Advances in Chronic Kidney Disease
Volume 12, Issue 2 , Pages 212-222 , April 2005

The next generation of diabetic nephropathy therapies: An update

  • Mark E. Williams

      Affiliations

    • Joslin Diabetes Center, Boston, MA
    • Corresponding Author InformationAddress correspondence to Mark E. Williams, MD, Renal Unit, Joslin Diabetes Center, 1 Joslin Place, Boston, MA 02215.
  • ,
  • Katherine R. Tuttle

      Affiliations

    • The Heart Institute of Spokane, Spokane, WA, USA, and Sacred Heart Medical Center, Spokane, WA.

References 

  1. Caramori ML , Mauer M . Diabetes and nephropathy . Curr Opin Nephrol Hypertens . 2003;12:273–282
  2. Locatelli F , Canaud B , Eckardt KU , et al.   The importance of diabetic nephropathy in current nephrological practice . Nephrol Dial Transplant . 2003;8:716–725
  3. Muntner P , Coresh J , Power NR , et al.   The contribution of increased diabetes prevalence and improved myocardial infarction and stroke survival to the increase in treated end-stage renal disease . J Am Soc Nephrol . 2003;14:1568–1577
  4. United States Renal Data System . Annual Data Report 2001 (Incidence and prevalence of ESRD) . Am J Kidney Dis . 2001;38(suppl):S37–S52
  5. United States Renal Data System . Annual Data Report 2003 (Incidence and prevalence of ESRD) . Am J Kidney Dis . 2003;42(suppl):S47–S60
  6. U.S. Renal Data System . USRDS 2004 Annual Data Report: Atlas of End-Stage Renal Disease in the United States. . Bethesda, MD: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; 2004;
  7. Gordois A , Scuffham P , Shearer A , et al.   The health care costs of diabetic nephropathy in the United States and the United Kingdom . J Diabetes Complications . 2004;18:18–26
  8. The Diabetes Control and Complications Trial Research Group . The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus . N Engl J Med . 1993;329:977–986
  9. UK Prospective Diabetes Study (UKPDS) Group . Intensive blood glucose control with sulfonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33) . Lancet . 1998;352:837–853
  10. Shichiri M , Kishikawa H , Ohkubo Y , et al.   Long-term results of the Kumamoto study on optimal diabetes control in type 2 diabetic patients . Diabetes Care . 2000;23:B21–B29
  11. Parving HH , Smidt UM , Hommel E , et al.   Effective antihypertensive treatment postpones renal insufficiency in diabetic nephropathy . Am J Kidney Dis . 1993;22:188–195
  12. Lewis EJ , Hunsicker LG , Bain RP , et al.   The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy . N Engl J Med . 1993;329:1456–1462
  13. Brenner BM , Cooper ME , de Zeeuw D , et al.   Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy . N Engl J Med . 2001;345:861–869
  14. Lewis EJ , Hunsicker LG , Clarke WR , et al.   Renoprotective effect of the angiotensin receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes . N Engl J Med . 2001;345:851–860
  15. Pedrini MT , Levey AS , Lau J , et al.   The effect of dietary protein restriction on the progression of diabetic and nondiabetic renal diseases (A meta-analysis) . Ann Intern Med . 1996;124:627–632
  16. Kasiske BL , Lakatua JDA , Ma JZ , et al.   A meta-analysis of the effects of dietary protein restriction on the rate of decline in renal function . Am J Kidney Dis . 1998;31:954–961
  17. Hansen HP , Tauber-Lassen E , Jensen BR , et al.   Effect of dietary protein restriction on prognosis in patients with diabetic nephropathy . Kidney Int . 2002;62:220–228
  18. Gaede P , Vedel P , Larsen N , et al.   Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes . N Engl J Med . 2003;348:383–393
  19. Dai C , Yang J , Bastacky S , et al.   Intravenous administration of heypatocyte growth factor gene ameliorates diabetic nephropathy in mice . J Am Soc Nephrol . 2004;15:2637–2647
  20. Hudson BI , Bucciarelli LG , Wendt T , et al.   Blockade of receptor for advanced glycation end products (A new target for therapeutic intervention in diabetic complications and inflammatory disorders) . Arch Biochem Biophys . 2003;419:80–88
  21. Cohen MP , Hud E , Wu V-Y . Amelioration of diabetic nephropathy by treatment with monoclonal antibodies against glycated albumin . Kidney Int . 1994;45:1673–1679
  22. Cohen MP . Intervention strategies to prevent pathogenetic effects of glycated albumin . Arch Biochem Biophys . 2003;419:25–30
  23. Kelly DJ , Zhang Y , Gow R , et al.   Tranilast attenuates structural and functional aspects of renal injury in the remnant kidney model . J Am Soc Nephrol . 2004;15:2619–2629
  24. Bolton WK , Cattran DC , Williams ME , et al.   Randomized trial of an inhibitor of formation of advanced glycation end products in diabetic nephropathy . Am J Nephrol . 2004;24:32–40
  25. Gambaro G , Kinalska I , Oksa A , et al.   Oral sulodexide reduces albuminuria in microalbuminuric and macroalbuminuric type 1 and type 2 diabetic patients: The Di.N.A.S. randomized trial . J Am Soc Nephrol . 2002;13:1615–1625
  26. Ofosu FA . Pharmacological actions of sulodexide . Semin Thromb Hemost . 1998;24:127–138
  27. Ceol M , Gambaro G , Sauer U , et al.   Glycosaminoglycan therapy prevents TGF-B1 overexpression and pathologic changes in renal tissue of long-term diabetic rats . J Am Soc Nephrol . 2000;11:2324–2336
  28. Gambaro G , Venturini AP , Noonan DM , et al.   Treatment with glycosaminoglycan formulation ameliorates experimental diabetic nephropathy . Kidney Int . 1994;46:797–806
  29. Gambaro G , Cavazzana AO , Luzi P , et al.   Glycosaminoglycans prevent morphological renal alterations and albuminuria in diabetic rats . Kidney Int . 1992;42:285–291
  30. Nader HB , Buonassisi V , Colburn P , et al.   Heparin stimulates the synthesis and modifies the sulfation pattern of heparan sulfate proteoglycan from endothelial cells . J Cell Physiol . 1989;140:305–310
  31. Caenazzo C , Garbisa S , Ceol M , et al.   Heparin modulates proliferation and proteoglycan biosynthesis in murine mesangial cells (Molecular clues for its activity in nephropathy) . Nephrol Dial Transplant . 1995;20:175–184
  32. Gambaro G , Baggio B . Glycosaminoglycans (A new paradigm in the prevention of proteinuria and progression of glomerular disease) . Nephrol Dial Transplant . 1996;11:762–764
  33. Solini A , Vergnani L , Ricci F , et al.   Glycosaminoglycans delay the progression of nephropathy in NIDDM . Diabetes Care . 1997;20:819–823
  34. Velussi M , Cernigoi AM , Dapas F , et al.   Glycosaminoglycans oral therapy reduces macroalbuminuria, blood fibrinogen levels and limb arteriopathy clinical signs in patients with non-insulin dependent diabetes mellitus . Diabetes Nutr Metab . 1996;9:53–58
  35. Poplawska A , Szelachowska M , Topolska B , et al.   Effect of glycosaminoglycans on urinary albumin excretion in insulin-dependent diabetic patients with micro- or macroalbuminuria . Diabetes Res Clin Pract . 1997;38:109–114
  36. Raj DSC , Choudhury D , Welbourne TC , et al.   Advanced glycation end-products (A nephrologist’s perspective) . Am J Kidney Dis . 2000;35:365–380
  37. Heidland A , Sebekova K , Schinzel R . Advanced glycation end products and the progressive course of renal disease . Am J Kidney Dis . 2001;38(suppl 1):S100–S106
  38. Forbes JM , Cooper ME , Oldfield MD , et al.   Role of advanced glycation end products in diabetic nephropathy . J Am Soc Nephrol . 2003;14(suppl):S54–S58
  39. Williams ME . New therapies for advanced glycation end product nephrotoxicity (Current challenges) . Am J Kidney Dis . 2003;41(suppl 1):S42–S47
  40. Brownlee M . Biochemistry and molecular cell biology of diabetic complications . Nature . 2001;414:813–820
  41. Hou FF , Ren H , Owen WF , et al.   Enhanced expression of receptor for advanced glycation end products in chronic kidney disease . J Am Soc Nephrol . 2004;15:1889–1896
  42. Lu C , He JC , Cai W , et al.   Advanced glycation end product (AGE) receptor 1 is a negative regulator of the inflammatory response to AGE in mesangial cells . Proc Natl Acad Sci USA . 2004;101:11767–11772
  43. Jerums G , Panagiotopoulos S , Forbes J , et al.   Evolving concepts in advanced glycation, diabetic nephropathy, and diabetic vascular disease . Arch Biochem Biophysics . 2003;419:55–62
  44. Sabbatini M , Sansone G , Uccello F , et al.   Early glycosylation products induce glomerular hyperfiltration in normal rats . Kidney Int . 1992;42:875–881
  45. Bendayan M . Immunocytochemical detectin of advanced glycated end products in rat renal tissue as a function of age and diabetes . Kidney Int . 1998;54:438–447
  46. Youssef S , Nguyen DT , Soulis T , et al.   Effect of diabetes and aminoguanidine therapy on renal advanced glycation end-product binding . Kidney Int . 1999;55:907–916
  47. Abdel-Rahman E , Bolton WK . Pimagedine (A novel therapy for diabetic nephropathy) . Expert Opin Investig Drugs . 2002;11:565–574
  48. Williams ME . Clinical studies of advanced glycation end-product inhibitors and diabetic kidney disease . Curr Diabetes Rep . 2004;4:441–446
  49. Kalousova M , Zima T , Vesai V , et al.   Advanced glycation end products in clinical nephrology . Kidney Blood Press Res . 2004;27:18–28
  50. Edelstein D , Brownlee M . Mechanistic studies of advanced glycosylation end product inhibition by aminoguanidine . Diabetes . 1992;41:26–29
  51. Metz TO , Alderson NL , Thorpe SR , et al.   Pyridoxamine, an inhibitor of advanced glycation and lipoxidation reactions (A novel therapy for treatment of diabetic complications) . Arch Biochem Biophys . 2003;419:41–49
  52. Alderson NL , Chachich ME , Youssef NY , et al.   The AGE inhibitor pyridoxamine inhibits lipemia and development of renal and vascular disease in Zucker obese rats . Kidney Int . 2003;63:2123–2133
  53. Degenhardt TP , Alderson NL , Arrington DD . Pyridoxamine inhibits early renal disease and dyslipidemia in the streptozotocin-diabetic rat . Kidney Int . 2000;61:939–950
  54. Stitt A , Gardiner TA , Anderson NL , et al.   The AGE inhibitor pyridoxamine inhibits development of retinopathy in experimental diabetes . Diabetes . 2002;51:2826–2832
  55. Williams ME , Bolton WK , Degenhardt TP , et al.   A phase 2 clinical trial of pyridoxamine (Pyridorin) in type 2 and type 2 diabetic patients with overt nephropathy (PYR-206) . J Am Soc Nephrol . 2003;14:7A
  56. Schaumburg H , Kaplan J , Windebakn A , et al.   Sensory neuropathy from pyridoxine abuse (A new megavitamin syndrome) . N Engl J Med . 1983;309:445–448
  57. Miiyata T , Van Ypersele de Strihou C , Euda Y , et al.   Angiotensin II receptor antagonists and angiotensin-converting enzyme inhibitors lower in vitro the formation of advanced glycation end products (Biochemical mechanisms) . J Am Soc Nephrol . 2002;13:2478–2487
  58. McGill JB , Williams ME , Degenhardt TP , et al.   A phase 2 clinical investigation of pyridoxamine (Pyridorine) in type 1 and type 2 diabetic patients with overt diabetic nephropathy (PYR 205-207) . J Am Soc Nephrol . 2004;15:565A
  59. Vasan S , Foiles P , Founds H . Therapeutic potential of breakers of advanced glycation end product-protein crosslinks . Arch Biochem Biophys . 2003;419:89–96
  60. Rahbar S , Figarola JL . Novel inhibitors of advanced glycation end products . Arch Biochem Biophys . 2003;419:63–79
  61. Bailey AJ , Paul RG , Knott L , et al.   Mechanisms of maturation of ageing of collagen . Mech Ageing Dev . 1998;106:1–56
  62. Singh R , Barden A , Mori T , et al.   Advanced glycation end-products (A review) . Diabetologia . 2001;44:129–146
  63. Huijberts MSP , Wolffenbuttel BHR , Boudier H , et al.   Aminoguanidine treatment increases elasticity and decreases fluid filtration of large arteries from diabetic rats . J Clin Invest . 1993;92:1407–1411
  64. Brownlee M , Vlassara H , Kooney A , et al.   Aminoguanidine prevents diabetes-induced arterial wall protein cross-linking . Science . 1986;232:1629–1632
  65. Vasan S , Zhang X , Zhang X , et al.   An agent cleaving glucose-derived protein crosslinks in vitro and in vivo . Nature . 1996;382:275–278
  66. Tallas-Bonke V , Lindschau C , Rizkalla B , et al.   Attenuation of extracellular matrix accumulation in diabetic nephropathy by the advanced glycation end product cross-link breaker ALT-711, a protein kinase C-alpha-dependent pathway . Diabetes . 2004;53:2921–2930
  67. Susic D , Varagic J , Ahn J , et al.   Cardiovascular and renal effects of a collagen cross-link breaker (ALT-711) in adult and aged spontaneously hypertensive rats . AJH . 2004;17:328–333
  68. Kass DA , Shapiro EP , Kawaguchi M , et al.   Improved arterial compliance by a novel advanced glycation end-product crosslink breaker . Circulation . 2001;104:1464–1470
  69. Susic D , Varagic J , Ahn J , et al.   Crosslink breakers (A new approach to cardiovascular therapy) . Curr Opin Cardiol . 2004;19:336–340
  70. Tuttle KR , Anderson PW . A novel potential therapy for diabetic nephropathy and vascular complications (Protein kinase C beta inhibition) . Am J Kidney Dis . 2003;42:456–465
  71. Craven PA , DeRubertis FR . Protein kinase C is activated in glomeruli from streptozotocin diabetic rats (Possible mediation by glucose) . J Clin Invest . 1989;83:1667–1675
  72. Ayo SH , Radnik R , Garoni JA , et al.   High glucose increases diacylglycerol mass and activates protein kinase C in mesangial cell cultures . Am J Physiol . 1991;261:F571–F577
  73. DeRubertis FR , Craven PA . Activation of protein kinase C in glomerular cells in diabetes (Mechanisms and potential links to the pathogenesis of diabetic glomerulopathy) . Diabetes . 1994;43:1–8
  74. Inoguchi T , Sonta T , Tsubouchi H , et al.   Protein kinase C-dependent increase in reactive oxygen species (ROS) production in vascular tissues of diabetes (Role of vascular NAD(P)H oxidase) . J Am Soc Nephrol . 2003;14(suppl):S227–S232
  75. Tuttle KR , Johnson EC , Cooney SK , et al.   Amino acids injure mesangial cells by advanced glycation end products, oxidative stress, and protein kinase C . Kidney Int . 2005;67:953–968
  76. Inoguchi T , Battan R , Handler E , et al.   Preferential elevation of protein kinase C isoform βII and diacylglycerol levels in the aorta and heart of diabetic rats (Differential reversibility to glycemic control by islet cell transplantation) . Proc Natl Acad Sci USA . 1992;89:11059–11063
  77. Shiba T , Inoguchi T , Sportsman JR , et al.   Correlation of diacylglycerol level and protein kinase C activity in rat retinal circulation . Am J Physiol . 1993;265:E783–E793
  78. Ishii H , Jirousek MR , Koya D , et al.   Amelioration of vascular dysfunctions in diabetic rats by an oral PKC β inhibitor . Science . 1996;272:728–731
  79. Jirousek MR , Gillig JR , Gonzalez CM , et al.   (S)-13-[(dimethylamino)methyl]-10,11,14,15-tetrahydro-4,9:16,21-dimetheno-1H,13H-dibenzo[e,k]pyrrolo[3,4-h][1,4,13]-oxadiazacyclohexadecene-1,3(2H)-dione(ruboxistaurin) and related analogues (Isozyme selective inhibitors of protein kinase Cβ) . J Med Chem . 1996;39:2664–2671
  80. Koya D , Jirousek MR , Lin Y-W , et al.   Characterization of protein kinase C β isoform activation on the gene expression of transforming growth factor-β, extracellular matrix components and prostanoids in the glomeruli of diabetic rats . J Clin Invest . 1997;100:115–126
  81. Koya D , Haneda M , Nakagawa H , et al.   Amelioration of accelerated diabetic mesangial expansion by treatment with a PKC beta inhibitor in diabetic db/db mice, a rodent model for type 2 diabetes . FASEB J . 2000;14:439–447
  82. Kelly DJ , Zhang Y , Hepper C , et al.   PKC β inhibition attenuates the progression of experimental diabetic nephropathy in the presence of continued hypertension . Diabetes . 2003;52:512–518
  83. Scivittaro V , Ganz MB , Weiss MF . AGEs induce oxidative stress and activate protein kinase C-bII in neonatal mesangial cells . Am J Physiol Renal Physiol . 2000;278:F676–F683
  84. Whiteside CI , Dlugosz JA . Mesangial cell protein kinase C isozyme activation in the diabetic milieu . Am J Physiol Renal Physiol . 2002;282:F975–F980
  85. Kitada M , Koya D , Sugimoto T . Translocation of glomerular p47phox and p67phox by protein kinase C-β activation is required for oxidative stress in diabetic nephropathy . Diabetes . 2003;52:2603–2614
  86. Malhotra M , Kang BPS , Cheung S , et al.   Angiotensin II promotes glucose-induced activation of cardiac protein kinase C isozymes and phosphorylation of troponin I . Diabetes . 2001;50:1918–1926
  87. Osiicka TM , Yu Y , Lee V , et al.   Aminoguanidine and ramipril prevent diabetes-induced increases in protein kinase C activity in glomeruli, retina, and mesenteric artery . Clin Sci . 2001;100:249–257
  88. American Diabetes Association . Standards of medical care for patients with diabetes mellitus . Diabetes Care . 2002;25:213–229
  89. K/DOQI Clinical Practice Guidelines on Hypertension and Antihypertensive Agents in Chronic Kidney Disease. Pharmacological therapy (diabetic kidney disease) . Am J Kidney Dis . 2004;43(suppl):S142–S158

 Mark E. Williams has served as a consultant for Biostratum, Inc., and Katherine R. Tuttle has served as a consultant for Eli Lilly and Co.

PII: S1548-5595(05)00035-2

doi: 10.1053/j.ackd.2005.01.011

Advances in Chronic Kidney Disease
Volume 12, Issue 2 , Pages 212-222 , April 2005