钠-葡萄糖共转运蛋白2抑制剂治疗慢性肾脏病的研究进展

蔓 董(承德医学院附属医院肾脏内科，中国)
万欣 陈(承德医学院附属医院肾脏内科，中国)

摘要

慢性肾脏病（CKD）在全球范围内呈上升趋势，目前对于保护CKD患者肾功能的治疗主要包括应用肾素-血管紧张素-醛固酮系统抑制剂（RASi）、醛固酮受体拮抗剂（MRA）以及钠-葡萄糖共转运蛋白2抑制剂（SGLT2i），近年来SGLT2i应用于CKD的治疗成为研究热点，SGLT2i具有多效性，除了降低血糖，对血压、体重、血脂、肝功能有有益作用外，还能减低血清尿酸、减少白蛋白尿、减少足细胞损伤、改善肾脏缺氧保护肾功能，论文就SGLT2i对于肾脏研究实验进展及潜在的肾脏保护机制进行综述。

关键词

钠-葡萄糖共转运蛋白；2（SGLT-2）抑制剂；慢性肾脏病

参考

Khan, M.A.B., Hashim, M.J., King, J.K., Govender, R.D., Mustafa, H., Al Kaabi, J. Epidemiology of Type 2 Diabetes—Global Burden of Disease and Forecasted Trends[J]. J. Epidemiol. Glob. Health, 2020(10): 107-111.

Group E.-K.C. Design, recruitment, and baseline characteristics of the EMPA-KIDNEY trial[J]. Nephrol. Dial. Transplant, 2022(37): 1317-1329.

Heerspink H.J.L., Stefansson B.V., Correa-Rotter R., Chertow G.M., Greene T., Hou F.F., Mann J.F.E., McMurray J.J.V., Lindberg M., Rossing P., et al. Dapagliflozin in Patients with Chronic Kidney Disease[J]. N. Engl. J. Med, 2020(383): 1436-1446.

Perkovic V., Jardine M.J., Neal B., Bompoint S., Heerspink H.J.L., Charytan D.M., Edwards R., Agarwal R., Bakris G., Bull S., et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy[J]. N. Engl. J. Med, 2019(380): 2295-2306.

Busch M., Franke S., Ruster C., Wolf G. Advanced glycation end-products and the kidney[J]. Eur. J. Clin. Investig, 2010(40) :742-755.

Kahn B.B., Shulman G.I., DeFronzo R.A., Cushman S.W., Rossetti L. Normalization of blood glucose in diabetic rats with phlorizin treatment reverses insulin-resistant glucose transport in adipose cells without restoring glucose transporter gene expression[J]. J. Clin. Investig, 1991(87): 561-570.

Vasilakou D., Karagiannis T., Athanasiadou E., Mainou M., Liakos A., Bekiari E., Sarigianni M., Matthews D.R., Tsapas A. Sodium-glucose cotransporter 2 inhibitors for type 2 diabetes: A systematic review and meta-analysis[J]. Ann. Intern. Med, 2013(159): 262-274.

Cherney D.Z., Perkins B.A., Soleymanlou N., Maione M., Lai V., Lee A., Fagan N.M., Woerle H.J., Johansen O.E., Broedl U.C., et al. Renal hemodynamic effect of sodium-glucose cotransporter 2 inhibition in patients with type 1 diabetes mellitus[J]. Circulation, 2014(129): 587-597.

Van Bommel E. J. M., Muskiet M. H. A., van Baar M. J. B., Tonneijck L., Smits M. M., Emanuel A. L., Bozovic A., Danser A. H. J., Geurts F., Hoorn E. J., et al. The renal hemodynamic effects of the SGLT2 inhibitor dapagliflozin are caused by post-glomerular vasodilatation rather than pre-glomerular vasoconstriction in metformin-treated patients with type 2 diabetes in the randomized, double-blind RED trial[J]. Kidney Int, 2020(97): 202-212.

Heerspink H.J.L., Stefansson B.V., Chertow G.M., Correa-Rotter R., Greene T., Hou F.F., Lindberg M., McMurray J., Rossing P., Toto R., et al. Rationale and protocol of the Dapagliflozin And Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD) randomized controlled trial[J]. Nephrol. Dial. Transplant, 2020(35): 274-282.

Neal B., Perkovic V., Mahaffey K.W., de Zeeuw D., Fulcher G., Erondu N., Shaw W., Law G., Desai M., Matthews D.R., et al. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes[J]. N. Engl. J. Med, 2017(377): 644-657.

Perkovic V., Jardine M.J., Neal B., Bompoint S., Heerspink H.J.L., Charytan D.M., Edwards R., Agarwal R., Bakris G., Bull S., et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy[J]. N. Engl. J. Med, 2019(380): 2295-2306.

Wheeler D.C., Stefansson B.V., Jongs N., Chertow G.M., Greene T., Hou F.F., McMurray J.J.V., Correa-Rotter R., Rossing P., Toto R.D., et al. Effects of dapagliflozin on major adverse kidney and cardiovascular events in patients with diabetic and non-diabetic chronic kidney disease: A prespecified analysis from the DAPACKD trial[J]. Lancet Diabetes Endocrinol, 2021(9): 22-31.

Richette P., Perez-Ruiz F., Doherty M., Jansen T.L., Nuki G., Pascual E., Punzi L., So A.K., Bardin T. Improving cardiovascular and renal outcomes in gout: What should we target?[J].Nat. Rev. Rheumatol, 2014(10): 654-661.

Chino Y., Samukawa Y., Sakai S., Nakai Y., Yamaguchi J., Nakanishi T., Tamai I. 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): 391-404.

Anders H.J., Davis J.M., Thurau K. Nephron Protection in Diabetic Kidney Disease[J]. N. Engl. J. Med, 2016(375): 2096-2098.

DOI: http://dx.doi.org/10.12345/yzlcyxzz.v7i1.15604