Author(s):
Haziq Khan, Parkhi Rastogi, Lubhan Singh
Email(s):
Haziqkhann56802@gmail.com , rastogi.parkhi@gmail.com , lubhansingh@gmail.com
DOI:
10.52711/2231-5713.2026.00023
Address:
Haziq Khan, Parkhi Rastogi*, Lubhan Singh
Department of Pharmacology, Kharvel Subharti College of Pharmacy, Swami Vivekanand Subharti University, Meerut 250005, Uttar Pradesh, India.
*Corresponding Author
Published In:
Volume - 16,
Issue - 2,
Year - 2026
ABSTRACT:
Diabetic nephropathy (DN) is one of the severest micro-vascular complications of diabetes mellitus and it becomes the primary inducement of end-stage renal disease (ESRD) in the world. Although the pathophysiology of DN has been widely addressed, therapeutic measures are restricted, mainly due to the complexity of genetic, metabolic, and hemodynamic cross-links that may exist in this condition. Here we present an overview of the most recent in vivo and in vitro models adopted for detection of DN, discussing the advantages, limitations, and applications of each model. The paper systematically clusters animal models into surgical, chemical, viral, genetic, and gestational approaches, and covers the advent of state-of-the-art organ-on-chip (OOC) technologies. Surgical models including nephrectomy are more comparable to human renal injury, but are restricted by ethical considerations and species differences. Chemical models that mimic it, such as those produced by streptozotocin (STZ), are reproducible and easy to use, but are limited as more often than not they do not truly recapitulate the situations in human DN. Genetic models allow for specific control of disease pathways, but are expensive and may miss effects of factors in the environment. Furthermore, gestational models provide important insights pertaining to transgenerational risks and maternal-fetal interactions. Recent advances in OOC systems provide one such alternative, by enabling an approach that combines physiological relevance with human cells, thereby reducing animal use and facilitating HTS. In addition, the review highlights the advantages of animal models, including the convenience of studying whole-organism responses, systemic effects, and chronic disease that are challenging to recapitulate in vitro. Yet it also identifies the constraints that require additional methods. Taken together, the review emphasizes the necessity to adopt integrated model systems for more precise and comprehensive interpretation of DN toward the rapid discovery of effective therapeutics.
Cite this article:
Haziq Khan, Parkhi Rastogi, Lubhan Singh. Diabetic Nephropathy: A Review on Pathological Relevant Models. Asian Journal of Pharmacy and Technology. 2026; 16(2):161-0. doi: 10.52711/2231-5713.2026.00023
Cite(Electronic):
Haziq Khan, Parkhi Rastogi, Lubhan Singh. Diabetic Nephropathy: A Review on Pathological Relevant Models. Asian Journal of Pharmacy and Technology. 2026; 16(2):161-0. doi: 10.52711/2231-5713.2026.00023 Available on: https://ajptonline.com/AbstractView.aspx?PID=2026-16-2-8
REFERENSE:
1. Umanath K, Lewis JB. Update on Diabetic Nephropathy: Core Curriculum 2018. American Journal of Kidney Diseases [Internet]. 2018 Feb 3; 71(6): 884–95. Available from: https://doi.org/10.1053/j.ajkd.2017.10.026
2. Diabetes and the kidney [Internet]. Contributions to nephrology. 2011. Available from: https://doi.org/10.1159/isbn.978-3-8055-9743-2
3. Van Dijk C, Berl T. Pathogenesis of diabetic nephropathy. Reviews in Endocrine and Metabolic Disorders [Internet]. 2004 Jun 22; 5(3): 237–48. Available from: https://doi.org/10.1023/b:remd.0000032412.91984.ec
4. Tesch GH. Diabetic nephropathy – is this an immune disorder? Clinical Science [Internet]. 2017 Jul 31; 131(16): 2183–99. Available from: https://doi.org/10.1042/cs20160636
5. Papadopoulou‐Marketou N, Chrousos GP, Kanaka‐Gantenbein C. Diabetic nephropathy in type 1 diabetes: a review of early natural history, pathogenesis, and diagnosis. Diabetes/Metabolism Research and Reviews [Internet]. 2016 Jul 26; 33(2). Available from: https://doi.org/10.1002/dmrr.2841
6. Gallagher H, Suckling RJ. Diabetic nephropathy: where are we on the journey from pathophysiology to treatment? Diabetes Obesity and Metabolism [Internet]. 2016 Jan 8; 18(7): 641–7. Available from: https://doi.org/10.1111/dom.12630
7. Gross JL, De Azevedo MJ, Silveiro SP, Canani LH, Caramori ML, Zelmanovitz T. Diabetic nephropathy: diagnosis, prevention, and treatment. Diabetes Care [Internet]. 2005 Jan 1;28(1):164–76. Available from: https://doi.org/10.2337/diacare.28.1.164
8. Umanath K, Lewis JB. Update on Diabetic Nephropathy: Core Curriculum 2018. American Journal of Kidney Diseases [Internet]. 2018 Feb 3; 71(6): 884–95. Available from: https://doi.org/10.1053/j.ajkd.2017.10.026
9. Fineberg D, Jandeleit-Dahm K a. M, Cooper ME. Diabetic nephropathy: diagnosis and treatment. Nature Reviews Endocrinology [Internet]. 2013 Oct 8; 9(12): 713–23. Available from: https://doi.org/10.1038/nrendo.2013.184
10. Zoja C, Xinaris C, Macconi D. Diabetic nephropathy: Novel molecular mechanisms and therapeutic targets. Frontiers in Pharmacology [Internet]. 2020 Dec 21; 11. Available from: https://doi.org/10.3389/fphar.2020.586892
11. Cooper ME, Gilbert RE, Epstein M. Pathophysiology of diabetic nephropathy. Metabolism [Internet]. 1998 Dec 1; 47: 3–6. Available from: https://doi.org/10.1016/s0026-0495(98)90362-6
12. Cooper ME, Gilbert RE, Epstein M. Pathophysiology of diabetic nephropathy. Metabolism [Internet]. 1998 Dec 1; 47: 3–6. Available from: https://doi.org/10.1016/s0026-0495(98)90362-6
13. Feigerlová E, Battaglia-Hsu SF. IL-6 signaling in diabetic nephropathy: From pathophysiology to therapeutic perspectives. Cytokine & Growth Factor Reviews [Internet]. 2017 Mar 23; 37: 57–65. Available from: https://doi.org/10.1016/j.cytogfr.2017.03.003
14. Rao VR a/L BV, Tan SH, Candasamy M, Bhattamisra SK. Diabetic nephropathy: An update on pathogenesis and drug development. Diabetes & Metabolic Syndrome Clinical Research & Reviews [Internet]. 2018 Nov 30; 13(1): 754–62. Available from: https://doi.org/10.1016/j.dsx.2018.11.054
15. Soldatos G, Cooper ME. Diabetic nephropathy: Important pathophysiologic mechanisms. Diabetes Research and Clinical Practice [Internet]. 2008 Nov 1; 82: S75–9. Available from: https://doi.org/10.1016/j.diabres.2008.09.042
16. Lehmann R, Schleicher ED. Molecular mechanism of diabetic nephropathy. Clinica Chimica Acta [Internet]. 2000 Jul 1; 297(1–2): 135–44. Available from: https://doi.org/10.1016/s0009-8981(00)00240-0
17. Gnudi L, Coward RJM, Long DA. Diabetic Nephropathy: Perspective on novel molecular mechanisms. Trends in Endocrinology and Metabolism [Internet]. 2016 Jul 26;27(11):820–30. Available from: https://doi.org/10.1016/j.tem.2016.07.002
18. Arora MK, Singh UK. Molecular mechanisms in the pathogenesis of diabetic nephropathy: An update. Vascular Pharmacology [Internet]. 2013 Jan 11; 58(4): 259–71. Available from: https://doi.org/10.1016/j.vph.2013.01.001
19. Warren AM, Knudsen ST, Cooper ME. Diabetic nephropathy: an insight into molecular mechanisms and emerging therapies. Expert Opinion on Therapeutic Targets [Internet]. 2019 Jun 3; 23(7): 579–91. Available from: https://doi.org/10.1080/14728222.2019.1624721
20. Rostène W, De Meyts P. Insulin: a 100-Year-Old discovery with a fascinating history. Endocrine Reviews [Internet]. 2021 Jul 17; 42(5): 503–27. Available from: https://doi.org/10.1210/endrev/bnab020
21. Pandey S, Chmelir T, Dvorakova MC. Animal Models in Diabetic Research—History, Presence, and Future Perspectives. Biomedicines [Internet]. 2023 Oct 20; 11(10): 2852. Available from: https://doi.org/10.3390/biomedicines11102852
22. Allen, F.M. Studies Concerning Glycosuria and Diabetes; Harvard University Press: Cambridge, UK, 1913
23. Stamler J, Katz LN, Bolene C. The effect of pancreatectomy on lipemia, tissue lipidosis and atherogenesis in chicks. Circulation [Internet]. 1951 Aug 1; 4(2): 255–61. Available from: https://doi.org/10.1161/01.cir.4.2.255
24. Stamler J, Katz LN, Bolene C. The effect of pancreatectomy on lipemia, tissue lipidosis and atherogenesis in chicks. Circulation [Internet]. 1951 Aug 1; 4(2): 255–61. Available from: https://doi.org/10.1161/01.cir.4.2.255
25. Imamura T, Koffler M, Helderman JH, Prince D, Thirlby R, Inman L, et al. Severe diabetes induced in subtotally depancreatized dogs by sustained hyperglycemia. Diabetes [Internet]. 1988 May 1; 37(5): 600–9. Available from: https://doi.org/10.2337/diab.37.5.600
26. Yokozawa T, Nakagawa T, Wakaki K, Koizumi F. Animal model of diabetic nephropathy. Experimental and Toxicologic Pathology [Internet]. 2001 Jan 1;53(5):359–63. Available from: https://doi.org/10.1078/0940-2993-00203
27. Motojima M, Hosokawa A, Yamato H, Muraki T, Yoshioka T. Uremic toxins of organic anions up-regulate PAI-1 expression by induction of NF-κB and free radical in proximal tubular cells. Kidney International [Internet]. 2003 May 1; 63(5): 1671–80. Available from: https://doi.org/10.1046/j.1523-1755.2003.00906.x
28. Phelps RG, Rees AJ. The HLA complex in Goodpasture’s disease: A model for analyzing susceptibility to autoimmunity. Kidney International [Internet]. 1999 Nov 1; 56(5): 1638–53. Available from: https://doi.org/10.1046/j.1523-1755.1999.00720.x
29. Fleuren HWHA, Kho Y, Schuurmans MMJ, Vollaard EJ. Drug interaction between sevelamer and furosemide. Nephrology Dialysis Transplantation [Internet]. 2005 Jul 26;20(10):2288–9. Available from: https://doi.org/10.1093/ndt/gfi020
30. Singh G, Dhuria R, Kaur A, Kaur R, Kaur T. Current status and patent prospective of animal models in diabetic research. Advanced Biomedical Research [Internet]. 2015 Jan 1; 4(1): 117. Available from: https://doi.org/10.4103/2277-9175.157847
31. Szkudelski T. The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiological Research. 2001; 50(6): 537–546.
32. Pandey S, Chmelir T, Dvorakova MC. Animal Models in Diabetic Research—History, Presence, and Future Perspectives. Biomedicines [Internet]. 2023 Oct 20; 11(10): 2852. Available from: https://doi.org/10.3390/biomedicines11102852
33. Islam MdS. Animal Models of Diabetic Neuropathy: progress since 1960s. Journal of Diabetes Research [Internet]. 2013 Jan 1; 2013: 1–9. Available from: https://doi.org/10.1155/2013/149452
34. Ghasemi A, Khalifi S, Jedi S. Streptozotocin-nicotinamide-induced rat model of type 2 diabetes (review). Acta Physiologica Hungarica [Internet]. 2014 Dec 1; 101(4): 408–20. Available from: https://doi.org/10.1556/aphysiol.101.2014.4.2
35. Rafacho A, Cestari TM, Taboga SR, Boschero AC, Bosqueiro JR. High doses of dexamethasone induce increased β-cell proliferation in pancreatic rat islets. AJP Endocrinology and Metabolism [Internet]. 2009 Jan 21; 296(4): E681–9. Available from: https://doi.org/10.1152/ajpendo.90931.2008
36. Bernard H, Teijeiro A, Chaves-Pérez A, Perna C, Satish B, Novials A, et al. Coxsackievirus B Type 4 Infection in β Cells Downregulates the Chaperone Prefoldin URI to Induce a MODY4-like Diabetes via Pdx1 Silencing. Cell Reports Medicine [Internet]. 2020 Oct 1; 1(7): 100125. Available from: https://doi.org/10.1016/j.xcrm.2020.100125
37. Yoon JW, Ray UR. Perspectives on the Role of Viruses in Insulin-dependent Diabetes. Diabetes Care [Internet]. 1985 Sep 1; 8: 39–44. Available from: https://care.diabetesjournals.org/content/8/Supplement_1/39
38. Onodera T, Ray UR, Melez KA, Suzuki H, Toniolo A, Notkins AL. Virus-induced diabetes mellitus: autoimmunity and polyendocrine disease prevented by immunosuppression. Nature [Internet]. 1982 May 6; 297(5861): 66–8. Available from: https://www.nature.com/articles/297066a0
39. Huffman JH. Studies on Encephalomyocarditis Virus-Induced Diabetes in Mice. 1988 Jan 1; Available from: https://digitalcommons.usu.edu/etd/4046/
40. Jordan GW, Cohen SH. Encephalomyocarditis virus-induced diabetes mellitus in mice: model of viral pathogenesis. Clinical Infectious Diseases [Internet]. 1987 Sep 1; 9(5): 917–24. Available from: https://pubmed.ncbi.nlm.nih.gov/2825321/
41. Rayfield EJ, Kelly KJ, Yoon JW. Rubella Virus–Induced Diabetes in the Hamster. Diabetes [Internet]. 1986 Nov 1; 35(11): 1278–81. Available from: https://diabetes.diabetesjournals.org/content/35/11/1278
42. Qi Z, Fujita H, Jin J, Davis LS, Wang Y, Fogo AB, et al. Characterization of Susceptibility of Inbred Mouse Strains to Diabetic Nephropathy. Diabetes [Internet]. 2005 Sep 1; 54(9): 2628–37. Available from: https://diabetes.diabetesjournals.org/content/54/9/2628
43. Franzén S, Friederich-Persson M, Fasching A, Hansell P, Nangaku M, Palm F. Differences in susceptibility to develop parameters of diabetic nephropathy in four mouse strains with type 1 diabetes. American Journal of Physiology-renal Physiology [Internet]. 2014 May 15; 306(10). Available from: https://pubmed.ncbi.nlm.nih.gov/24623147/
44. Gurley SB, Ghosh S, Johnson SA, Azushima K, Sakban RB, George SE, et al. Inflammation and Immunity Pathways Regulate Genetic Susceptibility to Diabetic Nephropathy. Diabetes [Internet]. 2018 Oct 1; 67(10): 2096–106. Available from: https://diabetes.diabetesjournals.org/content/diabetes/67/10/2096.full.pdf
45. Wang Y, Sun G, Sun J, Liu S jun, Wang J, Xu X, et al. Spontaneous Type 2 Diabetic Rodent Models. Experimental Diabetes Research [Internet]. 2013 Feb 28; 2013: 401723. Available from: https://downloads.hindawi.com/journals/jdr/2013/401723.pdf
46. Sasase T, Yokoi N, Pezzolesi MG, Shinohara M. Animal models of diabetes and metabolic disease 2014. Experimental Diabetes Research [Internet]. 2013 Jun 25; 2015: 571809. Available from: https://downloads.hindawi.com/journals/jdr/2013/281928.pdf
47. Aubin AM, Lombard-Vadnais F, Collin R, Aliesky HA, McLachlan SM, Lesage S. The NOD Mouse Beyond Autoimmune Diabetes. Frontiers in Immunology [Internet]. 2022 Apr 29; 13. Available from: https://www.frontiersin.org/articles/10.3389/fimmu.2022.874769/
48. Kitada M, Ogura Y, Koya D. Rodent models of diabetic nephropathy: their utility and limitations. International Journal of Nephrology and Renovascular Disease [Internet]. 2016 Nov 14; 9: 279–90. Available from: https://www.dovepress.com/getfile.php?fileID=33582
49. Brosius FC, Alpers CE, Bottinger EP, Breyer MD, Coffman TM, Gurley SB, et al. Mouse Models of Diabetic Nephropathy. Journal of The American Society of Nephrology [Internet]. 2009 Dec 1; 20(12): 2503–12. Available from: https://www.mmpc.org/shared/document.aspx?id=270
50. You S, Chatenoud L. Autoimmune Diabetes: An Overview of Experimental Models and Novel Therapeutics. In Humana Press, New York, NY; 2016. p. 117–42. Available from: https://link.springer.com/protocol/10.1007/978-1-4939-3139-2_8
51. Cauvi DM, Hultman P, Pollard KM. Autoimmune Models. In Elsevier BV; 2024.
52. Kleinert M, Clemmensen C, Hofmann SM, Moore MC, Renner S, Woods SC, et al. Animal models of obesity and diabetes mellitus. Nature Reviews Endocrinology [Internet]. 2018 Jan 19; 14(3): 140–62. Available from: https://escholarship.org/content/qt3z3879vp/qt3z3879vp.pdf?t=ptt41u
53. Shafrir E, Ziv E. A useful list of spontaneously arising animal models of obesity and diabetes. American Journal of Physiology-endocrinology and Metabolism [Internet]. 2009 Jun 1; 296(6). Available from: https://www.ncbi.nlm.nih.gov/pubmed/19468077
54. Hudkins KL, Pichaiwong W, Wietecha T, Kowalewska J, Banas MC, Spencer M, et al. BTBR Ob/Ob Mutant Mice Model Progressive Diabetic Nephropathy. Journal of The American Society of Nephrology [Internet]. 2010 Sep 1; 21(9): 1533–42.
55. Nandi A, Kitamura Y, Kahn CR, Accili D. Mouse models of insulin resistance. Physiological Reviews [Internet]. 2004 Apr 1; 84(2): 623–47. Available from: https://pubmed.ncbi.nlm.nih.gov/15044684/
56. Azizah DU, Bahtiar A, Angelina M. Animal models of diabetic nephropathy. Asian Journal of Pharmaceutical and Clinical Research. 2023 Aug 7; 11–23.
57. Li G, Guo J zhi, Cao M, Li X guo, Li R nan, Chen C yan. Induction of Type 2 Diabetes SD Rats Model with Intragastric Administration of High-fat and Cholesterol.
58. Spasov AA, Babkov DA, Prilepskaya DR, Zakharyashcheva OYu. Type 2 Diabetes Mellitus in Rats on a High-Fat Diet with Streptozotocin Induction: Evaluation of the Model. 2018 Jun 30; 3(1): 20.
59. Correia-Santos AM, Suzuki A, dos Anjos JS, Rêgo T de S, de Almeida KCL, Gilson T. Induction of Type 2 Diabetes by low dose of streptozotocin and high-fat diet-fed in wistar rats. 2012 Jan 1;
60. Arti MK, Balaji S, kirti A. Exploring the Diversity of Organ-on-a-chip Models. International journal of all research education and scientific methods. 2025 Jan 1; 13(1): 153–9.
61. Wysoczański B, Świątek M, Wójcik-Gładysz A. Organ-On-A-Chip Models—New Possibilities in Experimental Science and Disease Modeling. Biomolecules. 2024 Dec 9; 14(12): 1569.
62. Martinez-Rivas A, González-Quijano GK. Micro and nanoengineering advances for the development and commercialization of Organ-on-chips. Bioelectromagnetics [Internet]. 2017 Jan 1; 2(3). Available from: https://www.oatext.com/micro-and-nanoengineering-advances-for-the-development-and-commercialization-of-organ-on-chips.php
63. Ingber, D. E. (). Human organs-on-chips for disease modelling, drugdevelopmand personalized medicine. Nature Reviews Genetics. 2022; 23(8): 467–491. https://doi.org/10.1038/s41576-022-00466-9
64. Luo, W., Tang, S., Xiao, X., Luo, S., Yang, Z., Huang, W., & Tang, S. Translation Animal models of Diabetic kidney Disease: Biochemical and histological phenotypes, Advantages and limitations. Diabetes Metabolic Syndrome and Obesity. 2023; 16: 1297–1321. https://doi.org/10.2147/dmso.s408170
65. Betz B, Conway BR. An Update on the Use of Animal Models in Diabetic Nephropathy Research. Current Diabetes Reports [Internet]. 2016 Jan 27; 16(2): 18. Available from: https://www.research.ed.ac.uk/portal/files/25258167/art_10.1007_s11892_015_0706_2.pdf
66. Naseri M, Ranaei Pirmardan E, Melhorn MI, Zhang Y, Barakat A, Hafezi‐Moghadam A. A translational model of chronic diabetic nephropathy in the Nile grass rat. The FASEB Journal. 2024 Jul 17; 38(14).
67. Zhang X, Lyu D, Li S, Xiao H, Qiu Y, Xu K, et al. Discovery of a SUCNR1 antagonist for potential treatment of diabetic nephropathy: In silico and in vitro studies. International Journal of Biological Macromolecules [Internet]. 2024 Apr 26; 268: 131898. Available from: https://doi.org/10.1016/j.ijbiomac.2024.131898
68. Shaikh RQ, Das S, Chaurasiya A, Ashtamy M, Sheikh AB, Fernandes M, et al. Discovery of free glycated amines and glycated urea as potential markers of diabetic nephropathy. bioRxiv (Cold Spring Harbor Laboratory) [Internet]. 2024 Feb 21; Available from: https://doi.org/10.1101/2024.02.17.580794
69. Yanoff M, Sassani JW. Diabetes mellitus. In: Elsevier eBooks [Internet]. 2024. p. 643-679.e10. Available from: https://doi.org/10.1016/b978-0-323-87822-7.00015-8
70. Abdulrazaaq ZA. Evaluation of Tumor necrosis factor (TNF-α) Concertation and Renal function in the Sera of patients with Type 2 diabetes in Erbil city. Medicra (Journal of Medical Laboratory Science/Technology) [Internet]. 2024 Aug 13; 7(2): 49–54. Available from: https://doi.org/10.21070/medicra.v7i2.1751
71. Hosszu A, Kaucsar T, Seeliger E, et al. Animal Models of Renal Pathophysiology and Disease. 2021
72. Olsson IA, Franco NH, Weary DM, Sandøe P (2012). "The 3Rs Principle – Mind the Ethical Gap
73. Luo W, Tang S, Xiao X, Luo S, Yang Z, Huang W, et al. Translation Animal models of Diabetic kidney Disease: Biochemical and histological phenotypes, Advantages and limitations. Diabetes Metabolic Syndrome and Obesity [Internet]. 2023 May 1; 16: 1297–321. Available from: https://doi.org/10.2147/dmso.s408170
74. Kitada M, Ogura Y, Koya D. Rodent models of diabetic nephropathy: their utility and limitations. International Journal of Nephrology and Renovascular Disease [Internet]. 2016 Nov 1; 9: 279–90. Available from: https://doi.org/10.2147/ijnrd.s103784.