Current Science

Open Access Open Access  Restricted Access Subscription Access

Diabetic nephropathy: prevalence, pathogenesis and signalling pathways


Affiliations
1 Department of Pharmacology, GITAM School of Pharmacy, GITAM (Deemed to be University), Rushikonda, Visakhapatnam 530 045, India, India
 

One of the main causes of death and morbidity in people with diabetes mellitus is diabetic nephropathy (DN). Diabetes and DN have a complicated pathophysiology that includes the connection between metabolic and hemodynamic pathways, oxidative stress, development of cytokines and growth factors, eventually resulting in renal impairment. Three key lesions, viz. diffuse mesangial enlargement, thickened glomerular basement membrane, and arteriole hyalinosis, represent the pathological hallmarks of the illness. The mesangial cells, glomerular capillary membrane, tubulo-interstitium and vasculature as well as other functional structures are all dysfunctional in the pathogenesis. In low- to middle-income countries, the prevalence of diabetic kidney disease is gradually rising but irregularly. Also, it is underappreciated as a major global health concern. DN is caused by a number of anomalies in the signalling pathways. This article aims to clarify the nature of DN risk factors, prevalence, phases, aetio­logy and signal transduction pathways

Keywords

Diabetic nephropathy, oxidative stress, patho-genesis, renal impairment, signalling pathways.
User
Notifications
Font Size

  • Gudisa, B., Complication of diabetes mellitus: microvascular and macrovascular complications. Int. J. Diabetes, 2019, 3, 123–128.

  • Poonam, S. et al., Chalcone-based aryloxypropanolamine as a potential antidiabetic and antidyslipidaemic agent. Curr. Sci., 2017, 112, 1675–1689.

  • Michael, J. and Fowler, M. D., Microvascular and macrovascular complications of diabetes. Clin. Diabetes, 2008, 26, 77–82.

  • Aastha, C., Rajeev, C. and Shalini, J., Microvasular and macrovascular complications in diabetes mellitus. Indian J. Endocrinol. Metab., 2016, 20, 546–551.

  • Craig, K. J., Donovan, K., Munnery, M., Owens, D. R., Williams, J. D. and Phillips, A. O., Identification and management of diabetic nephropathy in the diabetes clinic. Diabetes Care, 2003, 26, 1806–1814.

  • Hahr, A. J. and Molitch, M. E., Management of diabetes mellitus in patients with chronic kidney disease. Clin. Diabetes Endocrinol., 2015, 1, 2–9.

  • Ramanjaneyulu, M. et al., Target identification and validation for diabetic nephropathy using molecular docking studies. Der Pharma Chem., 2013, 5, 353–363.

  • Suma, D., Irena, D. and George, L. B., The pathogenesis of diabetic nephropathy. Nature Clin. Pract. Endocrinol. Metabol., 2008, 4, 444–452.

  • Vijayakumar, N. and Sung-Jin, K., Diabetic nephropathy: a review of risk factors, progression, mechanism, and dietary management. Biomol. Ther., 2021, 29, 365–372.

  • Satko, S. G., Langefeld, C. D., Daeihagh, P., Bowden, D. B., Rich, S. S. and Freedman, B. I., Nephropathy in siblings of African Americans with overt type 2 diabetic nephropathy. Am. J. Kidney Dis., 2002, 40, 489–494.

  • Brancati, F. L., Whittle, J. C., Whelton, P. K., Seidler, A. J. and Klag, M. J., The excess incidence of diabetic end-stage renal disease among blacks. A population-based study of potential explanatory factors. J. Am. Med. Assoc., 1992, 268, 3079–3084.

  • Svensson, M., Nystrom, L., Schon, S. and Dahlquist, G., Age at onset of childhood-onset type 1 diabetes and the development of end-stage renal disease: a nation wide population-based study. Diabetes Care, 2006, 29, 538–542.

  • Tap, R. J, Shaw, J. E., Zimmet, P. Z., Balkau, B., Chadban, S. J. and Tonkin. A. M., Albuminuria is evident in the early stages of diabe-tes onset: results from the Australian Diabetes, Obesity, and Life-style Study (AusDiab). Am. J. Kidney Dis., 2004, 44, 792–798.

  • Salman, H., Mohammad, C. J., Anwar, H., Sarfaraj Hussaind, M. D., Akhtare M. D. and Abul Kalam, N., Diabetic kidney disease: an overview of prevalence, risk factors, and biomarkers. Clin. Epi-demiol. Global Health, 2021, 9, 2–6.

  • Wagnew, F., Eshetie, S. and Kibret, G. D., Diabetic nephropathy and hypertension in diabetes patients of sub-Saharan countries: a systematic review and meta-analysis. BMC Res. Notes, 2018, 11, 560–565.

  • Chehade, J. M., Gladysz, M. and Mooradian, A. D., Dyslipidemia in type 2 diabetes: prevalence, pathophysiology, and management. Drugs, 2013, 73, 327–339.

  • Hill, C. J. et al., Obesity and kidney disease in type 1 and 2 diabetes: an analysis of the National Diabetes Audit. Int. J. Med., 2013, 106, 933–942.

  • Feodoroff, M., Harjutsalo, V. and Forsblom, C., Smoking and pro-gression of diabetic nephropathy in patients with type 1 diabetes. Acta Diabetol., 2016, 53, 525–533.

  • Sun, H. S. et al., IDF Diabetes Atlas: global, regional and country level diabetes prevalence estimates for 2021 and projections for 2045. Diabet. Res. Clin. Pract., 2022, 183, 109119.

  • Ellen, K. H., The epidemiology of diabetic kidney disease. Kidney Dial., 2022, 2, 433–442.

  • Pradeepa, R. and Mohan, V., Epidemiology of type 2 diabetes in India. Indian J. Ophthalmol., 2021, 69, 2932–2938.

  • Hussain, S., Habib, A. and Najmi, A. K., Limited knowledge of chronic kidney disease among type 2 diabetes mellitus patients in India. Int. J. Environ. Res. Public Health, 2019, 16, 1443–1448.

  • Duan, J. et al., Prevalence and risk factors of chronic kidney disease and diabetic kidney disease in Chinese rural residents: a cross-sectional survey. Sci. Rep., 2019, 9, 1–11.

  • Al-Shamsi, S., Regmi, D. and Govender, R., Chronic kidney dis-ease in patients at high risk of cardiovascular disease in the United Arab Emirates: a population-based study. PLoS ONE, 2018, 13–19.

  • Ali, H. M., Diabetes mellitus and chronic kidney disease in the eastern Mediterranean Region: findings from the Global Burden of Disease 2015 Study. Int. J. Public Health, 2018, 63, 177–186.

  • Yokoyama, H., Sone, H., Oishi, M., Kawai, K., Fukumoto, Y. and Kobayashi, M., Prevalence of albuminuria and renal insufficiency and associated clinical factors in type 2 diabetes: the Japan Diabetes Clinical Data Management study (JDDM15). Nephrol Dial. Trans-plant., 2009, 24, 1212–1219.

  • Retnakaran, R., Cull, C. A., Thorne, K. I., Adler, A. I. and Holman, R. R., Risk factors for renal dysfunction in type 2 diabetes: UK Prospective Diabetes Study. Diabetes, 2006, 55, 1832–1839.

  • De Boer, I. H., Rue, T. C., Hall, Y. N., Heagerty, P. J., Weiss, N. S. and Himmelfarb, J., Temporal trends in the prevalence of diabetic kidney disease in the United States. J. Am. Med. Assoc., 2011, 305, 2532–2539.

  • Mogensen, C. E., Microalbuminuria, blood presure and diabetic renal disease: origin and development of ideas. Diabetologia, 1999, 42, 263–285.

  • Astha, J., Bhupesh, C. and Sonia, S., A compressive review on novel molecular target of diabetic nephropathy. Res. J. Pharm. Technol., 2022, 15, 1398–1404.

  • Saleem, N., Naeem, M., Rashid, A., Naheed, A., Imtiaz, M. T. and Mohin, K., Diabetic nephropathy pathogenesis and therapeutic management. Pak. J. Med. Biol. Sci., 2018, 2, 64–74.

  • Vasavada, N. and Agarwal, R., Role of oxidative stress in diabetic nephropathy. Adv. Chronic Kidney Dis., 2005, 12, 146–154.

  • Sharma, V. and Sharma, P. L., Role of different molecular pathways in the development of diabetes induced nephropathy. J. Diabetes Metab., 2013, 9, 1–7.

  • Zhou, G., Li, C. and Cai, L., Advanced glycation end-products in-duce connective tissue growth factor-mediated renal fibrosis pre-dominately through transforming growth factor beta-independent pathway. Am. J. Pathol., 2004, 165, 2033–2043.

  • Noh, H. and King, G. L., The role of protein kinase C activation in diabetic nephropathy. Kidney Int. Suppl., 2007, 106, 49–53.

  • Forbes, J. M., Fukami, K. and Cooper, M. E., Diabetic nephropathy: where hemodynamics meets metabolism. Exp. Clin. Endocrinol. Diabetes, 2007, 115, 1–16.

  • Yi-Chih, L., Yu-Hsing, C., Shao-Yu, Y., Kwan-Dun, W. and Tzong-Shinn, C., Update of pathophysiology and management of diabetic kidney disease. J. Formosan Med. Assoc., 2018, 117, 662–675.

  • Atul, A., Sahil, A. and Harlokesh, N. Y., Pathogenesis of diabetic nephropathy. Int. J. Pharm. Pharm. Sci., 2010, 4, 24–29.

  • Sarika, A., Role of the renin–angiotensin system in diabetic nephropathy. World J. Diabetes, 2010, 1, 141–145.

  • Nguyen, G. and Contrepas, A., The (pro) renin receptors. J. Mol. Med., 2008, 86, 643–646.

  • Fradin, S. et al., Relationship between polymorphisms in the renin–angiotensin system and nephropathy in type 2 diabetic patients. Diabe-tes Metab., 2002, 28, 27–32.

  • Zohreh, R., The role of renin–angiotensin aldosterone system genes in diabetic nephropathy. Can. J. Diabetes, 2015, 40, 1–6.

  • Komers, R., Paradoxes of nitric oxide in the diabetic kidney. Am. J. Physiol.–Renal Physiol., 2003, 284, 1121–1137.

  • Muller, R. et al., The mitogen-activated protein kinase p38 alpha regulates tubular damage in murine anti-glomerular basement membrane nephritis. PLoS ONE, 2013, 8, 1–11.

  • Fujita, H., Omori, S., Ishikura, K., Hida, M. A. and Awazu, M., ERK and p38 mediate high glucose-induced hypertrophy and TGF-beta expression in renal tubular cells. Am. J. Physiol.–Renal Physiol., 2004, 8, 120–126.

  • Marrero, M. B., Banes-Berceli, A. K., Stern, D. M. and Eaton, D. C., Role of the JAK/STAT signaling pathway in diabetic nephropathy. Am. J. Physiol.–Renal Physiol., 2006, 290, 762–768.

  • Yuqing, Z., DeJin1, J., Xiaomin, K., Rongrong, Z., Yuting, S., Fengmei, L. and Xiaolin, T., Signaling pathways involved in dia-betic renal fibrosis. Front. Cell Dev. Biol., 2021, 9, 1–17.

  • Haiying, W. et al., The Wnt signaling pathway in diabetic nephropathy. Front. Cell Dev. Biol., 2022, 9, 1–11.

  • Ho, C., Lee, P. H., Hsu, Y. C., Wang, F. S., Huang, Y. T. and Lin, C. L., Sustained Wnt/beta-catenin signaling rescues high glucose induction of transforming growth factor-beta1-mediated renal fibrosis. Am. J. Med. Sci., 2012, 344, 374–382.

  • Xiaoyun, C., Wenke, G., Yongyan, D., Xia, L., Yujuan, L., Xu, P. and Xiyun, Y., ERK/MAPK and TGF-beta/Smad signaling path-ways play a role in the kidney fibrosis of diabetic mice accelerated by blood glucose fluctuation. J. Diabetes Res., 2013, 13, 740–748.

  • Gorin, Y. and Block, K., Nox4 and diabetic nephropathy. Free Radic. Biol. Med., 2013, 61, 130–142.

  • Sae, R. L., Eun, J. A., Jaesang, K. and Yun, S. B., Function of NADPH oxidases in diabetic nephropathy and development of Nox inhibitors. Biomol. Ther., 2020, 28, 25–33.

  • Akira, M., Inflammation and oxidative stress in diabetic nephropathy: new insights on its inhibition as new therapeutic targets. J. Diabetes Res., 2013, 9, 1–8.

  • Qichao, H., Yuan, C., Xinyu, D., Yubing, L., Xiao, M., Jinhao, Z. and Yanling, Z., Diabetic nephropathy: focusing on pathological signals, clinical treatment, and dietary regulation. Biomed. Pharma-cother., 2023, 159, 1142–1152.

  • Rayego-Mateos, S. et al., Pathogenic pathways and therapeutic ap-proaches targeting inflammation in diabetic nephropathy. Int. J. Mol. Sci., 2020, 21, 3798–3804.

  • Zoja1, C., Xinaris, C. and Macconi, D., Diabetic nephropathy: novel molecular mechanisms and therapeutic targets. Front. Pharmacol., 2020, 11, 892–899.


Abstract Views: 262

PDF Views: 109




  • Diabetic nephropathy: prevalence, pathogenesis and signalling pathways

Abstract Views: 262  |  PDF Views: 109

Authors

Swetha Bindu Chintala
Department of Pharmacology, GITAM School of Pharmacy, GITAM (Deemed to be University), Rushikonda, Visakhapatnam 530 045, India, India
Suhasin Ganta
Department of Pharmacology, GITAM School of Pharmacy, GITAM (Deemed to be University), Rushikonda, Visakhapatnam 530 045, India, India

Abstract


One of the main causes of death and morbidity in people with diabetes mellitus is diabetic nephropathy (DN). Diabetes and DN have a complicated pathophysiology that includes the connection between metabolic and hemodynamic pathways, oxidative stress, development of cytokines and growth factors, eventually resulting in renal impairment. Three key lesions, viz. diffuse mesangial enlargement, thickened glomerular basement membrane, and arteriole hyalinosis, represent the pathological hallmarks of the illness. The mesangial cells, glomerular capillary membrane, tubulo-interstitium and vasculature as well as other functional structures are all dysfunctional in the pathogenesis. In low- to middle-income countries, the prevalence of diabetic kidney disease is gradually rising but irregularly. Also, it is underappreciated as a major global health concern. DN is caused by a number of anomalies in the signalling pathways. This article aims to clarify the nature of DN risk factors, prevalence, phases, aetio­logy and signal transduction pathways

Keywords


Diabetic nephropathy, oxidative stress, patho-genesis, renal impairment, signalling pathways.

References





DOI: https://doi.org/10.18520/cs%2Fv124%2Fi8%2F899-909