Skip to main content
SpringerLink
Log in

Pathogenesis of Diabetic Nephropathy: Hemodynamic Alterations/Renin Angiotensin System

  • Chapter
  • First Online:
Diabetes and Kidney Disease

  • 2102 Accesses

Abstract

Diabetic nephropathy, a microvascular complication of diabetes, is clinically characterized by an initial increase in glomerular filtration rate (GFR) and microalbuminuria (Semin Nephrol 23(2), 194–199, 2003). If left untreated, these early pathophysiologic changes will progress to renal fibrosis and tubulointerstitial damage along with a decline in GFR, ultimately leading to kidney failure (Curr Opin Nephrol Hypertens 12(3), 273–282, 2007; J Hypertens 23(11), 1931–1937, 2005).

Diabetic nephropathy and its related pathophysiologic alterations in renal microcirculation is thought to develop as a result of the interaction between metabolic and hemodynamic factors that together activate common intracellular pathways that trigger the production of various cytokines and growth factors leading to kidney disease. Persistent elevations in blood glucose alter renal hemodynamics through activation of several vasoactive hormonal pathways, including the renin-angiotensin-aldosterone system, endothelin, and urotensin (Diabet Med 21(Suppl 1), 15–18, 2004; Curr Hypertens Rep 6(2), 98–105, 2004). These hormones then in turn can activate second messenger signaling pathways, including protein kinase C, transcription factors, including NK-κB, and cytokines, including TGF-β, VEGF, and PDGF, all of which can lead to the development of albuminuria, glomerulosclerosis, and tubulointerstitial fibrosis characteristic of diabetic nephropathy (Kidney Int Suppl 106, S49–S53, 2007; Semin Nephrol 27(2), 153–160, 2007). This chapter will provide a detailed review of these hemodynamic and hormonal mechanisms that underlie the development of diabetic nephropathy.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Hostetter TH. Hyperfiltration and glomerulosclerosis. Semin Nephrol. 2003;23(2):194–9.

    Article  CAS  PubMed  Google Scholar 

  2. Caramori ML, Mauer M. Diabetes and nephropathy. Curr Opin Nephrol Hypertens. 2007;12(3):273–82.

    Article  Google Scholar 

  3. Leon CA, Raij L. Interaction of haemodynamic and metabolic pathways in the genesis of diabetic nephropathy. J Hypertens. 2005;23(11):1931–7.

    Article  CAS  PubMed  Google Scholar 

  4. Cooper M, Boner G. Dual Blockade of the renin-angiotensin-aldosterone system in diabetic nephropathy. Diabet Med. 2004;21 Suppl 1:15–8.

    Article  PubMed  Google Scholar 

  5. Hanes DS, Nahar A, Weir MR. The tissue renin-angiotensin-aldosterone system in diabetic mellitus. Curr Hypertens Rep. 2004;6(2):98–105.

    Article  PubMed  Google Scholar 

  6. Noh H, King GL. The role of protein kinase C activation in diabetic nephropathy. Kidney Int Suppl. 2007;106:S49–53.

    Article  CAS  PubMed  Google Scholar 

  7. Zhu Y, Usui HK, Sharma K. Regulation of transforming growth factor beta in diabetic nephropathy: implications for treatment. Semin Nephrol. 2007;27(2):153–60.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Hollenberg NK, Price DA, Fisher ND, Lansang MC, Perkins B, Gordon MS, Williams GH, Laffel LM. Glomerular hemodynamics and renin-angiotensin system in patients with type I diabetes mellitus. Kidney Int. 2003;63:172–8.

    Article  CAS  PubMed  Google Scholar 

  9. Zimpelmann J, Kumar D, Levine DZ, Wehbi G, Imig JD, Navar LG, Burns KD. Early diabetes mellitus stimulates proximal tubule renin mRNA expression in the rat. Kidney Int. 2000;58(6):2320–30.

    Article  CAS  PubMed  Google Scholar 

  10. Schmieder RE. The potential role of prorenin in diabetic nephropathy. J Hypertens. 2007;25(7):1323–6.

    Article  CAS  PubMed  Google Scholar 

  11. Benter IF, Yousif MH, Anim JT, Cojocel C, Diz DI. Angiotensin (1-7) prevents the development of severe hypertension and end-organ damage in spontaneously hypertensive rats treated with L-NAME. Am J Physiol Heart Circ Physiol. 2006;290(2):H684–91.

    Article  CAS  PubMed  Google Scholar 

  12. Singh R, Singh AK, Leehey DJ. A novel mechanism for angiotensin II formation in streptozotocin-diabetic rat glomeruli. Am J Physiol Renal Physiol. 2005;288(6):F1183–90.

    Article  CAS  PubMed  Google Scholar 

  13. Kobori H, Nangaku M, Navar LG, Nishiyama A. The intrarenal renin-angiotensin system: from physiology to the pathobiology of hypertension and the kidney disease. Pharmacol Rev. 2007;59(3):251–87.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Dzau VJ, Re R. Tissue angiotensin system in cardiovascular medicine. A paradigm shift? Circulation. 1994;89(1):493–8.

    Article  CAS  PubMed  Google Scholar 

  15. Trask AJ, Ferraio CM. Angiotensin (1-7): pharmacology and new perspectives in cardiovascular treatments. Cardiovasc Drug Rev. 2007;25(2):162–74.

    Article  CAS  PubMed  Google Scholar 

  16. Hamming I, Cooper ME, Haagmans BL, Hooper NM, Korstanje R, Osterhaus AD, Tiemens W, Turner AJ, Navis G, van Goor H. The emerging role of ACE2 in physiology and disease. J Pathol. 2007;212(1):1–11.

    Article  CAS  PubMed  Google Scholar 

  17. Wolf G, Ziyadeh FN. The role of angiotensin II in diabetic nephropathy: an emphasis on nonhemodynamic mechanisms. Am J Kidney Dis. 1997;29(1):153–63.

    Article  CAS  PubMed  Google Scholar 

  18. Kennefick TM, Oyama TT, Thompson MM, Vora JP, Anderson S. Enhanced renal sensitivity to angiotensin actions in diabetes mellitus in the rat. Am J Physiol. 1996;271(3):F595–602.

    CAS  PubMed  Google Scholar 

  19. He W, Miao FJ, Lin DC, Schwander RT, Wang Z, Gao J, Chen JL, Tian H, Ling L. Citric acid cycle intermediates as ligands for orphan G-protein-coupled receptors. Nature. 2004;429(6988):1881–93.

    Article  CAS  Google Scholar 

  20. Toma I, Kang JJ, Sipos A, Vargas S, Bansal E, Hanner F, Meer E, Peti-Pterdi J. Succinate receptor GPR91 provides a direct link between high glucose levels and renin release in murine and rabbit kidney. J Clin Invest. 2008;118(7):2526–34.

    CAS  PubMed Central  PubMed  Google Scholar 

  21. Anderson S. Physiologic actions and molecular expression of the renin-angiotensin system in the diabetic rat. Miner Electrolyte Metab. 1998;24(6):406–11.

    Article  CAS  PubMed  Google Scholar 

  22. Kobori H, Katsurada A, Miyata K, Ohashi N, Satou R, Saito T, Hagiwara Y, Miyashita K, Navar LG. Determination of plasma and urinary angiotensinogen levels in rodents by newly developed ELISA. Am J Physiol Renal Physiol. 2008;294(5):F1257–63.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Yamamoto T, Nakagawa T, Suzuki H, Ohashi N, Fukusawa H, Fujigaki Y, Kato A, Nakamura Y, Suzuki F, Hishida A. Urinary angiotensinogen as a marker of intrarenal angiotensin II activity associated with deterioration of renal function in patients with chronic kidney disease. J Am Soc Nephrol. 2007;18(5):1558–65.

    Article  CAS  PubMed  Google Scholar 

  24. Kobori H, Ozawa Y, Suzaki Y, Prieto-Carrasquero MC, Nishiyama A, Shoji T, Cohen EP, Navar LG. Young scholars award lecture: intratubular angiotensinogen in hypertension and kidney disease. Am J Hypertens. 2006;19(5):541–50.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Huang XR, Chen WY, Truong LD, Lan HY. Chymase is upregulated in diabetic nephropathy: implications for an alternative pathway of angiotensin II-mediated diabetic renal and vascular disease. J Am Soc Nephrol. 2003;14(7):1738–47.

    Article  CAS  PubMed  Google Scholar 

  26. Jones SE, Gilbert RE, Kelly DJ. Tranilast reduces mesenteric vascular collagen deposition and chymase-positive mast cells in experimental diabetes. J Diab Comp. 2004;18(10):309–15.

    Article  CAS  Google Scholar 

  27. Park S, Bivona BJ, Kobori H, Seth DM, Chappell MC, Lazartigues C, Harrison-Bernard LM. Major role for ACE-independent intrarenal ANG II formation in type II diabetes. Am J Physiol Renal Physiol. 2010;298(1):F37–48.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Zhuo JL, Li XC. Novel roles of intracrine angiotensin II and signaling mechanisms in kidney cells. J Renin Angiotensin Aldosterone Syst. 2007;8(1):23–33.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Wehbi GJ, Zippelmann J, Carey RM, Levine DZ, Burns KD. Early streptozotocin-diabetes mellitus downregulates rat kidney AT2 receptors. Am J Physiol Renal Physiol. 2001;280(2):F254–65.

    CAS  PubMed  Google Scholar 

  30. Griffin KA, Bidani AK. Progression of renal disease: renoprotective specificity of the renin-angiotensin system blockade. Clin J Am Soc Nephrol. 2006;1(5):1054–65.

    Article  PubMed  Google Scholar 

  31. Hakam AC, Siddiqui AH, Hussain T. Renal angiotensin II AT2 receptors promote natriuresis in streptozotocin-induced diabetic rats. Am J Physiol Renal Physiol. 2006;290(2):F503–8.

    Article  CAS  PubMed  Google Scholar 

  32. Bonnet F, Candido R, Carey RM, Casley D, Russo LM, Osicka TM, Cooper ME, Cao Z. Renal expression of angiotensin receptors in long-term diabetes and the effects of angiotensin type I receptor blockade. J Hypertens. 2002;20(8):1615–24.

    Article  CAS  PubMed  Google Scholar 

  33. Gurley SB, Coffman TM. The renin-angiotensin system and diabetic nephropathy. Semin Nephrol. 2007;27(2):144–52.

    Article  CAS  PubMed  Google Scholar 

  34. Carmines PK, Ohishi K. Renal arteriolar contractile responses to angiotensin II in rats with poorly controlled diabetes. Clin Exp Pharmacol Physiol. 1999;26(11):877–82.

    Article  CAS  PubMed  Google Scholar 

  35. Maric C, Zheng W, Walther T. Interactions between angiotensin II and atrial natriuretic peptide in renomedullary interstitial cells: the role of neutral endopeptidase. Nephron Physiol. 2006;103(3):149–56.

    Article  CAS  Google Scholar 

  36. Ruiz-Ortega M, Lorenzo O, Rupurez M, Konig S, Wittig B, Egido J. Angiotensin II activates nuclear transcription factor kappaB through AT(1) and AT(2) in vascular smooth muscle cells: molecular mechanisms. Circ Res. 2000;86(12):1266–72.

    Article  CAS  PubMed  Google Scholar 

  37. Ruiz-Ortega M, Bustos C, Hernandez-Presa MA, Lorenzo O, Plaza JJ, Egido J. Angiotensin II participates in mononuclear cell recruitment in experimental immune complex nephritis through nuclear factor-kappa B activation and monocyte chemoattractant protein-J synthesis. J Immunol. 1998;161(1):430–9.

    CAS  PubMed  Google Scholar 

  38. Doublier S, Salvidio G, Lupia E, Ruotsalainen V, Verzola D, Defarri G, Camussi G. Nephrin expression is reduced in human diabetic nephropathy: evidence for a distinct role for glycated albumin and angiotensin II. Diabetes. 2003;52(4):1023–30.

    Article  CAS  PubMed  Google Scholar 

  39. Macconi D, Abbate M, Morigi M, Angioletti S, Mister M, Buelli S, Bonomelli M, Mundel P, Endlich K, Remuzzi A, Remuzzi G. Permselective dysfunction of podocyte-podocyte contact upon angiotensin II unravels the molecular target for renoprotective intervention. Am J Pathol. 2006;168(4):1073–85.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  40. Chen S, Lee JS, Iglesias-de la Cruz MC, Wang A, Izqquierdo-Lahuerta A, Gandhi NK, Danesh FR, Wolf G, Ziyadeh FN. Angiotensin II stimulates alpha3(IV) collagen production in mouse podocytes via TGF-beta and VEGF signaling: implications for diabetic glomerulopathy. Nephrol Dial Transplant. 2005;20(7):1320–8.

    Article  CAS  PubMed  Google Scholar 

  41. Wolf G, Ziyadeh FN. Renal tubular hypertrophy induced by angiotensin II. Semin Nephrol. 1997;17(5):448–54.

    CAS  PubMed  Google Scholar 

  42. Pettersson-Fernholm K, Frojdo S, Fagerudd J, Thomas MC, Forsblom C, Wessman M, Groop PH. The AT2 gene may have a gender-specific effect on kidney function and pulse pressure in type I diabetic patients. Kidney Int. 2006;69(10):1880–4.

    Article  CAS  PubMed  Google Scholar 

  43. Cao Z, Bonnet F, Candido R, Nesteroff SP, Burns WC, Kawachi H, Shimizu F, Carey RM, DeGasparo M, Cooper ME. Angiotensin type 2 receptor antagonism confers renal protection in a rat model of progressive renal injury. J Am Soc Nephrol. 2002;13(7):1773–87.

    Article  CAS  PubMed  Google Scholar 

  44. Esteban V, Lorenzo O, Ruperez M, Suzuki Y, Mezzano S, Blanco J, Kretzler M, Sugaya T, Egido J, Ruiz-Ortega M. Angiotensin II, via AT1 and AT2 receptors and NF-kappaB pathway, regulates the inflammatory response in unilateral ureteral obstruction. J Am Soc Nephrol. 2004;15(6):1514–29.

    Article  CAS  PubMed  Google Scholar 

  45. Ferrario CM, Chappell MC. Novel angiotensin peptides. Cell Mol Life Sci. 2004;61(21):2720–7.

    Article  CAS  PubMed  Google Scholar 

  46. Tipnis SR, Hooper NM, Hyde R, Karran E, Chrisitie G, Turner AJ. A human homolog angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase. J Biol Chem. 2000;275(43):33238–43.

    Article  CAS  PubMed  Google Scholar 

  47. Danilczyk U, Sarao R, Remy C, Benabbas C, Stange G, Richter A, Arya S, Pospisilik JA, Singer D, Camargo SMR, Makrides V, Ramadan T, Verrey F, Wagner CA, Penninger JM. Essential role of collectrin in renal acid transport. Nature. 2006;444(7122):1088–91.

    Article  CAS  PubMed  Google Scholar 

  48. Santos RAS, e Silva ACS, Maric C, Silva DMR, Machado RP, de Buhr I, Heringer-Walther S, Pinheiro SVB, Lopes MT, Bader M, Mendes EP, Lemos VS, Campagnole-Santos MJ, Schultheiss HP, Speth R, Walther T. Angiotensin(1-7) is an endogenous ligand for the G protein-coupled receptor Mas. Proc Natl Acad Sci. 2003;100(14):8258–63.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  49. Paula RD, Lima CV, Khosla MC, Santo RAS. Angiotensin(1-7) potentiated the hypotensive effect of bradykinin in conscious rats. Hypertension. 1995;26(6 Pt 2):1154–9.

    Article  CAS  PubMed  Google Scholar 

  50. Tikellis C, Johnston CI, Forbes JM, Burns WC, Burrell LM, Risvanis J, Cooper ME. Characterization of renal angiotensin-converting enzyme 2 in diabetic nephropathy. Hypertension. 2003;41(3):392–7.

    Article  CAS  PubMed  Google Scholar 

  51. Ye M, Wysocki J, William J, Soler MJ, Cokic I, Batlle D. Glomerular localization and expression of angiotensin-converting enzyme 2 and angiotensin converting enzyme: implications for albuminuria in diabetes. J Am Soc Nephrol. 2006;17(11):3067–75.

    Article  CAS  PubMed  Google Scholar 

  52. Mizuiri S, Hemmi H, Arita M, Ohashi Y, Tanaka Y, Miyagi M, Sakai K, Ishikawa Y, Shibuya K, Hase H, Aikawa A. Expression of ACE and ACE2 in individuals with diabetic kidney disease and healthy controls. Am J Kidney Dis. 2008;51(4):613–23.

    Article  CAS  PubMed  Google Scholar 

  53. Soler MJ, Wysocki J, Ye M, Lloveras J, Kanwar Y, Batlle D. ACE2 inhibition worsens glomerular injury in association with increased ACE expression in streptozotocin-induced diabetic mice. Kidney Int. 2007;72(8):614–23.

    Article  CAS  PubMed  Google Scholar 

  54. Wong DW, Oudit GY, Reich H, Kassiri Z, Zhou J, Liu QC, Backx PH, Penninger JM, Herzenberg AM, Schlet JW. Loss of angiotensin-converting enzyme-2 (Ace2) accelerate diabetic kidney injury. Am J Pathol. 2007;171(2):439–51.

    Article  CAS  Google Scholar 

  55. Ferrario CM. Angiotensin(1-7) and antihypertensive mechanisms. J Nephrol. 1998;11(6):278–83.

    CAS  PubMed  Google Scholar 

  56. Ronchi FA, Irigoyen MC, Casarini DE. Association of somatic and N-domain angiotensin-converting enzymes from Wistar rat tissue with renal dysfunction in diabetes mellitus. J Renin Angiotensin Aldosterone Syst. 2007;8(1):34–41.

    Article  CAS  PubMed  Google Scholar 

  57. Ward PE, Sheridan MS. Converting enzyme, kininase, and angiotensinase of renal and intestinal brush border. Exp Med Biol. 1983;156(Pt B):835–44.

    Google Scholar 

  58. Benter IF, Yousif MH, Dhaunsi GS, Kaur J, Chappell MC, Diz DI. Angiotensin(1-7) prevents activation of NADPH oxidase and renal vascular dysfunction in diabetic hypertensive rats. Am J Nephrol. 2008;28(1):25–33.

    Article  CAS  PubMed  Google Scholar 

  59. Heitsch H, Brovkovych S, Malinski T, Wiemer G. Angiotensin(1-7) stimulated nitric oxide and superoxide release from endothelial cells. Hypertension. 2001;37:72–6.

    Article  CAS  PubMed  Google Scholar 

  60. Brosnihan KB, Li P, Ferrario CM. Angiotensin(1-7) dilates canine coronary through kinins and nitric oxide. Hypertension. 1996;27(3 pt 2):523–8.

    Article  CAS  PubMed  Google Scholar 

  61. Sampaio WO, Nascimento AA, Santos RA. Systemic and regional hemodynamic effects of angiotensin(1-7) in rats. Am J Physiol Heart Circ Physiol. 2003;284(6):H1985–94.

    CAS  PubMed  Google Scholar 

  62. Dharmani M, Mustafa MR, Achike FI, Sim MK. Effects of angiotensin(1-7) on the action of angiotensin II in the renal and mesenteric vasculature of hypertensive and streptozotocin-induced diabetic rats. Eur J Pharmacol. 2007;561(1–3):144–50.

    Article  CAS  PubMed  Google Scholar 

  63. Ferrario CM, Iyer SN. Angiotensin(1-7): a bioactive fragment of the renin-angiotensin system. Regul Pept. 1998;78(1–3):13–8.

    Article  CAS  PubMed  Google Scholar 

  64. Ocaranza MP, Godoy I, Jalil JE, Varas M, Collantes P, Pinto M, Roman M, Ramirez C, Copaja M, Diaz-Araya G, Castro P, Lavandero S. Enalapril attenuates downregulation of angiotensin-converting enzyme 2 in the late phase of ventricular dysfunction in the myocardial infarcted rat. Hypertension. 2006;48(4):572–8.

    Article  CAS  PubMed  Google Scholar 

  65. Ruiz-Ortega M, Esteban V, Egido J. The regulation of the inflammatory response through nuclear-factor kappaB pathway by angiotensin IV extends the role of the renin angiotensin system in cardiovascular diseases. Trends Cardiovasc Med. 2007;17(1):19–25.

    CAS  PubMed  Google Scholar 

  66. Abrahamsen CT, Pullen MA, Schnackenberg CG, Grygielko ET, Edwards RM, Laping NJ, Brooks DP. Effects of angiotensin II and IV on blood pressure, renal function, and PAI-1 expression in the heart and kidney of the rat. Pharmacology. 2002;66(1):26–30.

    Article  CAS  PubMed  Google Scholar 

  67. Athyros VG, Mikhaildis DP, Kakafika AI, Tziomalos K, Karagiannis A. Angiotensin II reactivation and aldosterone escape phenomena in renin-angiotensin-aldosterone system blockade: is oral renin inhibition the solution? Expert Opin Pharmacother. 2007;8(5):529–35.

    Article  CAS  PubMed  Google Scholar 

  68. Kelly DJ, Skinner SL, Gilbert RE, Cox AJ, Cooper ME, Wilkinson-Berka JL. Effects of endothelin or angiotensin II receptor blockade on diabetes in transgenic (mRen-2)27 rat. Kidney Int. 2000;57(5):1882–94.

    Article  CAS  PubMed  Google Scholar 

  69. Prieto-Carrasquero MC, Kobori H, Ozawa Y, Guiterrez A, Seth D, Navar LG. AT1 receptor-mediated enhancement of collecting duct renin in angiotensin I-dependent hypertensive rats. Am J Physiol Renal Physiol. 2005;289(3):F632–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  70. Kang JJ, Toma I, Sipos A, Meer EJ, Vargas SL, Peti-Peterdi J. The collecting duct is the major source of prorenin in diabetes. Hypertension. 2008;51(6):1597–604.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  71. Daneman D, Crompton CH, Balfe JW, Sochett EB, Chatzilias A, Cotter BR, Osmond DH. Plasma prorenin as an early marker of nephropathy in diabetic (IDDM) adolescents. Kidney Int. 1994;46(4):1154–9.

    Article  CAS  PubMed  Google Scholar 

  72. Danser AH, Deinum J. Renin, prorenin, and the putative (pro)renin receptor. J Renin Angiotensin Aldosterone Syst. 2005;6(3):163–5.

    Article  CAS  PubMed  Google Scholar 

  73. Nguyen G, Delarue F, Burckle C, Bouzhir L, Giller T, Sraer JD. Pivotal role of the renin/prorenin receptor in angiotensin II production and cellular responses to renin. J Clin Invest. 2002;109(11):1417–27.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  74. Huang Y, Wongamorntham S, Kasting J, McQuilan D, Owens RT, Yu L, Noble NA, Border W. Renin increases mesangial cell transforming growth factor-β1 and matrix proteins through receptor-mediated, angiotensin II-mediated independent mechanisms. Kidney Int. 2006;69(1):105–13.

    Article  CAS  PubMed  Google Scholar 

  75. Sakoda M, Ichihara A, Kurauchi-Mito A, Narita T, Kinouchi K, Murohashi-Bokuda K, Saleem MA, Nishiyama A, Suzuki F, Itoh H. Aliskiren inhibits intracellular angiotensin II levels without affecting (pro)renin receptor signals in human podocytes. Am J Hypertens. 2010;23(5):575–80.

    Article  CAS  PubMed  Google Scholar 

  76. Ichihara A, Hayashi M, Kaneshiro Y, Suzuki F, Nakagawa T, Tada Y, Koura Y, Nishiyama A, Okada H, Uddin MN, Nabi AH, Ishida Y, Inagami T, Saruta T. Inhibition of diabetic nephropathy by a decoy peptide corresponding to the “handle” region for nonproteolytic activation of prorenin. J Clin Invest. 2004;114(8):1128–35.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  77. Ichihara A, Kaneshiro Y, Suzuki F. Prorenin receptor blockers: effects on cardiovascular complications of diabetes and hypertension. Expert Opin Investig Drugs. 2006;15(10):1137–9.

    Article  CAS  PubMed  Google Scholar 

  78. Han SY, Kim CH, Kim HS, Jee YH, Song HK, Lee MH, Han KH, Kim HK, Kang YS, Han JY, Kim YS, Cha DR. Spironolactone prevents diabetic nephropathy through an anti-inflammatory mechanism in type II diabetic rats. J Am Soc Nephrol. 2006;17(5):1362–72.

    Article  CAS  PubMed  Google Scholar 

  79. Matsumoto S, Takebayashi K, Aso Y. The effect of spironolactone on circulating adipocytokines in patients with type 2 diabetes complicated by diabetic nephropathy. Metabolism. 2006;55(12):1645–52.

    Article  CAS  PubMed  Google Scholar 

  80. Epstein M, Williams GH, Weinberger M, Lewin A, Krause S, Mukherjee R, Patni R, Beckerman B. Selective aldosterone blockade with eplerenone reduces albuminuria in patients with type 2 diabetes. Clin J Am Soc Nephrol. 2006;1(5):940–51.

    Article  CAS  PubMed  Google Scholar 

  81. Sato A, Hayashi K, Naruse M, Saruta T. Effectiveness of aldosterone blockade in patients with diabetic nephropathy. Hypertension. 2003;41(1):64–8.

    Article  CAS  PubMed  Google Scholar 

  82. Xue C, Siragy HM. Local renal aldosterone system and its regulation by salt, diabetes, and angiotensin II type-1 receptor. Hypertension. 2005;46(3):584–90.

    Article  CAS  PubMed  Google Scholar 

  83. Rebsomen L, Khammar A, Raccah D, Tsimaratos M. C-peptide effects on renal physiology and diabetes. Exp Diabetes Res. 2008;2008:281536.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  84. Vague P, Coste TC, Jannot MF. C-peptide, Na+, K+ ATPase and diabetes. Exp Diabesity Res. 2004;5(1):37–50.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  85. Nordquist L, Lai EY, Sjoquist M, Patzak A, Persson AE. Proinsulin C-peptide constricts glomerular afferent arterioles in diabetic mice. A potential renoprotective mechanism. Am J Physiol Regul Integ Comp Physiol. 2008;294(3):R836–41.

    Article  CAS  Google Scholar 

  86. Komers R, Lindsley JN, Oyama TT, Schutzer WE, Reed JF, Mader SL, Anderon S. Immunohistochemical and functional correlations of renal cyclooxygenase-2 in experimental diabetes. J Clin Invest. 2001;107(7):889–98.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  87. Li H, Chen YJ, Quilley J. Effect of tempol on renal cyclooxygenase expression and activity in experimental diabetes in the rat. J Pharmacol Exp Ther. 2005;314(2):818–24.

    Article  CAS  PubMed  Google Scholar 

  88. Chen YJ, Li J, Quiley J. Effect of inhibition of nitric oxide synthase on renal cyclooxygenase in the diabetic rat. Eur J Pharmacol. 2006;541(1–2):80–6.

    Article  CAS  PubMed  Google Scholar 

  89. Cherney DZ, Miller JA, Scholey JW, Bradley TJ, Slorach C, Curtis JR, Dekker MG, Nassallah R, Hebert RL, Sochett EB. The effect of cyclooxygenase-2 inhibition on renal hemodynamic function in humans with type I diabetes. Diabetes. 2008;57(3):688–95.

    Article  CAS  PubMed  Google Scholar 

  90. Cherney DZI, Scholey JW, Nasrallah R, Dekker MG, Slorach C, Bradley TJ, Hebert RL, Sochett EB, Miller JA. Renal hemodynamic effect of cyclooxygenase 2 inhibition in young men and women with uncomplicated type I diabetes mellitus. Am J Physiol Renal Physiol. 2008;294(6):F1336–41.

    Article  CAS  PubMed  Google Scholar 

  91. Hostetter TH, Renke HG, Brenner BM. Case for intrarenal hypertension in initiation and progression of diabetic and other glomerulopathies. Am J Med. 1982;72(3):375–80.

    Article  CAS  PubMed  Google Scholar 

  92. Hashimoto S, Yamada K, Kawata T, Mochizuki T, Schnermann J, Koike T. Abnormal autoregulation and tubuloglomerular feedback in prediabetic and diabetic OLETF rats. Am J Physiol Renal Physiol. 2009;296(3):F598–604.

    Article  CAS  PubMed  Google Scholar 

  93. Lau C, Sudbury I, Thomson M, Howard PL, Magil AB, Cupples WA. Salt-resistant blood pressure and salt-sensitive renal autoregulation in chronic streptozotocin diabetes. Am J Physiol Reg Integ Comp Physiol. 2009;296(6):R1761–70.

    Article  CAS  Google Scholar 

  94. Hashimoto Y, Ideura T, Yoshimura A, Koshikawa S. Autoregulation of renal blood flow in streptozotocin-induced diabetic rats. Diabetes. 1989;38(9):1109–13.

    Article  CAS  PubMed  Google Scholar 

  95. Schjoedt KJ, Christensen PK, Jorsal A, Boomsma F, Rossing P, Parving HH. Autoregulation of glomerular filtration rate during spironolactone treatment in hypertensive patients with type I diabetes: a randomized crossover trial. Nephrol Dial Transplant. 2009;24(11):3343–9.

    Article  CAS  PubMed  Google Scholar 

  96. Serri O, Beauregard H, Brazeau P, Abribat T, Lambert J, Harris A, Vachon L. Somatostatin analog, octreotide, reduces increased intraglomerular filtration rate and kidney size in insulin-dependent diabetes. JAMA. 1991;265(7):888–92.

    Article  CAS  PubMed  Google Scholar 

  97. Hirschberg R, Brunori G, Kopple JD, Guler HP. Effects of insulin-like growth factor 1 on renal function in normal men. Kidney Int. 1993;43(2):387–97.

    Article  CAS  PubMed  Google Scholar 

  98. Hirschberg R, Kopple JD. The growth hormone-insulin-like growth factor axis and renal glomerular function. J Am Soc Nephrol. 1992;9:1417–22.

    Google Scholar 

  99. Passariello N, Sepe J, Marrazzo G, De Cicco A, Peluso A, Pisano MC, Sgambato S, Tesauro P, D’Onoforio F. Effect of aldose reductase inhibitor (tolrestat) on urinary albumin excretion rate and glomerular filtration rate in IDDM subjects with nephropathy. Diabetes Care. 1993;16(5):789–95.

    Article  CAS  PubMed  Google Scholar 

  100. Sabbatini M, Sansone G, Uccello F, Giliberti A, Conte G, Andreucci VE. Early glycosylation products induce glomerular hyperfiltration in normal rats. Kidney Int. 1992;42(4):875–81.

    Article  CAS  PubMed  Google Scholar 

  101. Thomson SC, Vallon V, Blantz RC. Kidney function in early diabetes: the tubular hypothesis of glomerular filtration. Am J Physiol Renal Physiol. 2004;286(1):F8–15.

    Article  CAS  PubMed  Google Scholar 

  102. Ikenaga H, Bast JP, Fallet RW. Exaggerated impact of ATP-sensitive K+ channels on afferent arteriolar diameter in diabetes mellitus. J Am Soc Nephrol. 2000;11(7):1199–206.

    CAS  PubMed Central  PubMed  Google Scholar 

  103. Thomas MC, Tikellis C, Burns WM, Biakowski K, Cao Z, Coughlin MT, Jandeleit-Dahm K, Cooper ME, Forbes JM. Interaction between renin angiotensin system and advanced glycation in the kidney. J Am Soc Nephrol. 2005;16(10):2976–84.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Section of Nephrology, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA, 70112, USA

    Arnold B. Alper Jr. M.D., M.P.H.

Authors
  1. Arnold B. Alper Jr. M.D., M.P.H.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Arnold B. Alper Jr. M.D., M.P.H. .

Editor information

Editors and Affiliations

  1. University of Illinois, Chicago, Illinois, USA

    Edgar V. Lerma

  2. Nephrology Section, Tulane University Medical School, New Orleans, Louisiana, USA

    Vecihi Batuman

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this chapter

Cite this chapter

Alper, A.B. (2014). Pathogenesis of Diabetic Nephropathy: Hemodynamic Alterations/Renin Angiotensin System. In: Lerma, E., Batuman, V. (eds) Diabetes and Kidney Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-0793-9_4

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-0793-9_4

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4939-0792-2

  • Online ISBN: 978-1-4939-0793-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation