Роль подоцитарной дисфункции в прогрессировании хронического гломерулонефрита
Роль подоцитарной дисфункции в прогрессировании хронического гломерулонефрита
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Аннотация
В обзоре рассмотрены механизмы повреждения подоцитов, лежащие в основе развития протеинурии и прогрессирования гломерулосклероза при хроническом гломерулонефрите, представлены результаты экспериментальных и клинических исследований по данным вопросам. Описывается, как под действием различных иммунных и неиммунных факторов подоциты формируют стереотипный ответ на повреждение, заключающийся в перестройке актинового цитоскелета, сглаживании ножковых отростков, отщеплении подоцитов с гломерулярной базальной мембраны и появлении в моче специфических подоцитарных белков и/или целых клеток (подоцитурия). Массивная подоцитурия при ограниченной пролиферативной способности подоцитов способствует снижению их общей массы в клубочке (подоцитопении) и развитию гломерулосклероза. Авторами описан спектр маркеров подоцитарного повреждения, освещены методы их инвазивной и неинвазивной оценки, проанализирована взаимосвязь их уровня с выраженностью протеинурии и дисфункции почек, рассмотрены перспективы исследования подоцитарных белков в моче для оценки тяжести гломерулярного повреждения, риска развития гломерулосклероза.
Ключевые слова: подоцитурия, нефринурия, подоцитарная дисфункция, подоцитопения, хронический гломерулонефрит.
Keywords: podocyturia, nephrinuria, podocyte dysfunction, podocytopenia, chronic glomerulonephritis.
Ключевые слова: подоцитурия, нефринурия, подоцитарная дисфункция, подоцитопения, хронический гломерулонефрит.
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Keywords: podocyturia, nephrinuria, podocyte dysfunction, podocytopenia, chronic glomerulonephritis.
Список литературы
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6. Kriz W, Shirato I, Nagata M, Le Hir M, Lemley KV. The podocyte’s response to stress: The enigma of foot process effacement. Am J Physiol Renal Physiol. 2013;304:333-47. doi: 10.1152/ajprenal.00478.2012
7. Neal CR. Podocytes: What’s under yours? (Podocytes and foot processes and how they change in nephropathy). Front Endocrinol. 23 February 2015. Available from: https://doi.org/10.3389/fendo.2015.00009
8. Huber TB, Bensing T. The slit diaphragm: a signaling platform to regulate podocyte function. Curr Opin Nephrol Hypertens. 2005;14 (3):211-6.
9. Trimarchi H. Podocyturia: what is in a name? J Transl Int Med. 2015;3(2):51-6. doi: 10.1515/jtim-2015-0003
10. Barisoni L, Schnaper HW, Kopp JB. A Proposed Taxonomy for the Podocytopathies: A Reassessment of the Primary Nephrotic Diseases. Clin J Am Soc Nephrol. 2007;2:529-42. doi: 10.2215/CJN.04121206
11. Greka A, Mundel P. Cell biology and pathology of podocytes. Ann Rev Physiol. 2012;74:299-323. doi: 10.1146/annurev-physiol-020911-153238
12. Couser WG. Basic and translational concepts of immune-mediated glomerular diseases. J Am Soc Nephrol. 2012;23:381-99. doi: 10.1681/ ASN.2011030304
13. Jefferson JA, Shankland SJ, Pichler RH. Proteinuria in diabetic kidney disease: A mechanistic viewpoint. Kidney Int. 2008;74:22-36.
doi: 10.1038/ki.2008.128
14. George B, Verma R, Soofi A, Garg P, Zhang J, Park TJ, Giardino L, Ryzhova L, Johnstone D, Wong H, Nihalani D, Salant D, Hanks S, Curran T, Rastaldi M, Holzman L. Crk1/2-dependent signaling is necessary for podocyte foot process spreading in mouse models of glomerular disease. J Clin Invest. 2012;122:674-92. doi: 10.1172/ JCI60070
15. Reiser J, von Gersdorff G, Loos M, Oh J, Asanuma K, Giardino L, Rastaldi M, Calvaresi N, Watanabe H, Schwarz K, Faul C, Kretzler M, Davidson A, Sugimoto H, Kalluri R, Sharpe A, Kreidberg J, Mundel P. Induction of B7–1 in podocytes is associated with nephrotic syndrome. J Clin Invest. 2004;113:1390-7. doi: 10.1172/JCI20402
16. Shirato I. Podocyte process effacement in vivo. Micros Res Tech. 2002;57:241-6. doi: 10.1002/jemt.10082
17. Le Hir M, Keller C, Eschmann V, Hähnel B, Hosser H, Kriz W. Podocyte bridges between the tuft and Bowman’s capsule: an early event in experimental crescentic glomerulonephritis. J Am Soc Nephrol. 2001;12:2060-71.
18. Nagata M. Podocyte injury and its consequences. Kidney Int. 2016 Jun; 89(6):1221-30. doi: 10.1016/j.kint.2016.01.012
19. Neal C, Crook H, Bell E, Harper S, Bates D. Three-dimensional reconstruction of glomeruli by electron microscopy reveals a distinct restrictive urinary subpodocyte space. J Am Soc Nephrol. 2005;16:1223-35. doi: 10.1681/ASN.2004100822
20. Liapis H, Romagnani P, Anders HJ. New insights into the pathology of podocyte loss: mitotic catastrophe. Am J Pathol. 2013;183:1364-74. doi: 10.1016/j.ajpath.2013.06.033
21. Vogelmann SU, Nelson WJ, Myers BD, Lemley KV. Urinary excretion of viable podocytes in health and renal disease. Am J Physiol Renal Physiol. 2003;285(1):40-8. doi: 10.1152/ajprenal.00404.2002
22. Garovic VD, Wagner SJ, Petrovic LM, Gray CE, Hall P, Sugimoto H, Kalluri R, Grande JP. Glomerular expression of nephrin and synaptopodin but not podocin is decreased in kidney sections from women with preeclampsia. Nephrol Dial Transplant. 2007;22:1136-43.
doi: 10.1093/ndt/gfl711
23. Hara A, Wada T, Furuchi K, Sakai N, Kawachi H, Shimizu F, Shibuya M, Matsushima K, Yokoyama H, Egashira K, Kaneko S. Blokade of VEGF accelerates proteinuria via decrease in nephrin expression in rat crescentic glomerulonephritis. Kidney Int. 2006;69(11):1986-95.
doi: 10.1038/sj.ki.5000439
24. Liu Y. New insights into epithelial-mesenchymal transitition contribute in kidney fibrosis. J Am Soc Nephrol. 2010;21:212-22.
doi: 10.1681/ASN.2008121226
25. Kriz W, Lemley K. A potential role for mechanical forces in the detachment of podocytes and the progression of CKD. J Am Soc Nephrol. 2015;26:258-69. doi: 10.1681/ASN.2014030278
26. Hara M, Yanagihara T, Kihara I. Urinary podocytes in primary focal segmental glomerulosclerosis. Nephron. 2001;89:342-7. doi: 10.1159/ 000046097
27. Hara M, Yanagihara T, Kihara I, Higashi K, Fujimoto K, Kajita T. Apical cell membranes are shed into urine from injured podocytes: A novel phenomenon of podocyte injury. J Am Soc Nephrol. 2005;16:408-16. doi: 10.1681/ASN.2004070564
28. Hara M, Yanagihara T, Kihara I. Cumulative excretion of urinary podocytes reflects disease progression in IgA nephropathy and Schönlein-Henoch purpura nephritis. Clin J Am Soc Nephrol. 2007;2:231-8. doi: 10.2215/CJN.01470506
29. Sato Y, Wharram BL, Lee SK, Wickman L, Goyal M, Venkatareddy M, et al. Urine podocyte mRNAs mark progression of renal disease. J Am Soc Nephrol. 2009;20:1041-52. doi: 10.1681/ASN.2007121328
30. Nakamura T, Ushiyama C, Suzuki S, Hara M, Shimada N, Sekizuka K, et al. Urinary podocytes for the assessment of disease activity in lupus nephritis. Am J Med Sci. 2000;320:112-6. doi: 10.1097/00000441-200008000-00009
31. Mansur JB, Sabino AR, Nishida SK, Kirsztajn GM. Is there a role for urinary podocyte excretion assessment in lupus nephritis? Ren Fail. 2016;38(4):643-7. doi: 10.3109/0886022X.2016.1150099
32. Xu L, Yang H-C, Hao C-M, Lin S-T, Gu Y, Ma J. Podocyte number predicts progression of proteinuria in IgA nephropathy. Modern Pathology. 2010;23:1241-50. doi: 10.1038/modpathol.2010.110
33. Morioka Y, Koike H, Ikezumi Y, Ito Y, Oyanagi A, Gejyo F, Shimizu F, Kawachi H. Podocyte exacerbate mesangial proliferative glomerulonephritis. Kidney Int. 2001;60(6):2192-204. doi: 10.1046/j.1523-1755.2001.00047.x
34. Yu D, Petermann A, Kunter U, Rong S, Shankland SJ, Floege J. Urinary podocyte loss is a more specific marker of ongoing glomerular damage than proteinuria. J Am Soc Nephrol. 2005;16:1733-41.
doi: 10.1681/ASN.2005020159
35. Doublier S, Ruotsalainen V, Salvidio G, Lupia E, Biancone L, Conal-
di PG, Reponen P, Tryggvason K, Camussi G. Nephrin redistribution on podocytes is a potential mechanism for proteinuria in patients with primary acquired nephritic syndrome. Am J Pathol. 2001;158(5):1723-31. doi: 10.1016/S0002-9440(10)64128-4
36. Yuan H, Takeuchi E, Taylor GA, McLaughlin M, Brown D, Salant DJ. Nephrin dissociates from actin, and its expression is reduced in early experimental membranous nephropathy. J Am Soc Nephrol. 2002;13: 946-56.
37. Luimula P, Aaltonen P, Ahola H, Palmen T, Holthofer H. Alternatively spliced nephrin in experimental glomerular disease of the rat. Pediatr Res. 2000;48:759-62. doi: 10.1203/00006450-200012000-00010
38. Nakatsue T, Koike H, Han GD, Suzuki K, Miyauchi N, Yuan H, Salant DJ, Gejyo F, Shimizu F, Kawachi H. Nephrin and podocin dissociate at the onset of proteinuria in experimental membranous nephropathy. Kidney Int. 2005; 67:2239-53. doi: 10.1111/j.1523-1755.2005.00328.x
39. Benzing T. Signaling at the slit diaphragm. J Am Soc Nephrol. 2004;15:1382-91. doi: 10.1097/01.ASN.0000130167.30769.55
40. Gadliardini E, Benigni A, Tomasoni S, Abbate M, Kalluri R, Remuzzi G. Targeted downregulation of extracellular nephrin in human IgA nephropathy. Am J Nephrol. 2003;23:277-86. doi: 10.1159/000072281
41. Patrakka J, Ruotsalainen V, Ketola I, Holmberg C, Heikinheimo M, Tryggvason K, Jalanko H. Expression of nephrin in pediatric kidney diseases. J Am Soc Nephrol. 2001;12:289-96.
42. [Yarkova NA. Nephrin is an early marker of kidney damage in type 2 diabetes mellitus. Laboratornaya Diagnostika. 2017;2(47):101-3 (In Russ.)]. doi: 10.21145/2499-9954-2017-2-101-103
43. Huh W, Kim DJ, Kim M-K, Kim YG, Oh H-Y, Ruotsalainen V, Tryggvason K. Expression of nephrin in acquired human glomerular disease. Nephrol Dial Transplant. 2002;17:478-84 doi: 10.1093/ndt/ 17.3.478
44. [Chebotareva IN, Bobkova LV, Kozlovskaya LV. Nephrinuria as a marker of structure-functional glomerular dysfunction in patients with proteinuric glomerulonephritis forms. Klinicheskaya Nefrologiya = Clinical Nephrology. 2010;(4):45-51 (In Russ)].
45. [Chebotareva NV, Bobkova IN, Neprintseva NV, Kozlovskaya LV, Malkandueva ZT. Urinary biomarkers for podocyte injury: Significance for evaluating the course and prognosis of chronic glomerulonephritis. Terapevticheskiy Arkhiv. 2015;(6):34-9 (In Russ.)]. doi: 10.17116/terarkh 201587634-39
46. Proletov I, Galkina O, Bogdanova E, Zubina I, Sipovskii V, Smirnov A. Clinical significance of podocyte injury markers evaluation in patients with primary glomerulopathies. Nephrol Dial Transplant. 2014;29: iii193.
47. Kriz W, Greitz N, Lemley KV. Progression of glomerular diseases: is the podocyte the culprit? Kidney Int. 1998;54:687-97. doi: 10.1046/j. 1523-1755.1998.00044.x
48. Luyckx VA, Brenner BM. The clinical importance of nephron mass.
J Am Soc Nephrol. 2010;21:898-910. doi: 10.1681/ASN.2009121248
49. Romagnani P, Lasagni L, Remuzzi G. Renal progenitors: An evolutionary conserved strategy for kidney regeneration. Nat Rev Nephrol. 2013;9:137-46. doi: 10.1038/nrneph.2012.290
50. Angelotti ML, Ronconi E, Ballerini L, Peired A, Mazzinghi B, Sagrinati C, et al. Characterization of renal progenitors committed toward the tubular lineage and their regenerative potential in renal tubular injury. Stem Cells. 2012;30:1714-25. doi: 10.1002/stem.1130
51. Ronconi E, Sagrinati C, Angelotti ML, Lazzeri E, Mazzinghi B, et al. Regeneration of glomerular podocytes by human renal progenitors.
J Am Soc Nephrol. 2009;20(2):322-32. doi: 10.1681/asn.2008070709
52. Pavenstadt H. Roles of the podocyte in glomerular function. Am J Physiol. 2000;278:173-9. doi: 10.1152/ajprenal.2000.278.2.F173
53. Schiffer M, Bitzer M, Roberts IS. Apoptosis in podocytes induced by TGF-beta and Smad7. J Clin Invest. 2001;108:807-16. doi: 10.1172/ JCI12367
54. Kim YH, Goyal M, Kurnit D. Podocyte depletion and glomerulosclerosis have a direct relationship in the PAN-treated rat. Kidney Int. 2001;60:957-68. doi: 10.1046/j.1523-1755.2001.060003957.x
55. Yamaguchi Y, Iwano M, Suzuki D. Epithelial-mesenchymal transition as a potential explanation for podocyte depletion in diabetic nephropathy. Am J Kidney Dis. 2009;54:653-64. doi: 10.1053/j.ajkd. 2009.05.009
56. Miyauchi M, Toyoda M, Kobayashi K. Hypertrophy and loss of podocytes in diabetic nephropathy. Intern Med. 2009;48:1615-20.
doi: 10.2169/internalmedicine.48.2137
57. Reidy K, Susztak K. Epithelial-mesenchymal transition and podocyte loss in diabetic kidney disease. Am J Kidney Dis. 2009;54:590-3.
doi: 10.1053/j.ajkd.2009.07.003
58. Petermann AT, Pippin J, Durvasula R, Pichler R, Hiromuda K, Monkawa T, Couser WG, Shankland SJ. Mechanical stretch induces podocyte hypertrophy in vitro. Kidney Int. 2005;67(1):157-66.
doi: 10.1111/j.1523-1755.2005.00066.x
59. Petermann A, Floege J. Podocyte damage resulting in podocyturia: a potential diagnostic marker to assess glomerular disease activity. Nephron Clin Pract. 2007;106(2):61-6. doi: 10.1159/000101799
60. Colucci G, Floege J, Schena FP. The urinary sediment beyond light microscopical examination. Nephrol Dial Transplant. 2006;21(6):
1482-5. doi: 10.1093/ndt/gfl223
61. Li Y, Kang YS, Dai C, Kiss LP, Wen X, Liu Y. Epithelial-to-mesenchymal transition is a potential pathway leading to podocyte dysfunction and proteinuria. Am J Pathol. 2008;172(2):299-308. doi: 10.2353/ajpath.2008.070057
62. Cheng S, Lovett DH, Gelatinase A. (MMP-2) is necessary and sufficient for renal tubular cell epithelial-mesenchymal transformation. Am J Pathol. 2003;162:1937-49. doi: 10.1016/S0002-9440(10)64327-1
63. Tan TK, Zheng G, Hsu TT, Wang Y, Lee VW, Tian X, Wang Y, Cao Q, Wang Y, Harris DC. Macrophage matrix metalloproteinase-9 mediates epithelial-mesenchymal transition in vitro in murine renal tubular cells. Am J Pathol. 2010;176:1256-70. doi: 10.2353/ajpath.2010.090188
64. Cheng S, Pollock AS, Mahimkar R, Olson JL, Lovett DH. Matrix metalloproteinase 2 and basement membrane integrity: a unifying mechanism for progressive renal injury. FASEB J. 2006;20:1898-900.
doi: 10.1096/fj.06-5898fje
65. Lemley KV, Lafayette A, Safai G, Derby G, Blouch K, Squarer A, Myers BD. Podocytopenia and disease severity in IgA nephropathy. Kidney Int. 2002;61:1475-85. doi: 10.1046/j.1523-1755.2002.00269.x
66. Patari A, Forsblom C, Havana M, et al. Nephrinuria in diabetic nephropathy of type 1 diabetes. Diabetes. 2003;52:2969-74.
doi: 10.2337/diabetes.52.12.2969
67. Mallipattu SK, He JC. The podocyte as a direct target for treatment of glomerular disease? Am J Physiol Renal Physiol. 2016;311(1):F46-F51. doi: 10.1152/ajprenal.00184.2016
68. Müller-Deile J, Schiffer M. Podocytes from the diagnostic and therapeutic point of view. Pflugers Arch. 2017;469(7-8):1007-15.
doi: 10.1007/s00424-017-1993-z
2. Pavenstadt H, Kriz W, Kretzler M. Cell biology of the glomerular podocyte. Physiol Rev. 2003;83:253-307. doi: 10.1152/physrev.00020. 2002
3. Pollak MR. Inherited Podocytopathies: FSGS and Nephrotic Syndrome from a Genetic Viewpoint. J Am Soc Nephrol. 2002;13:3016-23.
doi: 10.1097/01.ASN.0000039569.34360.5E
4. Koop K, Eikmans M, Baelde HJ, Kawachi H, de Heer E, Paul LC, Bruijn JA. Expression of podocyte-associated molecules in acquired human kidney diseases. J Am Soc Nephrol. 2003;14:2063-71. doi: 10.1097/01. ASN.0000078803.53165.C9
5. Patrakka J, Tryggvason K. New insights into the role of podocytes in proteinuria. Nat Rev Nephrol. 2009;5:463-8. doi:10.1038/nrneph. 2009.108
6. Kriz W, Shirato I, Nagata M, Le Hir M, Lemley KV. The podocyte’s response to stress: The enigma of foot process effacement. Am J Physiol Renal Physiol. 2013;304:333-47. doi: 10.1152/ajprenal.00478.2012
7. Neal CR. Podocytes: What’s under yours? (Podocytes and foot processes and how they change in nephropathy). Front Endocrinol. 23 February 2015. Available from: https://doi.org/10.3389/fendo.2015.00009
8. Huber TB, Bensing T. The slit diaphragm: a signaling platform to regulate podocyte function. Curr Opin Nephrol Hypertens. 2005;14 (3):211-6.
9. Trimarchi H. Podocyturia: what is in a name? J Transl Int Med. 2015;3(2):51-6. doi: 10.1515/jtim-2015-0003
10. Barisoni L, Schnaper HW, Kopp JB. A Proposed Taxonomy for the Podocytopathies: A Reassessment of the Primary Nephrotic Diseases. Clin J Am Soc Nephrol. 2007;2:529-42. doi: 10.2215/CJN.04121206
11. Greka A, Mundel P. Cell biology and pathology of podocytes. Ann Rev Physiol. 2012;74:299-323. doi: 10.1146/annurev-physiol-020911-153238
12. Couser WG. Basic and translational concepts of immune-mediated glomerular diseases. J Am Soc Nephrol. 2012;23:381-99. doi: 10.1681/ ASN.2011030304
13. Jefferson JA, Shankland SJ, Pichler RH. Proteinuria in diabetic kidney disease: A mechanistic viewpoint. Kidney Int. 2008;74:22-36.
doi: 10.1038/ki.2008.128
14. George B, Verma R, Soofi A, Garg P, Zhang J, Park TJ, Giardino L, Ryzhova L, Johnstone D, Wong H, Nihalani D, Salant D, Hanks S, Curran T, Rastaldi M, Holzman L. Crk1/2-dependent signaling is necessary for podocyte foot process spreading in mouse models of glomerular disease. J Clin Invest. 2012;122:674-92. doi: 10.1172/ JCI60070
15. Reiser J, von Gersdorff G, Loos M, Oh J, Asanuma K, Giardino L, Rastaldi M, Calvaresi N, Watanabe H, Schwarz K, Faul C, Kretzler M, Davidson A, Sugimoto H, Kalluri R, Sharpe A, Kreidberg J, Mundel P. Induction of B7–1 in podocytes is associated with nephrotic syndrome. J Clin Invest. 2004;113:1390-7. doi: 10.1172/JCI20402
16. Shirato I. Podocyte process effacement in vivo. Micros Res Tech. 2002;57:241-6. doi: 10.1002/jemt.10082
17. Le Hir M, Keller C, Eschmann V, Hähnel B, Hosser H, Kriz W. Podocyte bridges between the tuft and Bowman’s capsule: an early event in experimental crescentic glomerulonephritis. J Am Soc Nephrol. 2001;12:2060-71.
18. Nagata M. Podocyte injury and its consequences. Kidney Int. 2016 Jun; 89(6):1221-30. doi: 10.1016/j.kint.2016.01.012
19. Neal C, Crook H, Bell E, Harper S, Bates D. Three-dimensional reconstruction of glomeruli by electron microscopy reveals a distinct restrictive urinary subpodocyte space. J Am Soc Nephrol. 2005;16:1223-35. doi: 10.1681/ASN.2004100822
20. Liapis H, Romagnani P, Anders HJ. New insights into the pathology of podocyte loss: mitotic catastrophe. Am J Pathol. 2013;183:1364-74. doi: 10.1016/j.ajpath.2013.06.033
21. Vogelmann SU, Nelson WJ, Myers BD, Lemley KV. Urinary excretion of viable podocytes in health and renal disease. Am J Physiol Renal Physiol. 2003;285(1):40-8. doi: 10.1152/ajprenal.00404.2002
22. Garovic VD, Wagner SJ, Petrovic LM, Gray CE, Hall P, Sugimoto H, Kalluri R, Grande JP. Glomerular expression of nephrin and synaptopodin but not podocin is decreased in kidney sections from women with preeclampsia. Nephrol Dial Transplant. 2007;22:1136-43.
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23. Hara A, Wada T, Furuchi K, Sakai N, Kawachi H, Shimizu F, Shibuya M, Matsushima K, Yokoyama H, Egashira K, Kaneko S. Blokade of VEGF accelerates proteinuria via decrease in nephrin expression in rat crescentic glomerulonephritis. Kidney Int. 2006;69(11):1986-95.
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24. Liu Y. New insights into epithelial-mesenchymal transitition contribute in kidney fibrosis. J Am Soc Nephrol. 2010;21:212-22.
doi: 10.1681/ASN.2008121226
25. Kriz W, Lemley K. A potential role for mechanical forces in the detachment of podocytes and the progression of CKD. J Am Soc Nephrol. 2015;26:258-69. doi: 10.1681/ASN.2014030278
26. Hara M, Yanagihara T, Kihara I. Urinary podocytes in primary focal segmental glomerulosclerosis. Nephron. 2001;89:342-7. doi: 10.1159/ 000046097
27. Hara M, Yanagihara T, Kihara I, Higashi K, Fujimoto K, Kajita T. Apical cell membranes are shed into urine from injured podocytes: A novel phenomenon of podocyte injury. J Am Soc Nephrol. 2005;16:408-16. doi: 10.1681/ASN.2004070564
28. Hara M, Yanagihara T, Kihara I. Cumulative excretion of urinary podocytes reflects disease progression in IgA nephropathy and Schönlein-Henoch purpura nephritis. Clin J Am Soc Nephrol. 2007;2:231-8. doi: 10.2215/CJN.01470506
29. Sato Y, Wharram BL, Lee SK, Wickman L, Goyal M, Venkatareddy M, et al. Urine podocyte mRNAs mark progression of renal disease. J Am Soc Nephrol. 2009;20:1041-52. doi: 10.1681/ASN.2007121328
30. Nakamura T, Ushiyama C, Suzuki S, Hara M, Shimada N, Sekizuka K, et al. Urinary podocytes for the assessment of disease activity in lupus nephritis. Am J Med Sci. 2000;320:112-6. doi: 10.1097/00000441-200008000-00009
31. Mansur JB, Sabino AR, Nishida SK, Kirsztajn GM. Is there a role for urinary podocyte excretion assessment in lupus nephritis? Ren Fail. 2016;38(4):643-7. doi: 10.3109/0886022X.2016.1150099
32. Xu L, Yang H-C, Hao C-M, Lin S-T, Gu Y, Ma J. Podocyte number predicts progression of proteinuria in IgA nephropathy. Modern Pathology. 2010;23:1241-50. doi: 10.1038/modpathol.2010.110
33. Morioka Y, Koike H, Ikezumi Y, Ito Y, Oyanagi A, Gejyo F, Shimizu F, Kawachi H. Podocyte exacerbate mesangial proliferative glomerulonephritis. Kidney Int. 2001;60(6):2192-204. doi: 10.1046/j.1523-1755.2001.00047.x
34. Yu D, Petermann A, Kunter U, Rong S, Shankland SJ, Floege J. Urinary podocyte loss is a more specific marker of ongoing glomerular damage than proteinuria. J Am Soc Nephrol. 2005;16:1733-41.
doi: 10.1681/ASN.2005020159
35. Doublier S, Ruotsalainen V, Salvidio G, Lupia E, Biancone L, Conal-
di PG, Reponen P, Tryggvason K, Camussi G. Nephrin redistribution on podocytes is a potential mechanism for proteinuria in patients with primary acquired nephritic syndrome. Am J Pathol. 2001;158(5):1723-31. doi: 10.1016/S0002-9440(10)64128-4
36. Yuan H, Takeuchi E, Taylor GA, McLaughlin M, Brown D, Salant DJ. Nephrin dissociates from actin, and its expression is reduced in early experimental membranous nephropathy. J Am Soc Nephrol. 2002;13: 946-56.
37. Luimula P, Aaltonen P, Ahola H, Palmen T, Holthofer H. Alternatively spliced nephrin in experimental glomerular disease of the rat. Pediatr Res. 2000;48:759-62. doi: 10.1203/00006450-200012000-00010
38. Nakatsue T, Koike H, Han GD, Suzuki K, Miyauchi N, Yuan H, Salant DJ, Gejyo F, Shimizu F, Kawachi H. Nephrin and podocin dissociate at the onset of proteinuria in experimental membranous nephropathy. Kidney Int. 2005; 67:2239-53. doi: 10.1111/j.1523-1755.2005.00328.x
39. Benzing T. Signaling at the slit diaphragm. J Am Soc Nephrol. 2004;15:1382-91. doi: 10.1097/01.ASN.0000130167.30769.55
40. Gadliardini E, Benigni A, Tomasoni S, Abbate M, Kalluri R, Remuzzi G. Targeted downregulation of extracellular nephrin in human IgA nephropathy. Am J Nephrol. 2003;23:277-86. doi: 10.1159/000072281
41. Patrakka J, Ruotsalainen V, Ketola I, Holmberg C, Heikinheimo M, Tryggvason K, Jalanko H. Expression of nephrin in pediatric kidney diseases. J Am Soc Nephrol. 2001;12:289-96.
42. Яркова Н.А. Нефрин – ранний маркер повреждения почек при сахарном диабете 2-го типа. Лабораторная диагностика. 2017;2(47):101-3 [Yarkova NA. Nephrin is an early marker of kidney damage in type 2 diabetes mellitus. Laboratornaya Diagnostika. 2017;2(47):101-3 (In Russ.)]. doi: 10.21145/2499-9954-2017-2-101-103
43. Huh W, Kim DJ, Kim M-K, Kim YG, Oh H-Y, Ruotsalainen V, Tryggvason K. Expression of nephrin in acquired human glomerular disease. Nephrol Dial Transplant. 2002;17:478-84 doi: 10.1093/ndt/ 17.3.478
44. Чеботарева Н.В., Бобкова И.Н., Козловская Л.В. Нефринурия как показатель структурно-функциональных нарушений гломерулярного фильтра у больных протеинурическими формами нефрита. Клиническая нефрология. 2010;(4):45-51 [Chebotareva IN, Bobkova LV, Kozlovskaya LV. Nephrinuria as a marker of structure-functional glomerular dysfunction in patients with proteinuric glomerulonephritis forms. Klinicheskaya Nefrologiya = Clinical Nephrology. 2010;(4):45-51 (In Russ)].
45. Чеботарева Н.В., Бобкова И.Н., Непринцева Н.В., Козловская Л.В., Малкандуева З.Т. Мочевые биомаркеры подоцитарного повреждения, значение для оценки течения и прогноза хронического гломерулонефрита. Терапевтический архив. 2015;(6):34-9 [Chebotareva NV, Bobkova IN, Neprintseva NV, Kozlovskaya LV, Malkandueva ZT. Urinary biomarkers for podocyte injury: Significance for evaluating the course and prognosis of chronic glomerulonephritis. Terapevticheskiy Arkhiv. 2015;(6):34-9 (In Russ.)]. doi: 10.17116/terarkh 201587634-39
46. Proletov I, Galkina O, Bogdanova E, Zubina I, Sipovskii V, Smirnov A. Clinical significance of podocyte injury markers evaluation in patients with primary glomerulopathies. Nephrol Dial Transplant. 2014;29: iii193.
47. Kriz W, Greitz N, Lemley KV. Progression of glomerular diseases: is the podocyte the culprit? Kidney Int. 1998;54:687-97. doi: 10.1046/j. 1523-1755.1998.00044.x
48. Luyckx VA, Brenner BM. The clinical importance of nephron mass.
J Am Soc Nephrol. 2010;21:898-910. doi: 10.1681/ASN.2009121248
49. Romagnani P, Lasagni L, Remuzzi G. Renal progenitors: An evolutionary conserved strategy for kidney regeneration. Nat Rev Nephrol. 2013;9:137-46. doi: 10.1038/nrneph.2012.290
50. Angelotti ML, Ronconi E, Ballerini L, Peired A, Mazzinghi B, Sagrinati C, et al. Characterization of renal progenitors committed toward the tubular lineage and their regenerative potential in renal tubular injury. Stem Cells. 2012;30:1714-25. doi: 10.1002/stem.1130
51. Ronconi E, Sagrinati C, Angelotti ML, Lazzeri E, Mazzinghi B, et al. Regeneration of glomerular podocytes by human renal progenitors.
J Am Soc Nephrol. 2009;20(2):322-32. doi: 10.1681/asn.2008070709
52. Pavenstadt H. Roles of the podocyte in glomerular function. Am J Physiol. 2000;278:173-9. doi: 10.1152/ajprenal.2000.278.2.F173
53. Schiffer M, Bitzer M, Roberts IS. Apoptosis in podocytes induced by TGF-beta and Smad7. J Clin Invest. 2001;108:807-16. doi: 10.1172/ JCI12367
54. Kim YH, Goyal M, Kurnit D. Podocyte depletion and glomerulosclerosis have a direct relationship in the PAN-treated rat. Kidney Int. 2001;60:957-68. doi: 10.1046/j.1523-1755.2001.060003957.x
55. Yamaguchi Y, Iwano M, Suzuki D. Epithelial-mesenchymal transition as a potential explanation for podocyte depletion in diabetic nephropathy. Am J Kidney Dis. 2009;54:653-64. doi: 10.1053/j.ajkd. 2009.05.009
56. Miyauchi M, Toyoda M, Kobayashi K. Hypertrophy and loss of podocytes in diabetic nephropathy. Intern Med. 2009;48:1615-20.
doi: 10.2169/internalmedicine.48.2137
57. Reidy K, Susztak K. Epithelial-mesenchymal transition and podocyte loss in diabetic kidney disease. Am J Kidney Dis. 2009;54:590-3.
doi: 10.1053/j.ajkd.2009.07.003
58. Petermann AT, Pippin J, Durvasula R, Pichler R, Hiromuda K, Monkawa T, Couser WG, Shankland SJ. Mechanical stretch induces podocyte hypertrophy in vitro. Kidney Int. 2005;67(1):157-66.
doi: 10.1111/j.1523-1755.2005.00066.x
59. Petermann A, Floege J. Podocyte damage resulting in podocyturia: a potential diagnostic marker to assess glomerular disease activity. Nephron Clin Pract. 2007;106(2):61-6. doi: 10.1159/000101799
60. Colucci G, Floege J, Schena FP. The urinary sediment beyond light microscopical examination. Nephrol Dial Transplant. 2006;21(6):
1482-5. doi: 10.1093/ndt/gfl223
61. Li Y, Kang YS, Dai C, Kiss LP, Wen X, Liu Y. Epithelial-to-mesenchymal transition is a potential pathway leading to podocyte dysfunction and proteinuria. Am J Pathol. 2008;172(2):299-308. doi: 10.2353/ajpath.2008.070057
62. Cheng S, Lovett DH, Gelatinase A. (MMP-2) is necessary and sufficient for renal tubular cell epithelial-mesenchymal transformation. Am J Pathol. 2003;162:1937-49. doi: 10.1016/S0002-9440(10)64327-1
63. Tan TK, Zheng G, Hsu TT, Wang Y, Lee VW, Tian X, Wang Y, Cao Q, Wang Y, Harris DC. Macrophage matrix metalloproteinase-9 mediates epithelial-mesenchymal transition in vitro in murine renal tubular cells. Am J Pathol. 2010;176:1256-70. doi: 10.2353/ajpath.2010.090188
64. Cheng S, Pollock AS, Mahimkar R, Olson JL, Lovett DH. Matrix metalloproteinase 2 and basement membrane integrity: a unifying mechanism for progressive renal injury. FASEB J. 2006;20:1898-900.
doi: 10.1096/fj.06-5898fje
65. Lemley KV, Lafayette A, Safai G, Derby G, Blouch K, Squarer A, Myers BD. Podocytopenia and disease severity in IgA nephropathy. Kidney Int. 2002;61:1475-85. doi: 10.1046/j.1523-1755.2002.00269.x
66. Patari A, Forsblom C, Havana M, et al. Nephrinuria in diabetic nephropathy of type 1 diabetes. Diabetes. 2003;52:2969-74.
doi: 10.2337/diabetes.52.12.2969
67. Mallipattu SK, He JC. The podocyte as a direct target for treatment of glomerular disease? Am J Physiol Renal Physiol. 2016;311(1):F46-F51. doi: 10.1152/ajprenal.00184.2016
68. Müller-Deile J, Schiffer M. Podocytes from the diagnostic and therapeutic point of view. Pflugers Arch. 2017;469(7-8):1007-15.
doi: 10.1007/s00424-017-1993-z
________________________________________________
2. Pavenstadt H, Kriz W, Kretzler M. Cell biology of the glomerular podocyte. Physiol Rev. 2003;83:253-307. doi: 10.1152/physrev.00020. 2002
3. Pollak MR. Inherited Podocytopathies: FSGS and Nephrotic Syndrome from a Genetic Viewpoint. J Am Soc Nephrol. 2002;13:3016-23.
doi: 10.1097/01.ASN.0000039569.34360.5E
4. Koop K, Eikmans M, Baelde HJ, Kawachi H, de Heer E, Paul LC, Bruijn JA. Expression of podocyte-associated molecules in acquired human kidney diseases. J Am Soc Nephrol. 2003;14:2063-71. doi: 10.1097/01. ASN.0000078803.53165.C9
5. Patrakka J, Tryggvason K. New insights into the role of podocytes in proteinuria. Nat Rev Nephrol. 2009;5:463-8. doi:10.1038/nrneph. 2009.108
6. Kriz W, Shirato I, Nagata M, Le Hir M, Lemley KV. The podocyte’s response to stress: The enigma of foot process effacement. Am J Physiol Renal Physiol. 2013;304:333-47. doi: 10.1152/ajprenal.00478.2012
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Авторы
N.V. Chebotareva, I.N. Bobkova, L.V. Lysenko
I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of Russia, Moscow, Russia
I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of Russia, Moscow, Russia
I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of Russia, Moscow, Russia
________________________________________________
I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of Russia, Moscow, Russia
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