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The FimAsartaN proTeinuriA SusTaIned reduCtion in comparison with losartan in diabetic chronic kidney disease (FANTASTIC) trial

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Abstract

As angiotensin II type 1 receptor blockers (ARBs) may have different antiproteinuric effects in diabetic kidney disease (DKD), we ascertained the albuminuria-reducing effect of fimasartan and losartan in patients with DKD. This was a randomized, multicenter, double-blind, 4-parallel-group, dose-titration, phase III study designed to compare the efficacy of fimasartan and losartan in reducing albuminuria in patients with DKD (NCT02620306). The primary endpoint was the rate of change in albuminuria from baseline to week 24. A total of 341 patients were randomized to different groups. The urinary albumin-to-creatinine ratio (ACR), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were not different between the fimasartan and losartan groups at baseline (ACR: 1376.84 vs. 1521.07 mg/gCr, SBP: 154.69 vs. 154.47 mmHg, DBP: 83.96 vs. 83.83 mmHg). However, ACR reduction was significantly larger in the fimasartan group than in the losartan group during the entire study period (% changes in the ACR at 4, 8, 12, and 24 weeks were –23.58, –33.06, –35.00, and –38.13 in the fimasartan group vs. –8.74, –10.17, –14.91, and –19.71 in the losartan group, p < 0.01, respectively). The superior antiproteinuric effect of fimasartan compared to losartan was still significant after adjustment for SBP levels. There were no significant differences in adverse events, including the incidences of estimated glomerular filtration decline and hyperkalemia. This study demonstrates that compared to losartan, fimasartan significantly reduces albuminuria in patients with DKD, even after adjustment for SBP and DBP.

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References

  1. Hong YA, Ban TH, Kang CY, Hwang SD, Choi SR, Lee H, et al. Trends in epidemiologic characteristics of end-stage renal disease from 2019 Korean Renal Data System (KORDS). Kidney Res Clin Pract. 2021;40:52–61.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Atkins RC, Briganti EM, Lewis JB, Hunsicker LG, Braden G, Champion de Crespigny PJ, et al. Proteinuria reduction and progression to renal failure in patients with type 2 diabetes mellitus and overt nephropathy. Am J Kidney Dis. 2005;45:281–7.

    Article  PubMed  Google Scholar 

  3. Berl T, Hunsicker LG, Lewis JB, Pfeffer MA, Porush JG, Rouleau JL, et al. Cardiovascular outcomes in the Irbesartan Diabetic Nephropathy Trial of patients with type 2 diabetes and overt nephropathy. Ann Intern Med. 2003;138:542–9.

    Article  CAS  PubMed  Google Scholar 

  4. Gross JL, de Azevedo MJ, Silveiro SP, Canani LH, Caramori ML, Zelmanovitz T. Diabetic nephropathy: diagnosis, prevention, and treatment. Diabetes Care. 2005;28:164–76.

    Article  PubMed  Google Scholar 

  5. de Zeeuw D, Remuzzi G, Parving HH, Keane WF, Zhang Z, Shahinfar S, et al. Proteinuria, a target for renoprotection in patients with type 2 diabetic nephropathy: lessons from RENAAL. Kidney Int. 2004;65:2309–20.

    Article  PubMed  Google Scholar 

  6. Eijkelkamp WB, Zhang Z, Remuzzi G, Parving HH, Cooper ME, Keane WF, et al. Albuminuria is a target for renoprotective therapy independent from blood pressure in patients with type 2 diabetic nephropathy: post hoc analysis from the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) trial. J Am Soc Nephrol. 2007;18:1540–6.

    Article  CAS  PubMed  Google Scholar 

  7. Coresh J, Heerspink HJL, Sang Y, Matsushita K, Arnlov J, Astor BC, et al. 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;7:115–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001;345:861–9.

    Article  CAS  PubMed  Google Scholar 

  9. Parving HH, Hommel E, Smidt UM. Protection of kidney function and decrease in albuminuria by captopril in insulin dependent diabetics with nephropathy. BMJ. 1988;297:1086–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Whelton PK, Carey RM, Aronow WS, Casey DE,Jr., Collins KJ, Dennison Himmelfarb C. et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2018;138:e426–e483.

    PubMed  Google Scholar 

  11. Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J. 2018;39:3021–104.

    Article  PubMed  Google Scholar 

  12. Yoo TH, Li JJ, Kim JJ, Jung DS, Kwak SJ, Ryu DR, et al. Activation of the renin-angiotensin system within podocytes in diabetes. Kidney Int. 2007;71:1019–27.

    Article  CAS  PubMed  Google Scholar 

  13. Lee SH, Yoo TH, Nam BY, Kim DK, Li JJ, Jung DS, et al. Activation of local aldosterone system within podocytes is involved in apoptosis under diabetic conditions. Am J Physiol Ren Physiol. 2009;297:F1381–1390.

    Article  CAS  Google Scholar 

  14. Kim JY, Son JW, Park S, Yoo TH, Kim YJ, Ryu DR, et al. FimAsartaN proTeinuriA SusTaIned reduCtion in comparison with losartan in diabetic chronic kidney disease (FANTASTIC): study protocol for randomized controlled trial. Trials. 2017;18:632.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Lee HY, Oh BH. Fimasartan: a new angiotensin receptor blocker. Drugs. 2016;76:1015–22.

    Article  CAS  PubMed  Google Scholar 

  16. Levey AS, Coresh J, Greene T, Stevens LA, Zhang YL, Hendriksen S, et al. Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med. 2006;145:247–54.

    Article  CAS  PubMed  Google Scholar 

  17. Bakris G, Burgess E, Weir M, Davidai G, Koval S. Telmisartan is more effective than losartan in reducing proteinuria in patients with diabetic nephropathy. Kidney Int. 2008;74:364–9.

    Article  CAS  PubMed  Google Scholar 

  18. Lee SE, Kim YJ, Lee HY, Yang HM, Park CG, Kim JJ, et al. Efficacy and tolerability of fimasartan, a new angiotensin receptor blocker, compared with losartan (50/100 mg): a 12-week, phase III, multicenter, prospective, randomized, double-blind, parallel-group, dose escalation clinical trial with an optional 12-week extension phase in adult Korean patients with mild-to-moderate hypertension. Clin Ther. 2012;34:552–68. 568.e551-559

    Article  CAS  PubMed  Google Scholar 

  19. Kim TW, Yoo BW, Lee JK, Kim JH, Lee KT, Chi YH, et al. Synthesis and antihypertensive activity of pyrimidin-4(3H)-one derivatives as losartan analogue for new angiotensin II receptor type 1 (AT1) antagonists. Bioorg Med Chem Lett. 2012;22:1649–54.

    Article  CAS  PubMed  Google Scholar 

  20. Paik SH, Chi YH, Lee JH, Han HS, Lee KT. Pharmacological profiles of a highly potent and long-acting angiotensin ii receptor antagonist, fimasartan, in rats and dogs after oral administration. Biol Pharm Bull. 2017;40:992–1001.

    Article  CAS  PubMed  Google Scholar 

  21. Kim S, Kim SJ, Yoon HE, Chung S, Choi BS, Park CW, et al. Fimasartan, a novel angiotensin-receptor blocker, protects against renal inflammation and fibrosis in mice with unilateral ureteral obstruction: the possible role of Nrf2. Int J Med Sci. 2015;12:891–904.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Heerspink HJL, Greene T, Tighiouart H, Gansevoort RT, Coresh J, Simon AL, et al. Change in albuminuria as a surrogate endpoint for progression of kidney disease: a meta-analysis of treatment effects in randomised clinical trials. Lancet Diabetes Endocrinol. 2019;7:128–39.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This study was supported by Boryung Co., Ltd., Seoul, Korea. The sponsor supported the supply of investigational products, laboratory tests, and expenses incurred for clinical research coordination and data analyses.

We would also like to thank Seung Hwan Han MD, PhD; Jae-Hyun Chang MD, PhD; Bum-Soon Choi MD, PhD; Il-Suk Sohn MD, PhD; Ki Chul Sung MD, PhD; Chan-Duck Kim MD, PhD; Ea Wha Kang MD, PhD; Moo-Yong Rhee MD, PhD; Jae Yoon Park MD, PhD; Cheol Ho Kim MD, PhD; Hu Jun Chin MD, PhD; Seok Yeon Kim MD; Jang-Young Kim MD, PhD; Kihwan Kwon MD, PhD; Dong-Ryeol Ryu MD, PhD; Sung Yun Lee MD, PhD; Eun Hui Bae MD, PhD; Jin-ok Jeong MD, PhD; Jinho Shin MD, PhD; Sang Heon Song MD, PhD; Su-Hyun Kim MD, PhD; Kee Ho Song MD, PhD; Young Min Cho MD, PhD; Dae Jung Kim ME, PhD; Jung Hyun Noh MD, PhD; Sang-Yong Kim MD, PhD; Sung Wan Chun MD, PhD; Hyung-Seop Kim MD, PhD; Ho Cheol Song MD, PhD; and Hyosang Kim MD, PhD for their valuable contributions to this study.

Funding

This study was supported by Boryung Co., Ltd., Seoul, Korea. SP received lecture fees from Pfizer, Boryoung, Hanmi, Daewoong, Donga, Celltrion, Servier, Daiichi Sankyo, and Daewon. SP also received a research grant from Daiichi Sankyo. YJK received consultation fees from Celltrion and lecture fees from Yuhan, Daewoong, Daiichi Sankyo, Bayer, Takeda, and GC Pharma. SJH received lecture fees and research sponsoring from Hanmi, InnoN, Samjin, and Boryung. SGK received lecture fees and research sponsorships from Yuhan, JW Pharma, AstraZeneca, GSK, Fibrogen, Akebia, Omeros, Chinook, MorphoSys, Otsuka and Boryung. JCW received lecture fees and research sponsorships from Chong Kun Dang, Daewoong, Eli Lilly, Yuhan, and Boryung.

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Authors and Affiliations

  1. Division of Nephrology, Severance Hospital, Seoul, Korea

    Tae-Hyun Yoo

  2. Department of Cardiology, Korea University Anam Hospital, Seoul, Korea

    Soon Jun Hong

  3. Division of Nephrology, Hallym University Sacred Heart Hospital, Ansan, Korea

    Sunggyun Kim

  4. Division of Nephrology, Incheon St. Mary’s Hospital, The Catholic University, Incheon, Korea

    Seokjoon Shin

  5. Division of Nephrology, Seoul National University Hospital, Seoul, Korea

    Dong Ki Kim

  6. Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea

    Jung Pyo Lee

  7. Division of Nephrology, Inje University Ilsan-Paik Hospital, Goyang, Korea

    Sang Youb Han

  8. Department of Nephrology, College of Medicine, Kyung Hee University, Seoul, Korea

    Sangho Lee

  9. Division of Endocrinology and Metabolism, Inje University Sanggye-Paik Hospital, Inje University School of Medicine, Seoul, Korea

    Jong Chul Won

  10. Division of Nephrology, Korea University Ansan Hospital, Ansan, Korea

    Young Sun Kang

  11. Division of Nephrology, Ulsan University Hospital, Ulsan, Korea

    Jongha Park

  12. Department of Nephrology, Yonsei University Wonju College of Medicine, Wonju, Korea

    Byoung-Geun Han

  13. Division of Nephrology, Chungnam National University Hospital, Daejeon, Korea

    Ki-Ryang Na

  14. Division of Endocrinology and Metabolism, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

    Kyu Yeon Hur

  15. Division of Cardiology, Seoul National University Hospital, Seoul, Korea

    Yong-Jin Kim

  16. Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Korea

    Sungha Park

Authors
  1. Tae-Hyun Yoo
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  2. Soon Jun Hong
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  15. Yong-Jin Kim
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  16. Sungha Park
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Contributions

SP made substantial contributions to the study design. THY contributed to manuscript writing and figure creation. All authors contributed equally to the data collection, data interpretation, and literature research and were involved in all stages of manuscript development.

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Correspondence to Sungha Park.

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Yoo, TH., Hong, S.J., Kim, S. et al. The FimAsartaN proTeinuriA SusTaIned reduCtion in comparison with losartan in diabetic chronic kidney disease (FANTASTIC) trial. Hypertens Res 45, 2008–2017 (2022). https://doi.org/10.1038/s41440-022-01028-6

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