Inflammation in Diabetic Kidney Disease: Focus on New Therapeutic Considerations
Main Article Content
Abstract
Diabetic kidney disease (DKD) is the most common cause of end-stage renal disease (ESRD) in the U.S. and worldwide. A role of chronic low-grade inflammation in the microvascular complications in diabetic patients has now been widely accepted, and anti-inflammatory therapies for DKD are being actively pursued. Such therapies may be especially useful in the treatment of patients with chronic kidney disease (CKD) with normal to only moderately increased albuminuria, a DKD phenotype which is becoming more frequent. Current pharmacologic treatment for DKD includes inhibitors of the renin-angiotensin-aldosterone system (RAAS) and the sodium-glucose co-transporter 2 (SGLT2) in the proximal tubule. Both classes of agents are known to reduce blood pressure but also are thought to have anti-inflammatory, antioxidant, and anti-fibrotic effects independent of their hemodynamic actions. Large clinical trials with experimental agents such as bardoxolone and selonsertib that target inflammation and oxidative stress in DKD have been carried out or are in progress. The non-specific phosphodiesterase inhibitor pentoxifylline (PTX) is also being studied in a large US trial to see if this FDA-approved drug may be able to be repurposed to treat DKD. Other agents have also shown promising effects in small clinical trials but require further large-scale investigation.
Keywords:
diabetes, , chronic kidney disease, diabetic kidney disease, inflammation, therapy
Article Details
How to Cite
LEEHEY, David; ZHANG, Xin.
Inflammation in Diabetic Kidney Disease: Focus on New Therapeutic Considerations.
Medical Research Archives, [S.l.], v. 11, n. 2, feb. 2023.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/3614>. Date accessed: 02 may 2025.
doi: https://doi.org/10.18103/mra.v11i2.3614.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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3. Gnudi L, Gentile G, Ruggenenti P. Oxford Textbook of Clinical Nephrology. 4 ed. Volume 2. Oxford University Press, Oxford, UK; 2016: 1199–1247.
4. Cravedi P, Remuzzi G. Pathophysiology of proteinuria and its value as an outcome measure in chronic kidney disease. Br J Clin Pharmacol. 2013; 76(4): 516–523.
5. Rossing K, Christensen PK, Hovind P, Tarnow L, Rossing P, Parving HH. Progression of nephropathy in type 2 diabetic patients. Kidney Int. 2004; 66(4): 1596–1605.
6. Kawabata N, Kawamura T, Utsunomiya K, Kusano E. High salt intake is associated with renal involvement in Japanese patients with type 2 diabetes mellitus. Intern Med. 2015; 54(3): 311–317.
7. Haffner S, Lehto S, Rönnemaa T, Pyörälä K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial Infarction. N Engl J Med. 1998; 339(4): 229–234.
8. Afkarian M, Sachs M, Kestenbaum B, Hirsch I, Tuttle K, Himmelfarb J, de Boer IH. Kidney disease and increased mortality risk in type 2 diabetes. J Am Soc Nephrol. 2013; 24(2): 302–308.
9. Hasegawa G, Nakano K, Sawada M, Uno K, Shibayama Y, Ienaga K, Kondo M. Possible role of tumor necrosis factor and interleukin-1 in the development of diabetic nephropathy. Kidney Int. 1991; 40(6): 1007-1012.
10. Matoba K, Takeda Y, Nagai Y, Kawanami D, Utsunomiya K, Nishimura R. Unraveling the role of inflammation in the pathogenesis of diabetic kidney disease. Int J Mol Sci. 2019; 20(14). pii: E3393.
11. Nguyen D, Ping F, Mu W, Hill P, Atkins RC, Chadban SJ. Macrophage accumulation in human progressive diabetic nephropathy. Nephrology (Carlton) 2006; 11: 226–231.
12. Alexandraki K, Piperi C, Kalofoutis C, Singh J, Alaveras A, Kalofoutis A. Inflammatory process in type 2 diabetes: The role of cytokines. Ann N Y Acad Sci. 2006; 1084: 89-117.
13. Katsuki A, Sumida Y, Murashima S, Murata K, Takarada Y, Ito K, Fujii M, Tsuchihashi K, Goto H, Nakatani K, Yano Y. Serum levels of tumor necrosis factor-alpha are increased in obese patients with noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab. 1998; 83: 859–862.
14. Pickup JC, Chusney GD, Thomas SM, Burt D. Plasma interleukin-6, tumour necrosis factor alpha and blood cytokine production in type 2 diabetes. Life Sci. 2000; 67: 291–300.
15. Festa A, D'Agostino R, Howard G, Mykkänen L, Tracy RP, Haffner SM. Inflammation and microalbuminuria in nondiabetic and type 2 diabetic subjects: The Insulin Resistance Atherosclerosis Study. Kidney Int. 2000; 58: 1703–1710.
16. Bruno G, Merletti F, Biggeri A, Bargero G, Ferrero S, Pagano G, Cavallo Perin P; Casale Monferrato Study. Progression to overt nephropathy in type 2 diabetes: the Casale Monferrato Study. Diabetes Care 2003; 26: 2150–2155.
17. Elmarakby A, Sullivan J. Relationship between oxidative stress and inflammatory cytokines in diabetic nephropathy. Cardiovasc Ther. 2012; 30(1): 49–59.
18. Mora C, Navarro JF. Inflammation and diabetic nephropathy. Curr Diab Rep. 2006; 6: 463–468.
19. Leehey DJ. Targeting inflammation in diabetic kidney disease: Is there a role for pentoxifylline?
Kidney360. 2020; 1(4): 292-299.
20. Leehey DJ, Singh AK, Singh R. Angiotensin II and its receptors in diabetic nephropathy. In: Mogensen CE, Cortes P, eds. The Diabetic Kidney. Humana Press; 2006: 3-21.
21. Ziyadeh FN, Wolf G. Pathogenesis of the podocytopathy and proteinuria in diabetic glomerulopathy. Curr Diabetes Rev. 2008; 4(1): 39-45.
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