Lessons learned from early-stage clinical trials for diabetic nephropathy

References

• Qi C, Mao X, Zhang Z, et al. Classification and differential diagnosis of diabetic nephropathy. J Diabetes Res. 2017;2017:8637138. doi: 10.1155/2017/8637138
   PubMed Web of Science ®Google Scholar
• Mogensen CE, Christensen CK, Vittinghus E. The stages in diabetic renal disease. With emphasis on the stage of incipient diabetic nephropathy. Diabetes. 1983;32 Suppl 2(Supplement_2):64–78.
   PubMedGoogle Scholar
• Pugliese G. Updating the natural history of diabetic nephropathy. Acta Diabetol. 2014;51(6):905–915. doi: 10.1007/s00592-014-0650-7
   PubMed Web of Science ®Google Scholar
• Inker LA, Eneanya ND, Coresh J. Chronic kidney disease epidemiology collaboration. Et al. New creatinine- and cystatin C-based equations to estimate GFR without race. N Engl J Med. 2021;385(19):1737–1749.
   PubMed Web of Science ®Google Scholar
• Delgado C, Baweja M, Crews DC, et al. A unifying approach for GFR estimation: recommendations of the NKF-ASN task force on reassessing the inclusion of race in diagnosing kidney disease. Am J Kidney Dis. 2022;79(2):268–288.e1. doi: 10.1053/j.ajkd.2021.08.003
   PubMed Web of Science ®Google Scholar
• ) U.S. Renal Data System. 2020 USRDS annual data report: epidemiology of kidney disease in the United States. National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, US Department of Health and Human Services; 2020.
   Google Scholar
• Centers for Disease Control and Prevention. Chronic kidney disease in the United States, 2021. Centers for disease Control and Prevention. Atlanta, Georgia: US Department of Health and Human Services; 2021.
   Google Scholar
• Coresh J, Heerspink HJL, Sang Y, et al. Chronic kidney disease prognosis consortium and chronic kidney disease epidemiology collaboration. Change in albuminuria and subsequent risk of end-stage kidney disease: an individual participant-level consortium meta-analysis of observational studies. Lancet Diabetes Endocrinol. 2019;7(2):115–127. doi: 10.1016/S2213-8587(18)30313-9
   PubMed Web of Science ®Google Scholar
• Said SM, Nasr SH. Nasr SH silent diabetic nephropathy. Kidney Int. 2016;90(1):24–26. doi: 10.1016/j.kint.2016.02.042
   PubMed Web of Science ®Google Scholar
• Krolewski M, Eggers PW, Warram JH. Magnitude of end-stage renal disease in IDDM: a 35 year follow-up study. Kidney Int. 1996;50(6):2041. doi: 10.1038/ki.1996.527
   PubMed Web of Science ®Google Scholar
• Ritz E, Orth SR. Nephropathy in patients with type 2 diabetes mellitus. N Engl J Med. 1999;341(15):1127. doi: 10.1056/NEJM199910073411506
   PubMed Web of Science ®Google Scholar
• DCCT/EDIC Research Group, de Boer IH, Sun W, et al. Intensive diabetes therapy and glomerular filtration rate in type 1 diabetes. N Engl J Med. 2011;365(25):2366–2376.
   PubMed Web of Science ®Google Scholar
• Lv J, Ehteshami P, Sarnak MJ, et al. Effects of intensive blood pressure lowering on the progression of chronic kidney disease: a systematic review and meta-analysis. CMAJ. 2013;185(11):949–957. doi: 10.1503/cmaj.121468
   PubMed Web of Science ®Google Scholar
• Lewis EJ, Hunsicker LG, Bain RP, et al. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The collaborative study group. N Engl J Med. 1993;329(20):1456–62. doi: 10.1056/NEJM199311113292004
   PubMed Web of Science ®Google Scholar
• Izumi Y, Iwao H. Angiotensin II Peptides. Handbook Biol Act Peptides. 2nd ed. 2013; p. 1369–1376.
   Google Scholar
• ApdO L, Li XC, Nwia SM, et al. Angiotensin II and AT1a receptors in the proximal tubules of the kidney: new roles in blood pressure control and hypertension. Int J Mol Sci. 2022;23(5):2402. doi: 10.3390/ijms23052402
   PubMed Web of Science ®Google Scholar
• Smith RD, Timmermans PB, Timmermans &. Human angiotensin receptor subtypes. Nephrol Hypertens. 1994;3(1):112–122. doi: 10.1097/00041552-199401000-00016
   PubMedGoogle Scholar
• Naito T, Ma LJ, Yang H, et al. Angiotensin type 2 receptor actions contribute to angiotensin type 1 receptor blocker effects on kidney fibrosis. Am J Physiol Renal Physiol. 2010;298(3):F683–91. doi: 10.1152/ajprenal.00503.2009
   PubMed Web of Science ®Google Scholar
• Kohler C, Drexler H, Drexler H. Role of bradykinin in mediating vascular effects of angiotensin-converting enzyme inhibitors in human circulation. Circulation. 1997;95(5):1115–1118. doi: 10.1161/01.CIR.95.5.1115
   PubMed Web of Science ®Google Scholar
• Cohn JN, Goldman JM. Angiotensin peptides. Establishing a new option for target-organ protection: rationale for ARB plus ACE inhibitor combination therapy. Am J Hypertens. 2008;21(3):248–256. doi: 10.1038/ajh.2007.56
   PubMed Web of Science ®Google Scholar
• Wu H-Y, Huang J-W, Lin H-J, et al. Comparative effectiveness of renin-angiotensin system blockers and other antihypertensive drugs in patients with diabetes: systematic review and Bayesian network meta-analysis BMJ. BMJ. 2013;347(oct24 2):f6008. doi: 10.1136/bmj.f6008
   PubMedGoogle Scholar
• van de Wal RMA, van Veldhuisen DJ, van Gilst WH, et al. Addition of an angiotensin receptor blocker to full-dose ACE-inhibition: controversial or common sense? Eur Heart J. 2005;26(22):2361–2367. doi: 10.1093/eurheartj/ehi454
   PubMed Web of Science ®Google Scholar
• Messerli FH, Yuzefpolskaya M. Q: is an ACE inhibitor plus an ARB more effective than either drug alone? Cleve Clin J Med. 2009;76(12):693–696. doi: 10.3949/ccjm.76a.09052
   PubMed Web of Science ®Google Scholar
• Alsahli M, Gerich JE. Renal glucose metabolism in normal physiological conditions and in diabetes. Diabet Res Clin Pract. 2017;133:1–9. doi: 10.1016/j.diabres.2017.07.033
   PubMed Web of Science ®Google Scholar
• Wright EM. SGLT2 inhibitors: physiology and pharmacology. Kidney. 2021;360(12):2027–2037. doi: 10.34067/KID.0002772021
   Google Scholar
• Abdul-Ghani MA, Norton L, DeFronzo RA. Renal sodium-glucose cotransporter inhibition in the management of type 2 diabetes mellitus. Am J Physiol Renal Physiol. 2015;309(4):F889–900. doi: 10.1152/ajprenal.00267.2015
   PubMedGoogle Scholar
• Ghezzi C, Loo DDF, Wright EM. Physiology of renal glucose handling via SGLT1, SGLT2 and GLUT2. Diabetologia. 2018;61(10):2087–2097. doi: 10.1007/s00125-018-4656-5
   PubMed Web of Science ®Google Scholar
• Perry RJ, Shulman GI. Sodium-glucose cotransporter-2 inhibitors: understanding the mechanisms for therapeutic promise and persisting risks. J Biol Chem. 2020;295(42):14379–14390. doi: 10.1074/jbc.REV120.008387
   PubMed Web of Science ®Google Scholar
• ) U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER). Clinical Medical Guidance for Industry. Diabetes Mellitus – Evaluating Cardiovascular Risk in New Antidiabetic Therapies to Treat Type 2 Diabetes. Office of Communications, Division of Drug Information, Center for Drug Evaluation and Research, Food and Drug Administration; 2008 Dec. Available from: https://www.federalregister.gov/documents/2008/12/19/E8-30086
   Google Scholar
• Rendell M. The path to approval of new drugs for diabetes. Expert Opin Drug Saf. 2013;12(2):195–207.
   PubMed Web of Science ®Google Scholar
• Zinman B, Wanner C, Lachin JM, et al. EMPA-REG OUTCOME Investigators. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015;374(11):2117–2128. doi: 10.1056/NEJMoa1504720
   Google Scholar
• Wanner C, Inzucchi SE, Lachin JM, et al. EMPA-REG OUTCOME investigators. Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med. 2016;375(18):323–334. doi: 10.1056/NEJMoa1515920
   PubMedGoogle Scholar
• Herrington WG, Staplin N, Staplin N, et al. Wanner C et al empagliflozin in patients with chronic kidney disease. N Engl J Med. 2023;388(2):117–127. doi: 10.1056/NEJMoa2204233
   PubMed Web of Science ®Google Scholar
• W,; CANVAS Program Collaborative Group, Neal B, Perkovic V, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377(7):644–657.
   PubMed Web of Science ®Google Scholar
• Perkovic V, Jardine MJ, Neal B, et al. CREDENCE trial investigators canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med. 2019;380(24):2295–2306. doi: 10.1056/NEJMoa1811744
   PubMed Web of Science ®Google Scholar
• Wiviott SD, Raz I, Bonaca MP, et al. DECLARE–TIMI 58 Investigators. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2019;380(4):347–357. doi: 10.1056/NEJMoa1812389
   PubMed Web of Science ®Google Scholar
• Heerspink HJL, Stefánsson BV, Correa-Rotter R, et al. DAPA-CKD trial committees and investigators. Dapagliflozin in patients with chronic kidney disease. N Engl J Med. 2020;383(15):1436–1446. doi: 10.1056/NEJMoa2024816
   PubMed Web of Science ®Google Scholar
• Bhatt DL, Szarek M, Pitt B. SCORED investigators. Sotagliflozin in patients with diabetes and chronic kidney disease. N Engl J Med. 2021;384(2):129–139. doi: 10.1056/NEJMoa2030186
   PubMed Web of Science ®Google Scholar
• Cherney DZI, Charbonnel B, Cosentino F. VERTIS CV investigators. Effects of ertugliflozin on kidney composite outcomes, renal function and albuminuria in patients with type 2 diabetes mellitus: an analysis from the randomized VERTIS CV trial. Diabetologia. 2021;64(6):1256–1267. doi: 10.1007/s00125-021-05407-5
   PubMed Web of Science ®Google Scholar
• Vaduganathan M, Docherty KF, Claggett BL, et al. SGLT-2 inhibitors in patients with heart failure: a comprehensive meta-analysis of five randomized controlled trials lancet. Lancet. 2022;400(10354):757–767. doi: 10.1016/S0140-6736(22)01429-5
   PubMed Web of Science ®Google Scholar
• Nuffield Department of Population Health Renal Studies Group. SGLT2 inhibitor Meta-Analysis Cardio-Renal Trialists’ consortium impact of diabetes on the effects of sodium glucose co-transporter-2 inhibitors on kidney outcomes: collaborative meta-analysis of large placebo-controlled trials. Lancet. 2022;400(10365):1788–1801. doi: 10.1016/S0140-6736(22)02074-8
   PubMed Web of Science ®Google Scholar
• Jafar TH. FDA approval of dapagliflozin for chronic kidney disease: a remarkable achievement. Lancet. 2021;398(10297):283–284.
   PubMed Web of Science ®Google Scholar
• de Boer IH, Kahn SE. SGLT2 inhibitors-sweet success for diabetic kidney disease? J Am Soc Nephrol. 2017;28(1):7–10. doi: 10.1681/ASN.2016060650
   PubMed Web of Science ®Google Scholar
• Mende CW. Chronic kidney disease and SGLT2 inhibitors: a review of the evolving treatment landscape. Adv Ther. 2022;39(1):148–164. doi: 10.1007/s12325-021-01994-2
   PubMed Web of Science ®Google Scholar
• Peti-Peterdi J. Newly stemming functions of macula densa–derived prostanoids- 2015. Hypertension. 2015;65(5):987–988. doi: 10.1161/HYPERTENSIONAHA.115.04739
   PubMed Web of Science ®Google Scholar
• Vallon V, Thomson SC. The tubular hypothesis of nephron filtration and diabetic kidney disease. Nat Rev Nephrol. 2020;16(6):317–336. doi: 10.1038/s41581-020-0256-y
   PubMed Web of Science ®Google Scholar
• Wilcox CS -. Antihypertensive and renal mechanisms of SGLT2 (Sodium-Glucose Linked Transporter 2) Inhibitors. Hypertension. 2020;75(4):894–901. doi: 10.1161/HYPERTENSIONAHA.119.11684
   PubMed Web of Science ®Google Scholar
• Gérard AO, Laurain A, Favre G, et al. Activation of the tubulo-glomerular feedback by SGLT2 inhibitors in patients with type 2 diabetes and advanced chronic kidney disease: toward the end of a myth? Diabetes Care. 2022;45(10):e148–e149. doi: 10.2337/dc22-0921
   PubMed Web of Science ®Google Scholar
• Puglisi S, Rossini A, Poli R, et al. Effects of SGLT2 inhibitors and glp-1 receptor agonists on renin-angiotensin-aldosterone system. Front Endocrinol. 2021;12:738848. doi: 10.3389/fendo.2021.738848
   PubMed Web of Science ®Google Scholar
• Raza S, Osasan S, Sethia S, et al. A systematic review of sodium-glucose cotransporter 2 (SGLT2) inhibitors and sympathetic nervous system inhibition: an underrated mechanism of cardiorenal protection. Cureus. 2022;14(6):e26313. doi: 10.7759/cureus.26313
   PubMed Web of Science ®Google Scholar
• Wichaiyo S, Saengklub N. Alterations of sodium-hydrogen exchanger 1 function in response to SGLT2 inhibitors: what is the evidence? Heart Fail Rev. 2022;27(6):1973–1990. doi: 10.1007/s10741-022-10220-2
   PubMed Web of Science ®Google Scholar
• Al-Shamasi AA, Elkaffash R, Mohamed M, et al. Crosstalk between sodium-glucose cotransporter inhibitors and sodium-hydrogen exchanger 1 and 3 in cardiometabolic diseases. Int J Mol Sci. 2021;22(23):12677. doi: 10.3390/ijms222312677
   PubMed Web of Science ®Google Scholar
• Gonzalez-Franquesa A, Patti ME. Insulin resistance and mitochondrial dysfunction. Adv Exp Med Biol. 2017;982:465–520.
   PubMed Web of Science ®Google Scholar
• Packer M -. Critical reanalysis of the mechanisms underlying the cardiorenal benefits of sglt2 inhibitors and reaffirmation of the nutrient deprivation signaling/autophagy hypothesis circulation. 2022;146(18):1383–1405. doi: 10.1161/CIRCULATIONAHA.122.061732
   Google Scholar
• Skrabic R, Kumric M, Vrdoljak J, et al. SGLT2 inhibitors in chronic kidney disease: from mechanisms to clinical practice. Biomedicines. 2022;10(10):2458. doi: 10.3390/biomedicines10102458
   PubMed Web of Science ®Google Scholar
• Rendell MS. Obesity and diabetes: the final frontier. Expert Rev Endocrinol Metab. 2023;18(1):81–94. doi: 10.1080/17446651.2023.2168643
   PubMed Web of Science ®Google Scholar
• Sattar N, Lee MMY, Kristensen SL, et al. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of randomised trials. Lancet Diabetes Endocrinol. 2021;9(10):653–662. doi: 10.1016/S2213-8587(21)00203-5
   PubMed Web of Science ®Google Scholar
• Mosterd CM, Bjornstad P, van Raalte DH. Nephroprotective effects of GLP-1 receptor agonists: where do we stand? J Nephrol. 2020;33(5):965–975. doi: 10.1007/s40620-020-00738-9
   PubMed Web of Science ®Google Scholar
• Wexler DJ, de Boer IH, Ghosh A, et al. Comparative effects of glucose-lowering medications on kidney outcomes in type 2 diabetes: the GRADE randomized clinical trial. JAMA Intern Med. 2023;183(7):705–714. doi: 10.1001/jamainternmed.2023.1487
   PubMed Web of Science ®Google Scholar
• Rossing P, Baeres FMM, Bakris G, et al. The rationale, design and baseline data of FLOW, a kidney outcomes trial with once-weekly semaglutide in people with type 2 diabetes and chronic kidney disease. Nephrol Dial Transplant. 2023;38(9):2041–2051. doi: 10.1093/ndt/gfad009
   PubMed Web of Science ®Google Scholar
• Williams JS, Williams GH. 50th anniversary of aldosterone. J Clin Endo Metab. 2003;88(6):2364–2372. doi: 10.1210/jc.2003-030490
   PubMed Web of Science ®Google Scholar
• Erraez S, López-Mesa M, Gómez-Fernández P. Mineralocorticoid receptor blockers in chronic kidney disease. Nefrologia (Engl Ed). 2021;41(3):258–275. doi: 10.1016/j.nefroe.2021.08.001
   Web of Science ®Google Scholar
• Agrawal S, Agrawal N, Garg J, et al. Heart failure and chronic kidney disease: should we use spironolactone? Am J Med Sci. 2015;350(2):147–51. doi: 10.1097/MAJ.0000000000000514
   PubMed Web of Science ®Google Scholar
• Hu H, Cao M, Sun Y, et al. Efficacy and safety of eplerenone for treating chronic kidney disease: a meta-analysis. Int J Hypertens. 2023;2023:1–18. doi: 10.1155/2023/6683987
   Web of Science ®Google Scholar
• González-Juanatey JR, Górriz JL, Ortiz A, et al. Cardiorenal benefits of finerenone: protecting kidney and heart. Ann Med 2023. 55(1):502–513. doi: 10.1080/07853890.2023.2171110
   Google Scholar
• Fu Y, Hall JE, Lu D, et al. Aldosterone blunts tubuloglomerular feedback by activating macula densa mineralocorticoid receptors. Hypertension. 2012;59(3):599–606. doi: 10.1161/HYPERTENSIONAHA.111.173195
   PubMed Web of Science ®Google Scholar
• Bauersachs J, López-Andrés N. Mineralocorticoid receptor in cardiovascular diseases—clinical trials and mechanistic insights. Br J Pharmacol. 2022;179(13):3119–3134. doi: 10.1111/bph.15708
   PubMed Web of Science ®Google Scholar
• Luther JM, Fogo AB. The role of mineralocorticoid receptor activation in kidney inflammation and fibrosis. Kidney Int Suppl. 2022;12(1):63–68. doi: 10.1016/j.kisu.2021.11.006
   Web of Science ®Google Scholar
• López-Novoa JM, Rodríguez-Peña AB, Ortiz A, et al. Etiopathology of chronic tubular, glomerular and renovascular nephropathies: clinical implications. J Transl Med. 2011;9(1):13. doi: 10.1186/1479-5876-9-13
   PubMedGoogle Scholar
• Rhodin J. Electron microscopy of the kidney. Am J Med. 1958;24(5):661–675. doi: 10.1016/0002-9343(58)90373-5
   PubMed Web of Science ®Google Scholar
• Yu Y, Leng CG, Terada N, et al. Scanning electron microscopic study of the renal glomerulus by an in vivo cryotechnique combined with freeze-substitution. J Anat. 1998;192(Pt 4):595–603. doi: 10.1046/j.1469-7580.1998.19240595.x
   PubMedGoogle Scholar
• Pullman JM. New views of the glomerulus: advanced microscopy for advanced diagnosis. Front Med. 2019;6:37. doi: 10.3389/fmed.2019.00037
   Web of Science ®Google Scholar
• Reynolds PA. The mechanobiology of kidney podocytes in health and disease. Clin Sci (Lond). 2020;134(11):1245–1253. doi: 10.1042/CS20190764
   PubMed Web of Science ®Google Scholar
• Nagata M. Podocyte injury and its consequences. Kidney Int. 2016;89(6):1221–1230. doi: 10.1016/j.kint.2016.01.012
   PubMed Web of Science ®Google Scholar
• Shibata S, Nagase M, Yoshida S, et al. Podocyte as the target for aldosterone: roles of oxidative stress and SGK1. Hypertension. 2007;49(2):355–364. doi: 10.1161/01.HYP.0000255636.11931.a2
   PubMed Web of Science ®Google Scholar
• Parker BM, Wertz SL, Pollard CM, et al. Novel insights into the crosstalk between mineralocorticoid receptor and G protein-coupled receptors in heart adverse remodeling and disease. Int J Mol Sci. 2018;19(12):3764. doi: 10.3390/ijms19123764
   PubMed Web of Science ®Google Scholar
• Mihailidou AS, Funder JW. Nongenomic effects of mineralocorticoid receptor activation in the cardiovascular system. Steroids. 2005;70(5–7):347–351. doi: 10.1016/j.steroids.2005.02.004
   PubMed Web of Science ®Google Scholar
• Maning J, KA M, Pollard CM. Antagonistic roles of GRK2 and GRK5 in cardiac aldosterone signaling reveal GRK5-mediated cardioprotection via mineralocorticoid receptor inhibition. Int J Mol Sci. 2020;21(8):2868. doi: 10.3390/ijms21082868
   PubMed Web of Science ®Google Scholar
• Buonafine M, Bonnard B, Jaisser F. Mineralocorticoid receptor and cardiovascular disease. Am J Hypertens. 2018;31(11):1165–1174. doi: 10.1093/ajh/hpy120
   PubMed Web of Science ®Google Scholar
• Ito S, Kashihara N, Shikata K, et al. 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):1715–1727. doi: 10.2215/CJN.06870520
   PubMed Web of Science ®Google Scholar
• Wada T, Inagaki M, Yoshinari T, et al. Apararenone in patients with diabetic nephropathy: results of a randomized, double-blind, placebo-controlled phase 2 dose-response study and open-label extension study. Clin Exp Nephrol. 2021;25(2):120–130. doi: 10.1007/s10157-020-01963-z
   PubMed Web of Science ®Google Scholar
• Orena S, Maurer TS, She L, et al. PF-03882845, a non-steroidal mineralocorticoid receptor antagonist, prevents renal injury with reduced risk of hyperkalemia in an animal model of nephropathy. Front Pharmacol. 2013;4:115. doi: 10.3389/fphar.2013.00115
   PubMed Web of Science ®Google Scholar
• BLOCK-CKD Study Group, Bakris G, Pergola PE, et al. Effect of KBP-5074 on blood pressure in advanced chronic kidney disease: results of the BLOCK-CKD study. Hypertension. 2021;78(1):74–81.
   PubMed Web of Science ®Google Scholar
• Bakris GL, Yang YF, McCabe JM, et al. Efficacy and safety of ocedurenone: subgroup analysis of the BLOCK-CKD study. Am J Hypertens. 2023;36(11):612–618. doi: 10.1093/ajh/hpad066
   PubMed Web of Science ®Google Scholar
• Laffin LJ, Rodman D, Luther JM, et al. Aldosterone synthase inhibition with lorundrostat for uncontrolled hypertension: the target-HTN randomized clinical trial. JAMA. 2023;330(12):1140–1150. doi: 10.1001/jama.2023.16029
   PubMed Web of Science ®Google Scholar
• Rossing P, Strand J, Avogaro A, et al. Effects of the chymase inhibitor fulacimstat in diabetic kidney disease-results from the CADA DIA trial. Nephrol Dial Transplant. 2021;36(12):2263–2273. doi: 10.1093/ndt/gfaa299
   PubMed Web of Science ®Google Scholar
• Miller MC, Mayo KH. Chemokines from a structural perspective. Int J Mol Sci. 2017;18(10):2088. doi: 10.3390/ijms18102088
   PubMed Web of Science ®Google Scholar
• Hughes CE, Nibbs RJB. A guide to chemokines and their receptors. FEBS J. 2018;285(16):2944–2971. doi: 10.1111/febs.14466
   PubMed Web of Science ®Google Scholar
• Flanagan K, Kaufman HL. Chemokines and cancer. Cancer Invest. 2002;20(5–6):825–834. doi: 10.1081/CNV-120003548
   PubMed Web of Science ®Google Scholar
• Vilgelm AE, Richmond A. Chemokines modulate immune surveillance in tumorigenesis, metastasis, and response to immunotherapy. Front Immunol. 2019;10:333. doi: 10.3389/fimmu.2019.00333
   PubMed Web of Science ®Google Scholar
• Anders HJ, Vielhauer V, Schlöndorff D. Chemokines and chemokine receptors are involved in the resolution or progression of renal disease. Kidney Int. 2003;63(2):401–415. doi: 10.1046/j.1523-1755.2003.00750.x
   PubMed Web of Science ®Google Scholar
• Rayego-Mateos S, Morgado-Pascual JL, Opazo-Ríos L, et al. Pathogenic pathways and therapeutic approaches targeting inflammation in diabetic nephropathy. Int J Mol Sci. 2020;21(11):3798. doi: 10.3390/ijms21113798
   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(4):772–777. doi: 10.1016/j.bbrc.2007.06.148
   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 Transplant. 2017;32(2):307–315. doi: 10.1093/ndt/gfv459
   PubMed Web of Science ®Google Scholar
• Heerspink HJL, Law G, Psachoulia K, et al. Design of FLAIR: a phase 2b study of the 5-lipoxygenase activating protein inhibitor AZD5718 in patients with proteinuric CKD. Kidney Int Rep. 2021;6(11):2803–2810. doi: 10.1016/j.ekir.2021.08.018
   PubMed Web of Science ®Google Scholar
• Brosius FC, Tuttle KR, Kretzler M. JAK inhibition in the treatment of diabetic kidney disease. Diabetologia. 2016;59(8):1624–1627. doi: 10.1007/s00125-016-4021-5
   PubMed Web of Science ®Google Scholar
• Broderick C, Forster R, Abdel-Hadi M, et al. Pentoxifylline for intermittent claudication. Cochrane Database Of Syst Rev. 2020;(10):CD005262. doi: 10.1002/14651858.CD005262.pub4
   PubMed Web of Science ®Google Scholar
• Graninger W, Wenisch C. Pentoxifylline in severe inflammatory response syndrome. J Cardiovasc Pharmacol. 1995;25 Suppl 2:S134–8. doi: 10.1097/00005344-199500252-00028
   PubMed Web of Science ®Google Scholar
• Donate-Correa J, Tagua VG, Ferri C, et al. Pentoxifylline for renal protection in diabetic kidney disease. A model of old drugs for new horizons. J Clin Med. 2019;27(8):287. doi: 10.3390/jcm8030287
   Google Scholar
• Shan D, Wu HM, Yuan QY, et al. Pentoxifylline for diabetic kidney disease. Cochrane Database Syst Rev. 2012 2;CD006800. doi: 10.1002/14651858.CD006800.pub2
   PubMed Web of Science ®Google Scholar
• Leehey DJ, Carlson K, Reda DJ, et al. Pentoxifylline in diabetic kidney disease (VA PTXRx): protocol for a pragmatic randomised controlled trial. BMJ Open. 2021;11(8):e053019. doi: 10.1136/bmjopen-2021-053019
   PubMedGoogle 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(4):314–325. doi: 10.1002/cpdd.241
   PubMed Web of Science ®Google Scholar
• Fiorucci S, Biagioli M, Sepe V, et al. Bile acid modulators for the treatment of nonalcoholic steatohepatitis (NASH). Expert Opin Investig Drugs. 2020;29(6):623–632. doi: 10.1080/13543784.2020.1763302
   PubMed Web of Science ®Google Scholar
• Harrison SA, Wong VW, Okanoue T. STELLAR-4 investigators. Selonsertib for patients with bridging fibrosis or compensated cirrhosis due to NASH: results from randomized phase III STELLAR trials. J Hepatol. 2020;73(1):26–39. doi: 10.1016/j.jhep.2020.02.027
   PubMed Web of Science ®Google Scholar
• Jones D, Carbone M, Invernizzi P, et al. Impact of setanaxib on quality of life outcomes in primary biliary cholangitis in a phase 2 randomized controlled trial. Hepatol Commun. 2023;7(3):e0057. doi: 10.1097/HC9.0000000000000057
   PubMed Web of Science ®Google Scholar
• Chianelli D, Rucker PV, Roland J, et al. Nidufexor (LMB763), a novel FXR modulator for the treatment of nonalcoholic steatohepatitis. J Med Chem. 2020;63(8):3868–3880. doi: 10.1021/acs.jmedchem.9b01621
   PubMed Web of Science ®Google Scholar
• de Zeeuw D, Akizawa T, Audhya P, et al. BEACON trial investigators. Bardoxolone methyl in type 2 diabetes and stage 4 chronic kidney disease. N Engl J Med. 2013;369(26):2492–2450. doi: 10.1056/NEJMoa1306033
   PubMed Web of Science ®Google Scholar
• Chin MP, Wrolstad D, Bakris GL, et al. Risk factors for heart failure in patients with type 2 diabetes mellitus and stage 4 chronic kidney disease treated with bardoxolone methyl. J Card Fail. 2014;20(12):953–958. doi: 10.1016/j.cardfail.2014.10.001
   PubMed Web of Science ®Google Scholar
• Available from: https://www.kyowakirin.com/media_center/news_releases/2023
   Google Scholar
• Kang Y, Liu R, Wu JX, et al. Structural insights into the mechanism of human soluble guanylate cyclase. Nature. 2019;574:206–210. doi: 10.1038/s41586-019-1584-6
   PubMed Web of Science ®Google Scholar
• Koress C, Swan K, Kadowitz P. Soluble guanylate cyclase stimulators and activators: novel therapies for pulmonary vascular disease or a different method of increasing cGMP? Curr Hypertens Rep. 2016;18(5):42. doi: 10.1007/s11906-016-0645-6
   PubMed Web of Science ®Google Scholar
• Dasgupta A, Bowman L, D’Arsigny CL, et al. Soluble guanylate cyclase: a new therapeutic target for pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. Clin Pharmacol Ther. 2015;97(1):88–102. doi: 10.1002/cpt.10
   PubMed Web of Science ®Google Scholar
• Reinhart GA, Harrison PC, Lincoln K. The novel, clinical-stage soluble guanylate cyclase activator BI 685509 protects from disease progression in models of renal injury and disease. J Pharmacol Exp Ther. 2023;384(3):382–392. doi: 10.1124/jpet.122.001423
   PubMed Web of Science ®Google Scholar
• PERL Study Group, Doria A, Galecki AT, et al. Serum urate lowering with allopurinol and kidney function in type 1 diabetes. N Engl J Med. 2020;382(26):2493–2503.
   PubMed Web of Science ®Google Scholar
• Chua JT, Argueta DA, DiPatrizio NV, et al. Endocannabinoid system and the kidneys: from renal physiology to injury and disease. Cannabis Cannabinoid Res. 2019;4(1):10–20. doi: 10.1089/can.2018.0060
   PubMedGoogle Scholar
• Jourdan T, Park JK, Varga ZV, et al. Cannabinoid-1 receptor deletion in podocytes mitigates both glomerular and tubular dysfunction in a mouse model of diabetic nephropathy. Diab Obes Metab. 2018;20(3):698–708. doi: 10.1111/dom.13150
   PubMed Web of Science ®Google Scholar
• Rubaiy HN. Treasure troves of pharmacological tools to study transient receptor potential canonical 1/4/5 channels. Br J Pharmacol. 2019;176(7):832–846. doi: 10.1111/bph.14578
   PubMed Web of Science ®Google Scholar
• Available from: https://www.businesswire.com/news/home/20220228005093/en/Goldfinch-Bio-Announces-Positive-Preliminary-Data-from-Phase-2-Clinical-Trial-Evaluating-GFB-887-as-a-Precision-Medicine-for-Patients-with-Focal-Segmental-Glomerular-Sclerosis-FSGS
   Google Scholar
• Dhaun N, Goddard J, Webb D. The endothelin system and its antagonism in chronic kidney disease. J Am Soc Nephrol. 2006;17(4):943–955. doi: 10.1681/ASN.2005121256
   PubMed Web of Science ®Google Scholar
• Kohan DE, Barton M. Endothelin and endothelin antagonists in chronic kidney disease. Kidney Int. 2014;86(5):896–904. doi: 10.1038/ki.2014.143
   PubMed Web of Science ®Google Scholar
• Schneider MP, Boesen EI, Pollock DM. Contrasting actions of endothelin ETA and ETB receptors in cardiovascular disease. Annu Rev Pharmacol Toxicol. 2007;47(1):731–759. doi: 10.1146/annurev.pharmtox.47.120505.105134
   PubMedGoogle Scholar
• Vercauteren M, Trensz F, Pasquali A, et al. Endothelin ETA receptor blockade, by activating ETB receptors, increases vascular permeability and induces exaggerated fluid retention. J Pharmacol Exp Ther. 2017;361(2):322–333. doi: 10.1124/jpet.116.234930
   PubMed Web of Science ®Google Scholar
• Gomez-Garre D, Ruiz-Ortega M, Ortego M, et al. Effects and interactions of endothelin-1 and angiotensin II on matrix protein expression and synthesis and mesangial cell growth. Hypertension. 1996;27(4):885–892. doi: 10.1161/01.HYP.27.4.885
   PubMed Web of Science ®Google Scholar
• Opocenský M, Kramer HJ, Bäcker A, et al. Late-onset endothelin-a receptor blockade reduces podocyte injury in homozygous ren-2 rats despite severe hypertension. Hypertension. 2006;48(5):965–971. doi: 10.1161/01.HYP.0000245117.57524.d6
   PubMed Web of Science ®Google Scholar
• Gagliardini E, Corna D, Zoja C, et al. Unlike each drug alone, lisinopril if combined with avosentan promotes regression of renal lesions in experimental diabetes. Am J Physiol Renal Physiol. 2009;297(5):F1448–F1456. doi: 10.1152/ajprenal.00340.2009
   PubMed Web of Science ®Google Scholar
• Ortmann J, Amann K, Brandes RP, et al. Role of podocytes for reversal of glomerulosclerosis and proteinuria in the aging kidney after endothelin inhibition. Hypertension. 2004;44(6):974–981. doi: 10.1161/01.HYP.0000149249.09147.b4
   PubMed Web of Science ®Google Scholar
• Chung EYM, Badve SV, Heerspink HJL, et al. Endothelin receptor antagonists in kidney protection for diabetic kidney disease and beyond? Nephrology (Carlton). 2023;28(2):97–108. doi: 10.1111/nep.14130
   PubMed Web of Science ®Google Scholar
• Heerspink HJL, Parving HH, Andress DL, et al. SONAR committees and investigators. 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):1937–1947. doi: 10.1016/S0140-6736(19)30772-X
   PubMed Web of Science ®Google Scholar
• Komers R, Diva U, Inrig JK, et al. Study design of the phase 3 sparsentan versus irbesartan (DUPLEX) study in patients with focal segmental glomerulosclerosis. Kidney Int Rep. 2020;5(4):494–502. doi: 10.1016/j.ekir.2019.12.017
   PubMed Web of Science ®Google Scholar
• Available from: https://nephcure.org/2023/05/travere-therapeutics-announces-results-from-duplex-study-in-fsgs/#:~:text=More%20than%202x%20greater%20remission%20rate%20%E2%80%94%2018%25,with%20a%20consistent%20safety%20profile%20comparable%20to%20irbesartan.SyedYY.
   Google Scholar
• Heerspink HJL, Radhakrishnan J, Alpers CE, et al. PROTECT Investigators.Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomised, double-blind, active-controlled clinical trial. Lancet. 2023;401(10388):1584–1594. doi: 10.1016/S0140-6736(23)00569-X
   PubMed Web of Science ®Google Scholar
• Syed YY. Sparsentan: First approval. Drugs. 2023;83(6):563–568.
   PubMed Web of Science ®Google Scholar
• Rangaswami J, Bhalla V, Blair JE, et al. Cardiorenal syndrome: classification, pathophysiology, diagnosis, and treatment strategies: a scientific statement from the American heart association. Circulation. 2019;139(16):e840–e878. doi: 10.1161/CIR.0000000000000664.
   PubMed Web of Science ®Google Scholar
• Li X, Hongli W, Huifang P, et al. Comparison the effects of finerenone and SGLT2i on cardiovascular and renal outcomes in patients with type 2 diabetes mellitus: a network meta-analysis.Frontiers in endocrinology. Front Endocrinol (Lausanne). 2022;13:1078686. doi: 10.3389/fendo.2022.1078686
   PubMed Web of Science ®Google Scholar
• Green JB, Mottl AK, Bakris G, et al. Design of the COmbinatioN effect of FInerenone and EmpaglifloziN in participants with chronic kidney disease and type 2 diabetes using a UACR endpoint study (CONFIDENCE). Nephrol Dial Transplant. 2023;38(4):894–903. doi: 10.1093/ndt/gfac198
   PubMed Web of Science ®Google Scholar
• Available from: https://classic.clinicaltrials.gov/ct2/show/NCT05254002
   Google Scholar