Preview

Нефрология

Расширенный поиск

ЭТИОПАТОЛОГИЯ ХРОНИЧЕСКОЙ ТУБУЛЯРНОЙ, ГЛОМЕРУЛЯРНОЙ И РЕНОВАСКУЛЯРНОЙ НЕФРОПАТИЙ: КЛИНИЧЕСКИЕ АСПЕКТЫ

https://doi.org/10.24884/1561-6274-2013-17-2-9-38

Аннотация

Хроническая болезнь почек (ХБП) включает в себя группу патологичеcких состояний, при которых стойко снижена экскреторная функция почек. Большинство из них, хотя и не все формы ХБП, представляют собой прогрессирующие и необратимые патологические процессы, которые начинаются незаметно (без явного снижения функции), протекают с развитием нарушения функции почек и завершаются терминальной почечной недостаточностью. На последнем этапе появляется необходимость выполнения трансплантации почки или проведения диализа (т.е. заместительной почечной терапии, ЗПТ) для предотвращения летального исхода, обусловленного неспособностью почек обеспечить очищение крови и поддержание водно-электролитного баланса. Во всем мире около 1,5 млн человек нуждаются в ЗПТ, причем число новых случаев ХБП значительно возросло за последние десятилетия. Ведущими причинами терминальной почечной недостаточности являются сахарный диабет и артериальная гипертензия, хотя аутоиммунные заболевания, атеросклеротическое поражение почек, ряд инфекционных заболеваний, медикаменты, токсины, обструкция мочевыводящих путей, генетические нарушения и другие повреждающие факторы могут инициировать развитие ХБП, вызывая повреждение гломерул, канальцев, сосудов и интерстиция почки. Во всех случаях при ХБП, в конечном итоге, поражаются все указанные выше структуры, что приводит к появлению одинаковых изменений вне зависимости от этиологии основного заболевания. В этом обзоре с помощью комплексного подхода описывается патофизиологический процесс тубулоинтерстициальных, гломерулярных и реноваскулярных заболеваний, акцентируется внимание на ключевых клеточных и молекулярных процессах. Далее проводится анализ основных механизмов формирования сходных изменений, исследуется патофизиологический сценарий прогрессирования разных по этиологии заболеваний. В завершении обсуждаются клинические проявления, перспективы экспериментальных исследований и терапии.

Об авторах

Дж. М. Лопес-Новойя
Instituto de Estudios de Ciencias de la Salud de Castilla y León (IECSCYL); Unidad de Fisiopatología Renal y Cardiovascular. Departamento de Fisiología y Farmacología, Universidad de Salamanca; Renal and Vascular Research Laboratory, IIS-Fundación Jiménez Díaz and Universidad Autonoma de Madrid
Испания

López-Novoa JM

 



А. Б. Родригес-Пена
National Institutes of Health, Bethesda MD
Соединённые Штаты Америки


А. Ортис
Renal and Vascular Research Laboratory, IIS-Fundación Jiménez Díaz and Universidad Autonoma de Madrid; Instituto Reina Sofía de Investigación Nefrológica, Fundación Íñigo Álvarez de Toledo
Испания


К. Мартинес-Салдаго
Instituto de Estudios de Ciencias de la Salud de Castilla y León (IECSCYL); Unidad de Investigación, Hospital Universitario de Salamanca; Unidad de Fisiopatología Renal y Cardiovascular. Departamento de Fisiología y Farmacología, Universidad de Salamanca; Instituto Reina Sofía de Investigación Nefrológica, Fundación Íñigo Álvarez de Toledo
Испания


Ф. Дж. Лопес Эрнандес
Instituto de Estudios de Ciencias de la Salud de Castilla y León (IECSCYL); Unidad de Investigación, Hospital Universitario de Salamanca; Unidad de Fisiopatología Renal y Cardiovascular. Departamento de Fisiología y Farmacología, Universidad de Salamanca; Instituto Reina Sofía de Investigación Nefrológica, Fundación Íñigo Álvarez de Toledo
Испания


Список литературы

1. Mitch WE, Walser M, Buffington GA et al. A simple method of stimating progression of chronic renal failure. Lancet 1976;2:1326–1328

2. Remuzzi G, Benigni A, Remuzzi A. Mechanisms of progression and regression of renal lesions of chronic nephropathies and diabetes. J Clin Inves 2006;116:288–296

3. Chin C. Renal failure: Pharmacologic issues. Pharmacy Practice 2002, 1–8

4. Levey AS, Coresh J, Balk E, et al. National Kidney Foundation. National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann Intern Med 2003;139:137–147

5. Snively CS, Gutierrez C. Chronic kidney disease: Prevention and treatment of chronic complications. American Family Physician 2004;70:1921–1928

6. Snyder S, Pendergraph B. Detection and evaluation of chronic kidney disease. American Family Physician 2005;72:1723– 1732

7. Feig DI. Uric acid: a novel mediator and marker of risk in chronic kidney disease? Curr Opin Nephrol Hypertens. 2009;18:526–530

8. Goicoechea M, de Vinuesa SG, Verdalles U, et al. Effect of allopurinol in chronic kidney disease progression and cardiovascular risk. Clin J Am Soc Nephrol 2010;5:1388–1393

9. Bellomo G, Venanzi S, Verdura C, et al. Association of uric acid with change in kidney function in healthy normotensive individuals. Am J Kidney Dis 2010;56: 264–272

10. Brenner BM. Nephron adaptation to renal injury or ablation. Am J Physiol 1985;249 (3):F324–F337

11. Molitch ME, DeFronzo RA, Franz MJ, et al. American Diabetes Association. Nephropathy in diabetes. Diabetes Care 2004;7 [Suppl 1]:S79–S83

12. U.S. Renal Data System, USRDS 2009 Annual Data Report: Atlas of Chronic Kidney Disease and End-Stage Renal Disease in the United States, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2009

13. Brosnahan G, Fraer M. Chronic kidney disease: whom to screen and how to treat, part 1: definition, epidemiology, and laboratory testing. South Med J 2010;103:140–146

14. Stengel B, Tarver-Carr ME, Powe NR, et al. Lifestyle factors, obesity and the risk of chronic kidney disease. Epidemiology 2003;14:479–487

15. Hsu CY, Mc Culloch ChE, Iribarren C, et al. Body mass index and risk for end-stage renal disease. Ann Intern Med 2006;144:21–28

16. Ejerblad E, Foerd M, Lindblad P, et al. Obesity and risk for chronic renal failure. J Am Soc Nephrol 2006;17:1695–1702

17. Ritz E. Metabolic syndrome and kidney disease. Blood Purif 2008;26:59–62

18. Hall JE, Crook ED, Jones DW, et al. Mechanisms of obesity-associated cardiovascular and renal disease. Am J Medical Sciences 2002;324:127–137

19. Chen J, Muntner P, Hamm LL, et al. The metabolic syndrome and chronic kidney disease in U.S. adults. Ann Intern Med 2004;140:167–174

20. Ting SM, Nair H, Ching I, et al. Overweight, obesity and chronic kidney disease. Nephron Clin Pract 2009;112:c121–127

21. Faronato PP, Maioli M, Tonolo G, et al. Clusterin of albumin excretion rate abnormalities in Caucassian patients with NIDDM. The Italian NIDDM nephropathy study group. Diabetologia 1997;40:816–823

22. Satko SG, Freedman BI. The importance of family history on the development of renal disease. Curr Opin Nephrol Hypertens 2004;13:337–341

23. Gohda T, Tanimoto M, Watanabe-Yamada K, et al. Genetic susceptibility to type 2 diabetic nephropathy in human and animal models. Nephrology (Carlton) 2005;10 [Suppl]:S22–S25.

24. Satko SG, Freedman BI, Moossavi S. Genetic factors in end-stage renal disease. Kidney Int 2005;94 [Suppl]: S46–S49

25. Kao WH, Klag MJ, Meoni LA, et al. Family Investigation of Nephropathy and Diabetes Research Group. MYH9 is associated with nondiabetic end-stage renal disease in African Americans. Nat Genet 2008;40:1185–1192

26. Freedman BI, Hicks PJ, Bostrom MA, et al. Polymorphisms in the non-muscle myosin heavy chain 9 gene (MYH9) are strongly associated with end-stage renal disease historically attributed to hypertension in African Americans. Kidney Int 2009;75:736–745

27. Divers J, Freedman BI. Susceptibility genes in common complex kidney disease. Curr Opin Nephrol Hypertens 2010;19:79–84

28. Genovese G, Friedman DJ, Ross MD, et al. Association of trypanolytic ApoL1 variants with kidney disease in African Americans. Science 2010;329:841–845

29. Tsukaguchi H, Sudhakar A, Le TC, et al .NPHS2 mutations in late-onset focal segmental glomerulosclerosis: R229Q is a common disease-associated allele. J Clin Invest 2002;110:1659–1666

30. Franceschini N, North KE, Kopp JB, et al. NPHS2 gene, nephrotic syndrome and focal segmental glomerulosclerosis: a HuGE review. Genet Med 2006;8:63–75

31. Brown EJ, Schlöndorff JS, Becker DJ, et al. Mutations in the formin gene INF2 cause focal segmental glomerulosclerosis. Nat Genet 2010;42:72–76

32. Mukerji N, Damodaran TV, Winn MP. TRPC6 and FSGS: the latest TRP channelopathy. Biochim Biophys Acta 2007;1772:859–868

33. Korstanje R, DiPetrillo K. Unraveling the genetics of chronic kidney disease using animal models. Am J Physiol Renal Physiol 2004;287:F347–352

34. Imperatore G, Hanson RL, Pettitt DJ, et al. Sib-pair linkage analysis for susceptibility genes for microvascular complications among Pima Indians with type 2 diabetes. Pima Diabetes Genes Group. Diabetes 1998;47:821–830

35. DeWan AT, Arnett DK, Atwood LD, et al. A genome scan for renal function among hypertensives: the HyperGEN study. Am J Hum Genet 2001;68:136–144

36. Perez-Luque E, Malacara JM, Olivo-Diaz A, et al. Contribution of HLA class II genes to end stage renal disease in mexican patients with type 2 diabetes mellitus. Hum Immunol 2000;61:1031–1038

37. Dyck R, Bohm C, Klomp H. Increased frequency of HLA A2/DR4 and A2/DR8 haplotypes in young saskatchewan aboriginal people with diabetic end-stage renal disease. Am J Nephrol 2003;23:178–185

38. Freedman BI, Spray BJ, Dunston GM, et al. HLA associations in end-stage renal disease due to membranous glomerulonephritis: HLA-DR3 associations with progressive renal injury. Southeastern Organ Procurement Foundation. Am J Kidney Dis 1994;23:797–802

39. Cogan MG. Medical Staff Conference. Tubulo-interstitial nephropathies – a pathophysiologic approach. West J Med 1980;132:134–140

40. Strutz F, Neilson EG. The role of lymphocytes in the progression of interstitial disease. Kidney Int 1994;45 [Suppl]: S106–S110

41. Braden GL, O‘Shea MH, Mulhern JG. Tubulointerstitial diseases. Am J Kidney Dis 2005;46:560–572

42. Norman JT, Fine LG. Progressive renal disease: fibroblasts, extracellular matrix, and integrins. Exp Nephrol 1999;7:167–177

43. Okoń K, Sułowicz W, Smoleński O, et al. Interstitial, tubular and vascular factors in progression of primary glomerulonephritis. Pol J Pathol 2007;58:73–78

44. Piscator M. Early detection of tubular dysfunction. Kidney Int 1991;34:S15–17

45. Blythe WB. Natural history of hypertension in renal parenchymal disease. Am J Kidney Dis 1985;5 (4):A50–56

46. Rosario RF, Wesson DE. Primary hypertension and nephropathy. Curr Opin Nephrol Hypertens 2006;15:130–134

47. Sugiura T, Wada A. Resistive index predicts renal prognosis in chronic kidney disease. Nephrol Dial Transplant 2009;24:2780–2785

48. Mujais S, Batlle DC. Functional correlates of tubulointerstitial damage. Semin Nephrol 1988;8:94–99

49. Eknoyan G, Qunibi WY, Grissom RT, et al. Renal papillary necrosis: an update. Medicine (Baltimore) 1982;61:55–73

50. Kelly CJ. Cellular immunity and the tubulointerstitium. Semin Nephrol 1999;19:182–187

51. Eddy AA. Molecular insights into renal interstitial fibrosis. J Am Soc Nephrol 1996;7:2495–2508

52. Johnson DW, Saunders HJ, Baxter RC, et al. Paracrine stimulation of human renal fibroblasts by proximal tubule cells. Kidney Int 1998;54:747–757

53. Klahr S, Morrissey JJ. The role of growth factors, cytokines, and vasoactive compounds in obstructive nephropathy. Semin Nephrol 1998;18:622–632

54. Palmer BF. The renal tubule in the progression of chronic renal failure. J Investig Med 1997;45:346–361

55. Wardle EN. Modulatory proteins and processes in alliance with immune cells, mediators, and extracellular proteins in renal interstitial fibrosis. Ren Fail 1999;21:121–133

56. Nony PA, Schnellmann RG. Interactions between collagen IV and collagen-binding integrins in renal cell repair after sublethal injury. Mol Pharmacol 2001;60:1226–1234

57. Liu Y. Epithelial to mesenchymal transition in renal fibrogenesis: pathologic significance, molecular mechanism, and therapeutic intervention. J Am Soc Nephrol 2004;15:1–12

58. Lopez-Novoa JM, Nieto MA. Inflammation and EMT: an alliance towards organ fibrosis and cancer progression. EMBO Mol Med 2009;1:303–314

59. Iwano M, Plieth D, Danoff TM, et al. Evidence that fibroblasts derive from epithelium during tissue fibrosis. J Clin Invest 2002;110:341–350

60. Zeisberg M, Kalluri R. The role of epithelial-to-mesenchymal transition in renal fibrosis. J Mol Med 2004;82:175–181

61. Grande MT, López-Novoa JM. Fibroblast activation and myofibroblast generation in obstructive nephropathy. Nat Rev Nephrol 2009;5:319–328

62. Zeisberg M, Duffield JS. Resolved: EMT produces fibroblasts in the kidney. J Am Soc Nephrol 2010;21:1247–1253

63. Humphreys BD, Valerius MT, Kobayashi A, et al. Intrinsic epithelial cells repair the kidney after injury. Cell Stem Cell 2008;2:284–291

64. Humphreys BD, Lin SL, Kobayashi A, et al. Fate tracing reveals the pericyte and not epithelial origin of myofibroblasts in kidney fibrosis. Am J Pathol 2010;176:85–97

65. Becker GJ, Hewitson TD. The role of tubulointerstitial injury in chronic renal failure. Curr Opin Nephrol Hypertens 2000;9:133–138

66. Gibbs SR, Goins RA, Belvin EL, et al. Characterization of the collagen phenotype of rabbit proximal tubule cells in culture. Connect Tissue Res. 1999;40:173–188

67. Matsumoto Y, Ueda S, Yamagishi S, et al. Dimethylarginine dimethylaminohydrolase prevents progression of renal dysfunction by inhibiting loss of peritubular capillaries and tubulointerstitial fibrosis in a rat model of chronic kidney disease. J Am Soc Nephrol 2007;18:1525–1533

68. Eddy AA. Progression in chronic kidney disease. Adv Chronic Kidney Dis 2005;12:353–365

69. Nath KA. Tubulointerstitial changes as a major determinant in the progression of renal damage. Am J Kidney Dis 1992;20:1–17

70. Lan HY, Nikolic-Paterson DJ, Mu W, et al. Local macrophage proliferation in the progression of glomerular and tubulointerstitial injury in rat anti-GBM glomerulonephritis. Kidney Int 1995;48:753–760

71. Nath KA. The tubulointerstitium in progressive renal disease. Kidney Int 1998;54:992–994.

72. Wang Y, Chen J, Chen L, et al. Induction of monocyte chemoattractant protein-1 in proximal tubule cells by urinary protein. J Am Soc Nephrol 1997;8:1537–1545.]

73. 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

74. Tesch GH, Maifert S, Schwarting A, et al. Monocyte chemoattractant protein 1-dependent leukocytic infiltrates are responsible for autoimmune disease in MRL-Fas(lpr) mice. J Exp Med 1999;190:1813–1824

75. Rodemann HP, Muller GA. Abnormal growth and clonal proliferation of fibroblasts derived from kidneys with interstitial fibrosis. Proc Soc Exp Biol Med 1990;195:57–63

76. Rodemann HP, Muller GA. Characterization of human renal fibroblasts in health and disease: II. In vitro growth, differentiation, and collagen synthesis of fibroblasts from kidneys with interstitial fibrosis. Am J Kidney Dis 1991;17:684–686

77. El Nahas AM, Bello AK. Chronic kidney disease: the global challenge. Lancet 2005;365:331–340

78. Chevalier RL. Obstructive nephropathy: towards biomarker discovery and gene therapy. Nat Clin Pract Nephrol 2006;2:157–168

79. Essawy M, Soylemezoglu O, Muchaneta-Kubara EC, et al. Myofibroblasts and the progression of diabetic nephropathy. Nephrol Dial Transplant 1997;12:43–50

80. Roberts IS, Burrows C, Shanks JH, et al. Interstitial myofibroblasts: predictors of progression in membranous nephropathy. J Clin Pathol 1997;50:123–127

81. Boukhalfa G, Desmouliere A, Rondeau E, et al. Relationship between alpha-smooth muscle actin expression and fibrotic changes in human kidney. Exp Nephrol 1996;4:241–247

82. Strutz F, Okada H, Lo CW, et al. Identification and characterization of a fibroblast marker: FSP1. J Cell Biol 1995;130:393–405

83. Schlondorff D. The role of chemokines in the initiation and progression of renal disease. Kidney Int 1995;49 [Suppl]: S44–S47

84. 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

85. Mezzano SA, Aros CA, Droguett A, et al. Renal angiotensin II up-regulation and myofibroblast activation in human membranous nephropathy. Kidney Int 2003;86 [Suppl]: S39–S45

86. García-Sánchez O, López-Hernández FJ, Lopez-Novoa JM. An integrative view on the role of TGF-beta in the progressive tubular deletion associated with chronic kidney disease. Kidney Int 2010;77:950–955

87. Eddy AA. Molecular basis of renal fibrosis. Pediatr Nephrol 2000;15:290–301

88. Liu Y. Renal fibrosis: new insights into the pathogenesis and therapeutics. Kidney Int 2006;69:213–217

89. Singer AJ, Clark RA. Cutaneous wound healing. N Engl J Med 1999;341:738–746

90. Eddy AA. Role of cellular infiltrates in response to proteinuria. Am J Kidney Dis 2001;37:S25–29

91. Nishida M, Fujinaka H, Matsusaka T, et al. Absence of angiotensin II type 1 receptor in bone marrow-derived cells is detrimental in the evolution of renal fibrosis. J Clin Invest 2002;110:1859–1868

92. Van Goor H, Ding G, Kees-Folts D, et al. Macrophages and renal disease. Lab Invest 1994;71:456–464

93. Vleming LJ, Bruijn JA, van Es LA. The pathogenesis of progressive renal failure. Neth J Med 1999;54:114–128

94. Gharaee-Kermani M, Wiggins R, Wolber F, et al. Fibronectin is the major fibroblast chemoattractant in rabbit anti-glomerular basement membrane disease. Am J Pathol 1996;148:961–967

95. Eddy AA. Experimental insights into the tubulointerstitial disease accompanying primary glomerular lesions. J Am Soc Nephrol 1994;5:1273–1277

96. Van Vliet A, Baelde HJ, Vleming LJ, et al. Distribution of fibronectin isoforms in human renal disease. J Pathol 2001;193:256–262

97. Wells AF, Larsson E, Tengblad A, et al. The localization of hyaluronan in normal and rejected human kidneys. Transplantation 1990;50:240–243

98. Beck-Schimmer B, Oertli B, Pasch T, et al. Hyaluronan induces monocyte chemoattractant protein-1 expression in renal tubular epithelial cells. J Am Soc Nephrol 1998;9:2283–2290

99. Crawford SE, Stellmach V, Murphy-Ullrich JE,et al. Thrombospondin-1 is a major activator of TGF-beta1 in vivo. Cell 1998;93:1159–1170

100. Hugo C, Shankland SJ, Pichler RH, et al. Thrombospondin 1 precedes and predicts the development of tubulointerstitial fibrosis in glomerular disease in the rat. Kidney Int 1998;53:302– 311

101. Diamond JR, Levinson M, Kreisberg R, et al. Increased expression of decorin in experimental hydronephrosis. Kidney Int 1997;51:1133–1139

102. Schaefer L, Hausser H, Altenburger M, et al. Decorin, biglycan and their endocytosis receptor in rat renal cortex. Kidney Int 1998;54:1529–1541

103. Gonzalez-Avila G, Vadillo-Ortega F, Perez-Tamayo R. Experimental diffuse interstitial renal fibrosis. A biochemical approach. Lab Invest 1988;59:245–252

104. Border WA, Noble NA. Transforming growth factor beta in tissue fibrosis. N Engl J Me 1994;331:1286–1292

105. Cheng J, Grande JP. Transforming growth factor-beta signal transduction and progressive renal disease. Exp Biol Med (Maywood) 2002;227:943–956

106. Roberts AB, McCune BK, Sporn MB. TGF-beta: regulation of extracellular matrix. Kidney Int 1992;41:557–559

107. Hultström M, Leh S, Skogstrand T,et al. Upregulation of tissue inhibitor of metalloproteases-1 (TIMP-1) and procollagenN-peptidase in hypertension-induced renal damage. Nephrol Dial Transplant 2008;23:896–903

108. Kim H, Oda T, Lopez-Guisa J, et al. TIMP-1 deficiency does not attenuate interstitial fibrosis in obstructive nephropathy. J Am Soc Nephrol 2000;12:736–748

109. Klahr S. Progression of chronic renal disease. Heart Dis 2001;3:205–209

110. García-Sánchez O, López-Hernández FJ, López-Novoa JM. An integrative view on the role of TGF-beta in the progressive tubular deletion associated with chronic kidney disease. Kidney Int 2010;77:950–955

111. Nangaku M. Chronic hypoxia and tubulointerstitial injury: a final common pathway to end-stage renal failure. J Am Soc Nephrol 2006;17:17–25

112. Ortiz A, Lorz C, Egido J. The Fas ligand/Fas system in renal injury. Nephrol Dial Transplant 1999;14:1831–1834

113. Kelly DJ, Stein-Oakley A, Zhang Y, et al. Fas-induced apoptosis is a feature of progressive diabetic nephropathy in transgenic (mRen-2)27 rats: attenuation with renin-angiotensin blockade. Nephrology 2004;9:7–13

114. Lorz C, Ortiz A, Justo P, et al. Proapoptotic Fas ligand is expressed by normal kidney tubular epithelium and injured glomeruli. J Am Soc Nephrol 2000;11:1266–1277

115. Khan S, Koepke K, Jarad G, et al. Apoptosis and JNK activation are differentially regulated by Fas expression level in renal tubular epithelial cells. Kidney Int 2001;60:65–76

116. Jarad G, Wang B, Khan S, et al. Fas activation induces renal tubular epithelial cell beta 8 integrin expression and function in the absence of apoptosis. J Biol Chem 2002;277:47826–47833

117. Santiago B, Galindo M, Palao G,et al. Intracellular regulation of Fas-induced apoptosis in human fibroblasts by extracellular factors and cycloheximide. J Immunol 2004;172:560– 566

118. Miyajima A, Chen J, Lawrence C, et al. Antibody to transforming growth factor-beta ameliorates tubular apoptosis in unilateral ureteral obstruction. Kidney Int 2000;58:2301–2313

119. Kelly DJ, Cox AJ, Tolcos M, et al. Attenuation of tubular apoptosis by blockade of the renin-angiotensin system in diabetic Ren-2 rats. Kidney Int 2002;61:31–39

120. Bhaskaran M, Reddy K, Radhakrishanan N, et al. Angiotensin II induces apoptosis in renal proximal tubular cells. Am J Physiol Ren Physiol 2003;284:F955–965

121. Ortiz-Arduan A, Danoff TM, Kalluri R, et al. Regulation of Fas and Fas ligand expression in cultured murine renal cells and in the kidney during endotoxemia. Am J Physiol 1996;271:F1193– 1201

122. Schelling JR, Nkemere N, Kopp JB, et al. Fas-dependent fratricidal apoptosis is a mechanism of tubular epithelial cell deletion in chronic renal failure. Lab Invest 1998;78:813–824

123. Khan S, Cleveland RP, Koch CJ, et al. Hypoxia induces renal tubular epithelial cell apoptosis in chronic renal disease. Lab Invest 1999;79:1089–1099

124. Koesters R, Kaissling B, Lehir M,et al. Tubular overexpression of transforming growth factor-beta1 induces autophagy and fibrosis but not mesenchymal transition of renal epithelial cells. Am J Pathol 2010;177:632–643

125. Sanz AB, Santamaria B, Ruiz Ortega M, et al. Mechanisms of renal apoptosis in health and disease. J Am Soc Nephrol 2008;19:1634–1642

126. Ichikawi I, Harris RC. Angiotensin actions in the kidney: renewed insight into the old hormone. Kidney Int 1991;40:583–596

127. Wang CZ, Hsu YM, Tang MJ. Function of discoidin domain receptor I in HGF-induced branching tubulogenesis of MDCK cells in collagen gel. J Cell Physiol 2005;203:295–304

128. Hughes J. Life and death in the kidney: prospects for future therapy. Nephrol Dial Transplant 2001;16:879–882

129. De Broe ME. Apoptosis in acute renal failure. Nephrol Dial Transplant 2001;16 [Suppl 6]: 23–26

130. Nilakantan V, Maenpaa C, Jia G, et al. 20-HETE-mediated cytotoxicity and apoptosis in ischemic kidney epithelial cells. Am J Physiol Renal Physiol 2008;294:F562–570

131. Orphanides C, Fine LG, Norman JT. Hypoxia stimulates proximal tubular cell matrix production via a TGF-beta1- independent mechanism. Kidney Int 1997;52:637–647

132. Haase VH. Pathophysiological Consequences of HIF Activation: HIF as a modulator of fibrosis. Ann N Y Acad Sci 2009;1177:57–65

133. López-Novoa JM, Nieto MA. Inflammation and EMT: an alliance towards organ fibrosis and cancer progression. EMBO Mol Med 2009;1:303–314

134. Serón 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

135. Couser WG. Pathogenesis of glomerular damage in glomerulonephritis. Nephrol Dial Transplant 1998;13:10–15

136. Isaka Y, Akagi Y, Ando Y, et al. Cytokines and glomerulosclerosis. Nephrol Dial Transplant 1999;14:30–32

137. Nangaku M, Couser WG. Mechanisms of immunedeposit formation and the mediation of immune renal injury. Clin Exp Nephrol 2005;9:183–191

138. C o u s e r W G . C o m p l e m e n t i n h i b i t o r s a n d glomerulonephritis: are we there yet? J Am Soc Nephrol 2003;14:815–818

139. Cunard R, Jelly CJ. Immune-mediated renal disease. J Allergy Clin Immunol 2003;111:S637–644

140. Shimizu A, Masuda Y, Kitamura H, et al. Recovery of damaged glomerular capillary network with endothelial cell apoptosis in experimental proliferative glomerulonephritis. Nephron 1998;79:206–214

141. U.S. Renal Data System, USRDS 2005 Annual Data Report: Atlas of End-Stage Renal Disease in the United States, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2005

142. López-Hernández FJ, López-Novoa JM. The lord of the ring: Mandatory role of the kidney in drug therapy of hypertension. Pharmacol Ther 2006;111:53–80

143. López-Novoa JM, Martínez-Salgado C, Rodríguez-Peña AB, et al. Common pathophysiological mechanisms of chronic kidney disease: Therapeutic perspectives. Pharmacol Ther 2010;128:61–81

144. Tervaert TW, Mooyaart AL, Amann K, et al. Renal Pathology Society. Pathologic Classification of Diabetic Nephropathy. J Am Soc Nephrol 2010;21:556–563

145. Wesson LG. Physical factors and glomerulosclerosis. Cause or coincidence? Nephron 1998;78:125–130 146. Wiggins RC. The spectrum of podocytopathies: a unifying view of glomerular diseases. Kidney Int 2007;71:1205–1214

146. Ziyadeh FN, Wolf G. Pathogenesis of the podocytopathy and proteinuria in diabetic glomerulopathy. Curr Diabetes Rev 2008;4:39–45

147. Moreno JA, Sanchez-Niño MD, Sanz AB, et al. A slit in podocyte death. Curr Med Chem 2008;15:1645–1654

148. Kang YS, Li Y, Dai C, et al. Inhibition of integrin-linked kinase blocks podocyte epithelial-mesenchymal transition and ameliorates proteinuria. Kidney Int 2010;78:363–373

149. Kriz W, LeHir M. Pathways to nephron loss starting from glomerular diseases-insights from animal models. Kidney Int 2005;67:404–419

150. Harris RC, Akai Y, Yasuda T, et al. The role of physical forces in alterations of mesangial cell function. Kidney Int 1994;45 [Suppl]: S17–S21

151. F u n a b i k i K , H o r i k o s h i S , To m i n o Y, e t a l . Immunohistochemical analysis of extracellular components in the glomerular sclerosis of patients with glomerulonephritis. Clin Nephrol 1990;34:239–246

152. Makino H, Kashihara N, Sugiyama H, et al. Role of apoptosis in the progression of glomerulosclerosis. Contrib Nephrol 1996;118:41–47

153. Kurogi Y. Mesangial cell proliferation inhibitors for the treatment of proliferative glomerular disease. Med Res Rev 2003;23:15–31

154. Morel-Maroger Striker L, Killen PD, Chi E, et al. The composition of glomerulosclerosis. I. Studies in focal sclerosis, crescentic glomerulonephritis, and membranoproliferative glomerulonephritis. Lab Invest 1984;51:181–192

155. Floege J, Johnson RJ, Couser WG. Mesangial cells in the pathogenesis of progressive glomerular disease in animal models. Clin Investig 1992;70:857–864

156. Massy ZA, Guijarro C, O’Donnell MP, et al. The central role of nuclear factor-kappa B in mesangial cell activation. Kidney Int 1999;71 [Suppl]: S76–S79

157. Johnson RJ, Alpers CE, Yoshimura A, et al. Renal injury from angiotensin II-mediated hypertension. Hypertension 1992;19:464–474

158. Ardaillou R, Chansel D, Chatziantoniou C, et al. Mesangial AT1 receptors: expression, signaling, and regulation. J Am Soc Nephrol 1999;10:S40–46

159. Kagami S, Kondo S, Löster K, et al. Alpha1beta1 integrin-mediated collagen matrix remodeling by rat mesangial cells is differentially regulated by transforming growth factorbeta and platelet-derived growth factor-BB. J Am Soc Nephrol 1999;10:779–789

160. Haberstroh U, Zahner G, Disser M, et al. TGF-beta stimulates rat mesangial cell proliferation in culture: role of PDGF beta-receptor expression. Am J Physiol 1993;264:F199–205

161. Bessho K, Mizuno S, Matsumoto K, et al. Counteractive effects of HGF on PDGF-induced mesangial cell proliferation in a rat model of glomerulonephritis. Am J Physiol Renal Physiol 2003;284:F1171–180

162. Gomez-Garre D, Ruiz-Ortega M, Ortego M, et al. Effects and interactions of endothelin-1 and angiotensin II on matrix protein expression and synthesis and mesangial cell growth. Hypertension 1996;27:885–892

163. Hahn S, Krieg RJ Jr, Hisano S, et al. Vitamin E suppresses oxidative stress and glomerulosclerosis in rat remnant kidney. Pediatr Nephrol 1999;13:195–198

164. Jaimes EA, Galceran JM, Raij L. Angiotensin II induces superoxide anion production by mesangial cells. Kidney Int 1998;54:775–784

165. Couser WG. Pathogenesis of glomerulonephritis. Kidney Int 1993;42 [Suppl]: S19–S26

166. Grande MT, Perez-Barriocanal F, Lopez-Novoa JM. Role of inflammation in túbulo-interstitial damage associated to obstructive nephropathy. J Inflamm (Lond) 2010;7:19

167. Johnson RJ, Iida H, Alpers CE, et al. Expression of smooth muscle cell phenotype by rat mesangial cells in immune complex nephritis. Alpha-smooth muscle actin is a marker of mesangial cell proliferation. J Clin Invest 1991;87:847–858

168. Alpers CE, Hudkins KL, Gown AM, et al. Enhanced expression of ”muscle-specific” actin in glomerulonephritis. Kidney Int 1992;41:1134–1142

169. Stokes MB, Holler S, Cui Y, et al. Expression of decorin, biglycan, and collagen type I in human renal fibrosing disease. Kidney Int 2000;57:487–498

170. Couser WG, Johnson RJ. Mechanisms of progressive renal disease in glomerulonephritis. Am J Kidney Dis 1994;23:193– 198

171. Justo P, Sanz AB, Sanchez-Niño MD, et al. Cytokine cooperation in renal tubular cell injury: the role of TWEAK. Kidney Int 2006;70:1750–1758

172. Sanchez-Niño MD, Benito-Martin A, Gonçalves S, et al. TNF superfamily: a growing saga of kidney injury modulators. Mediators Inflamm;2010. pii: 182958. Epub 2010 Oct 4

173. Strutz F, Neilson EG. New insights into mechanisms of fibrosis in immune renal injury. Springer Semin Immunopathol 2003;24:459–476

174. Border WA, Noble NA. TGF-beta in kidney fibrosis: a target for gene therapy. Kidney Int 1997;51:1388–1396

175. Tamaki K, Okuda S. Role of TGF-beta in the progression of renal fibrosis. Contrib Nephrol 2003;139:44–65

176. Chiarugi A. «Simple but not simpler»: toward a unified picture of energy requirements in cell death. FASEB J 2005;19:1783–1788

177. Rusterholz C, Gupta AK, Huppertz B, et al. Soluble factors released by placental villous tissue: Interleukin-1 is a potential mediator of endothelial dysfunction. Am J Obstet Gynecol 2005;192:618–624

178. Gao X, Zhang H, Belmadani S,et al. Role of TNF-alphainduced reactive oxygen species in endothelial dysfunction during reperfusion injury. Am J Physiol Heart Circ Physiol 2008;295:H2242–2249

179. Zhang C, Wu J, Xu X, et al. Direct relationship between levels of TNF-alpha expression and endothelial dysfunction in reperfusion injury. Basic Res Cardiol 2010;105:453–464

180. Camussi G, Turello E, Tetta C, et al. Tumor necrosis factor induces contraction of mesangial cells and alters their cytoskeletons. Kidney Int 1990;38:795–802

181. López-Farré A, Gómez-Garre D, Bernabeu F, Renal effects and mesangial cell contraction induced by endothelin are mediated by PAF. Kidney Int 1991;39:624–630

182. Bussolati B, Mariano F, Biancone L,et al. Interleukin-12 is synthesized by mesangial cells and stimulates platelet-activating factor synthesis, cytoskeletal reorganization, and cell shape change. Am J Pathol 1999;154:623–632

183. López-Novoa JM. Potential role of platelet activating factor in acute renal failure. Kidney Int 1999;55:1672–1682

184. Molitoris BA, Sutton TA. Endothelial injury and dysfunction: role in the extension phase of acute renal failure. Kidney Int 2004;66:496–499

185. Bonventre JV. Pathophysiology of AKI: injury and normal and abnormal repair. Contrib Nephrol 2010;165:9–17. full_text

186. Rodriguez-Barbero A, L’Azou B, Cambar J,et al. Potential use of isolated glomeruli and cultured mesangial cells as in vitro models to assess nephrotoxicity. Cell Biol Toxicol 2000;16:145–153

187. Wolf G, Ziyadeh FN. Cellular and molecular mechanisms of proteinuria in diabetic nephropathy. Nephron Physiol 2007;106:26–31

188. Ziyadeh FN, Wolf G. Pathogenesis of the podocytopathy and proteinuria in diabetic glomerulopathy. Curr Diabetes Rev 2008;4:39–45

189. Smeets B, Dijkman H, Wetzels J, et al. Lessons from studies on focal segmental glomerulosclerosis: an important role for parietal epithelial cells? J Pathol 2006;210:263–272

190. Asano T, Niimura F, Pastan I, et al. Permanent genetic tagging of podocytes: fate of injured podocytes in a mouse model of glomerular sclerosis. J Am Soc Nephrol 2005;16:2257–2262

191. Pätäri-Sampo A, Ihalmo P, Holthöfer H. Molecular basis of the glomerular filtration: nephrin and the emerging protein complex at the podocyte slit diaphragm. Ann Med 2006;38:483–492

192. Barisoni L, Mundel P. Podocyte biology and the emerging understanding of podocyte diseases. Am J Nephrol. 2003;23:353–360

193. Remuzzi G, Bertani T. Pathophysiology of progressive nephropathies. N Engl J Med 1998;339:1448–1456

194. Morioka Y, Koike H, Ikezumi Y, et al. Podocyte injuries exacerbate mesangial proliferative glomerulonephritis. Kidney Int 2001;60:2192–2204

195. Sawai K, Mori K, Mukoyama M, et al. Angiogenic protein Cyr61 is expressed by podocytes in anti-Thy-1 glomerulonephritis. J Am Soc Nephrol 2003;14:1154–1163

196. Chen S, Kasama Y, Lee JS, et al. Podocyte-derived vascular endothelial growth factor mediates the stimulation of alpha3(IV) collagen production by transforming growth factorbeta1 in mouse podocytes. Diabetes 2004;53:2939–2949

197. Kang YS, Park YG, Kim BK, et al. Angiotensin II stimulates the synthesis of vascular endothelial growth factor through the p38 mitogen activated protein kinase pathway in cultured mouse podocytes. J Mol Endocrinol 2006;36:377–388

198. Wang L, Kwak JH, Kim SI, et al. Transforming growth factor-beta1 stimulates vascular endothelial growth factor 164 via mitogen-activated protein kinase kinase 3-p38alpha and p38delta mitogen-activated protein kinase-dependent pathway in murine mesangial cells. J Biol Chem 2004;279:33213–33219

199. Kriz W, Gretz N, Lemley KV. Progression of glomerular diseases: Is the podocyte the culprit? Kidney Int 1998;54:687–697

200. Pagtalunan ME, Miller PL, Jumping-Eagle S, et al. Podocyte loss and progressive glomerular injury in type II diabetes. J Clin Invest 1997;99:342–348.

201. Lemley KV, Lafayette RA, Safai M, et al. Podocytopenia and disease severity in IgA nephropathy. Kidney Int 2002;61:1475– 1485

202. U.S. Renal Data System, USRDS 2002 Annual Data Report: Atlas of End-Stage Renal Disease in the United States, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2002

203. Olin JW. Atherosclerotic renal artery disease. Cardiol Clin. 2002;20:547–562.

204. De Mast Q, Beutler JJ. The prevalence of atherosclerotic renal artery stenosis in risk groups: a systematic literature review. J Hypertens 2009;27:1333–1340

205. Rihal CS, Textor SC, Breen JF, et al. Incidental renal artery stenosis among a prospective cohort of hypertensive patients undergoing coronary angiography. Mayo Clin Proc 2002;77:309–316

206. Garovic VD, Textor SC. Renovascular hypertension and ischemic nephropathy. Circulation 2005;112:1362–1374

207. Textor SC. Ischemic nephropathy: where are we now? J Am Soc Nephrol 2004;15:1974–1982

208. Chade AR, Rodriguez-Porcel M, Grande JP, et al. Mechanisms of renal structural alterations in combined hypercholesterolemia and renal artery stenosis. Arterioscler Thromb Vasc Biol 2003;23:1295–1301

209. Chade AR, Lerman A, Lerman LO. Kidney in early atherosclerosis. Hypertension 2005;45:1042–1049

210. Harrison D, Griendling KK, Landmesser U, et al. Role of oxidative stress in atherosclerosis. Am J Cardiol 2003;91:7A–11A

211. Rajagopalan S, Kurz S, Munzel T, et al. Angiotensin IImediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation. Contribution to alterations of vasomotor tone. J Clin Invest 1996;97:1916–1923

212. Reckelhoff JF, Romero JC. Role of oxidative stress in angiotensin-induced hypertension. Am J Physiol Regul Integr Comp Physiol 2003;284:R893–R912

213. Chade AR, Krier JD, Rodriguez-Porcel M, et al. Comparison of acute and chronic antioxidant interventions in experimental renovascular disease. Am J Physiol Renal Physiol 2004;286:F1079–F1086

214. Oliveira-Sales EB, Dugaich AP, Carillo BA, et al. Oxidative stress contributes to renovascular hypertension. Am J Hypertens 2008;21:98–104

215. Schnackenberg CG. Physiological and pathophysiological roles of oxygen radicals in the renal microvasculature. Am J Physiol Regul Integr Comp Physiol 2002;282:R335–R342

216. Textor SC, Novick AC, Tarazi RC, et al. Critical perfusion pressure for renal function in patients with bilateral atherosclerotic renal vascular disease. Ann Intern Med 1985;102:308–314

217. Epstein FH. Oxygen and renal metabolism. Kidney Int 1997;51:381–385

218. Spence JD. Treatment options for renovascular hypertension. Expert Opin Pharmacother 2002;3:411–416

219. Safian RD, Textor SC. Renal-artery stenosis. N Engl J Med 2001;344:431–442

220. Iliescu R, Fernandez SR, Kelsen S, et al. Role of renal microcirculation in experimental renovascular disease. Nephrol Dial Transplant 2010;25:1079–1087

221. Haase VH. Pathophysiological Consequences of HIF Activation: HIF as a modulator of fibrosis. Ann N Y Acad Sci 2009;1177:57–65

222. Moran K, Mulhall J, Kelly D, et al. Morphological changes and alterations in regional intrarenal blood flow induced by graded renal ischemia. J Urol 1992;148:463–466

223. Jeong JI, Lee YW, Kim YK. Chemical hypoxia-induced cell death in human glioma cells: role of reactive oxygen species, ATP depletion, mitochondrial damage and Ca2+. Neurochem Res 2003;28:1201–1211

224. Seppet E, Gruno M, Peetsalu A, et al. Mitochondria and energetic depression in cell pathophysiology. Int J Mol Sci 2009;10:2252–2303

225. Sato T, Oku H, Tsuruma K, et al. Effect of hypoxia on susceptibility of RGC-5 cells to nitric oxide. Invest Ophthalmol Vis Sci 2010;51:2575–2486

226. Kiang JG, Tsen KT. Biology of hypoxia. Chin J Physiol 2006;49:223–233

227. Voiculescu A, Grabensee B, Jung G, et al. Renovascular disease: a review of diagnostic and therapeutic procedures. Minerva Urol Nefrol 2006;58:127–149

228. Chade AR, Rodriguez-Porcel M, Grande JP, et al. Mechanisms of renal structural alterations in combined hypercholesterolemia and renal artery stenosis. Arterioscler Thromb Vasc Biol 2003;23:1295–1230

229. Gallego B, Arevalo MA, Flores O, et al. Renal fibrosis in diabetic and aortic-constricted hypertensive rats. Am J Physiol Regul Integr Comp Physiol 2001;280:R1823–R1829

230. Gallego B, Arevalo, Flores O,et al. Effect of chronic and progressive aortic constriction on renal function and structure in rats. Can J Physiol Pharmacol 2001;79:601–607

231. Textor SC. Pathophysiology of renovascular hypertension. Urol Clin North Am 1984;11:373–381

232. Navar LG, Von Thun AM, Zou L, et al. Enhancement of intrarenal angiotensin II levels in 2 kidney 1 clip and angiotensin II induced hypertension. Blood Press 1995;2 [Suppl]: 88–92

233. Zimmerman MC, Lazartigues E, Sharma RV, et al. Hypertension caused by angiotensin II infusion involves increased superoxide production in the central nervous system. Circ Res 2004;95:210–216

234. Wolf G, Schneider A, Wenzel U, et al. Regulation of glomerular TGF-beta expression in the contralateral kidney of two-kidney, one-clip hypertensive rats. J Am Soc Nephrol 1998;9:763–772

235. Bohle A, Muller GA, Wehrmann M,et al. Pathogenesis of chronic renal failure in the primary glomerulopathies, renal vasculopathies, and chronic interstitial nephritides. Kidney Int 1996;54 [Suppl]: S2–S9

236. Komlosi P, Bell PD, Zhang ZR. Tubuloglomerular feedback mechanisms in nephron segments beyond the macula densa. Curr Opin Nephrol Hypertens 2009;18:57–62

237. Kriz W, Hosser H, Hahnel B, et al. From segmental glomerulosclerosis to total nephron degeneration and interstitial fibrosis: a histopathological study in rat models and human glomerulopathies. Nephrol Dial Transplant 1998;13:2781–2798

238. Abbate M, Zoja C, Remuzzi G. How does proteinuria cause progressive renal damage? J Am Soc Nephrol 2006;17:2974–2984

239. Baines RJ, Brunskill NJ. Tubular toxicity of proteinuria. Nat Rev Nephrol 2011 Mar;7(3):177-180

240. Buelli S, Abbate M, Morigi M, et al. Protein load impairs factor H binding promoting complement-dependent dysfunction of proximal tubular cells. Kidney Int 2009;75:1050–1059

241. Macconi D, Chiabrando C, Schiarea S, et al. Proteasomal processing of albumin by renal dendritic cells generates antigenic peptides. J Am Soc Nephrol 2009;20:123–130.

242. Lapsley M, Flynn FV, Sansom PA. Beta 2-glycoprotein-1 (apolipoprotein H) excretion and renal tubular malfunction in diabetic patients without clinical proteinuria. J Clin Pathol 1993;46:465–469

243. Hong CY, Hughes K, Chia KS, et al. Urinary alpha1- microglobulin as a marker of nephropathy in type 2 diabetic Asian subjects in Singapore. Diabetes Care 2003;26:338–342

244. Thomas MC, Burns WC, Cooper ME. Tubular changes in early diabetic nephropathy. Adv Chronic Kidney Dis 2005;12:177– 186

245. Thomson SC, Vallon V, Blantz RC. Kidney function in early diabetes: the tubular hypothesis of glomerular filtration. Am J Physiol Renal Physiol 2006;286:F8–F15

246. Singh DK, Winocour P, Farrington K. Mechanisms of disease: the hypoxic tubular hypothesis of diabetic nephropathy. Nat Clin Pract Nephrol 2008;4:216–226

247. Koomans HA, Blankestijn PJ, Joles JA. Sympathetic hyperactivity in chronic renal failure: A wake-up call. J Am Soc Nephrol 2004;15:524–537

248. Perico N, Benigni A, Remuzzi G. Present and future drug treatments for chronic kidney diseases: evolving targets in renoprotection. Nat Rev Drug Discov 2008;7:936–953

249. Zeisberg M, Kalluri R. Reversal of experimental renal fibrosis by BMP7 provides insights into novel therapeutic strategies for chronic kidney disease. Pediatr Nephrol 2008;23:1395–1398

250. Wang S, Chen Q, Simon TC, et al. Bone morphogenic protein-7 (BMP-7), a novel therapy for diabetic nephropathy. Kidney Int 2003;63:2037–2049

251. Leask A, Abraham DJ. TGF-β signaling and the fibrotic response. FASEB J 2004;18 (7):816–827

252. Xu J, Lamouille S, Derynck R. TGF-beta-induced epithelial to mesenchymal transition. Cell Res 2009;19:156–172

253. Wang SN, Lapage J, Hirschberg R. Glomerular ultrafiltration and apical tubular action of IGF-I, TGF-beta, and HGF in nephrotic syndrome. Kidney Int 1999;56:1247–1251

254. Duncan MR, Frazier KS, Abramson S,et al. Connective tissue growth factor mediates transforming growth factor betainduced collagen synthesis: downregulation by cAMP. FASEB J 1999;13:1774–1786

255. Okada H, Danoff TM, Kalluri R,et al. Early role of Fsp1 in epithelial-mesenchymal transformation. Am J Physiol 1997;273:F563–574

256. Strutz F, Zeisberg M, Ziyadeh FN, et al. Role of basic fibroblast growth factor-2 in epithelial-mesenchymal transformation. Kidney Int 2002;61:1714–1728

257. Kriz W, Hahnel B, Rosener S, et al. Long-term treatment of rats with FGF-2 results in focal segmental glomerulosclerosis. Kidney Int 1995;48:1435–1450

258. Phillips AO, Topley N, Morrisey K, et al. Basic fibroblast growth factor stimulates the release of preformed transforming growth factor beta 1 from human proximal tubular cells in the absence of de novo gene transcription or mRNA translation. Lab Invest 1997;76:591–600

259. Bonner JC. Regulation of PDGF and its receptors in fibrotic diseases. Cytokine Growth Factor Rev 2004;15:255–273

260. Weston BS, Wahab NA, Mason RM. CTGF mediates TGF-beta-induced fibronectin matrix deposition by upregulating active alpha5beta1 integrin in human mesangial cells. J Am Soc Nephrol 2003;14:601–610

261. Wahab NA, Weston BS, Mason RM. Modulation of the TGFbeta/Smad signaling pathway in mesangial cells by CTGF/ CCN2. Exp Cell Res 2005;307:305–314

262. Francki A, Bradshaw AD, Bassuk JA, et al. SPARC regulates the expression of collagen type I and transforming growth factor-beta1 in mesangial cells. J Biol Chem 1999; 274:32145–32152

263. Okada H, Danoff TM, Kalluri R, et al. Early role of Fsp1 in epithelial-mesenchymal transformation. Am J Physiol 1997;273:F563–F574

264. Brown NJ, Vaughan DE, Fogo AB. Aldosterone and PAI-1: implications for renal injury. J Nephrol 2002;15:230–235

265. Biancone L, David S, Della Pietra V, et al. Alternative pathway activation of complement by cultured human proximal tubular epithelial cells. Kidney Int 1994;45:451–460

266. Tang S, Sheerin NS, Zhou W, et al. Apical proteins stimulate complement synthesis by cultured human proximal tubular epithelial cells. J Am Soc Nephrol 1999;10:69–76

267. Nangaku M, Pippin J, Couser WG. Complement membrane attack complex (C5b-9) mediates interstitial disease in experimental nephrotic syndrome. J Am Soc Nephrol 1999;10:2323–2331

268. Nomura A, Morita Y, Maruyama S, et al. Role of complement in acute tubulointerstitial injury of rats with aminonucleoside nephrosis. Am J Pathol 1997;151:539–547

269. Hill PA, Lan HY, Nikolic-Paterson DJ, et al. ICAM-1 directs migration and localization of interstitial leukocytes in experimental glomerulonephritis. Kidney Int 1994;45:32–42

270. Ricardo SD, Levinson ME, DeJoseph MR, et al. Expression of adhesion molecules in rat renal cortex during experimental hydronephrosis. Kidney Int 1996;50:2002–2010

271. Ophascharoensuk V, Giachelli CM, Gordon K, et al. Obstructive uropathy in the mouse: role of osteopontin in interstitial fibrosis and apoptosis. Kidney Int 1999;56:571–580

272. Zoja C, Morigi M, Figliuzzi M, et al. Proximal tubular cell synthesis and secretion of endothelin-1 on challenge with albumin and other proteins. Am J Kidney Dis 1995;26:934–941

273. Largo R, Gómez-Garre D, Soto K, et al. Angiotensinconverting enzyme is upregulated in the proximal tubules of rats with intense proteinuria. Hypertension 1999;33:732–739

274. Benigni A, Remuzzi G. How renal cytokines and growth factors contribute to renal disease progression. Am J Kidney Dis 2001;37 [1 Suppl 2]: S21–S24

275. Abe K, Li K, Sacks SH, et al. The membrane attack complex, C5b-9, up regulates collagen gene expression in renal tubular epithelial cells. Clin Exp Immunol 2004;136:60–66

276. Justo P, Sanz AB, Sanchez-Niño MD, et al. Cytokine cooperation in renal tubular cell injury: the role of TWEAK. Kidney Int 2006;70:1750–1758

277. Wolfs TG, Buurman WA, van Schadewijk A, et al. In vivo expression of Toll-like receptor 2 and 4 by renal epithelial cells: IFN-gamma and TNF-alpha mediated up-regulation during inflammation. J Immunol 2002;168:1286–1293

278. Guo G, Morrissey J, McCracken R, et al. Contributions of angiotensin II and tumor necrosis factor-alpha to the development of renal fibrosis. Am J Physiol Renal Physiol 2001;280:F777–F785

279. Longaretti L, Benigni A. Endothelin receptor selectivity in chronic renal failure. Eur J Clin Invest 2009;39 [Suppl 2]:32–37

280. Kagami S, Border WA, Miller DE, et al. Angiotensin II stimulates extracellular matrix protein synthesis through induction of transforming growth factor-beta expression in rat glomerular mesangial cells. J Clin Invest 1994;93:2431–2437

281. Gilbert RE, Wu LL, Kelly DJ, et al. Pathological expression of renin and angiotensin II in the renal tubule after subtotal nephrectomy. Implications for the pathogenesis of tubulointerstitial fibrosis. Am J Pathol 1999;155:429–440

282. Yang J, Dai C, Liu Y. Hepatocyte growth factor gene therapy and angiotensin II blockade synergistically attenuate renal interstitial fibrosis in mice. J Am Soc Nephrol 2002;13:2464–2477

283. Ursula C, Brewster MD, Mark A,et al. The reninangiotensin-aldosterone system and the kidney: effects on kidney disease. Am J Med 2004;116:263–272

284. Zeisberg M, Bonner G, Maeshima Y, et al. Renal fibrosis: collagen composition and assembly regulates epithelialmesenchymal transdifferentiation. Am J Pathol 2001;159:1313– 1321

285. Yang J, Liu Y. Dissection of key events in tubular epithelial to myofibroblast transition and its implications in renal interstitial fibrosis. Am J Pathol 2001;159:1465–1475

286. Liu Y. Hepatocyte growth factor promotes renal epithelial cell survival by dual mechanisms. Am J Physiol 1999;277:F624– F633

287. Yang J, Liu Y. Blockage of tubular epithelial to myofibroblast transition by hepatocyte growth factor prevents renal interstitial fibrosis. J Am Soc Nephrol 2002;13:96–107

288. Dworkin LD, Gong R, Tolbert E, et al. Hepatocyte growth factor ameliorates progression of interstitial fibrosis in rats with established renal injury. Kidney Int 2004;65:409–419

289. Esposito C, Parrilla B, De Mauri A,et al. Hepatocyte growth factor (HGF) modulates matrix turnover in human glomeruli. Kidney Int 2005;67:2143–2150

290. Vaidya VS, Ferguson MA, Bonventre JV. Biomarkers of acute kidney injury. Annu Rev Pharmacol Toxicol 2008;48:463–493


Рецензия

Для цитирования:


Лопес-Новойя Д., Родригес-Пена А., Ортис А., Мартинес-Салдаго К., Лопес Эрнандес Ф. ЭТИОПАТОЛОГИЯ ХРОНИЧЕСКОЙ ТУБУЛЯРНОЙ, ГЛОМЕРУЛЯРНОЙ И РЕНОВАСКУЛЯРНОЙ НЕФРОПАТИЙ: КЛИНИЧЕСКИЕ АСПЕКТЫ. Нефрология. 2013;17(2):9-38. https://doi.org/10.24884/1561-6274-2013-17-2-9-38

For citation:


López-Novoa J., Rodríguez-Peña A., Ortiz A., Martínez-Salgado C., López Hernández F. ETIOPATHOLOGY OF CHRONIC TUBULAR, GLOMERULAR AND RENOVASCULAR NEPHROPATHIES: CLINICAL IMPLICATIONS. Nephrology (Saint-Petersburg). 2013;17(2):9-38. (In Russ.) https://doi.org/10.24884/1561-6274-2013-17-2-9-38

Просмотров: 552


ISSN 1561-6274 (Print)
ISSN 2541-9439 (Online)