Targeting inflammation in diabetic nephropathy: a tale of hope

References

• National Kidney Foundation. KDOQI clinical practice guideline for diabetes and CKD: 2012 update. Am J Kidney Dis. 2012;60:850–886.
   PubMed Web of Science ®Google Scholar
• Fried LF, Emanuele N, Zhang JH, et al. Combined angiotensin inhibition for the treatment of diabetic nephropathy. N Engl J Med. 2013;369:1892–1903.
   PubMed Web of Science ®Google Scholar
• Chin MP, Bakris GL, Block GA, et al. Bardoxolone methyl improves kidney function in patients with chronic kidney disease stage 4 and type 2 diabetes: post-hoc analyses from bardoxolone methyl evaluation in patients with chronic kidney disease and type 2 diabetes study. Am J Nephrol. 2018;47:40–47.
   PubMed Web of Science ®Google Scholar
• Schena FP. Pathogenetic mechanisms of diabetic nephropathy. J Am Soc Nephrol. 2005;16:S30–S33.
   PubMed Web of Science ®Google Scholar
• Rahimi Z. The role of renin angiotensin aldosterone system genes in diabetic nephropathy. Can J Diabetes. 2016;40:178–183.
   PubMed Web of Science ®Google Scholar
• Pezzolesi MG, Poznik GD, Mychaleckyj JC, et al. Genome-wide association scan for diabetic nephropathy susceptibility genes in type 1 diabetes. Diabetes. 2009;58:1403–1410.
   PubMed Web of Science ®Google Scholar
• Cybulsky AV. Endoplasmic reticulum stress, the unfolded protein response and autophagy in kidney diseases. Nat Rev Nephrol. 2017;13:681–696.
   PubMed Web of Science ®Google Scholar
• Grahammer F, Schell C, Huber TB. The podocyte slit diaphragm - From a thin grey line to a complex signaling hub. Nat Rev Nephrol. 2013;9:587–598.
   PubMed Web of Science ®Google Scholar
• Brosius FC III. Trophic factors and cytokines in early diabetic glomerulopathy. Exp Diabesity Res. 2003;4:225–233.
   PubMedGoogle Scholar
• Campbell RC, Ruggenenti P, Remuzzi G. Proteinuria in diabetic nephropathy: treatment and evolution. Curr Diab Rep. 2003;3:497–504.
   PubMedGoogle Scholar
• Niewczas MA, Gohda T, Skupien J, et al. Circulating TNF receptors 1 and 2 predict ESRD in type 2 diabetes. J Am Soc Nephrol. 2012;23:507–515.
   PubMed Web of Science ®Google Scholar
• Gohda T, Niewczas MA, Ficociello LH, et al. Circulating TNF receptors 1 and 2 predict stage 3 CKD in type 1 diabetes. J Am Soc Nephrol. 2012;23:516–524.
   PubMed Web of Science ®Google Scholar
• Betz B, Conway BR. An update on the use of animal models in diabetic nephropathy research. Curr Diab Rep. 2016;16:18.
   PubMed Web of Science ®Google Scholar
• Alpers CE, Hudkins KL. Mouse models of diabetic nephropathy. Curr Opin Nephrol Hypertens. 2011;20:278–284.
   PubMed Web of Science ®Google Scholar
• Pichaiwong W, Hudkins KL, Wietecha T, et al. Reversibility of structural and functional damage in a model of advanced diabetic nephropathy. J Am Soc Nephrol. 2013;24:1088–1102.
   PubMed Web of Science ®Google Scholar
• Zhang M-Z, Wang S, Yang S, et al. Role of blood pressure and the renin-angiotensin system in development of diabetic nephropathy (DN) in eNOS-/- db/db mice. Am J Physiol Renal Physiol. 2012;302:F433–8.
   PubMed Web of Science ®Google Scholar
• Azushima K, Gurley SB, Coffman TM. Modelling diabetic nephropathy in mice. Nat Rev Nephrol. 2017;14:48–56.
   PubMed Web of Science ®Google Scholar
• Yamamoto T, Takabatake Y, Takahashi A, et al. High-fat diet-induced lysosomal dysfunction and impaired autophagic flux contribute to lipotoxicity in the kidney. J Am Soc Nephrol. 2017;28:1534–1551.
   PubMed Web of Science ®Google Scholar
• Moreno JA, Moreno S, Rubio-Navarro A, et al. Role of chemokines in proteinuric kidney disorders. Expert Rev Mol Med. 2014;16:e3.
   PubMed Web of Science ®Google Scholar
• Mezzano S, Aros C, Droguett A, et al. NF-kappaB activation and overexpression of regulated genes in human diabetic nephropathy. Nephrol Dial Transpl. 2004;19:2505–2512.
   PubMed Web of Science ®Google Scholar
• Elmarakby AA, Sullivan JC. Relationship between oxidative stress and inflammatory cytokines in diabetic nephropathy. Cardiovasc Ther. 2012;30:49–59.
   PubMed Web of Science ®Google Scholar
• Sayyed SG, Hägele H, Kulkarni OP, et al. 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;52:2445–2454.
   PubMed Web of Science ®Google Scholar
• Lee EY, Chung CH, Khoury CC, et al. The monocyte chemoattractant protein-1/CCR2 loop, inducible by TGF-beta, increases podocyte motility and albumin permeability. Am J Physiol Renal Physiol. 2009;297:F85–94.
   PubMed Web of Science ®Google Scholar
• Verhave JC, Bouchard J, Goupil R, et al. Clinical value of inflammatory urinary biomarkers in overt diabetic nephropathy: a prospective study. Diabetes Res Clin Pract. 2013;101:333–340.
   PubMed Web of Science ®Google Scholar
• Chow F, Ozols E, Nikolic-Paterson DJ, et al. Tesch, Macrophages in mouse type 2 diabetic nephropathy: correlation with diabetic state and progressive renal injury. Kidney Int. 2004;65:116–128.
   PubMed Web of Science ®Google Scholar
• Kanamori H, Matsubara T, Mima A, et al. Inhibition of MCP-1/CCR2 pathway ameliorates the development of diabetic nephropathy. Biochem Biophys Res Commun. 2007;360:772–777.
   PubMed Web of Science ®Google Scholar
• Darisipudi MN, Kulkarni OP, Sayyed SG, et al. Dual blockade of the homeostatic chemokine CXCL12 and the proinflammatory chemokine CCL2 has additive protective effects on diabetic kidney disease. Am J Pathol. 2011;179:116–124.
   PubMed Web of Science ®Google Scholar
• de Zeeuw D, Bekker P, Henkel E, et al. The effect of CCR2 inhibitor CCX140-B on residual albuminuria in patients with type 2 diabetes and nephropathy: a randomised trial. Lancet Diabetes Endocrinol. 2015;3:687–696.
   PubMed Web of Science ®Google Scholar
• Menne J, Eulberg D, Beyer D, et al. C-C motif-ligand 2 inhibition with emapticap pegol (NOX-E36) in type 2 diabetic patients with albuminuria. Nephrol Dial Transpl. 2017;32:307–315.
   PubMed Web of Science ®Google Scholar
• Matsui H, Suzuki M, Tsukuda R, et al. Expression of ICAM-1 on glomeruli is associated with progression of diabetic nephropathy in a genetically obese diabetic rat, Wistar fatty. Diabetes Res Clin Pract. 1996;32:1–9.
   PubMed Web of Science ®Google Scholar
• Clausen P, Jacobsen P, Rossing K, et al. Plasma concentrations of VCAM-1 and ICAM-1 are elevated in patients with Type 1 diabetes mellitus with microalbuminuria and overt nephropathy. Diabet Med. 2000;17:644–649.
   PubMed Web of Science ®Google Scholar
• Lin J, Glynn RJ, Rifai N, et al. Inflammation and progressive nephropathy in type 1 diabetes in the diabetes control and complications trial. Diabetes Care. 2008;31:2338–2343.
   PubMed Web of Science ®Google Scholar
• Rubio-Guerra AF, Vargas-Robles H, Lozano Nuevo JJ, et al. Correlation between circulating adhesion molecule levels and albuminuria in type-2 diabetic hypertensive patients. Kidney Blood Press Res. 2009;32:106–109.
   PubMed Web of Science ®Google Scholar
• Booth G, Stalker TJ, Lefer AM, et al. Mechanisms of amelioration of glucose-induced endothelial dysfunction following inhibition of protein kinase C in vivo. Diabetes. 2002;51:1556–1564.
   PubMed Web of Science ®Google Scholar
• Onozato ML, Tojo A, Goto A, et al. Radical scavenging effect of gliclazide in diabetic rats fed with a high cholesterol diet. Kidney Int. 2004;65:951–960.
   PubMed Web of Science ®Google Scholar
• Everett BM, Donath MY, Pradhan AD, et al. Anti-inflammatory therapy with canakinumab for the prevention and management of diabetes. J Am Coll Cardiol. 2018;71:2392–2401.
   PubMed Web of Science ®Google Scholar
• Ridker PM, Everett BM, Thuren T, et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med. 2017;377:1119–1131.
   PubMed Web of Science ®Google Scholar
• Cavelti-Weder C, Babians-Brunner A, Keller C, et al. Effects of gevokizumab on glycemia and inflammatory markers in type 2 diabetes. Diabetes Care. 2012;35:1654–1662.
   PubMed Web of Science ®Google Scholar
• Lemos DR, McMurdo M, Karaca G, et al. Interleukin-1β activates a MYC-dependent metabolic switch in kidney stromal cells necessary for progressive tubulointerstitial fibrosis. J Am Soc Nephrol. 2018;29:1690–1705.
   PubMed Web of Science ®Google Scholar
• Robert M, Miossec P. Effects of Interleukin 17 on the cardiovascular system. Autoimmun Rev. 2017;16:984–991.
   PubMed Web of Science ®Google Scholar
• Cortvrindt C, Speeckaert R, Moerman A, et al. The role of interleukin-17A in the pathogenesis of kidney diseases. Pathology. 2017;49:247–258.
   PubMed Web of Science ®Google Scholar
• Bellemore SM, Nikoopour E, Krougly O, et al. Pathogenic T helper type 17 cells contribute to type 1 diabetes independently of interleukin-22. Clin Exp Immunol. 2016;183:380–388.
   PubMed Web of Science ®Google Scholar
• Emamaullee JA, Davis J, Merani S, et al. Inhibition of Th17 cells regulates autoimmune diabetes in NOD mice. Diabetes. 2009;58:1302–1311.
   PubMed Web of Science ®Google Scholar
• Mohamed R, Jayakumar C, Chen F, et al. Low-dose IL-17 therapy prevents and reverses diabetic nephropathy, metabolic syndrome, and associated organ fibrosis. J Am Soc Nephrol. 2016;27:745–765.
   PubMed Web of Science ®Google Scholar
• Roohi A, Tabrizi M, Abbasi F, et al. Serum IL-17, IL-23, and TGF-β levels in type 1 and type 2 diabetic patients and age-matched healthy controls. Biomed Res Int. 2014;2014:718946.
   PubMedGoogle Scholar
• Takeuchi M, Sato T, Tanaka A, et al. Elevated levels of cytokines associated with Th2 and Th17 cells in vitreous fluid of proliferative diabetic retinopathy patients. PLoS One. 2015;10:e0137358.
   PubMed Web of Science ®Google Scholar
• Qiu A-W, Liu Q-H, Wang J-L. Blocking IL-17A alleviates diabetic retinopathy in rodents. Cell Physiol Biochem. 2017;41:960–972.
   PubMed Web of Science ®Google Scholar
• Baeten D, Sieper J, Braun J. Secukinumab, an Interleukin-17A Inhibitor, in Ankylosing Spondylitis. N Engl J Med. 2015;373:2534–2548.
   PubMed Web of Science ®Google Scholar
• Leonardi C, Matheson R, Zachariae C, et al. Anti–interleukin-17 monoclonal antibody ixekizumab in chronic plaque psoriasis. N Engl J Med. 2012;366:1190–1199.
   PubMed Web of Science ®Google Scholar
• Mease P, van der Heijde D, Landewé R, et al. Secukinumab improves active psoriatic arthritis symptoms and inhibits radiographic progression: primary results from the randomised, double-blind, phase III FUTURE 5 study. Ann Rheum Dis. 2018;77:890–897.
   PubMed Web of Science ®Google Scholar
• Elliott MJ, Maini RN, Feldmann M, et al. Randomised double-blind comparison of chimeric monoclonal antibody to tumour necrosis factor alpha (cA2) versus placebo in rheumatoid arthritis. Lancet (London England). 1994;344:1105–1110.
   PubMed Web of Science ®Google Scholar
• Ortiz A, Egido J. Is there a role for specific anti-TNF strategies in glomerular diseases? Nephrol Dial Transpl. 1995;10:309–311.
   PubMed Web of Science ®Google Scholar
• Umapathy D, Krishnamoorthy E, Mariappanadar V, et al. Ramkumar, Increased levels of circulating (TNF-α) is associated with (−308G/A) promoter polymorphism of TNF-α gene in Diabetic Nephropathy. Int J Biol Macromol. 2018;107:2113–2121.
   PubMed Web of Science ®Google Scholar
• Moriwaki Y, Inokuchi T, Yamamoto A, et al. Effect of TNF-α inhibition on urinary albumin excretion in experimental diabetic rats. Acta Diabetol. 2007;44:215–218.
   PubMed Web of Science ®Google Scholar
• Gupta-Ganguli M, Cox K, Means B, et al. Does therapy with anti-TNF-alpha improve glucose tolerance and control in patients with type 2 diabetes? Diabetes Care. 2011;34:e121.
   PubMedGoogle Scholar
• Sfikakis PP, Grigoropoulos V, Emfietzoglou I, et al. Infliximab for diabetic macular edema refractory to laser photocoagulation: a randomized, double-blind, placebo-controlled, crossover, 32-week study. Diabetes Care. 2010;33:1523–1528.
   PubMed Web of Science ®Google Scholar
• Garbers C, Heink S, Korn T, et al. Interleukin-6: designing specific therapeutics for a complex cytokine. Nat Rev Drug Discov. 2018;17:395–412.
   PubMed Web of Science ®Google Scholar
• Wolkow PP, Niewczas MA, Perkins B, et al. Association of urinary inflammatory markers and renal decline in microalbuminuric type 1 diabetics. J Am Soc Nephrol. 2008;19:789–797.
   PubMed Web of Science ®Google Scholar
• Saraheimo M, Teppo A-M, Forsblom C, et al. Diabetic nephropathy is associated with low-grade inflammation in Type 1 diabetic patients. Diabetologia. 2003;46:1402–1407.
   PubMed Web of Science ®Google Scholar
• Sanz AB, Sanchez-Niño MD, Ramos AM, et al. NF-kappaB in renal inflammation. J Am Soc Nephrol. 2010;21:1254–1262.
   PubMed Web of Science ®Google Scholar
• Starkey JM, Haidacher SJ, LeJeune WS, et al. Diabetes-induced activation of canonical and noncanonical nuclear factor-kappaB pathways in renal cortex. Diabetes. 2006;55:1252–1259.
   PubMed Web of Science ®Google Scholar
• Schmid H, Boucherot A, Yasuda Y, et al. Modular activation of nuclear factor-kappaB transcriptional programs in human diabetic nephropathy. Diabetes. 2006;55:2993–3003.
   PubMed Web of Science ®Google Scholar
• Kolati SR, Kasala ER, Bodduluru LN, et al. BAY 11-7082 ameliorates diabetic nephropathy by attenuating hyperglycemia-mediated oxidative stress and renal inflammation via NF-κB pathway. Environ Toxicol Pharmacol. 2015;39:690–699.
   PubMed Web of Science ®Google Scholar
• Oguiza A, Recio C, Lazaro I, et al. Peptide-based inhibition of IκB kinase/nuclear factor-κB pathway protects against diabetes-associated nephropathy and atherosclerosis in a mouse model of type 1 diabetes. Diabetologia. 2015;58:1656–1667.
   PubMed Web of Science ®Google Scholar
• Borgohain MP, Lahkar M, Ahmed S, et al. Small molecule inhibiting nuclear factor-kB ameliorates oxidative stress and suppresses renal inflammation in early stage of alloxan-induced diabetic nephropathy in rat. Basic Clin Pharmacol Toxicol. 2017;120:442–449.
   PubMed Web of Science ®Google Scholar
• Kuhad A, Chopra K. Attenuation of diabetic nephropathy by tocotrienol: involvement of NFkB signaling pathway. Life Sci. 2009;84:296–301.
   PubMed Web of Science ®Google Scholar
• Abou-Hany HO, Atef H, Said E, et al. Crocin mediated amelioration of oxidative burden and inflammatory cascade suppresses diabetic nephropathy progression in diabetic rats. Chem Biol Interact. 2018;284:90–100.
   PubMed Web of Science ®Google Scholar
• Li J, Bao L, Zha D, et al. Oridonin protects against the inflammatory response in diabetic nephropathy by inhibiting the TLR4/p38-MAPK and TLR4/NF-κB signaling pathways. Int Immunopharmacol. 2018;55:9–19.
   PubMed Web of Science ®Google Scholar
• Elsherbiny NM, El-Sherbiny M, Said E. Amelioration of experimentally induced diabetic nephropathy and renal damage by nilotinib. J Physiol Biochem. 2015;71:635–648.
   PubMed Web of Science ®Google Scholar
• Brosius FC, Alpers CE, Bottinger EP, et al. Mouse models of diabetic nephropathy. J Am Soc Nephrol. 2009;20:2503–2512.
   PubMed Web of Science ®Google Scholar
• Perez-Gomez MV, Sanchez-Niño MD, Sanz AB, et al. Targeting inflammation in diabetic kidney disease: early clinical trials. Expert Opin Investig Drugs. 2016;25:1045–1058.
   PubMed Web of Science ®Google Scholar
• Qiu S, Sun G, Zhang Y, et al. Involvement of the NF-κB signaling pathway in the renoprotective effects of isorhamnetin in a type 2 diabetic rat model. Biomed Reports. 2016;4:628–634.
   PubMed Web of Science ®Google Scholar
• Marrero MB, Banes-Berceli AK, Stern DM, et al. Role of the JAK/STAT signaling pathway in diabetic nephropathy. Am J Physiol Physiol. 2006;290:F762–F768.
   PubMed Web of Science ®Google Scholar
• Brosius FC, He JC. JAK inhibition and progressive kidney disease. Curr Opin Nephrol Hypertens. 2015;24:88–95.
   PubMed Web of Science ®Google Scholar
• O’Sullivan LA, Liongue C, Lewis RS, et al. Ward, Cytokine receptor signaling through the Jak–stat–socs pathway in disease. Mol Immunol. 2007;44:2497–2506.
   PubMed Web of Science ®Google Scholar
• Ortiz-Muñoz G, Lopez-Parra V, Lopez-Franco O, et al. Suppressors of cytokine signaling abrogate diabetic nephropathy. J Am Soc Nephrol. 2010;21:763–772.
   PubMed Web of Science ®Google Scholar
• Banes AK, Shaw S, Jenkins J, et al. Angiotensin II blockade prevents hyperglycemia-induced activation of JAK and STAT proteins in diabetic rat kidney glomeruli. Am J Physiol Renal Physiol. 2004;286:F653–9.
   PubMed Web of Science ®Google Scholar
• Berthier CC, Zhang H, Schin M, et al. Enhanced expression of Janus kinase-signal transducer and activator of transcription pathway members in human diabetic nephropathy. Diabetes. 2009;58:469–477.
   PubMed Web of Science ®Google Scholar
• Hodgin JB, Nair V, Zhang H, et al. Identification of cross-species shared transcriptional networks of diabetic nephropathy in human and mouse glomeruli. Diabetes. 2013;62:299–308.
   PubMed Web of Science ®Google Scholar
• Zhang H, Nair V, Saha J, et al. Podocyte-specific JAK2 overexpression worsens diabetic kidney disease in mice. Kidney Int. 2017;92:909–921.
   PubMed Web of Science ®Google Scholar
• Lu T-C, Wang Z-H, Feng X, et al. Knockdown of Stat3 activity in vivo prevents diabetic glomerulopathy. Kidney Int. 2009;76:63–71.
   PubMed Web of Science ®Google Scholar
• Fernandez-Fernandez B, Ortiz A, Gomez-Guerrero C, et al. Therapeutic approaches to diabetic nephropathy—beyond the RAS. Nat Rev Nephrol. 2014;10:325–346.
   PubMed Web of Science ®Google Scholar
• Hsu J-D, Wu -C-C, Hung C-N, et al. Myrciaria cauliflora extract improves diabetic nephropathy via suppression of oxidative stress and inflammation in streptozotocin-nicotinamide mice. J Food Drug Anal. 2016;24:730–737.
   PubMed Web of Science ®Google Scholar
• Hu J, Fan X, Meng X, et al. Evidence for the involvement of JAK/STAT/SOCS pathway in the mechanism of Tangshen formula-treated diabetic nephropathy. Planta Med. 2014;80:614–621.
   PubMed Web of Science ®Google Scholar
• Li P, Chen Y, Liu J, et al. Efficacy and safety of tangshen formula on patients with type 2 diabetic kidney disease: a multicenter double-blinded randomized placebo-controlled trial1. PLoS One. 2015;10:e0126027.
   PubMedGoogle Scholar
• Cetkovic-Cvrlje M, Dragt AL, Vassilev A, et al. Targeting JAK3 with JANEX-1 for prevention of autoimmune type 1 diabetes in NOD mice. Clin Immunol. 2003;106:213–225.
   PubMed Web of Science ®Google Scholar
• Said E, Zaitone SA, Eldosoky M, et al. Nifuroxazide, a STAT3 inhibitor, mitigates inflammatory burden and protects against diabetes-induced nephropathy in rats. Chem Biol Interact. 2018;281:111–120.
   PubMed Web of Science ®Google Scholar
• Banerjee S, Biehl A, Gadina M, et al. JAK-STAT signaling as a target for inflammatory and autoimmune diseases: current and future prospects. Drugs. 2017;77:521–546.
   PubMed Web of Science ®Google Scholar
• Tuttle KR, Brosius FC, Adler SG, et al. JAK1/JAK2 inhibition by baricitinib in diabetic kidney disease: results from a Phase 2 randomized controlled clinical trial. Nephrol Dial Transpl. 2018.
   PubMedGoogle Scholar
• Rastmanesh MM, Bluyssen HAR, Joles JA, et al. Increased expression of SOCS3 in monocytes and SOCS1 in lymphocytes correlates with progressive loss of renal function and cardiovascular risk factors in chronic kidney disease. Eur J Pharmacol. 2008;593:99–104.
   PubMed Web of Science ®Google Scholar
• Shi Y, Du C, Zhang Y, et al. Suppressor of cytokine signaling-1 ameliorates expression of MCP-1 in diabetic nephropathy. Am J Nephrol. 2010;31:380–388.
   PubMed Web of Science ®Google Scholar
• Zhou Y, Lv C, Wu C, et al. Suppressor of cytokine signaling (SOCS) 2 attenuates renal lesions in rats with diabetic nephropathy. Acta Histochem. 2014;116:981–988.
   PubMed Web of Science ®Google Scholar
• Recio C, Lazaro I, Oguiza A, et al. Suppressor of cytokine signaling-1 peptidomimetic limits progression of diabetic nephropathy. J Am Soc Nephrol. 2017;28:575–585.
   PubMed Web of Science ®Google Scholar
• Lopez-Sanz L, Bernal S, Recio C, et al. SOCS1-targeted therapy ameliorates renal and vascular oxidative stress in diabetes via STAT1 and PI3K inhibition. Lab Invest. 2018.
   PubMed Web of Science ®Google Scholar
• Cheng D, Wu R, Guo Y, et al. Regulation of keap1–Nrf2 signaling: the role of epigenetics. Curr Opin Toxicol. 2016;1:134–138.
   PubMedGoogle Scholar
• Yagishita Y, Fukutomi T, Sugawara A, et al. Nrf2 protects pancreatic -cells from oxidative and nitrosative stress in diabetic model mice. Diabetes. 2014;63:605–618.
   PubMed Web of Science ®Google Scholar
• Hong DS, Kurzrock R, Supko JG, et al. A phase I first-in-human trial of bardoxolone methyl in patients with advanced solid tumors and lymphomas, Clin. Cancer Res. 2012;18:3396–3406.
   Web of Science ®Google Scholar
• Pergola PE, Raskin P, Toto RD, et al. Bardoxolone methyl and kidney function in CKD with type 2 diabetes. N Engl J Med. 2011;365:327–336.
   PubMed Web of Science ®Google Scholar
• de Zeeuw D, Akizawa T, Audhya P, et al. Bardoxolone methyl in type 2 diabetes and stage 4 chronic kidney disease. N Engl J Med. 2013;369:2492–2503.
   PubMed Web of Science ®Google Scholar
• Gold R, Kappos L, Arnold DL, et al. Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. N Engl J Med. 2012;367:1098–1107.
   PubMed Web of Science ®Google Scholar
• Qiu -Y-Y, Tang L-Q. Roles of the NLRP3 inflammasome in the pathogenesis of diabetic nephropathy. Pharmacol Res. 2016;114:251–264.
   PubMed Web of Science ®Google Scholar
• Wang S, Zhao X, Yang S, et al. Salidroside alleviates high glucose-induced oxidative stress and extracellular matrix accumulation in rat glomerular mesangial cells by the TXNIP-NLRP3 inflammasome pathway. Chem Biol Interact. 2017;278:48–53.
   PubMed Web of Science ®Google Scholar
• Fu Y, Wu N, Zhao D. Function of NLRP3 in the pathogenesis and development of diabetic nephropathy. Med Sci Monit. 2017;23:3878–3884.
   PubMed Web of Science ®Google Scholar
• Samra YA, Said HS, Elsherbiny NM, et al. Cepharanthine and Piperine ameliorate diabetic nephropathy in rats: role of NF-κB and NLRP3 inflammasome. Life Sci. 2016;157:187–199.
   PubMed Web of Science ®Google Scholar
• Tsai TJ, Lin RH, Chang CC, et al. Vasodilator agents modulate rat glomerular mesangial cell growth and collagen synthesis. Nephron. 1995;70:91–99.
   PubMed Web of Science ®Google Scholar
• Shan D, Wu HM, Yuan QY, et al. Pentoxifylline for diabetic kidney disease. Cochrane Database Syst Rev. 2012;(2):CD006800.
   PubMed Web of Science ®Google Scholar
• Navarro-Gonzalez JF, Mora-Fernandez C, Muros de Fuentes M, et al. Effect of pentoxifylline on renal function and urinary albumin excretion in patients with diabetic kidney disease: the PREDIAN trial. J Am Soc Nephrol. 2015;26:220–229.
   PubMed Web of Science ®Google Scholar
• Chen Y-M, Chiang W-C, Lin S-L, et al. Therapeutic efficacy of pentoxifylline on proteinuria and renal progression: an update. J Biomed Sci. 2017;24:84.
   PubMed Web of Science ®Google Scholar
• Lai T-S, Chiang W-C, Chen Y-M. Pentoxifylline: evidence strong enough for renoprotection? J Formos Med Assoc. 2016;115:591–592.
   PubMed Web of Science ®Google Scholar
• Fantin M, Quintieri L, Kúsz E, et al. Pentoxifylline and its major oxidative metabolites exhibit different pharmacological properties. Eur J Pharmacol. 2006;535:301–309.
   PubMed Web of Science ®Google Scholar
• Braman V, Graham P, Cheng C, et al. A randomized phase I evaluation of CTP-499, a novel deuterium-containing drug candidate for diabetic nephropathy. Clin Pharmacol Drug Dev. 2013;2:53–66.
   PubMed Web of Science ®Google Scholar
• Sabounjian L, Graham P, Wu L, et al. A first-in-patient, multicenter, double-blind, 2-arm, placebo-controlled, randomized safety and tolerability study of a novel oral drug candidate, CTP-499, in chronic kidney disease. Clin Pharmacol Drug Dev. 2016;5:314–325.
   PubMed Web of Science ®Google Scholar
• Rhee SY, Kim YS. The role of advanced glycation end products in diabetic vascular complications. Diabetes Metab J. 2018;42:188.
   PubMed Web of Science ®Google Scholar
• Nandhini AA, Thirunavukkarasu V, Anuradha CV. Taurine modifies insulin signaling enzymes in the fructose-fed insulin resistant rats. Diabetes Metab. 2005;31:337–344.
   PubMed Web of Science ®Google Scholar
• Weigand T, Singler B, Fleming T, et al. Carnosine catalyzes the formation of the oligo/polymeric products of methylglyoxal. Cell Physiol Biochem. 2018;46:713–726.
   PubMed Web of Science ®Google Scholar
• Ahmad S, Shahab U, Baig MH, et al. Inhibitory effect of metformin and pyridoxamine in the formation of early, intermediate and advanced glycation end-products. PLoS One. 2013;8:e72128.
   PubMed Web of Science ®Google Scholar
• Rahbar S, Figarola JL. Novel inhibitors of advanced glycation endproducts. Arch Biochem Biophys. 2003;419:63–79.
   PubMed Web of Science ®Google Scholar
• Chiazza F, Cento AS, Collotta D, et al. Protective effects of pyridoxamine supplementation in the early stages of diet-induced kidney dysfunction. Biomed Res Int. 2017;2017:1–12.
   Google Scholar
• Pereira A, Fernandes R, Crisóstomo J, et al. The Sulforaphane and pyridoxamine supplementation normalize endothelial dysfunction associated with type 2 diabetes. Sci Rep. 2017;7:14357.
   PubMed Web of Science ®Google Scholar
• Abouzed TK, Munesue S, Harashima A, et al. Preventive effect of salicylate and pyridoxamine on diabetic nephropathy. J Diabetes Res. 2016;2016:1–10.
   Google Scholar
• Soulis-Liparota T, Cooper M, Papazoglou D, et al. Retardation by aminoguanidine of development of albuminuria, mesangial expansion, and tissue fluorescence in streptozocin-induced diabetic rat. Diabetes. 1991;40:1328–1334.
   PubMed Web of Science ®Google Scholar
• Coughlan MT, Thallas-Bonke V, Pete J, et al. Combination therapy with the advanced glycation end product cross-link breaker, alagebrium, and angiotensin converting enzyme inhibitors in diabetes: synergy or redundancy? Endocrinology. 2007;148:886–895.
   PubMed Web of Science ®Google Scholar
• Elbe H, Vardi N, Orman D, et al. Ameliorative effects of aminoguanidine on rat aorta in Streptozotocin-induced diabetes and evaluation of α-SMA expression. Anadolu Kardiyol Dergisi/The Anatol J Cardiol. 2014;14:679–684.
   PubMedGoogle Scholar
• Oldfield MD, Bach LA, Forbes JM, et al. Advanced glycation end products cause epithelial-myofibroblast transdifferentiation via the receptor for advanced glycation end products (RAGE). J Clin Invest. 2001;108:1853–1863.
   PubMed Web of Science ®Google Scholar
• Bakris GL, Bank AJ, Kass DA, et al. Advanced glycation end-product cross-link breakers: A novel approach to cardiovascular pathologies related to the aging process. Am J Hypertens. 2004;17:S23–S30.
   PubMed Web of Science ®Google Scholar
• Yonekura H, Yamamoto Y, Sakurai S, et al. Novel splice variants of the receptor for advanced glycation end-products expressed in human vascular endothelial cells and pericytes, and their putative roles in diabetes-induced vascular injury. Biochem J. 2003;370:1097–1109.
   PubMed Web of Science ®Google Scholar
• Nidorf SM, Eikelboom JW, Budgeon CA, et al. Low-dose colchicine for secondary prevention of cardiovascular disease. J Am Coll Cardiol. 2013;61:404–410.
   PubMed Web of Science ®Google Scholar
• Solak Y, Siriopol D, Yildiz A, et al. Colchicine in renal medicine: new virtues of an ancient friend. Blood Purif. 2017;43:125–135.
   PubMed Web of Science ®Google Scholar
• Li JJ, Lee SH, Kim DK, et al. Colchicine attenuates inflammatory cell infiltration and extracellular matrix accumulation in diabetic nephropathy. Am J Physiol Renal Physiol. 2009;297:F200–9.
   PubMed Web of Science ®Google Scholar
• Vallon V, Thomson SC. Targeting renal glucose reabsorption to treat hyperglycaemia: the pleiotropic effects of SGLT2 inhibition. Diabetologia. 2017;60:215–225.
   PubMed Web of Science ®Google Scholar
• Han JH, Oh TJ, Lee G, et al. The beneficial effects of empagliflozin, an SGLT2 inhibitor, on atherosclerosis in ApoE −/− mice fed a western diet. Diabetologia. 2017;60:364–376.
   PubMed Web of Science ®Google Scholar
• Vallon V, Gerasimova M, Rose MA, et al. SGLT2 inhibitor empagliflozin reduces renal growth and albuminuria in proportion to hyperglycemia and prevents glomerular hyperfiltration in diabetic Akita mice. AJP Ren Physiol. 2014;306:F194–F204.
   Google Scholar
• Lin B, Koibuchi N, Hasegawa Y, et al. Glycemic control with empagliflozin, a novel selective SGLT2 inhibitor, ameliorates cardiovascular injury and cognitive dysfunction in obese and type 2 diabetic mice. Cardiovasc Diabetol. 2014;13:148.
   PubMed Web of Science ®Google Scholar
• Terami N, Ogawa D, Tachibana H, et al. Long-term treatment with the sodium glucose cotransporter 2 inhibitor, dapagliflozin, ameliorates glucose homeostasis and diabetic nephropathy in db/db mice. PLoS One. 2014;9:e100777.
   PubMed Web of Science ®Google Scholar
• Panchapakesan U, Pegg K, Gross S, et al. Effects of SGLT2 inhibition in human kidney proximal tubular cells–renoprotection in diabetic nephropathy? PLoS One. 2013;8:e54442.
   PubMed Web of Science ®Google Scholar
• Jo CH, Kim S, Park J-S, et al. Anti-inflammatory action of sitagliptin and linagliptin in doxorubicin nephropathy. Kidney Blood Press Res. 2018;43:987–999.
   PubMed Web of Science ®Google Scholar
• Perretti M, Leroy X, Bland EJ, et al. Resolution pharmacology: opportunities for therapeutic innovation in inflammation. Trends Pharmacol Sci. 2015;36:737–755.
   PubMed Web of Science ®Google Scholar
• Trostel J, Garcia GE. Endogenous inhibitors of kidney inflammation. J Nephrol Res. 2015;1:61–68.
   PubMedGoogle Scholar
• Brennan EP, Mohan M, McClelland A, et al. Lipoxins regulate the early growth response-1 network and reverse diabetic kidney disease. J Am Soc Nephrol. 2018;29:1437–1448.
   PubMed Web of Science ®Google Scholar
• Börgeson E, Johnson AM, Lee YS, et al. Lipoxin A4 attenuates obesity-induced adipose inflammation and associated liver and kidney disease. Cell Metab. 2015;22:125–137.
   PubMed Web of Science ®Google Scholar
• Awad AS, Huang L, Ye H, et al. Adenosine A2A receptor activation attenuates inflammation and injury in diabetic nephropathy. Am J Physiol Renal Physiol. 2006;290:F828–37.
   PubMed Web of Science ®Google Scholar