Hong Kong Journal of Nephrology
Volume 13, Issue 1 , Pages 19-26 , April 2011

Novel Drug Treatment for Diabetic Nephropathy

  • Amitabh Dash

      Affiliations

    • Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India
    • Corresponding Author InformationCorrespondence to: Dr. Amitabh Dash, E-13, Kalkaji, New Delhi 110019, India
    • ,
  • Rituparna Maiti

      Affiliations

    • Department of Pharmacology, Prathima Institute of Medical Sciences, Karimnagar, Andhra Pradesh, India
    • ,
  • Tejaswi Kumar Akantappa Bandakkanavar

      Affiliations

    • Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India
    • ,
  • Bajrang Lal Pandey

      Affiliations

    • Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India

References 

  1. Guilbert JJ . The World Health Report 2006: Working Together with Health . Educ Health (Abingdon) . 2006;19:385–387
  2. Wu AY , Kong NC , De Leon FA , et al.   An alarmingly high prevalence of diabetic nephropathy in Asian type 2 diabetic patients: the Micro-Albuminuria Prevalence (MAP) study . Diabetologia . 2005;48:17–26
  3. Dalla Vestra M , A Saller , E Bortoloso , et al.   Structural involvement in type 1 and type 2 diabetic nephropathy . Diabetes Metab . 2000;26(Suppl 4):8–14
  4. Mogensen CE . Renal function changes in diabetes . Diabetes . 1976;25(Suppl):872–879
  5. Maiti R , Agrawal NK . Atherosclerosis in diabetes mellitus: role of inflammation . Indian J Med Sci . 2007;61:292–306
  6. Calcutt NA , Cooper ME , Kern TS , et al.   Therapies for hyperglycaemiainduced diabetic complications: from animal models to clinical trials . Nat Rev Drug Discov . 2009;8:417–429
  7. Ruggenenti P , Cravedi P , Remuzzi G . The RAAS in the pathogenesis and treatment of diabetic nephropathy . Nat Rev Nephrol . 2010;6:319–330
  8. V D'agati , AM Schmidt . RAGE and the pathogenesis of chronic kidney disease . Nat Rev Nephrol . 2010;6:352–360
  9. Decleves AE , Sharma K . New pharmacological treatments for improving renal outcomes in diabetes . Nat Rev Nephrol . 2010;6:371–380
  10. Wu D , Peng F , Zhang B , et al.   PKC-β1 mediates glucose-induced Akt activation and TGF-β1 upregulation in mesangial cells . J Am Soc Nephrol . 2009;20:554–566
  11. Durvasula RV , Shankland SJ . Activation of a local renin angiotensin system in podocytes by glucose . Am J Physiol Renal Physiol . 2008;294:F830–F839
  12. Lee SH , Yoo TH , Nam BY , et al.   Activation of local aldosterone system within podocytes is involved in apoptosis under diabetic conditions . Am J Physiol Renal Physiol . 2009;297:F1381–F1390
  13. Miceli I , Burt D , Tarabra E , et al.   Stretch reduces nephrin expression via an angiotensin II-AT(1)-dependent mechanism in human podocytes: effect of rosiglitazone . Am J Physiol Renal Physiol . 2010;298:F381–F390
  14. Jauregui A , Mintz DH , Mundel P , et al.   Role of altered insulin signaling pathways in the pathogenesis of podocyte malfunction and microalbuminuria . Curr Opin Nephrol Hypertens . 2009;18:539–545
  15. Welsh GI , Coward RJ . Podocytes, glucose and insulin . Curr Opin Nephrol Hypertens . 2010;19:379–384
  16. Welsh GI , Hale LJ , Eremina V , et al.   Insulin signaling to the glomerular podocyte is critical for normal kidney function . Cell Metab . 2010;12:329–340
  17. Siebel AL , Fernandez AZ , A El-Osta . Glycemic memory associated epigenetic changes . Biochem Pharmacol . 2010;80:1853–1859
  18. Tonna S , El-Osta A , Cooper ME , et al.   Metabolic memory and diabetic nephropathy: potential role for epigenetic mechanisms . Nat Rev Nephrol . 2010;6:332–341
  19. Villeneuve LM , Natarajan R . The role of epigenetics in the pathology of diabetic complications . Am J Physiol Renal Physiol . 2010;299:F14–F25
  20. Azizi M , Ménard J , Bissery A , et al.   Hormonal and hemodynamic effects of aliskiren and valsartan and their combination in sodiumreplete normotensive indivisuals . Clin J Am Soc Nephrol . 2007;2:947–955
  21. Kelly DJ , Zhang Y , Moe G , et al.   Aliskiren, a novel renin inhibitor, is renoprotective in a model of advanced diabetic nephropathy in rats . Diabetologia . 2007;50:2398–2404
  22. Parving HH , Persson F , Lewis JB , et al.   Aliskiren combined with losartan in type 2 diabetes and nephropathy . N Engl J Med . 2008;358:2433–2446
  23. Feldman DL , Jin L , Xuan H , et al.   Effects of aliskiren on blood pressure, albuminuria, and (pro)renin receptor expression in diabetic TG(mRen-2)27 rats . Hypertension . 2008;52:130–136
  24. Parving HH , Brenner BM , McMurray JJ , et al.   Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE): rationale and study design . Nephrol Dial Transplant . 2009;24:1663–1671
  25. Gaddam KK , Oparil S . Renin inhibition: should it supplant ACE inhibitors and ARBs in high risk patients? . Curr Opin Nephrol Hypertens . 2008;17:484–490
  26. Gilbert RE , Kim SA , Tuttle KR , et al.   Effect of ruboxistaurin on urinary transforming growth factor-beta in patients with diabetic nephropathy and type 2 diabetes . Diabetes Care . 2007;30:995–996
  27. Kelly DJ , Zhang Y , Hepper C , et al.   Protein kinase C beta inhibition attenuates the progression of experimental diabetic nephropathy in the presence of continued hypertension . Diabetes . 2003;52:512–518
  28. Kelly DJ , Buck D , Cox AJ , et al.   Effects on protein kinase C-beta inhibition on glomerular vascular endothelial growth factor expression and endothelial cells in advanced experimental diabetic nephropathy . Am J Physiol Renal Physiol . 2007;293:F565–F574
  29. Kelly DJ , Chanty A , Gow RM , et al.   Protein kinase C inhibition attenuates osteopontin expression, macrophage recruitment, and tubulointerstitial injury in advanced experimental diabetic nephropathy . J Am Soc Nephrol . 2005;16:1654–1660
  30. Tuttle KR , Bakris GL , Toto RD , et al.   The effect of ruboxistaurin on nephropathy in type 2 diabetes . Diabetes Care . 2005;28:2686–2690
  31. Lieberthal W , Levine JS . The role of the mammalian target of rapamycin (mTOR) in renal disease . J Am Soc Nephrol . 2009;20:2493–2502
  32. Sakaguchi M , Isono M , Isshiki K , et al.   Inhibition of mTOR signaling with rapamycin attenuates renal hypertrophy in the early diabetic mice . Biochem Biophys Res Commun . 2006;340:296–301
  33. Mori H , Inoki K , Masutani K , et al.   The mTOR pathway is highly activated in diabetic nephropathy and rapamycin has a strong therapeutic potential . Biochem Biophys Res Commun . 2009;384:471–475
  34. Yang Y , Wang J , Qin L , et al.   Rapamycin prevents early steps of the development of diabetic nephropathy in rats . Am J Nephrol . 2007;27:495–502
  35. Wittmann S , Daniel C , Stief A , et al.   Long-term treatment of sirolimus but not cyclosporine ameliorates diabetic nephropathy in rats . Transplantation . 2009;87:1290–1299
  36. Navarro JF , Milena FJ , Mora C , et al.   Renal pro-inflammatory cytokine gene expression in diabetic nephropathy: effect of angiotensinconverting enzyme inhibition and pentoxifylline administration . Am J Nephrol . 2006;26:562–570
  37. BB McCormick , A Sydor , A Akbari , et al.   The effect of pentoxifylline on proteinuria in diabetic kidney disease: a meta-analysis . Am J Kidney Dis . 2008;52:454–463
  38. R Leyva-Jiménez , AR Rodríguez-Orozco , LE Ortega-Pierres , et al.   Effect of pentoxifylline on the evolution of diabetic nephropathy . Med Clin (Barc) . 2009;132:772–778
  39. Navarro-González JF, Muros M, Mora-Fernández C, et al. Pentoxifylline for Renoprotection in Diabetic Nephropathy: the PREDIAN study-rationale and basal results. J Diabetes Complications 2010 Dec 6. [Epub ahead of print]
  40. T Dan , van Ypersele de Strihou C , T Miyata . Advanced glycation end products inhibitor . In: Studies on Renal Disorders: Oxidative Stress in Applied Basic Research and Clinical Practice, Part 3 . New York: Springer; 2011;p. 389–406
  41. Izuhara Y , Sada T , Yanagisawa H , et al.   A novel sartan derivative with very low angiotensin II type I receptor affinity protects the eye in type 2 diabetic rats . Arterioscler Thromb Vasc Biol . 2008;8:1767–1773
  42. Voziyan PA , Hudson BG . Pyridoxamine: the many virtues of a Maillard reaction inhibitor . Ann N Y Acad Sci . 2005;1043:807–816
  43. Murakoshi M , Tanimoto M , Gohda T , et al.   Pleiotropic effect of pyridoxamine on diabetic complications via CD36 expression in KK-Ay/Ta mice . Diabetes Res Clin Pract . 2009;83:183–189
  44. Waanders F , van den Berg E , Nagai R , et al.   Renoprotective effects of the AGE-inhibitor pyridoxamine in experimental chronic allograft nephropathy in rats . Nephrol Dial Transplant . 2008;23:518–524
  45. Williams ME , Bolton WK , Khalifah RG , et al.   Effects of pyridoxamine in combined phase 2 studies of patients with type 1 and type 2 diabetes and overt nephropathy . Am J Nephrol . 2007;27:605–614
  46. Balakumar P , Rohilla A , Krishan P , et al.   The multifaceted therapeutic potential of benfotiamine . Pharmacol Res . 2010;61:482–488
  47. Stirban A , Negrean M , Stratmann B , et al.   Benfotiamine prevents macro- and microvascular endothelial dysfunction and oxidative stress following a meal rich in advanced glycation end products in individuals with type 2 diabetes . Diabetes Care . 2006;29:2064–2071
  48. Marchetti V , Menghini R , Rizza S , et al.   Benfotiamine counteracts glucose toxicity effects on endothelial progenitor cell differentiation via Akt/FoxO signaling . Diabetes . 2006;55:2231–2237
  49. Alkhalaf A , Klooster A , van Oeveren W , et al.   A double-blind, randomized, placebo-controlled clinical trial on benfotiamine treatment in patients with diabetic nephropathy . Diabetes Care . 2010;33:1598–1601
  50. Coughlan MT , Forbes JM , Cooper ME . Role of the AGE crosslink breaker, alagebrium, as a renoprotective agent in diabetes . Kidney Int Suppl . 2007;106:S54–S60
  51. Dhar A , Desai KM , Wu L . Alagebrium attenuates acute methylglyoxal-induced glucose intolerance in Sprague-Dawley rats . Br J Pharmacol . 2010;159:166–175
  52. Peppa M , Brem H , Cai W , et al.   Prevention and reversal of diabetic nephropathy in db/db mice treated with alagebrium (ALT-711) . Am J Nephrol . 2006;26:430–436
  53. Yamagishi S , Nakamura K , Matsui T , et al.   Oral administration of AST-120 (Kremezin) is a promising therapeutic strategy for advanced glycation end product (AGE)-related disorders . Med Hypotheses . 2007;69:666–668
  54. Miyazaki T , Aoyama I , Ise M , et al.   An oral sorbent reduces overload of indoxyl sulphate and gene expression of TGF-beta1 in uraemic rat kidneys . Nephrol Dial Transplant . 2000;15:1773–1781
  55. Ueda S , Yamagishi S , Takeuchi M , et al.   Oral adsorbent AST-120 decreases serum levels of AGEs in patients with chronic renal failure . Mol Med . 2006;12:180–184
  56. Nicholas SB , Aguiniga E , Ren Y , et al.   Plasminogen activator inhibitor-1 deficiency retards diabetic nephropathy . Kidney Int . 2005;67:1297–1307
  57. Rerolle JP , Hertig A , Nguyen G , et al.   Plasminogen activator inhibitor type 1 is a potential target in renal fibrogenesis . Kidney Int . 2000;58:1841–1850
  58. Izuhara Y , Takahashi S , Nangaku M , et al.   Inhibition of plasminogen activator inhibitor-1: its mechanism and effectiveness on anticoagulation and anti-fibrosis . Arterioscler Thromb Vasc Biol . 2008;28:672–677
  59. Izuhara Y , Yamaoka N , Kodama H , et al.   A novel inhibitor of plasminogen activator inhibitor-1 provides antithrombotic benefits devoid of bleeding effect in nonhuman primates . J Cerebral Blood Flow Metab . 2010;30:904–912
  60. Huang Y , Haraguchi M , Lawrence DA , et al.   A mutant, noninhibitory plasminogen activator inhibitor type 1 decreases matrix accumulation in experimental glomerulonephritis . J Clin Invest . 2003;112:379–388
  61. Miyata T , van Ypersele de Strihou C . Translation of basic science into clinical medicine: novel targets for diabetic nephropathy . Nephrol Dial Transplant . 2009;24:1373–1377
  62. Blouza S , Dakhli S , Abid H , et al.   Efficacy of low-dose oral sulodexide in the management of diabetic nephropathy . J Nephrol . 2010;23:415–424
  63. Weiss R , Niecestro R , Raz I . The role of sulodexide in the treatment of diabetic nephropathy . Drugs . 2007;67:2681–2696
  64. 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
  65. Burney BO , Kalaitzidis RG , Bakris GL . Novel therapies of diabetic nephropathy . Curr Opin Nephrol Hypertens . 2009;18:107–111
  66. Sharma K , Ziyadeh FN , Alzahabi B , et al.   Increased renal production of transforming growth factor-beta1 in patients with type II diabetes . Diabetes . 1997;46:854–859
  67. T Yamamoto , T Nakamura , NA Noble , et al.   Expression of transforming growth factor beta is elevated in human and experimental diabetic nephropathy . Proc Natl Acad Sci USA . 1993;90:1814–1818
  68. Ramachandra Rao SP , Y Zhu , T Ravasi , et al.   Pirfenidone is reno-protective in diabetic kidney disease . J Am Soc Nephrol . 2009;20:1765–1775
  69. Mann JF , Green D , Jamerson K , et al.   Avosentan for overt diabetic nephropathy . J Am Soc Nephrol . 2010;21:527–535
  70. Sarafidis PA , Lasaridis AN . Diabetic nephropathy: endothelin antagonism for diabetic nephropathy . Nat Rev Nephrol . 2010;6:447–449
  71. Wenzel RR , Littke T , Kuranoff S , et al.   Avosentan reduces albumin excretion in diabetics with macroalbuminuria . J Am Soc Nephrol . 2009;20:655–664

PII: S1561-5413(11)60003-3

doi: 10.1016/S1561-5413(11)60003-3

Hong Kong Journal of Nephrology
Volume 13, Issue 1 , Pages 19-26 , April 2011

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