Research progress on the role of SGLT2 inhibitors in the treatment of chronic kidney disease

doi:10.3877/cma.j.issn.2095-3216.2021.06.007

Abstract

Abstract:

Chronic kidney disease (CKD) is a common disease that seriously endangers human health and life, with high morbidity and mortality. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new type of oral hypoglycemic agents. Studies have shown that SGLT2 inhibitors, in addition to lowering blood sugar, can also reduce creatinine and proteinuria to protect kidney function, which brings new ideas for delaying the disease progression of CKD patients. This article summarized the current research progress in the protective role and possible mechanism of SGLT2 in CKD, so as to provide theoretical support for the clinical application of SGLT2 inhibitors in the treatment of chronic kidney disease.

Key words: Chronic kidney disease, SGLT2 inhibitors, Dapagliflozin, Empagliflozin, Canagliflozin

Ting Xu, Chaojiang Su, Liting Liu, Yan Jiang, Yan Chen, Zongyang Liu, Shuai Zhang. Research progress on the role of SGLT2 inhibitors in the treatment of chronic kidney disease[J]. Chinese Journal of Kidney Disease Investigation(Electronic Edition), 2021, 10(06): 333-336.

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[1]	GBD Chronic Kidney Disease Collaboration. Global, regional, and national burden of chronic kidney disease, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017 [J]. Lancet, 2020, 395(10225): 709-733.
[2]	Heerspink HJ, Desai M, Jardine M, et al. Canagliflozin slows progression of renal function decline independently of glycemic effects [J]. J Am Soc Nephrol, 2017, 28(1): 368-375.
[3]	Alicic RZ, Johnson EJ, Tuttle KR. SGLT2 inhibition for the prevention and treatment of diabetic kidney disease: a review [J]. Am J Kidney Dis, 2018, 72(2): 267-277.
[4]	Chung S, Kim GH. Use of anti-diabetic agents in non-diabetic kidney disease: from bench to bedside [J]. Life (Basel), 2021, 11(5): 389.
[5]	Wheeler DC, Toto RD, Stefánsson BV, et al. A pre-specified analysis of the DAPA-CKD trial demonstrates the effects of dapagliflozin on major adverse kidney events in patients with IgA nephropathy [J]. Kidney Int, 2021, 100(1): 215-224.
[6]	Boeckhaus J, Gross O. Sodium-glucose cotransporter-2 inhibitors in patients with hereditary podocytopathies, Alport syndrome, and FSGS: a case series to better plan a large-scale study [J]. Cells, 2021, 10(7): 1815.
[7]	Wanner C, Inzucchi SE, Lachin JM, et al. Empagliflozin and progression of kidney disease in type 2 diabetes [J]. N Engl J Med, 2016, 375(4): 323-334.
[8]	Perkovic V, De Zeeuw D, Mahaffey KW, et al. Canagliflozin and renal outcomes in type 2 diabetes: results from the CANVAS program randomised clinical trials [J]. Lancet Diabetes Endocrinol, 2018, 6(9): 691-704.
[9]	Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes [J]. N Engl J Med, 2019, 380(4): 347-357.
[10]	Zelniker TA, Wiviott SD, Raz I, et al. SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials [J]. Lancet, 2019, 393(10166): 31-39.
[11]	Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy [J]. N Engl J Med, 2019, 380(24): 2295-2306.
[12]	Heerspink HJL, Stefansson BV, Correa-Rotter R, et al. Dapagliflozin in patients with chronic kidney disease [J]. N Engl J Med, 2020, 383(15): 1436-1446.
[13]	Herrington WG, Preiss D, Haynes R, et al. The potential for improving cardio-renal outcomes by sodium-glucose co-transporter-2 inhibition in people with chronic kidney disease: a rationale for the EMPA-KIDNEY study [J]. Clin Kidney J, 2018, 11(6): 749-761.
[14]	Kobayashi K, Toyoda M, Hatori N, et al. Retrospective analysis of the renoprotective effects of long-term use of six types of sodium-glucose cotransporter 2 inhibitors in Japanese patients with type 2 diabetes mellitus and chronic kidney disease [J]. Diabetes Technol Ther, 2021, 23(2): 110-119.
[15]	Wan N, Rahman A, Hitomi H, et al. The effects of sodium-glucose cotransporter 2 inhibitors on sympathetic nervous activity [J]. Front Endocrinol, 2018, 9: 421.
[16]	Packer M. Role of impaired nutrient and oxygen deprivation signaling and deficient autophagic flux in diabetic CKD development: implications for understanding the effects of sodium-glucose cotransporter 2-inhibitors [J]. J Am Soc Nephrol, 2020, 31(5): 907-919.
[17]	Heerspink HJL, Perco P, Mulder S, et al. Canagliflozin reduces inflammation and fibrosis biomarkers: a potential mechanism of action for beneficial effects of SGLT2 inhibitors in diabetic kidney disease [J]. Diabetologia, 2019, 62(7): 1154-1166.
[18]	Hussain M, Elahi A, Hussain A, et al. Sodium-glucose cotransporter-2 (SGLT-2) attenuates serum uric acid (SUA) level in patients with type 2 diabetes [J]. J Diabetes Res, 2021, 2021: 9973862.
[19]	Herat LY, Magno AL, Rudnicka C, et al. SGLT2 inhibitor-induced sympathoinhibition: a novel mechanism for cardiorenal protection [J]. JACC Basic Transl Sci, 2020, 5(2): 169-179.
[20]	Kaushal GP, Chandrashekar K, Juncos LA. Molecular interactions between reactive oxygen species and autophagy in kidney disease [J]. Int J Mol Sci, 2019, 20(15): 3791.
[21]	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 [J]. PLoS One, 2014, 9(6): e100777.
[22]	Udwan K, Abed A, Roth I, et al. Dietary sodium induces a redistribution of the tubular metabolic workload [J]. J Physiol, 2017, 595(22): 6905-6922.
[23]	Huang DY, Gao H, Boini KM, et al. In vivo stimulation of AMP-activated protein kinase enhanced tubuloglomerular feedback but reduced tubular sodium transport during high dietary NaCl intake [J]. Pflugers Arch, 2010, 460(1): 187-196.
[24]	Uthman L, Homayr A, Juni RP, et al. Empagliflozin and dapagliflozin reduce ROS generation and restore NO bioavailability in tumor necrosis factor α-stimulated human coronary arterial endothelial cells [J]. Cell Physiol Biochem, 2019, 53(5): 865-886.
[25]	Li L, Yang C, Zhao Y, et al. Is hyperuricemia an independent risk factor for new-onset chronic kidney disease? A systematic review and meta-analysis based on observational cohort studies [J]. BMC Nephrol, 2014, 15: 122.
[26]	Chino Y, Samukawa Y, Sakai S, et al. SGLT2 inhibitor lowers serum uric acid through alteration of uric acid transport activity in renal tubule by increased glycosuria [J]. Biopharm Drug Dispos, 2014, 35(7): 391-404.
[27]	郑淑芬，钟诗龙. SGLT2抑制剂不良反应信号的挖掘与评价[J]. 中国药房，2021, 32(8): 986-990.
[28]	Heerspink HJL, Oshima M, Zhang H, et al. Canagliflozin and kidney-related adverse events in type 2 diabetes and CKD: findings from the randomized CREDENCE trial [J]. Am J Kidney Dis, 2021, Epub ahead of print.
[29]	王翔宇，张倩，薛耀明. SGLT2抑制剂与肾脏安全性[J]. 中国实用内科杂志，2020, 40(8): 634-637.
[30]	Ye Y, Zhao C, Liang J, et al. Effect of sodium-glucose co-transporter 2 inhibitors on bone metabolism and fracture risk [J]. Front Pharmacol, 2018, 9: 1517.
[31]	Tang H, Dai Q, Shi W, et al. SGLT2 inhibitors and risk of cancer in type 2 diabetes: a systematic review and meta-analysis of randomised controlled trials [J]. Diabetologia, 2017, 60(10): 1862-1872.
[32]	Fitchett D. A safety update on sodium glucose co-transporter 2 inhibitors [J]. Diabetes Obes Metab, 2019, 21(Suppl 2): 34-42.

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