RENAL HEMODYNAMIC MECHANISMS DEVELOPMENT OF THE HYPERTENSIVE NEPHROPATHY
https://doi.org/10.24884/1561-6274-2009-13-4-28-36
Abstract
In the review are examined the contemporary concepts about the mechanisms of development and progression of hypertensive nephropathy, which is of the main reasons for the chronic kidney disease. Hypertensive nephropathy is the consequence of disruption of the work of renal hemodynamic mechanisms, which protect glomeruli from the damaging action increased arterial pressure. As a result in the kidneys are developed two principally different pathologic processes – ischemic and hypertrophic damage of the glomeruli, which lead to the formation of focal-segmental glomerulosclerosis and increasing loss of renal function. The reason for the first of them is the excessive autoregulatory reaction, which is complicated by obstructive hyalinosis of afferent arterioles, by the ischemic damage of glomeruli and by the loss of the part of functioning nephrons. Simultaneously the ischemic damage of the kidney in the preserved nephrons compensating by its nature phenomenon of hyperfiltration, which leads to the loss of renal autoregulation and steadfast glomerular hypertension, which becomes the major factor for future progression of the glomerular damage, is developed. As a result these hemodynamic disturbances in the kidney is developed hypertrophic (proliferating) glomerulosclerosis. The key role in its formation plays the hyperactivity of the cellular RAS of podocytes, which accompanied by the excess produce of TGF-β1 , VEGF and PDGF, causing profibrotic structural-functional reconstruction of podocytes and mesangial cells. The significant contribution to this pathologic process introduces also the direct mechanical damage of podocytes and mesangial cells, the facilities their sclerotic regeneration and development of inflammatory reaction in the surrounding mesangial tissue.
About the Authors
O. B. Kuzmin
Оренбургская государственная медицинская академия
Russian Federation
Russian Federation
N. V. Buchneva
Оренбургская государственная медицинская академия
Russian Federation
Russian Federation
M. O. Pugaeva
Оренбургская государственная медицинская академия
Russian Federation
Russian Federation
References
1. Бикбов БТ, Томилина НА. Состояние заместительной терапии больных с хронической почечной недостаточностью в Российской Федерации в 1998–2005 гг. (Отчет по данным регистра Российского диализного общества). Нефрология и диализ 2007; 9 (1): 6-85
2. Bidani AK, Griffin KA. Long-term renal consequences of hypertension for normal and diseased kidney. Curr Opin Nephrol Hypertens 2002; 11 (1): 73-80
3. Kriz W, Eberhard E, Nobiling R et al. A role podocytes to counteract capillary wall distension. Kidney Int 1994; 45 (2): 369-376
4. Loutzenhiser R, Griffin K, Williamson G, Bidani A. Renal autoregulation: new perspectives regarding the protective and regulatory roles of the underlying mechanisms. Am J Physiol Regul 2006; 290 (5): R1153-R1167
5. Just A. Mechanisms of renal blood flow autoregulation: dynamics and contributions. Am J Physiol Regul 2007; 292 (1): R1-R17
6. Brannstrom K, Morsing P, Arendshort WJ. Exaggerated tubuloglomerular feedback activity in genetic hypertension is mediated by Ang II and AT1 receptor. Am J Physiol Renal 1996; 270 (5): F749-F755
7. Karlsen FM, Leyssac PP, Holstein-Rathlon NH. Tubuloglomerular feedback in Dahl rats. Am J Physiol Regul 1998; 274 (6): R1561-R1569
8. Takabatake T, Ushioqi Y, Ohta K. Hattory N. Attenuation of enhanced tubuloglomerular feedback activity in SHR by renal denervation. Am J Physiol Renal 1990; 258 (4, Pt 2): F980-F985
9. Churg J, Sobin CH. Benign nephrosclerosis. In: Churg J ed. Renal disease – classification and atlas of glomerular diseases. Igaku-Shoin, Tokio, 1982; 211-224
10. Raij L. The pathophysiologic basis for blocking the renin-angiotensin system in hypertensive patients with renal disease. Am J Hypertens 2005; 18 [suppl 4s]: 95s-99s
11. Hills GS, Heudes D, Jacquot C et al. Morphometric evidence for impairment of renal autoregulation in advanced essential hypertension. Kidney Int 2006; 69 (5): 823-831
12. Cortes P, Zhao X, Riser BL, Narins RG. Regulation of glomerular volume in normal and partially nephrectomized rats. Am J Physiol Renal 1996; 270 (2, Pt 2): F356-F370
13. Friedrich C, Endlich N, Kriz W, Endlich K. Podocytes are sensitive to fluid shear stress in vitro. Am J Physiol Renal 2006; 291 (4): F856-F865
14. Seikaky MG, Arant BS, Seney FD. Endogenous angiotensin concentrations in special intrarenal fluid compartments in the rat. J Clin Invest 1990; 86 (9): 1352-1357
15. Velez JCQ, Bland AM, Arthur J et al. Characterization of renin-angiotensin system enzyme activities in cultured podocytes. Am J Physiol Renal 2007; 293 (1): F398-F407
16. Wang L, Flannery PJ, Spurney RF. Characterization of angiotensin II-receptor subtypes in podocytes. J Lab Clin Med 2003; 142 (5): 313-321
17. Liebau MC, Lang D, Bohm J et al. Functional expression of the renin-angiotensin system in human podocytes. Am J Physiol Renal 2006; 290 (3): F710-F719
18. Singh R, Singh AK, Alavi N, Leechy D. Mechanism of increased angiotensin II levels in glomerular mesangial cells cultured in high glucose. J Am Soc Nephrol 2003; 14 (4): 873-880
19. Ardaillou R, Chansel D, Chatziantoniou C, Dussaule JC. Mesangial AT1 receptors: expression, signaling and regulation. J Am Soc Nephrol 1999; 10 [suppl 11]: S40-S46
20. Goto M, Mukoyama M, Sugawara A et al. Expression and role of angiotensin II type 2 receptor in the kidney and mesangial cells of spontaneously hypertensive rats. Hypertens Res 2002; 25 (1): 125-133
21. Durvasula RV, Petermann AT, Hiromura K et al. Activation of local tissue angiotensin system in podocytes by mechanical strain. Kidney Int 2004; 65 (1): 30-39
22. Becker BN, Yasuda T, Kondo S et al. Mechanical stretch/relaxation stimulates a cellular renin-angiotensin system in cultured rat mesangial cells. Nephron Exp Nephrol 1998; 6 (1): 57-66
23. Gruden J, Thomas S, Burt D et al. Interaction of angiotensin II and mechanical stretch on vascular endothelial growth factor production by human mesangial cells. J Am Soc Nephrol 1999; 10 (3): 730-737
24. Hoffman S, Podlich D, Hahnel B et al. Angiotensin II type I receptor overexpression in podocytes induces glomerulosclerosis in transgenic rats. J Am Soc Nephrol 2004; 15 (6): 1475-1487
25. Obata J, Nakamura T, Takano H et al. Increased gene expression of components of the renin-angiotensin system in glomeruli of genetically hypertensive rats. J Hypertens 2000; 18 (9): 1247-1255
26. Kang YS, Park YJ, Kim BK. 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 (2): 377-378
27. Liy Y, Kang YS, Dai C et al. Epithelial-to-mesenchymal transition is a potential pathway to podocytes dysfunction and proteinuria. Am J Pathol 2008; 172 (2): 299-308
28. Ding G, Reddy K, Kapasi AA et al. Angiotensin II induces apoptosis in rat glomerular epithelial cells. Am J Physiol Renal 2002; 283 (1): F173-F180
29. Lai XX, Ding GH, Haang CX et al. Angiotensin II-induced podocytes apoptosis: a role of MAPK subtypes. Beijing Da Xue Bao 2004; 36 (2): 131-134
30. Shu S, Liu Y, Wang L, Meng QH. Transforming growth factor-beta 1 is associated with kidney damage in patients with essential hypertension: renoproctive effect of ACE inhibitor and/or angiotensin II receptor blocker. Nephrol Dial Transplant 2008; 23 (9): 2841-2846
31. Hirschberg R, Wang S, Mitu GM. Functional symbiosis between endothelium and epithelial cells in glomeruli. Cell Tissue Res 2008; 331 (2): 485-493
32. Eremina V, Baedle HJ, Quaggin SE. Role of the VEGF-signaling pathway in the glomerulus: evidence for crosstalk between components of glomerular filtration barrier. Nephron Physiol 2007; 106 (2): 32-37
33. Guan F, Villegas G, Teichman J et al. Autocrine VEGF-A system in podocytes regulates podocin and its interaction with CD2AP. Am J Physiol Renal 2006; 291 (2): F422-F428
34. Eremina V, Cui S, Gerber H et al. Vascular endothelial growth factor signaling in the podocytes-endothelial compartment is required for mesangial cell migration and survival. J Am Nephrol 2006; 17 (3): 724-735
35. Chen S, Lee JS, Iglesias-de la Cruz MC et al. Angiotensin II stimulates alpha3 (IV) collagen production in mouse podocytes via TGF-beta and VEGF signaling: implication for diabetic nephropathy. Nephrol Dial Transplant 2005; 20 (7): 1320-1328
36. Thomas S, Vanuystel J, Gruden G et al. Vascular endothelial growth factor receptors in human mesangium in vitro and in glomerular disease. J Am Soc Nephrol 2000; 11 (7): 1236-1243
37. Amamiya T, Sasamura H, Mifune M et al. Vascular endothelial growth factor activates MAP kinase and enhances collagen synthesis in human mesangial cells. Kidney Int 1999; 56 (6): 2055-2063
38. Liu E, Marimoto M, Kitajima S et al. Increased expression of vascular endothelial growth factor in kidney leads to progressive impairment of glomerular function. J Am Soc Nephrol 2007; 18 (7): 2094-2104
39. Yamauchi T, Ogura T, Oishi T et al. The angiotensin 1-converting enzyme inhibitor cilazapril inhibits the platelet-derived growth factor B chain expression in glomeruli of spontaneously hypertensive rats. Ren Physiol Biochem 1995; 18 (5): 237-245
40. Higueruelo S, Romero R. Angiotensin II requires PDGF-BB to induce DNA synthesis in rat mesangial cells cultured in exogenous insulin free medium. Nephrol Dial Transplant 1997; 12 (4): 694-700
41. Floege J, Eitner F, Alpers CE. A new look at platelet-derived growth factor in renal disease. J Am Soc Nephrol 2008; 19 (1): 12-23
42. Kretzler M. Regulation of adhesive interaction between podocytes and glomerular basement membrane. Microsc Res Tech 2002; 57 (4): 247-253
43. Dai C, Stolz DB, Bastacky Si et al. Essential role of integrin-linked kinase in podocytes biology: bridging the integrin and slit diaphragm signaling. J Am Soc Nephrol 2006; 17 (8): 2164-2175
44. Dessapt CBM, Hayward A, Viberti G, Gnudi L. TGF-β 1 and mechanical stretch reduce murine podocytes adhesion to extracellular matrix substrate and modulate β1 integrin expression/ maturation in vitro. Diabetologia 2005; [suppl 1]: A28 (abstract)
45. Kanasaki K, Kanda Y, Palmsten K et al. Integrin beta1-mediated matrix assembly and signaling are critical for the normal development and function of kidney glomerulus. Dev Biol 2008; 313 (2): 584-593
46. Riser BL, Ladson-Wofford S, Sharba A et al. TGF-beta receptor expression and binding in rat mesangial cells: modulation by glucose and cyclic mechanical strain. Kidney Int 1999; 56 (2): 428-439
47. Gruden G, Zonca S, Hayward A et al. Mechanical stretch-induced fibronectin and transforming growth factor-beta 1 production in human mesangial cells is p38 mitogen-activated protein kinase dependent. Diabetes 2000; 49 (4): 655-661
48. Harris RC, Haralson MA, Badr KF. Continuous stretch-relaxation in culture alters rat mesangial cell morphology, growth characteristics and metabolic activity. Lab Invest 1992; 66 (3): 548-554
49. Riser BL, Cortes P, Zhao X et al. Intraglomerular pressure and mesangial stretching stimulate extracellular matrix formation in the rat. J Clin Invest 1992; 90 (5): 1932-1943
50. Yasuda T, Kondo S, Homma T, Harris RC. Regulation of extracellular matrix by mechanical stress in rat glomerular mesangial cells. J Clin Invest 1996; 98 (9): 1991-2000
51. Heilig CW, Concepcion LA, Riser BL et al. Overexpression of glucose transporters in rat mesangial cells cultured in normal glucose milieu mimics diabetic phenotype. J Clin Invest 1995; 96 (8): 1802-1814
52. Chen S, Heilig KO, Brosius FC, Heilig CW. Diabetes increases glomerular GLUT1 and antisense-GLUT1 protects against diabetic glomerulosclerosis (Abstract). J Am Soc Nephrol 2003; 14: 46A
53. Gnudi L, Viberti G, Raij L et al. GLUT-1 overexpression: link between hemodynamic and metabolic factors in glomerular injury? Hypertension 2003; 42 (1): 19-24
54. Gnudi L, Viberti G. The link between mechanical stretch and glucose metabolism – a conceptual advance in understanding diabetic (and nondiabetic?) renal disease. Nephrol Dial Transplant 2007; 22 (2): 318-321
55. Gruden G, Setti G, Hayward A et al. Mechanical stretch induces monocyte chemoattractant activity via an NF-kappa B-dependent monocyte chemoattractant protein-1-mediated pathway in human mesangial cells: inhibition by rosiglitazone. J Am Soc Nephrol 2005; 16 (3): 688-696
56. Riser BL, Varani J, Cortes P et al. Cyclic stretching of mesangial cells up-regulated intercellular adhesion molecule-1 and leukocyte adherence: a possible new mechanism for glomerulosclerosis. Am J Pathol 2001; 158 (1): 11-17
57. Giunti S, Pinach S, Arnoldi L et al. The MCP/CCR2 system has direct proinflammatory effects in human mesangial cells. Kidney Int 2006; 69 (5): 856-863
58. Giunti S, Tesch GH, Pinach S et al. Monocyte chemoattractant protein-1 has prosclerotic effects both in a mouse model of experimental diabetes and in vitro in human mesangial cells. Diabetologia 2008; 51 (1): 198-207
59. Park J, Ryu S, Li JJ et al. MCP/CCR2 system is involved in high glucose-induced fibronectin and type IV collagen expression in cultured mesangial cells. Am J Physiol Renal 2008; 295 (3): F749-F757
Review
For citations:
Kuzmin O.B., Buchneva N.V., Pugaeva M.O. RENAL HEMODYNAMIC MECHANISMS DEVELOPMENT OF THE HYPERTENSIVE NEPHROPATHY. Nephrology (Saint-Petersburg). 2009;13(4):28-36. (In Russ.) https://doi.org/10.24884/1561-6274-2009-13-4-28-36
Views:
860
Email this article 