• Jayesh B Dhodi Institute of Chemical Technology,NP Marg, Matunga, Mumbai-400019, India
  • Snehal N Mestry Institute of Chemical Technology,NP Marg, Matunga, Mumbai-400019, India
  • Archana R Juvekar Institute of Chemical Technology,NP Marg, Matunga, Mumbai-400019, India


Diabetic Nephropathy (DN) is the foremost reason of End Stage Renal Disease (ESRD) and a major cause of premature deaths amongst people with diabetes. It is one of the most common complications of diabetes mellitus (DM) and has majorly influenced patients’ morbidity and mortality. About 50% of patients suffering from DM for more than 20 years develop this complication. The present review focuses on the global scenario of diabetic nephropathy and different molecular mechanisms involved in its pathogenesis i. e. increased formation of advanced glycation end products (AGEs), enhanced glucose flux into polyol and hexosamine pathways, activation of protein kinase C (PKC) and other proinflammatory transcription factors. This review also highlights the precautionary measures to be taken by people with diabetes along with the therapeutic interventions involving angiotensin converting enzyme (ACE) inhibitors, renin inhibitors, angiotensin receptor antagonists, aldosterone antagonists, protein kinase C inhibitors, mechanistic target of rapamycin (m-TOR) inhibitors, agents inhibiting plasminogen activator inhibitor-1 (PAI-1), advanced glycation end products inhibitors, anti-inflammatory agents and antioxidant agents.


Keywords: Diabetes Mellitus, Diabetic Nephropathy, End Stage Renal Disease, Advanced Glycation End Products, Protein Kinase C.


Download data is not yet available.

Author Biographies

Jayesh B Dhodi, Institute of Chemical Technology,NP Marg, Matunga, Mumbai-400019, India

Dept. of Pharmaceutical Sciences and Technology

Research Student

Snehal N Mestry, Institute of Chemical Technology,NP Marg, Matunga, Mumbai-400019, India

Dept. of Pharmaceutical Sciences and Technology

Research Student

Archana R Juvekar, Institute of Chemical Technology,NP Marg, Matunga, Mumbai-400019, India
Professor in Pharmacology and Physiology, Dept. of Pharmaceutical Sciences and Technology


1. Heydari I, Radi V, Razmjoua S, Amiri A. Chronic complications of diabetes mellitus in newly diagnosed patients. Int J Diabetes Mellitus 2010;2:61-3.
2. WHO. Definition, Diagnosis and Classification of Diabetes Mellitus and its Complications. Geneva, Switzerland: World Health Organization;1999.
3. David R, Guariguataa L, Clara W, Jonathan S. IDF Diabetes Atlas: Global Estimates of the Prevalence of Diabetes for 2011 and 2030. Diabetes Res Clin Pract 2011;94:311-21.
4. Ramkumar K, Ponmanickamb P, Velayuthaprabhub S, Govindaraju A, Rajagurua P. Protective effect of Gymnema Montanum against renal damage in experimental diabetic rats. Food Chem Toxicol 2009;47:2516–21.
5. Akram M, Akhtar N, Asif H, Shah P, Tariq S, Mahmood A, et al. A Review of Diabetes Mellitus. J Medicinal Plant Res 2011;22(5):5337–9.
6. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 2011;34(1):62–9.
7. Tiwari A, Rao J. Diabetes mellitus and multiple therapeutic approaches of phytochemicals: Present status and future prospects. Current Sci 2002;83(1):30–8.
8. Michael B. Biochemistry and molecular cell biology of diabetic complications. Nature 2001;414:813–20.
9. Nishikawa T, Edelstein D, Brownlee M. The Missing Link: a single unifying mechanism for diabetic complications. Kidney Int 2000;58(77):26–30.
10. Centers for Disease Control and Prevention. National diabetes fact sheet: general information and national estimates on diabetes in the United States, 2007. Atlanta, GA: U. S. Department of Health and Human Services, Centers for Disease Control and Prevention, 2008.
11. Stephen T, Gian Carlo V. Diabetic Nephropathy. Medicine 2003;31(7):91–4.
12. Jorge L, Mirela J, Sandra P, Lu´is H, Caramori M, Themis Z. Diabetic Nephropathy: Diagnosis, Prevention and Treatment. Diabetes Care 2005;28(1):164–76.
13. Phillips AO. Diabetic Nephropathy. Medicine 2011;39(8):470–4.
14. Cooper M. Pathogenesis, Prevention and treatment of diabetic nephropathy. Lancet 1998;352:213–9.
15. McLaughlin N, Bhatt U, Gil A, Mars R, Nahman N. A review of the diagnosis and therapy of diabetic nephropathy. Northeast Florida Medicine 2005;27–31.
16. Ritz E, Zeng X. Diabetic nephropathy-epidemiology in asia and the current state of treatment. Indian J Nephrology 2011;21(2):75–84.
17. Mehta G, Kashyap C, Das L. Diabetes Mellitus in India: the modern scourge. Med J Armed Forces India 2009;65(1):50–4.
18. Wolf G. New Insights into the Pathophysiology of Diabetic Nephropathy: from Haemodynamics to Molecular Pathology. Eur J Clin Invest 2004;34:785–96.
19. Enyioma N, Abdu A. Update in diabetic nephropathy. Int J Diabetes Metab 2005;13:1–9.
20. Eberhard R, Keller C, Bergis K, Strojek K. Pathogenesis and Course of Renal Disease in IDDM/NIDDM Differences and Similarities. Am J Hypertens 1997;10:202–7.
21. Paola F, Marino B, Isabella B, Marco A, Michele D. Diabetic nephropathy: an update of renal structure. Int Congress Series 2007;1303:51–9.
22. Lee H, Hunjoo H, George L. Reactive oxygen species and diabetic nephropathy. J Am Soc Nephrology 2003;209–10.
23. Tomlinson D. Aldose reductase inhibitors and the complications of diabetes mellitus. Diabetic Med 1993;10:214–30.
24. James M, Bron A, Peckar C, Petchey M, Ting H, Williams J. NADPH-Oxidising activity in lens and erythrocytes in diabetic and nondiabetic patients with cataract. Br J Ophthalmol 1983;67:696–9.
25. Dunlop M. Aldose reductase and the role of the polyol pathway in diabetic nephropathy. Kidney Int 2000;58(77):3–12.
26. Krishnan P, Chakkarwarb V. Diabetic nephropathy: aggressive involvement of oxidative stress. J Pharm Edu Res 2011;2(1):35–41.
27. Chung S, Ho E, Lam K, Chung S. Contribution of polyol pathway to diabetes-induced oxidative stress. J Am Soc Nephrology 2003;14:233–6.
28. Lorenzi M. The polyol pathway as a mechanism for diabetic retinopathy: attractive, elusive, and resilient. Experimental Diabetes Res 2007;2007:1–10.
29. Ohshiro Y, Lee Y, King G. Mechanism of diabetic nephropathy: role of protein kinase-c activiation. Adv Studies Med 2005;5:10–9.
30. Dickinson D, Forman H. Cellular glutathione and thiols metabolism. Biochem Pharmacol 2002;64:1019–26.
31. Koji A, Masahiko W, Toshio N. Regulation of neuronal glutathione synthesis. J Pharmacol Sci 2008;108:227–38.
32. Jedsadayanmata A. In Vitro antiglycation activity of arbutin. Naresuan University J 2005;13(2):35–41.
33. Munch G, Keis R, Weßels A, Riederer P, Bahner U, Heidland A, et al. Determination of advanced glycation end products in serum by fluorescence spectroscopy and competitive ELISA. Eur J Clinical Chem Clinical Biochem 1997;35(9):669–77.
34. Li J, Liu D, Sun L, Lu Y, Zhang Z. Advanced glycation end products and neurodegenerative diseases: mechanisms and perspective. J Neurol Sci 2012;317:1–5.
35. Brownlee M. Glycation products and the pathogenesis of diabetic complications. Diabetes Care 1992;15(12):1836–43.
36. Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature 2001;414:813–20.
37. Daroux M, Prevost G, Maillard H, Gaxatte C, D’Agati V, Schmidt A, et al. Advanced glycation end-products: implications for diabetic and non-diabetic nephropathies. Diabetes Metab 2012;36:1–10.
38. Soldatos G, Cooper M. Diabetic nephropathy: important pathophysiologic mechanisms. Diabetes Res Clin Pract 2008;8:75–9.

39. Matthias M, George L. Protein kinase c activation and its pharmacological inhibition in vascular disease. Vascular Medicine 2000;5:173–85.
40. Haneda M, Koya D, Kikkawa R. Cellular mechanisms in the development and progression of diabetic nephropathy: activation of the DAG-PKC-ERK pathway. Am J Kidney Dis 2001;38(4):178–81.
41. Maria M, Maria G, Muscurel C, Carmen D, Alexandra T. The sources and the targets of oxidative stress in the etiology of diabetic complications. Romanian J Biophysics 2001;17(2):63–84.
42. Arora M, Singh U. Molecular mechanisms in the pathogenesis of diabetic nephropathy: an update. Vascular Pharmacology 2013;58:259–71.
43. Brownlee M. The pathobiology of diabetic complications: a unifying mechanism. Diabetes 2005;54:1615–25.
44. Balakumar P, Arora M, Ganti S, Reddy J, Singh M. Recent advances in pharmacotherapy for diabetic nephropathy: current perspectives and future directions. Pharmacol Res 2009;60:24–32.
45. Rasch R. prevention of diabetic glomerulopathy in streptozotocin diabetic rats by insulin treatment¬¬-glomerular basement membrane thickness. Diabetologia 1979;16(5):319–24.
46. Rasch R. Prevention of diabetic glomerulopathy in streptozotocin diabetic rats by insulin treatment-albumin excretion. Diabetologia 1980;18(5):413–6.
47. Jeff K. A review of oral antidiabetic agents. Pharmacotherapy Update 2001;4(3):1–4.
48. Zanchia A, Lehmannb R, Philippec J. Antidiabetic drugs and kidney disease recommendations of the swiss society for endocrinology and diabetology. Swiss Medical Weekly 2012;142:1-8.
49. Madhu S. Use of oral anti-diabetic agents in diabetes with chronic kidney disease. Medicine Update 2011;156-9.
50. Abe M, Okada K, Soma M. Antidiabetic agents in patients with chronic kidney disease and end-stage renal disease on dialysis: metabolism and clinical practice. Curr Drug Metab 2011;12(1):57–69.
51. Thomas S, Viberti G. Complications of diabetes-diabetic nephropathy. Medicine 2002;33–6.
52. Bernstein A, Treyzon L, Li Z. Are High-Protein, Vegetable-Based Diets Safe for Kidney Function? A Review of the Literature. J Am Dietetic Association 2007;107:644–50.
53. Lee D, Ha M, Kim J, Jacobs D. Effects of smoking cessation on changes in blood pressure and incidence of hypertension: a 4-year follow-up study. Hypertension 2001;37:194–8.
54. Mehler P, Jeffers B, Biggerstaff S, Schrier R. Smoking as a risk factor for nephropathy in non-insulin-dependent diabetics. J General Internal Medicine 1998;13:842–5.
55. Chuahirun T, Khanna A, Kimball K, Wesson D. Cigarette smoking and increased urine albumin excretion are interrelated predictors of nephropathy progression in type 2 diabetes. Am J Kidney Dis 2003;1:13–21.
56. Davis G, Roberts D. Molecular genetics of the renin-angiotensin system: implications for angiotensin ii receptor blockade. Pharmacol Ther 1997;75(1):43–50.
57. Struthers A, MacDonald T. Review of Aldosterone-and Angiotensin II-Induced target organ damage and prevention. Cardiovasc Res 2004;61:663–70.
58. Leehey D, Singh A, Alavi N, Singh R. Role of angiotensin ii in diabetic nephropathy. Kidney Int 2000;58(77):93–8.
59. Chawla T, Sharma D, Singh A. Role of the rennin angiotensin system in diabetic nephropathy. World J Diabetes 2010;1(5):141–5.
60. Cooper M. Pathogenesis, Prevention and treatment of diabetic nephropathy. Lancet 1998;352:213–9.
61. Wittmann I, Molnar G, Degrell P, Wagner Z, Tamasko M, Laczy B, et al. Prevention and treatment of diabetic nephropathy. Diabetes Res Clin Pract 2005;68(1):36–42.
62. Dash A, Maiti R, Bandakkanavar T, Pandey. Novel drug treatment for diabetic nephropathy. Hong Kong J Nephrology 2011;13(1):19–26.
63. Zoncu R, Efeyan A, Sabatini D. mTOR: From growth signal integration to cancer, diabetes and ageing. Nat Rev Mol Cell Biol 2011;1:21–35.
64. Nangaku M, Miyata T, Sada T, Mizuno M, Inagi R, Ueda Y, et al. Anti-Hypertensive agents inhibit in vivo the formation of advanced glycation end products and improve renal damage in a type 2 diabetic nephropathy rat model. J Am Soc Nephrology 2003;22:1212–22.
65. Huijberts M, Schalkwijk C. Is AGE accumulation a therapeutic target for diabetic complications? J Medicine 2006;64(1):1–3.
66. Lee C, Huang T. Plasminogen activator inhibitor-1:the expression, biological functions, and effects on tumorigenesis and tumor cell adhesion and migration. J Cancer Mol 2005;1(1):25–36.
67. Hamodi Z, Ismail I, Ali R, Ahmed K, Muniandy S. Association of plasminogen activator inhibitor-1and tissue plasminogen activator with type 2 diabetes and metabolic syndrome in malaysian subjects. Cardiovasc Diabetol 2011;10(23):1–9.
68. Huang Y, Border W, Yu L, Zhang J, Lawrence D, Nobel N. A PAI-1 Mutant, PAI-1R, Slows progression of diabetic nephropathy. J Am Soc Nephrology 2008;19:329–38.
69. Negi G, Kumar A, Joshi R, Ruby K, Sharma S. Oxidative stress and diabetic neuropathy: current status of antioxidants. IIOAB J 2011;2(6):71–8.
70. Navarroa J, Fernandez C. The role of TNF-α in diabetic nephropathy: pathogenic and therapeutic implications. Cytokine Growth Factor Review 2006;17:441–50.
71. Sung J, Koh J, Lee M, Kim B, Nam S, Kim J, et al. Aldose reductase inhibitor ameliorates renal vascular endothelial growth factor expression in streptozotocin-induced diabetic rats. Yonsei Medical J 2010;51(3):385–91.
72. Zhu C. Aldose Reductase Inhibitors as Potential Therapeutic Drugs of Diabetic Complications. In: Oguntibeju Oluwafemi, editor. Diabetes Mellitus – Insights and Perspectives. Croatia: In Tech; 2013. p. 17–46.
661 Views | 7844 Downloads
How to Cite
Dhodi, J. B., S. N. Mestry, and A. R. Juvekar. “DIABETIC NEPHROPATHY – GENESIS, PREVENTION AND TREATMENT”. International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 6, no. 9, 1, pp. 42-47, https://innovareacademics.in/journals/index.php/ijpps/article/view/2468.
Review Article(s)