PREVENTING DIABETIC KIDNEY DISEASE: A SYSTEMATIC REVIEW OF CURRENT PHARMACOLOGICAL APPROACHES

Authors

DOI:

https://doi.org/10.22159/ijap.2025v17i1.52956

Keywords:

Diabetic kidney disease, Diabetic nephropathy, DN, DKD, Preventive therapy, Preventing diabetic nephropathy, Preventing DKD, Diabetes complications

Abstract

Objective: This review examines the growing global burden of Diabetic Nephropathy (DN), a major complication of Diabetes Mellitus (DM) and a leading cause of Chronic Kidney Disease (CKD) and End-Stage Renal Disease (ESRD). With diabetes rates increasing, DN presents a significant health challenge. Current treatments manage established DN, but preventive strategies targeting high-risk individuals are urgently needed. This review evaluates current and emerging therapies for DN prevention.

Methods: A comprehensive literature search was conducted across multiple databases (PubMed, Web of Science, SCOPUS and others) to identify studies on the treatment and prevention of DN in DM patients. Eligible studies included Randomized Controlled Trials (RCT), cohort studies and meta-analyses published upto 2024, focusing on outcomes like albuminuria, Glomerular Filtration Rate (GFR) and ESRD incidence.

Results: Current treatments, including Sodium Glucose Co-transporter 2 (SGLT2) inhibitors, Angiotensin-Converting Enzyme (ACE) inhibitors and Angiotensin Receptor Blocker (ARB), effectively reduce albuminuria and slow progression. Emerging therapies, such as antioxidants (Alpha-Lipoic Acid (ALA), Resveratrol), Mineralocorticoid Receptor Antagonists (MRA) and Endothelin Receptor Antagonists (ERA), show promise in improving kidney function and reducing inflammation. Other potential therapies targeting Oxidative Stress (OS), inflammation and fibrosis, such as Advanced Glycation End products(AGE) inhibitors and Tumor Necrosis Factor-α (TNF-α) inhibitors, have demonstrated preclinical efficacy but require further validation.

Conclusion: While current therapies slow DN progression, they do not offer definitive prevention. Emerging treatments targeting oxidative stress, inflammation and fibrosis show promise in reducing kidney damage. However, challenges like side effects and long-term safety remain. Further research is needed to establish the efficacy of these therapies and develop personalized strategies for preventing DN in high-risk populations.

Downloads

Download data is not yet available.

References

NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4.4 million participants. Lancet. 2016;387(10027):1513-30. doi: 10.1016/S0140-6736(16)00618-8, PMID 27061677.

Federation ID. IDF diabetes atlas brussels. Belgium: international diabetes federation; 2021.

Garg AX, Kiberd BA, Clark WF, Haynes RB, Clase CM. Albuminuria and renal insufficiency prevalence guides population screening: results from the NHANES III. Kidney Int. 2002;61(6):2165-75. doi: 10.1046/j.1523-1755.2002.00356.x, PMID 12028457.

Naaman SC, Bakris GL. Diabetic nephropathy: update on pillars of therapy slowing progression. Diabetes Care. 2023;46(9):1574-86. doi: 10.2337/dci23-0030, PMID 37625003.

Sagoo MK, Gnudi L. Diabetic nephropathy: an overview. Methods Mol Biol. 2020;2067:3-7. doi: 10.1007/978-1-4939-9841-8_1, PMID 31701441.

Thomas MC, Brownlee M, Susztak K, Sharma K, Jandeleit Dahm KA, Zoungas S. Diabetic kidney disease. Nat Rev Dis Primers. 2015 Jul 30;1:15018. doi: 10.1038/nrdp.2015.18, PMID 27188921.

Papadopoulou Marketou N, Kanaka Gantenbein C, Marketos N, Chrousos GP, Papassotiriou I. Biomarkers of diabetic nephropathy: a 2017 update. Crit Rev Clin Lab Sci. 2017;54(5):326-42. doi: 10.1080/10408363.2017.1377682, PMID 28956668.

Carey RM, Wang ZQ, Siragy HM. Role of the angiotensin type 2 receptor in the regulation of blood pressure and renal function. Hypertension. 2000;35(1 Pt 2):155-63. doi: 10.1161/01.hyp.35.1.155, PMID 10642292.

Ames MK, Atkins CE, Pitt B. The rennin angiotensin aldosterone system and its suppression. J Vet Intern Med. 2019;33(2):363-82. doi: 10.1111/jvim.15454, PMID 30806496.

Ruiz Ortega M, Lorenzo O, Suzuki Y, Ruperez M, Egido J. Proinflammatory actions of angiotensins. Curr Opin Nephrol Hypertens. 2001;10(3):321-9. doi: 10.1097/00041552-200105000-00005, PMID 11342793.

Poursharif S, Hamza S, Braam B. Changes in proximal tubular reabsorption modulate microvascular regulation via the TGF system. Int J Mol Sci. 2022;23(19)11203. doi: 10.3390/ijms231911203.

Tuttle KR. Back to the future: glomerular hyperfiltration and the diabetic kidney. Diabetes. 2017;66(1):14-6. doi: 10.2337/dbi16-0056, PMID 27999101.

Heerspink HJ, Perkins BA, Fitchett DH, Husain M, Cherney DZ. Sodium-glucose cotransporter 2 inhibitors in the treatment of diabetes mellitus: cardiovascular and kidney effects potential mechanisms and clinical applications. Circulation. 2016;134(10):752-72. doi: 10.1161/circulationaha.116.021887, PMID 27470878.

Tonneijck L, Muskiet MH, Smits MM, Van Bommel EJ, Heerspink HJ, Van Raalte DH. Glomerular hyperfiltration in diabetes: mechanisms clinical significance and treatment. J Am Soc Nephrol. 2017;28(4):1023-39. doi: 10.1681/ASN.2016060666, PMID 28143897.

Astor BC, Hallan SI, Miller ER 3rd, Yeung E, Coresh J. Glomerular filtration rate albuminuria and risk of cardiovascular and all-cause mortality in the US population. Am J Epidemiol. 2008;167(10):1226-34. doi: 10.1093/aje/kwn033, PMID 18385206.

Bello AK, Hemmelgarn B, Lloyd A, James MT, Manns BJ, Klarenbach S. Associations among estimated glomerular filtration rate proteinuria and adverse cardiovascular outcomes. Clin J Am Soc Nephrol. 2011;6(6):1418-26. doi: 10.2215/CJN.09741110, PMID 21527648.

El Sayed NA, Aleppo G, Aroda VR, Bannuru RR, Brown FM, Bruemmer D. Chronic kidney disease and risk management: standards of care in diabetes-2023. Diabetes Care. 2023;46 Suppl 1:S191-202. doi: 10.2337/dc23-S011, PMID 36507634.

Sarnak MJ, Levey AS, Schoolwerth AC, Coresh J, Culleton B, Hamm LL. Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on kidney in cardiovascular disease high blood pressure research clinical cardiology and epidemiology and prevention. Circulation. 2003;108(17):2154-69. doi: 10.1161/01.CIR.0000095676.90936.80, PMID 14581387.

Cantero Navarro E, Rayego Mateos S, Orejudo M, Tejedor Santamaria L, Tejera Munoz A, Sanz AB. Role of macrophages and related cytokines in kidney disease. Front Med (Lausanne). 2021 Jul 8;8:688060. doi: 10.3389/fmed.2021.688060, PMID 34307414.

Tesch GH. Macrophages and diabetic nephropathy. Semin Nephrol. 2010;30(3):290-301. doi: 10.1016/j.semnephrol.2010.03.007, PMID 20620673.

Usher MG, Duan SZ, Ivaschenko CY, Frieler RA, Berger S, Schutz G. Myeloid mineralocorticoid receptor controls macrophage polarization and cardiovascular hypertrophy and remodeling in mice. J Clin Invest. 2010;120(9):3350-64. doi: 10.1172/JCI41080, PMID 20697155.

American Diabetes Association. 6. Glycemic targets: standards of Medical Care in diabetes-2018. Diabetes Care. 2018 Jan;41 Suppl 1:S55-64. doi: 10.2337/dc18-S006, PMID 29222377.

Qaseem A, Wilt TJ, Kansagara D, Horwitch C, Barry MJ, Forciea MA. Hemoglobin A1c targets for glycemic control with pharmacologic therapy for nonpregnant adults with type 2 diabetes mellitus: a guidance statement update from the American College of Physicians. Ann Intern Med. 2018;168(8):569-76. doi: 10.7326/M17-0939, PMID 29507945.

Groop PH, Cooper ME, Perkovic V, Emser A, Woerle HJ, Von Eynatten M. Linagliptin lowers albuminuria on top of recommended standard treatment in patients with type 2 diabetes and renal dysfunction. Diabetes Care. 2013;36(11):3460-8. doi: 10.2337/dc13-0323, PMID 24026560.

Groop PH, Cooper ME, Perkovic V, Hocher B, Kanasaki K, Haneda M. Linagliptin and its effects on hyperglycaemia and albuminuria in patients with type 2 diabetes and renal dysfunction: the randomized MARLINA-T2D trial. Diabetes Obes Metab. 2017;19(11):1610-9. doi: 10.1111/dom.13041, PMID 28636754.

Scirica BM, Braunwald E, SAVOR-TIMI RI. 53 steering committee and investigators. Heart failure saxagliptin and diabetes mellitus: observations from the SAVOR-TIMI 53 randomized trial. Circulation. 2014;132(15):1579-88.

Marso SP, Daniels GH, Brown Frandsen K, Kristensen P, Mann JF, Nauck MA. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375(4):311-22. doi: 10.1056/NEJMoa1603827, PMID 27295427.

Fujita H, Morii T, Fujishima H, Sato T, Shimizu T, Hosoba M. The protective roles of GLP-1R signaling in diabetic nephropathy: possible mechanism and therapeutic potential. Kidney Int. 2014;85(3):579-89. doi: 10.1038/ki.2013.427, PMID 24152968.

Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jodar E, Leiter LA. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016;375(19):1834-44. doi: 10.1056/NEJMoa1607141, PMID 27633186.

Wanner C, Inzucchi SE, Lachin JM, Fitchett D, Von Eynatten M, Mattheus M. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med. 2016;375(4):323-34. doi: 10.1056/NEJMoa1515920, PMID 27299675.

Barnett AH, Mithal A, Manassie J, Jones R, Rattunde H, Woerle HJ. Efficacy and safety of empagliflozin added to existing antidiabetes treatment in patients with type-2 diabetes and chronic kidney disease: a randomised double blind placebo controlled trial. Lancet Diabetes Endocrinol. 2014;2(5):369-84. doi: 10.1016/S2213-8587(13)70208-0, PMID 24795251.

Sarafidis PA, Bakris GL. Protection of the kidney by thiazolidinediones: an assessment from bench to bedside. Kidney Int. 2006;70(7):1223-33. doi: 10.1038/sj.ki.5001620, PMID 16883325.

Whelton PK, Carey RM, Aronow WS. PCNA guideline for the prevention detection evaluation and management of high blood pressure in adults: a report of the American college of cardiology/American heart association task force on clinical practice guidelines. J Am Coll Cardiol. 2017;71(19):e127-248. doi: 10.1016/j.jacc.2017.11.005, PMID 29146533.

ACCORD Study Group, Cushman WC, Evans GW, Byington RP, Goff DC JR, Grimm RH JR. Effects of intensive blood pressure control in type 2 diabetes mellitus. N Engl J Med. 2010;362(17):1575-85. doi: 10.1056/NEJMoa1001286, PMID 20228401.

LV J, Perkovic V, Foote CV, Craig ME, Craig JC, Strippoli GF. Antihypertensive agents for preventing diabetic kidney disease. Cochrane Database Syst Rev. 2012;12(12):CD004136. doi: 10.1002/14651858.CD004136.pub3, PMID 23235603.

Haller H, Ito S, Izzo JL, Januszewicz A, Katayama S, Menne J. Olmesartan for the delay or prevention of microalbuminuria in type 2 diabetes. N Engl J Med. 2011;364(10):907-17. doi: 10.1056/NEJMoa1007994, PMID 21388309.

Currie G, Taylor AH, Fujita T, Ohtsu H, Lindhardt M, Rossing P. Effect of mineralocorticoid receptor antagonists on proteinuria and progression of chronic kidney disease: a systematic review and meta-analysis. BMC Nephrol. 2016;17(1):127. doi: 10.1186/s12882-016-0337-0, PMID 27609359.

Bolignano D, Palmer SC, Navaneethan SD, Strippoli GF. Aldosterone antagonists for preventing the progression of chronic kidney disease. Cochrane Database Syst Rev. 2014;(4):CD007004. doi: 10.1002/14651858.CD007004.pub3, PMID 24782282.

Menne J, Ritz E, Ruilope LM, Chatzikyrkou C, Viberti G, Haller H. The randomized olmesartan and diabetes microalbuminuria prevention (roadmap) observational follow up study: benefits of ras blockade with olmesartan treatment are sustained after study discontinuation. J Am Heart Assoc. 2014;3(2):e000810. doi: 10.1161/jaha.114.000810, PMID 24772521.

Berbenetz NM, Mrkobrada M. Mineralocorticoid receptor antagonists for heart failure: systematic review and meta-analysis. BMC Cardiovasc Disord. 2016;16(1):246. doi: 10.1186/s12872-016-0425-x, PMID 27905877.

Abdelhakim AM, Abd El Gawad M. Impact of mineralocorticoid receptor antagonist in renal transplant patients: a systematic review and meta-analysis of randomized controlled trials. J Nephrol. 2020;33(3):529-38. doi: 10.1007/s40620-019-00681-4, PMID 31828668.

Tromp J, Ouwerkerk W, Van Veldhuisen DJ, Hillege HL, Richards AM, Van Der Meer P. A systematic review and network metaanalysis of pharmacological treatment of heart failure with reduced ejection fraction. JACC Heart Fail. 2020;33(3):73-84.

Chung EY, Ruospo M, Natale P, Bolignano D, Navaneethan SD, Palmer SC. Aldosterone antagonists in addition to renin angiotensin system antagonists for preventing the progression of chronic kidney disease. Cochrane Database Syst Rev. 2020;10(10):CD007004. doi: 10.1002/14651858.CD007004.pub4, PMID 33107592.

Rossing K, Schjoedt KJ, Smidt UM, Boomsma F, Parving HH. Beneficial effects of adding spironolactone to recommended antihypertensive treatment in diabetic nephropathy: a randomized double masked cross over study. Diabetes Care. 2005;28(9):2106-12. doi: 10.2337/diacare.28.9.2106, PMID 16123474.

Esteghamati A, Noshad S, Jarrah S, Mousavizadeh M, Khoee SH, Nakhjavani M. Long term effects of addition of mineralocorticoid receptor antagonist to angiotensin II receptor blocker in patients with diabetic nephropathy: a randomized clinical trial. Nephrol Dial Transplant. 2013;28(11):2823-33. doi: 10.1093/ndt/gft281, PMID 24009294.

Epstein M, Williams GH, Weinberger M, Lewin A, Krause S, Mukherjee R. Selective aldosterone blockade with eplerenone reduces albuminuria in patients with type 2 diabetes. Clin J Am Soc Nephrol. 2006;1(5):940-51. doi: 10.2215/CJN.00240106, PMID 17699311.

El Mokadem M, Abd El Hady Y, Aziz A. A prospective single blind randomized trial of ramipril eplerenone and their combination in type 2 diabetic nephropathy. Cardiorenal Med. 2020;10(6):392-401. doi: 10.1159/000508670, PMID 32998143.

Bertocchio JP, Barbe C, Lavaud S, Toupance O, Nazeyrollas P, Jaisser F. Safety of eplerenone for kidney transplant recipients with impaired renal function and receiving cyclosporine A. Plos One. 2016;11(4):e0153635. doi: 10.1371/journal.pone.0153635, PMID 27088859.

Bakris GL, Agarwal R, Chan JC, Cooper ME, Gansevoort RT, Haller H. Effect of finerenone on albuminuria in patients with diabetic nephropathy: a randomized clinical trial. JAMA. 2015;314(9):884-94. doi: 10.1001/jama.2015.10081, PMID 26325557.

Bakris GL, Agarwal R, Anker SD, Pitt B, Ruilope LM, Rossing P. Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes. N Engl J Med. 2020;383(23):2219-29. doi: 10.1056/NEJMoa2025845, PMID 33264825.

Ito S, Shikata K, Nangaku M, Okuda Y, Sawanobori T. Efficacy and safety of esaxerenone (CS− 3150) for the treatment of type-2 diabetes with microalbuminuria: a randomized double blind placebo controlled phase II trial. Clin J Am Soc Nephrol. 2019;14(8):1161-72. doi: 10.2215/CJN.14751218, PMID 31248950.

Ito S, Kashihara N, Shikata K, Nangaku M, Wada T, Okuda Y. Esaxerenone (CS-3150) in patients with type 2 diabetes and microalbuminuria (esax-dn): phase 3 randomized controlled clinical trial. Clin J Am Soc Nephrol. 2020;15(12):1715-27. doi: 10.2215/CJN.06870520, PMID 33239409.

Bakris G, Pergola PE, Delgado B, Genov D, Doliashvili T, VO N. Effect of KBP-5074 on blood pressure in advanced chronic kidney disease: results of the block CKD study. Hypertension. 2021;78(1):74-81. doi: 10.1161/hypertensionaha.121.17073, PMID 33966452.

Grdovic N, Rajic J, Arambasic Jovanovic J, Dinic S, Tolic A, Dordevic M. α-Lipoic acid increases collagen synthesis and deposition in nondiabetic and diabetic rat kidneys. Oxid Med Cell Longev. 2021;2021:6669352. doi: 10.1155/2021/6669352, PMID 33777319.

Charlton A, Garzarella J, Jandeleit Dahm KA, Jha JC. Oxidative stress and inflammation in renal and cardiovascular complications of diabetes. Biology (Basel). 2020;10(1):18. doi: 10.3390/biology10010018, PMID 33396868.

Zhang H, MU J, DU J, Feng Y, XU W, Bai M. Alpha lipoic acid could attenuate the effect of chemerin induced diabetic nephropathy progression. Iran J Basic Med Sci. 2021;24(8):1107-16. doi: 10.22038/ijbms.2021.50792.11570, PMID 34804428.

Vakali E, Rigopoulos D, Carrillo AE, Flouris AD, Dinas PC. Effects of alpha lipoic acid supplementation on human diabetic nephropathy: a systematic review and meta-analysis. Curr Diabetes Rev. 2022;18(6):e140921196457. doi: 10.2174/1573399817666210914103329, PMID 34521329.

Jiang M, Sun H, Zhang H, Cheng Y, Zhai C. ALA/LA inhibited renal tubulointerstitial fibrosis of DKD db/db mice induced by oxidative stress. Research square; 2024. doi: 10.21203/rs.3.rs-3956527/v1.

Jeffrey S, Samraj PI, Raj BS. The role of alpha lipoic acid supplementation in the prevention of diabetes complications: a comprehensive review of clinical trials. Curr Diabetes Rev. 2021;17(9):e011821190404. doi: 10.2174/1573399817666210118145550, PMID 33461470.

Gowd V, Kang Q, Wang Q, Wang Q, Chen F, Cheng KW. Resveratrol: evidence for its nephroprotective effect in diabetic nephropathy. Adv Nutr. 2020;11(6):1555-68. doi: 10.1093/advances/nmaa075, PMID 32577714.

Xian Y, Gao Y, LV W, MA X, HU J, Chi J. Resveratrol prevents diabetic nephropathy by reducing chronic inflammation and improving the blood glucose memory effect in non obese diabetic mice. Naunyn Schmiedebergs Arch Pharmacol. 2020;393(10):2009-17. doi: 10.1007/s00210-019-01777-1, PMID 31970441.

Salami M, Salami R, Mafi A, Aarabi MH, Vakili O, Asemi Z. Therapeutic potential of resveratrol in diabetic nephropathy according to molecular signaling. Curr Mol Pharmacol. 2022;15(5):716-35. doi: 10.2174/1874467215666211217122523, PMID 34923951.

LI KX, JI MJ, Sun HJ. An updated pharmacological insight of resveratrol in the treatment of diabetic nephropathy. Gene. 2021;780:145532. doi: 10.1016/j.gene.2021.145532, PMID 33631244.

Sattarinezhad A, Roozbeh J, Shirazi Yeganeh B, Omrani GR, Shams M. Resveratrol reduces albuminuria in diabetic nephropathy: a randomized double-blind placebo-controlled clinical trial. Diabetes Metab. 2019;45(1):53-9. doi: 10.1016/j.diabet.2018.05.010, PMID 29983230.

Chen S, LI B, Chen L, Jiang H. Uncovering the mechanism of resveratrol in the treatment of diabetic kidney disease based on network pharmacology molecular docking and experimental validation. J Transl Med. 2023;21(1):380. doi: 10.1186/s12967-023-04233-0, PMID 37308949.

Zhu X, XU X, DU C, SU Y, Yin L, Tan X. An examination of the protective effects and molecular mechanisms of curcumin a polyphenol curcuminoid in diabetic nephropathy. Biomed Pharmacother. 2022;153:113438. doi: 10.1016/j.biopha.2022.113438, PMID 36076553.

Pricci M, Girardi B, Giorgio F, Losurdo G, Ierardi E, DI Leo A. Curcumin and colorectal cancer: from basic to clinical evidences. Int J Mol Sci. 2020;21(7):2364. doi: 10.3390/ijms21072364, PMID 32235371.

Asadi S, Goodarzi MT, Karimi J, Hashemnia M, Khodadadi I. Does curcumin or metformin attenuate oxidative stress and diabetic nephropathy in rats? J Nephropathol. 2018;8(1):8. doi: 10.15171/jnp.2019.08.

Al Tamimi JZ, Al Farga NA, Alshammari AM, Mowyna B, Yahya MN. Curcumin reverses diabetic nephropathy in streptozotocin-induced diabetes in rats by inhibition of PKC/p66Shc axis and activation of FOXO-3a. J Nutr Biochem. 2021 Jan;87:108515. doi: 10.1016/j.jnutbio.2020.108515.

Gao L, LV Q, Wang Y, Zhang D, Ding W, Cao L. Research on mechanism of curcumin with chitosan nanoparticles in regulating the activity of podocytes in diabetic nephropathy through alleviating oxidative stress and inflammation. Sci Adv Mater. 2022;14(4):752-9. doi: 10.1166/sam.2022.4249.

Ganugula R, Nuthalapati NK, Dwivedi S, Zou D, Arora M, Friend R. Nanocurcumin combined with insulin alleviates diabetic kidney disease through P38/P53 signaling axis. J Control Release. 2023;353:621-33. doi: 10.1016/j.jconrel.2022.12.012, PMID 36503070.

Shing CM, Adams MJ, Fassett RG, Coombes JS. Nutritional compounds influence tissue factor expression and inflammation of chronic kidney disease patients in vitro. Nutrition. 2011;27(9):967-72. doi: 10.1016/j.nut.2010.10.014, PMID 21295946.

Alvarenga L, Salarolli R, Cardozo LF, Santos RS, DE Brito JS, Kemp JA. Impact of curcumin supplementation on expression of inflammatory transcription factors in hemodialysis patients: a pilot randomized double-blind controlled study. Clin Nutr. 2020;39(12):3594-600. doi: 10.1016/j.clnu.2020.03.007, PMID 32204978.

Alvarenga L, Cardozo LF, DA Cruz BO, Paiva BR, Fouque D, Mafra D. Curcumin supplementation improves oxidative stress and inflammation biomarkers in patients undergoing hemodialysis: a secondary analysis of a randomized controlled trial. Int Urol Nephrol. 2022;54(10):2645-52. doi: 10.1007/s11255-022-03182-9, PMID 35347555.

Salarolli RT, Alvarenga L, Cardozo LF, Teixeira KT, DE SG Moreira L, Lima JD. Can curcumin supplementation reduce plasma levels of gut-derived uremic toxins in hemodialysis patients? A pilot randomized double-blind controlled study. Int Urol Nephrol. 2021;53(6):1231-8. doi: 10.1007/s11255-020-02760-z, PMID 33438085.

Ghaiad HR, Ali SO, Al Mokaddem AK, Abdelmonem M. Regulation of PKC/TLR-4/NF-kB signaling by sulbutiamine improves diabetic nephropathy in rats. Chem Biol Interact. 2023 Aug 25;381:110544. doi: 10.1016/j.cbi.2023.110544, PMID 37224990.

Liu W, LI F, Guo D, DU C, Zhao S, LI J. Schisandrin B alleviates renal tubular cell epithelial-mesenchymal transition and mitochondrial dysfunction by kielin/chordin-like protein upregulation via akt pathway inactivation and adenosine 5 monophosphate (amp) activated protein kinase pathway activation in diabetic kidney disease. Molecules. 2023 Nov 29;28(23):7851. doi: 10.3390/molecules28237851, PMID 38067580.

Cho CH, Yoo G, Kim M, Lee CJ, Choi IW, Ryu B. Diphlorethohydroxycarmalol a phlorotannin contained in brown edible seaweed Ishige okamurae, prevents AGE-related diabetic nephropathy by suppression of AGE-RAGE interaction. Food Biosci. 2023 Jun;53:102659. doi: 10.1016/j.fbio.2023.102659.

Coughlan MT, Cooper ME, Forbes JM. Can advanced glycation end-product inhibitors modulate more than one pathway to enhance renoprotection in diabetes? Ann N Y Acad Sci. 2005;1043(1):750-8. doi: 10.1196/annals.1333.087, PMID 16037302.

Bolton WK, Cattran DC, Williams ME, Adler SG, Appel GB, Cartwright K. Randomized trial of an inhibitor of formation of advanced glycation end products in diabetic nephropathy. Am J Nephrol. 2004;24(1):32-40. doi: 10.1159/000075627, PMID 14685005.

Forbes JM, Thorpe SR, Thallas Bonke V, Pete J, Thomas MC, Deemer ER. Modulation of soluble receptor for advanced glycation end products by angiotensin-converting enzyme-1 inhibition in diabetic nephropathy. J Am Soc Nephrol. 2005;16(8):2363-72. doi: 10.1681/ASN.2005010062, PMID 15930093.

Yang L, XU L, Hao X, Song Z, Zhang X, Liu P. An aldose reductase inhibitor WJ-39 ameliorates renal tubular injury in diabetic nephropathy by activating PINK1/Parkin signaling. Eur J Pharmacol. 2024;967:176376. doi: 10.1016/j.ejphar.2024.176376, PMID 38336014.

Song T, Wang R, Zhou X, Chen W, Chen Y, Liu Z. Metabolomics and molecular dynamics unveil the therapeutic potential of epalrestat in diabetic nephropathy. Int Immunopharmacol. 2024;140:112812. doi: 10.1016/j.intimp.2024.112812, PMID 39094360.

Okuda Y, Ito S, Kashihara N, Shikata K, Nangaku M, Wada T. The renoprotective effect of esaxerenone independent of blood pressure lowering: a post hoc mediation analysis of the ESAX-DN trial. Hypertens Res. 2023;46(2):437-44. doi: 10.1038/s41440-022-01008-w, PMID 36100672.

Liang F, Glascock CB, Schafer DL, Sandoval J, Cable LA, Melvin L. Darusentan is a potent inhibitor of endothelin signaling and function in both large and small arteries. Can J Physiol Pharmacol. 2010;88(8):840-9. doi: 10.1139/Y10-061, PMID 20725142.

Heerspink HJ, Parving HH, Andress DL, Bakris G, Correa Rotter R, Hou FF. Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised placebo-controlled trial. Lancet. 2019;393(10184):1937-47. doi: 10.1016/S0140-6736(19)30772-X, PMID 30995972.

Scott LJ. Sitaxentan: in pulmonary arterial hypertension. Drugs. 2007;67(5):761-70. doi: 10.2165/00003495-200767050-00007, PMID 17385944.

Enseleit F, Luscher TF, Ruschitzka F. Darusentan a selective endothelin a receptor antagonist for the oral treatment of resistant hypertension. Ther Adv Cardiovasc Dis. 2010;4(4):231-40. doi: 10.1177/1753944710373785, PMID 20660536.

Mann JF, Green D, Jamerson K, Ruilope LM, Kuranoff SJ, Littke T. Avosentan for overt diabetic nephropathy. J Am Soc Nephrol. 2010;21(3):527-35. doi: 10.1681/ASN.2009060593, PMID 20167702.

Anguiano L, Riera M, Pascual J, Soler MJ. Endothelin blockade in diabetic kidney disease. J Clin Med. 2015;4(6):1171-92. doi: 10.3390/jcm4061171, PMID 26239552.

Zhou Y, Chi J, Huang Y, Dong B, LV W, Wang YG. Efficacy and safety of endothelin receptor antagonists in type 2 diabetic kidney disease: a systematic review and meta-analysis of randomized controlled trials. Diabet Med. 2021;38(1):e14411. doi: 10.1111/dme.14411, PMID 33000477.

Thomas MC. Targeting the pathobiology of diabetic kidney disease. Adv Chronic Kidney Dis. 2021;28(4):282-9. doi: 10.1053/j.ackd.2021.07.001, PMID 34922684.

Sharov AV, Burkhanova TM, Taskın Tok T, Babashkina MG, Safin DA. Computational analysis of molnupiravir. Int J Mol Sci. 2022;23(21):13026. doi: 10.3390/ijms232113026, PMID 36362453.

Zang N, Cui C, Guo X, Song J, HU H, Yang M. Cgas-sting activation contributes to podocyte injury in diabetic kidney disease. Iscience. 2022;25(10):105145. doi: 10.1016/j.isci.2022.105145, PMID 36176590.

Yang Z, Liu F, QU H, Wang H, Xiao X, Deng H. 1, 25(OH)2D3 protects β cell against high glucose-induced apoptosis through mTOR suppressing. Mol Cell Endocrinol. 2015 Oct 15;414:111-9. doi: 10.1016/j.mce.2015.07.023, PMID 26213322.

Shi L, Xiao C, Zhang Y, Xia Y, Zha H, Zhu J. Vitamin D/vitamin D receptor/Atg16L1 axis maintains podocyte autophagy and survival in diabetic kidney disease. Ren Fail. 2022;44(1):694-705. doi: 10.1080/0886022X.2022.2063744, PMID 35469547.

Chen DP, MA YP, Zhuo L, Zhang Z, Zou GM, Yang Y. 1,25-dihydroxyvitamin D3 inhibits the proliferation of rat mesangial cells induced by high glucose via DDIT4. Oncotarget. 2018;9(1):418-27. doi: 10.18632/oncotarget.23063, PMID 29416624.

Wang B, Peng L, Ouyang H, Wang L, HE D, Zhong J. Induction of DDIT4 impairs autophagy through oxidative stress in dry eye. Invest Ophthalmol Vis Sci. 2019;60(8):2836-47. doi: 10.1167/iovs.19-27072, PMID 31266058.

Tervaert TW, Mooyaart AL, Amann K, Cohen AH, Cook HT, Drachenberg CB. Pathologic classification of diabetic nephropathy. J Am Soc Nephrol. 2010;21(4):556-63. doi: 10.1681/ASN.2010010010, PMID 20167701.

Herb M, Schramm M. Functions of ROS in macrophages and antimicrobial immunity. Antioxidants (Basel). 2021;10(2):313. doi: 10.3390/antiox10020313, PMID 33669824.

Kogot Levin A, Hinden L, Riahi Y, Israeli T, Tirosh B, Cerasi E. Proximal tubule mTORC1 is a central player in the pathophysiology of diabetic nephropathy and its correction by SGLT2 inhibitors. Cell Rep. 2020;32(4):107954. doi: 10.1016/j.celrep.2020.107954, PMID 32726619.

Reifsnyder PC, Flurkey K, TE A, Harrison DE. Rapamycin treatment benefits glucose metabolism in mouse models of type 2 diabetes. Aging (Albany NY). 2016;8(11):3120-30. doi: 10.18632/aging.101117, PMID 27922820.

Mori H, Inoki K, Masutani K, Wakabayashi Y, Komai K, Nakagawa R. The mTOR pathway is highly activated in diabetic nephropathy and rapamycin has a strong therapeutic potential. Biochem Biophys Res Commun. 2009;384(4):471-5. doi: 10.1016/j.bbrc.2009.04.136, PMID 19422788.

Murakami N, Riella LV, Funakoshi T. Risk of metabolic complications in kidney transplantation after conversion to mTOR inhibitor: a systematic review and meta-analysis. Am J Transplant. 2014;14(10):2317-27. doi: 10.1111/ajt.12852, PMID 25146383.

Paluri RK, Sonpavde G, Morgan C, Rojymon J, Mar AH, Gangaraju R. Renal toxicity with mammalian target of rapamycin inhibitors: a meta-analysis of randomized clinical trials. Oncol Rev. 2019;13(2):455. doi: 10.4081/oncol.2019.455, PMID 31857859.

Flaquer M, Lloberas N, Franquesa M, Torras J, Vidal A, Rosa JL. The combination of sirolimus and rosiglitazone produces a renoprotective effect on diabetic kidney disease in rats. Life Sci. 2010;87(5-6):147-53. doi: 10.1016/j.lfs.2010.06.004, PMID 20600147.

LI D, LU Z, XU Z, JI J, Zheng Z, Lin S. Spironolactone promotes autophagy via inhibiting PI3K/AKT/mTOR signalling pathway and reduce adhesive capacity damage in podocytes under mechanical stress. Biosci Rep. 2016;36(4):e00355. doi: 10.1042/BSR20160086, PMID 27129295.

Wang MZ, Wang J, Cao DW, TU Y, Liu BH, Yuan CC. Fucoidan alleviates renal fibrosis in diabetic kidney disease via inhibition of NLRP3 inflammasome-mediated podocyte pyroptosis. Front Pharmacol. 2022;13:790937. doi: 10.3389/fphar.2022.790937, PMID 35370636.

Liu H, Wang Q, Shi G, Yang W, Zhang Y, Chen W. Emodin ameliorates renal damage and podocyte injury in a rat model of diabetic nephropathy via regulating AMPK/Mtor mediated autophagy signaling pathway. Diabetes Metab Syndr Obes. 2021 Mar 18;14:1253-66. doi: 10.2147/DMSO.S299375, PMID 33776462.

LV L, Zhang J, Tian F, LI X, LI D, YU X. Arbutin protects HK-2 cells against high glucose-induced apoptosis and autophagy by up-regulating microRNA-27a. Artif Cells Nanomed Biotechnol. 2019;47(1):2940-7. doi: 10.1080/21691401.2019.1640231, PMID 31319730.

Wei L, Jian P, Erjiong H, Qihan Z. Ginkgetin alleviates high glucose evoked mesangial cell oxidative stress injury inflammation and extracellular matrix (ECM) deposition in an AMPK/mTOR mediated autophagy axis. Chem Biol Drug Des. 2021;98(4):620-30. doi: 10.1111/cbdd.13915, PMID 34148304.

Dong R, Zhang X, Liu Y, Zhao T, Sun Z, Liu P. Rutin alleviates end MT by restoring autophagy through inhibiting HDAC1 via PI3K/AKT/mTOR pathway in diabetic kidney disease. Phytomedicine. 2023 Apr;112:154700. doi: 10.1016/j.phymed.2023.154700, PMID 36774842.

Tao M, Zheng D, Liang X, WU D, HU K, Jin J. Tripterygium glycoside suppresses epithelial to mesenchymal transition of diabetic kidney disease podocytes by targeting autophagy through the mTOR/Twist1 pathway. Mol Med Rep. 2021;24(2):592. doi: 10.3892/mmr.2021.12231, PMID 34165172.

LI XY, Wang SS, Han Z, Han F, Chang YP, Yang Y. Triptolide restores autophagy to alleviate diabetic renal fibrosis through the miR-141-3P/PTEN/Akt/mTOR pathway. Mol Ther Nucleic Acids. 2017 Aug 25;9:48-56. doi: 10.1016/j.omtn.2017.08.011, PMID 29246323.

Yang F, QU Q, Zhao C, Liu X, Yang P, LI Z. Paecilomyces cicadae fermented Radix astragali activates podocyte autophagy by attenuating PI3K/AKT/mTOR pathways to protect against diabetic nephropathy in mice. Biomed Pharmacother. 2020 Sep;129:110479. doi: 10.1016/j.biopha.2020.110479, PMID 32768963.

Guo L, Tan K, Luo Q, Bai X. Dihydromyricetin promotes autophagy and attenuates renal interstitial fibrosis by regulating miR-155-5p/PTEN signaling in diabetic nephropathy. Bosn J Basic Med Sci. 2020;20(3):372-80. doi: 10.17305/bjbms.2019.4410, PMID 31668144.

Wang T, Gao Y, Yue R, Wang X, Shi Y, XU J. Ginsenoside Rg1 alleviates podocyte injury induced by hyperlipidemia via targeting the mTOR/NF-κB/NLRP3 axis. Evid Based Complement Alternat Med. 2020;2020(1):2735714. doi: 10.1155/2020/2735714, PMID 33133213.

Sheng H, Zhang D, Zhang J, Zhang Y, LU Z, Mao W. Kaempferol attenuated diabetic nephropathy by reducing apoptosis and promoting autophagy through AMPK/mTOR pathways. Front Med (Lausanne). 2022;9:986825. doi: 10.3389/fmed.2022.986825, PMID 36530875.

Wang WJ, Jiang X, Gao CC, Chen ZW. Salusin-α mitigates diabetic nephropathy via inhibition of the Akt/mTORC1/p70S6K signaling pathway in diabetic rats. Drug Chem Toxicol. 2022;45(1):283-90. doi: 10.1080/01480545.2019.1683572, PMID 31665937.

Zhang Y, Wang Y, Luo M, XU F, LU Y, Zhou X. Elabela protects against podocyte injury in mice with streptozocin-induced diabetes by associating with the PI3K/Akt/mTOR pathway. Peptides. 2019 Apr;114:29-37. doi: 10.1016/j.peptides.2019.04.005, PMID 30959144.

WU C, MA X, Zhou Y, Liu Y, Shao Y, Wang Q. Klotho restraining Egr1/TLR4/mTOR axis to reducing the expression of fibrosis and inflammatory cytokines in high glucose cultured rat mesangial cells. Exp Clin Endocrinol Diabetes. 2019;127(9):630-40. doi: 10.1055/s-0044-101601, PMID 29890551.

DI Petrillo K, Coutermarsh B, Gesek FA. Urinary tumor necrosis factor contributes to sodium retention and renal hypertrophy during diabetes. Am J Physiol Renal Physiol. 2003;284(1):F113-21. doi: 10.1152/ajprenal.00026.2002, PMID 12388406.

Moriwaki Y, Inokuchi T, Yamamoto A, KA T, Tsutsumi Z, Takahashi S. Effect of TNF-alpha inhibition on urinary albumin excretion in experimental diabetic rats. Acta Diabetol. 2007;44(4):215-8. doi: 10.1007/s00592-007-0007-6, PMID 17767370.

Omote K, Gohda T, Murakoshi M, Sasaki Y, Kazuno S, Fujimura T. Role of the TNF pathway in the progression of diabetic nephropathy in KK-A(y) mice. Am J Physiol Renal Physiol. 2014;306(11):F1335-47. doi: 10.1152/ajprenal.00509.2013, PMID 24647715.

Karkar AM, Smith J, Pusey CD. Prevention and treatment of experimental crescentic glomerulonephritis by blocking tumour necrosis factor alpha. Nephrol Dial Transplant. 2001;16(3):518-24. doi: 10.1093/ndt/16.3.518, PMID 11239025.

Ramesh G, Reeves WB. TNFR2-mediated apoptosis and necrosis in cisplatin induced acute renal failure. Am J Physiol Renal Physiol. 2003;285(4):F610-8. doi: 10.1152/ajprenal.00101.2003, PMID 12865254.

Zandi Nejad K, Eddy AA, Glassock RJ, Brenner BM. Why is proteinuria an ominous biomarker of progressive kidney disease? Kidney Int Suppl. 2004;66(92):S76-89. doi: 10.1111/j.1523-1755.2004.09220.x, PMID 15485426.

Lin SL, Chiang WC, Chen YM, Lai CF, Tsai TJ, Hsieh BS. The renoprotective potential of pentoxifylline in chronic kidney disease. J Chin Med Assoc. 2005;68(3):99-105. doi: 10.1016/S1726-4901(09)70228-X, PMID 15813241.

Garcia FA, Pinto SF, Cavalcante AF, Lucetti LT, Menezes SM, Felipe CF. Pentoxifylline decreases glycemia levels and TNF-alpha, iNOS and COX-2 expressions in diabetic rat pancreas. Springerplus. 2014;3(1):283. doi: 10.1186/2193-1801-3-283, PMID 24991532.

Goicoechea M, Garcia DE Vinuesa S, Quiroga B, Verdalles U, Barraca D, Yuste C. Effects of pentoxifylline on inflammatory parameters in chronic kidney disease patients: a randomized trial. J Nephrol. 2012;25(6):969-75. doi: 10.5301/jn.5000077, PMID 22241639.

Sahın S, Altok K, Pasaoglu H, Omeroglu S, Derıcı B, Erten U. The protective effects of pentoxifylline on contrast induced nephropathy in rats. Akdeniz Tıp Derg. 2019;5(3):429-38.

Gonzalez Espinoza L, Rojas Campos E, Medina Perez M, Pena Quintero P, Gomez Navarro B, Cueto Manzano AM. Pentoxifylline decreases serum levels of tumor necrosis factor alpha interleukin 6 and C-reactive protein in hemodialysis patients: results of a randomized double-blind controlled clinical trial. Nephrol Dial Transplant. 2012;27(5):2023-8. doi: 10.1093/ndt/gfr579, PMID 21968012.

Varma A, Das A, Hoke NN, Durrant DE, Salloum FN, Kukreja RC. Anti-inflammatory and cardioprotective effects of tadalafil in diabetic mice. Plos One. 2012;7(9):e45243. doi: 10.1371/journal.pone.0045243, PMID 23028874.

Kuwabara T, Mori K, Mukoyama M, Kasahara M, Yokoi H, Saito Y. Urinary neutrophil gelatinase-associated lipocalin levels reflect damage to glomeruli proximal tubules and distal nephrons. Kidney Int. 2009;75(3):285-94. doi: 10.1038/ki.2008.499, PMID 19148153.

Joy SV, Scates AC, Bearelly S, Dar M, Taulien CA, Goebel JA. Ruboxistaurin a protein kinase C β inhibitor as an emerging treatment for diabetes microvascular complications. Ann Pharmacother. 2005;39(10):1693-9. doi: 10.1345/aph.1E572, PMID 16160002.

Dash A, Maiti R, Bandakkanavar TK, Pandey BL. Novel drug treatment for diabetic nephropathy. HK J Nephrol. 2011;13(1):19-26. doi: 10.1016/S1561-5413(11)60003-3.

Pham TK, Nguyen TH, Yun HR, Vasileva EA, Mishchenko NP, Fedoreyev SA. Echinochrome prevents diabetic nephropathy by inhibiting the PKC-Iota pathway and enhancing renal mitochondrial function in DB/DB mice. Mar Drugs. 2023;21(4):222. doi: 10.3390/md21040222, PMID 37103361.

Gorin Y, Cavaglieri RC, Khazim K, Lee DY, Bruno F, Thakur S. Targeting NADPH oxidase with a novel dual Nox1/Nox4 inhibitor attenuates renal pathology in type 1 diabetes. Am J Physiol Renal Physiol. 2015;308(11):F1276-87. doi: 10.1152/ajprenal.00396.2014, PMID 25656366.

Menne J, Eulberg D, Beyer D, Baumann M, Saudek F, Valkusz Z. C-C motif ligand 2 inhibition with emapticap pegol (NOX-E36) in type 2 diabetic patients with albuminuria. Nephrol Dial Transplant. 2017;32(2):307-15. doi: 10.1093/ndt/gfv459.

Boels MG, Koudijs A, Avramut MC, Sol WM, Wang G, Van Oeveren Rietdijk AM. Systemic monocyte chemotactic protein-1 inhibition modifies renal macrophages and restores glomerular endothelial glycocalyx and barrier function in diabetic nephropathy. Am J Pathol. 2017;187(11):2430-40. doi: 10.1016/j.ajpath.2017.07.020, PMID 28837800.

DE Zeeuw D, Akizawa T, Agarwal R, Audhya P, Bakris GL, Chin M. Rationale and trial design of bardoxolone methyl evaluation in patients with chronic kidney disease and type 2 diabetes: the occurrence of renal events (beacon). Am J Nephrol. 2013;37(3):212-22. doi: 10.1159/000346948, PMID 23467003.

DE Zeeuw D, Akizawa T, Audhya P, Bakris GL, Chin M, Christ Schmidt H. Bardoxolone methyl in type 2 diabetes and stage 4 chronic kidney disease. N Engl J Med. 2013;369(26):2492-503. doi: 10.1056/NEJMoa1306033, PMID 24206459.

Taylor PC. Clinical efficacy of launched JAK inhibitors in rheumatoid arthritis. Rheumatol (Oxf Engl). 2019;58 Suppl 1:17-26. doi: 10.1093/rheumatology/key225, PMID 30806707.

Plosker GL. Ruxolitinib: a review of its use in patients with myelofibrosis. Drugs. 2015;75(3):297-308. doi: 10.1007/s40265-015-0351-8, PMID 25601187.

Schwartz DM, Kanno Y, Villarino A, Ward M, Gadina M, O Shea JJ. JAK inhibition as a therapeutic strategy for immune and inflammatory diseases. Nat Rev Drug Discov. 2017;16(12):843-62. doi: 10.1038/nrd.2017.201, PMID 29104284.

Kim HO. Development of JAK inhibitors for the treatment of immune mediated diseases: kinase targeted inhibitors and pseudokinase targeted inhibitors. Arch Pharm Res. 2020;43(11):1173-86. doi: 10.1007/s12272-020-01282-7, PMID 33161563.

Brosius FC, Tuttle KR, Kretzler M. JAK inhibition in the treatment of diabetic kidney disease. Diabetologia. 2016;59(8):1624-7. doi: 10.1007/s00125-016-4021-5, PMID 27333885.

Tuttle KR, Brosius FC, Adler SG, Kretzler M, Mehta RL, Tumlin JA. JAK1/JAK2 inhibition by baricitinib in diabetic kidney disease: results from a phase 2 randomized controlled clinical trial. Nephrol Dial Transplant. 2018;33(11):1950-9. doi: 10.1093/ndt/gfx377, PMID 29481660.

El Kady MM, Naggar RA, Guimei M, Talaat IM, Shaker OG, Saber Ayad M. Early renoprotective effect of ruxolitinib in a rat model of diabetic nephropathy. Pharmaceuticals (Basel). 2021;14(7):608. doi: 10.3390/ph14070608, PMID 34202668.

Elsherbiny NM, Zaitone SA, Mohammad HM, El Sherbiny M. Renoprotective effect of nifuroxazide in diabetes-induced nephropathy: impact on NFκB oxidative stress and apoptosis. Toxicol Mech Methods. 2018;28(6):467-73. doi: 10.1080/15376516.2018.1459995, PMID 29606028.

Zhu M, Wang H, Chen J, Zhu H. Sinomenine improve diabetic nephropathy by inhibiting fibrosis and regulating the JAK2/STAT3/SOCS1 pathway in streptozotocin-induced diabetic rats. Life Sci. 2021 Jan 15;265:118855. doi: 10.1016/j.lfs.2020.118855, PMID 33278392.

Gholami M, Moallem SA, Afshar M, Amoueian S, Etemad L, Karimi G. Teratogenic effects of silymarin on mouse fetuses. Avicenna J Phytomed. 2016;6(5):542-9. PMID 27761424.

Winiarska A, Knysak M, Nabrdalik K, Gumprecht J, Stompor T. Inflammation and oxidative stress in diabetic kidney disease: the targets for SGLT2 inhibitors and GLP-1 receptor agonists. Int J Mol Sci. 2021;22(19):10822. doi: 10.3390/ijms221910822, PMID 34639160.

Yang Y, Lei Y, Liang Y, FU S, Yang C, Liu K. Vitamin D protects glomerular mesangial cells from high glucose-induced injury by repressing JAK/STAT signaling. Int Urol Nephrol. 2021;53(6):1247-54. doi: 10.1007/s11255-020-02728-z, PMID 33942213.

Navarro Gonzalez JF, Mora Fernandez C, Muros DE Fuentes M, Garcia Perez J. Inflammatory molecules and pathways in the pathogenesis of diabetic nephropathy. Nat Rev Nephrol. 2011;7(6):327-40. doi: 10.1038/nrneph.2011.51, PMID 21537349.

LI HY, Lin HA, Nien FJ, WU VC, Jiang YD, Chang TJ. Serum vascular adhesion protein-1 predicts end-stage renal disease in patients with type 2 diabetes. Plos One. 2016;11(2):e0147981. doi: 10.1371/journal.pone.0147981, PMID 26845338.

Qian Y, LI S, YE S, Chen Y, Zhai Z, Chen K. Renoprotective effect of rosiglitazone through the suppression of renal intercellular adhesion molecule-1 expression in streptozotocin-induced diabetic rats. J Endocrinol Invest. 2008;31(12):1069-74. doi: 10.1007/BF03345654, PMID 19246972.

Rubio Guerra AF, Vargas Robles H, Lozano Nuevo JJ, Escalante Acosta BA. Correlation between circulating adhesion molecule levels and albuminuria in type-2 diabetic hypertensive patients. Kidney Blood Press Res. 2009;32(2):106-9. doi: 10.1159/000210554, PMID 19342863.

DE Zeeuw D, Renfurm RW, Bakris G, Rossing P, Perkovic V, Hou FF. Efficacy of a novel inhibitor of vascular adhesion protein1 in reducing albuminuria in patients with diabetic kidney disease (ALBUM): a randomised placebo-controlled phase 2 trial. Lancet Diabetes Endocrinol. 2018;6(12):925-33. doi: 10.1016/S2213-8587(18)30289-4, PMID 30413396.

Wada J, Makino H. Inflammation and the pathogenesis of diabetic nephropathy. Clin Sci (Lond). 2013;124(3):139-52. doi: 10.1042/CS20120198, PMID 23075333.

Giunti S, Barutta F, Perin PC, Gruden G. Targeting the MCP-1/CCR2 system in diabetic kidney disease. Curr Vasc Pharmacol. 2010;8(6):849-60. doi: 10.2174/157016110793563816, PMID 20180766.

Sayyed SG, Hagele H, Kulkarni OP, Endlich K, Segerer S, Eulberg D. Podocytes produce homeostatic chemokine stromal cell-derived factor-1/CXCL12 which contributes to glomerulosclerosis podocyte loss and albuminuria in a mouse model of type 2 diabetes. Diabetologia. 2009;52(11):2445-54. doi: 10.1007/s00125-009-1493-6, PMID 19707743.

Enevoldsen FC, Sahana J, Wehland M, Grimm D, Infanger M, Kruger M. Endothelin receptor antagonists: status quo and future perspectives for targeted therapy. J Clin Med. 2020;9(3):824. doi: 10.3390/jcm9030824, PMID 32197449.

Wang Y, Chen S, DU J. Bosentan for treatment of pediatric idiopathic pulmonary arterial hypertension: state of the art. Front Pediatr. 2019 Jul 23;7:302. doi: 10.3389/fped.2019.00302, PMID 31396496.

Schlaich MP, Bellet M, Weber MA, Danaietash P, Bakris GL, Flack JM. Dual endothelin antagonist aprocitentan for resistant hypertension (Precision): a multicentre blinded randomised parallel-group phase 3 trial. Lancet. 2022;400(10367):1927-37. doi: 10.1016/S0140-6736(22)02034-7, PMID 36356632.

Murugesan N, GU Z, Fadnis L, Tellew JE, Baska RA, Yang Y. Dual angiotensin II and endothelin a receptor antagonists: synthesis of 2 substituted N-3-isoxazolyl biphenylsulfonamides with improved potency and pharmacokinetics. J Med Chem. 2005;48(1):171-9. doi: 10.1021/jm049548x, PMID 15634011.

Zhao Q, Guo N, Chen J, Parks D, Tian Z. Comparative assessment of efficacy and safety of ambrisentan and bosentan in patients with pulmonary arterial hypertension: a meta analysis. J Clin Pharm Ther. 2022;47(2):146-56. doi: 10.1111/jcpt.13481, PMID 34319626.

Persson BP, Rossi P, Weitzberg E, Oldner A. Inhaled tezosentan reduces pulmonary hypertension in endotoxin-induced lung injury. Shock. 2009;32(4):427-34. doi: 10.1097/SHK.0b013e31819e2cbb, PMID 19197226.

Iglarz M, Binkert C, Morrison K, Fischli W, Gatfield J, Treiber A. Pharmacology of macitentan an orally active tissue targeting dual endothelin receptor antagonist. J Pharmacol Exp Ther. 2008;327(3):736-45. doi: 10.1124/jpet.108.142976, PMID 18780830.

Published

07-01-2025

How to Cite

DHARANI, B., SEBASTIAN, S., NAZRIN, S., & A., S. (2025). PREVENTING DIABETIC KIDNEY DISEASE: A SYSTEMATIC REVIEW OF CURRENT PHARMACOLOGICAL APPROACHES. International Journal of Applied Pharmaceutics, 17(1), 68–81. https://doi.org/10.22159/ijap.2025v17i1.52956

Issue

Section

Original Article(s)