Scholar · View at Scopus
  33. L. G. Sánchez-Lozada, E. Tapia, C. Avila-Casado et al., “Mild hyperuricemia induces glomerular hypertension in normal rats,” The American Journal of Physiology—Renal Physiology, vol. 283, no. 5, pp. F1105–F1110, 2002. View at Google Scholar · View at Scopus
  34. L. G. Sánchez-Lozada, E. Tapia, V. Soto et al., “Effect of febuxostat on the progression of renal disease in 5/6 nephrectomy rats with and without hyperuricemia,” Nephron—Physiology, vol. 108, no. 4, pp. p69–p78, 2008. View at Publisher · View at Google Scholar · View at Scopus
  35. M. Mazzali, Y.-G. Kim, S.-I. Suga et al., “Hyperuricemia exacerbates chronic cyclosporine nephropathy,” Transplantation, vol. 71, no. 7, pp. 900–905, 2001. View at Google Scholar · View at Scopus
  36. F. C. Mazali, R. J. Johnson, and M. Mazzali, “Use of uric acid-lowering agents limits experimental cyclosporine nephropathy,” Nephron—Experimental Nephrology, vol. 120, no. 1, pp. e12–e19, 2012. View at Publisher · View at Google Scholar · View at Scopus
  37. T. Kosugi, T. Nakayama, M. Heinig et al., “Effect of lowering uric acid on renal disease in the type 2 diabetic db/db mice,” The American Journal of Physiology—Renal Physiology, vol. 297, no. 2, pp. F481–F488, 2009. View at Publisher · View at Google Scholar · View at Scopus
  38. S. M. Kim, Y. W. Choi, H. Y. Seok et al., “Reducing serum uric acid attenuates TGF-β1-induced profibrogenic progression in type 2 diabetic nephropathy,” Nephron Experimental Nephrology, vol. 121, no. 3-4, pp. e109–e121, 2012. View at Publisher · View at Google Scholar
  39. B. N. Ames, R. Cathcart, E. Schwiers, and P. Hochstein, “Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 78, no. 11, pp. 6858–6862, 1981. View at Google Scholar · View at Scopus
  40. D. B. Corry, P. Eslami, K. Yamamoto, M. D. Nyby, H. Makino, and M. L. Tuck, “Uric acid stimulates vascular smooth muscle cell proliferation and oxidative stress via the vascular renin-angiotensin system,” Journal of Hypertension, vol. 26, no. 2, pp. 269–275, 2008. View at Publisher · View at Google Scholar · View at Scopus
  41. Y. Y. Sautin, T. Nakagawa, S. Zharikov, and R. J. Johnson, “Adverse effects of the classic antioxidant uric acid in adipocytes: NADPH oxidase-mediated oxidative/nitrosative stress,” The American Journal of Physiology—Cell Physiology, vol. 293, no. 2, pp. C584–C596, 2007. View at Publisher · View at Google Scholar · View at Scopus
  42. Y. Y. Sautin and R. J. Johnson, “Uric acid: the oxidant-antioxidant paradox,” Nucleosides, Nucleotides and Nucleic Acids, vol. 27, no. 6-7, pp. 608–619, 2008. View at Publisher · View at Google Scholar · View at Scopus
  43. B. Frei, R. Stocker, and B. N. Ames, “Antioxidant defenses and lipid peroxidation in human blood plasma,” Proceedings of the National Academy of Sciences of the United States of America, vol. 85, no. 24, pp. 9748–9752, 1988. View at Google Scholar · View at Scopus
  44. Z. F. Yu, A. J. Bruce-Keller, Y. Goodman, and M. P. Mattson, “Uric acid protects neurons against excitotoxic and metabolic insults in cell culture, and against focal ischemic brain injury in vivo,” Journal of Neuroscience Research, vol. 53, no. 5, pp. 613–625, 1998. View at Google Scholar
  45. D. C. Hooper, S. Spitsin, R. B. Kean et al., “Uric acid, a natural scavenger of peroxynitrite, in experimental allergic encephalomyelitis and multiple sclerosis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 2, pp. 675–680, 1998. View at Publisher · View at Google Scholar · View at Scopus
  46. K. Tsukada, T. Hasegawa, S. Tsutsumi et al., “Effect of uric acid on liver injury during hemorrhagic shock,” Surgery, vol. 127, no. 4, pp. 439–446, 2000. View at Google Scholar · View at Scopus
  47. B. F. Becker, N. Reinholz, T. Ozcelik, B. Leipert, and E. Gerlach, “Uric acid as radical scavenger and antioxidant in the heart,” Pflugers Archiv European Journal of Physiology, vol. 415, no. 2, pp. 127–135, 1989. View at Google Scholar · View at Scopus
  48. L. G. Sánchez-Lozada, V. Soto, E. Tapia et al., “Role of oxidative stress in the renal abnormalities induced by experimental hyperuricemia,” The American Journal of Physiology—Renal Physiology, vol. 295, no. 4, pp. F1134–F1141, 2008. View at Publisher · View at Google Scholar · View at Scopus
  49. L. G. Sánchez-Lozada, E. Tapia, R. López-Molina et al., “Effects of acute and chronic L-arginine treatment in experimental hyperuricemia,” The American Journal of Physiology—Renal Physiology, vol. 292, no. 4, pp. 1238–1244, 2007. View at Google Scholar
  50. L. G. Sánchez-Lozada, M. A. Lanaspa, M. Cristóbal-García et al., “Uric acid-induced endothelial dysfunction is associated with mitochondrial alterations and decreased intracellular ATP concentrations,” Nephron Experimental Nephrology, vol. 121, no. 3-4, pp. e71–e78, 2012. View at Publisher · View at Google Scholar
  51. S. J. Hwang, K. H. Lee, H. H. Jang et al., “Febuxostat contributes to improvement of endothelial dysfunction in an experimental model of streptozocin-induced diabetic rats,” International Journal of Cardiology, vol. 171, no. 3, pp. e110–e112, 2014. View at Publisher · View at Google Scholar
  52. J. Kanellis, S. Watanabe, J. H. Li et al., “Uric acid stimulates monocyte chemoattractant protein-1 production in vascular smooth muscle cells via mitogen-activated protein kinase and cyclooxygenase-2,” Hypertension, vol. 41, no. 6, pp. 1287–1293, 2003. View at Publisher · View at Google Scholar · View at Scopus
  53. D.-H. Kang, S.-K. Park, I.-K. Lee, and R. J. Johnson, “Uric acid-induced C-reactive protein expression: implication on cell proliferation and nitric oxide production of human vascular cells,” Journal of the American Society of Nephrology, vol. 16, no. 12, pp. 3553–3562, 2005. View at Publisher · View at Google Scholar · View at Scopus
  54. H. J. Han, M. J. Lim, Y. J. Lee, J. H. Lee, I. S. Yang, and M. Taub, “Uric acid inhibits renal proximal tubule cell proliferation via at least two signaling pathways involving PKC, MAPK, cPLA2, and NF-κB,” The American Journal of Physiology—Renal Physiology, vol. 292, no. 1, pp. F373–F381, 2007. View at Publisher · View at Google Scholar · View at Scopus
  55. Z. Yang, W. Xiaohua, J. Lei et al., “Uric acid increases fibronectin synthesis through upregulation of lysyl oxidase expression in rat renal tubular epithelial cells,” The American Journal of Physiology—Renal Physiology, vol. 299, no. 2, pp. F336–F346, 2010. View at Publisher · View at Google Scholar · View at Scopus
  56. J. Nomura, N. Busso, A. Ives et al., “Febuxostat, an inhibitor of xanthine oxidase, suppresses lipopolysaccharide-induced MCP-1 production via MAPK phosphatase-1-mediated inactivation of JNK,” PLoS ONE, vol. 8, no. 9, Article ID e75527, 2013. View at Google Scholar
  57. R. P. Brandes, G. Koddenberg, W. Gwinner et al., “Role of increased production of superoxide anions by NAD(P)H oxidase and xanthine oxidase in prolonged endotoxemia,” Hypertension, vol. 33, no. 5, pp. 1243–1249, 1999. View at Google Scholar · View at Scopus
  58. P. M. Hassoun, F.-S. Yu, C. G. Cote et al., “Upregulation of xanthine oxidase by lipopolysaccharide, interleukin-1, and hypoxia: role in acute lung injury,” The American Journal of Respiratory and Critical Care Medicine, vol. 158, no. 1, pp. 299–305, 1998. View at Google Scholar · View at Scopus
  59. U. S. Kayyali, C. Donaldson, H. Huang, R. Abdelnour, and P. M. Hassoun, “Phosphorylation of xanthine dehydrogenase/oxidase in hypoxia,” Journal of Biological Chemistry, vol. 276, no. 17, pp. 14359–14365, 2001. View at Google Scholar · View at Scopus
  60. K. Nakai, M. B. Kadiiska, J.-J. Jiang, K. Stadler, and R. P. Mason, “Free radical production requires both inducible nitric oxide synthase and xanthine oxidase in LPS-treated skin,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 12, pp. 4616–4621, 2006. View at Publisher · View at Google Scholar · View at Scopus
  61. H. Omori, N. Kawada, K. Inoue et al., “Use of xanthine oxidase inhibitor febuxostat inhibits renal interstitial inflammation and fibrosis in unilateral ureteral obstructive nephropathy,” Clinical and Experimental Nephrology, vol. 16, pp. 549–556, 2012. View at Publisher · View at Google Scholar · View at Scopus
  62. H. Tsuda, N. Kawada, J. Y. Kaimori et al., “Febuxostat suppressed renal ischemia-reperfusion injury via reduced oxidative stress,” Biochemical and Biophysical Research Communications, vol. 427, no. 2, pp. 266–272, 2012. View at Publisher · View at Google Scholar
  63. A. Kushiyama, H. Okubo, H. Sakoda et al., “Xanthine oxidoreductase is involved in macrophage foam cell formation and atherosclerosis development,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 32, no. 2, pp. 291–298, 2012. View at Publisher · View at Google Scholar · View at Scopus
  64. K. Schröder, C. Vecchione, O. Jung et al., “Xanthine oxidase inhibitor tungsten prevents the development of atherosclerosis in ApoE knockout mice fed a Western-type diet,” Free Radical Biology and Medicine, vol. 41, no. 9, pp. 1353–1360, 2006. View at Publisher · View at Google Scholar · View at Scopus
  65. N. Engberding, S. Spiekermann, A. Schaefer et al., “Allopurinol attenuates left ventricular remodeling and dysfunction after experimental myocardial infarction: a new action for an old drug?” Circulation, vol. 110, no. 15, pp. 2175–2179, 2004. View at Publisher · View at Google Scholar · View at Scopus
  66. R. M. Wright, L. A. Ginger, N. Kosila et al., “Mononuclear phagocyte xanthine oxidoreductase contributes to cytokine-induced acute lung injury,” The American Journal of Respiratory Cell and Molecular Biology, vol. 30, no. 4, pp. 479–490, 2004. View at Publisher · View at Google Scholar · View at Scopus
  67. Y. Liu, “New insights into epithelial-mesenchymal transition in kidney fibrosis,” Journal of the American Society of Nephrology, vol. 21, no. 2, pp. 212–222, 2010. View at Publisher · View at Google Scholar · View at Scopus
  68. R. M. Carew, B. Wang, and P. Kantharidis, “The role of EMT in renal fibrosis,” Cell and Tissue Research, vol. 347, no. 1, pp. 103–116, 2012. View at Publisher · View at Google Scholar · View at Scopus
  69. E. S. Ryu, M. J. Kim, H. S. Shin et al., “Uric acid-induced phenotypic transition of renal tubular cells as a novel mechanism of chronic kidney disease,” The American Journal of Physiology—Renal Physiology, vol. 304, no. 5, pp. F471–F480, 2013. View at Publisher · View at Google Scholar
  70. R. Kalluri, “EMT: when epithelial cells decide to become mesenchymal-like cells,” Journal of Clinical Investigation, vol. 119, no. 6, pp. 1417–1419, 2009. View at Publisher · View at Google Scholar · View at Scopus
  71. R. Kalluri and E. G. Neilson, “Epithelial-mesenchymal transition and its implications for fibrosis,” Journal of Clinical Investigation, vol. 112, no. 12, pp. 1776–1784, 2003. View at Publisher · View at Google Scholar · View at Scopus
  72. D. A. J. Neal, B. D. M. Tom, A. E. S. Gimson, P. Gibbs, and G. J. M. Alexander, “Hyperuricemia, gout, and renal function after liver transplantation,” Transplantation, vol. 72, no. 10, pp. 1689–1691, 2001. View at Google Scholar · View at Scopus
  73. L. D. Fairbanks, J. S. Cameron, G. Venkat-Raman et al., “Early treatment with allopurinol in familial juvenil hyerpuricaemic nephropathy (FJHN) ameliorates the long-term progression of renal disease,” QJM—Monthly Journal of the Association of Physicians, vol. 95, no. 9, pp. 597–607, 2002. View at Google Scholar · View at Scopus
  74. Y.-P. Siu, K.-T. Leung, M. K.-H. Tong, and T.-H. Kwan, “Use of allopurinol in slowing the progression of renal disease through its ability to lower serum uric acid level,” The American Journal of Kidney Diseases, vol. 47, no. 1, pp. 51–59, 2006. View at Publisher · View at Google Scholar · View at Scopus
  75. M. Kanbay, A. Ozkara, Y. Selcoki et al., “Effect of treatment of hyperuricemia with allopurinol on blood pressure, creatinine clearence, and proteinuria in patients with normal renal functions,” International Urology and Nephrology, vol. 39, no. 4, pp. 1227–1233, 2007. View at Publisher · View at Google Scholar · View at Scopus
  76. M. Kanbay, B. Afsar, and A. Covic, “Uric acid as a cardiometabolic risk factor: to be or not to be,” Contributions to Nephrology, vol. 171, pp. 62–67, 2011. View at Publisher · View at Google Scholar · View at Scopus
  77. M. Goicoechea, S. G. de Vinuesa, U. Verdalles et al., “Effect of allopurinol in chronic kidney disease progression and cardiovascular risk,” Clinical Journal of the American Society of Nephrology, vol. 5, no. 8, pp. 1388–1393, 2010. View at Publisher · View at Google Scholar · View at Scopus
  78. B. H. Pai, G. Swarnalatha, R. Ram, and K. V. Dakshinamurty, “Allopurinol for prevention of progression of kidney disease with hyperuricemia,” Indian Journal of Nephrology, vol. 23, no. 4, pp. 280–286, 2013. View at Publisher · View at Google Scholar
  79. H.-C. Yang, Y. Zuo, and A. B. Fogo, “Models of chronic kidney disease,” Drug Discovery Today: Disease Models, vol. 7, no. 1-2, pp. 13–19, 2010. View at Publisher · View at Google Scholar · View at Scopus
  80. G. J. Becker and T. D. Hewitson, “Animal models of chronic kidney disease: useful but not perfect,” Nephrology Dialysis Transplantation, vol. 28, no. 10, pp. 2432–2438, 2013. View at Publisher · View at Google Scholar
  81. “Febuxostat (Uloric) for chronic treatment of gout,” The Medical letter on drugs and therapeutics, vol. 51, no. 1312, pp. 37–38, 2009.
  82. D. Tampe and M. Zeisberg, “Potential approaches to reverse or repair renal fibrosis,” Nature Reviews Nephrology, vol. 10, no. 4, pp. 226–237, 2014. View at Google Scholar
  83. S. P. Srivastava, D. Koya, and K. Kanasaki, “MicroRNAs in kidney fibrosis and diabetic nephropathy: roles on EMT and EndMT,” BioMed Research International, vol. 2013, Article ID 125469, 10 pages, 2013. View at Publisher · View at Google Scholar