USE OF SODIUM-GLUCOSE TRANSPORT PROTEIN 2 (SGLT2) INHIBITORS IN DIABETIC KIDNEY DISEASE (DKD)
DOI:
https://doi.org/10.53555/nnmhs.v9i4.1653Keywords:
Diabetic kidney disease, Glomerular filtration rate, SGLT2 inhibitors, SodiumAbstract
SGLT2 inhibitors have emerged as a major disease-modifying therapy for preventing the development of chronic kidney disease (CKD). These agents can be used to prevent the decline in renal function through the reduction of glomerular hypertension mediated through tubuloglomerular feedback apart from their effects on glycemic control. The indications for SGLT2 inhibitors have evolved based on growing evidence from randomized controlled trials and broadly fit into five categories, including: glycemic control/metabolic risk, reduced ASCVD, heart failure, diabetic kidney disease with albuminuria, and nondiabetic CKD with albuminuria. . The initial trial was performed in patients with relatively good overall renal function, although sub-analyses suggest that the beneficial effect may extend to patients with CKD. SGLT2 inhibitors block glucose reabsorption in the renal tubules and are effective in reducing glucose levels based on the amount of glucose filtered, thereby increasing the glomerular filtration rate. The greatest transport burden on the diabetic kidney is in the early proximal tubule. SGLT2 inhibitors make the transport load more evenly distributed between the tubular segments. In addition, the total tubular transport load is reduced by lowering GFR. The SGLT2 inhibitory effect helps maintain mitochondrial function and tubular cell metabolism which can maintain tubular function and GFR in the long term.
References
International Diabetes Federation. Diabetes. Brussels: IDF; 2017.
Evans K. Diabetic ketoacidosis: update on management. Clin Med. 2019 Sep;19(5):396–8.
Association AD. 15. Diabetes Care in the Hospital: Standards of Medical Care in Diabetes—2019. Diabetes Care
[Internet] 2018 Dec 7;42(Supplement_1):S173–81. Available from: https://doi.org/10.2337/dc19-S015
American Diabetes Association. Diagnosis and Classification of Diabetes Mellitus. Diabetes Care. 2016;62–9.
Soelistijo SA, Lindarto D, Decroli E, et al. Pedoman Pengelolaan dan Pencegahan Diabetes Melitus Tipe 2 Dewasa di Indonesia. Jakarta: PB Perkeni; 2021.
Patoulias D, Papadopoulos C, Stavropoulos K, et al. Prognostic value of arterial stiffness measurements in cardiovascular disease, diabetes, and its complications: The potential role of sodium-glucose co-transporter-2 inhibitors. J Clin Hypertens. 2020;22(4):562–71.
Inker LA, Astor BC, Fox CH, Isakova T, Lash JP, Peralta CA, et al. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for the evaluation and management of CKD. Am J kidney Dis Off J Natl Kidney Found. 2014 May;63(5):713–35.
Alicic RZ, Rooney MT, Tuttle KR. Diabetic kidney disease: challenges, progress, and possibilities. Clin J Am Soc Nephrol. 2017;12(12):2032–45.
Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):2095–128.
Sacks FM, Hermans MP, Fioretto P, Valensi P, Davis T, Horton E, et al. Association between plasma triglycerides and high-density lipoprotein cholesterol and microvascular kidney disease and retinopathy in type 2 diabetes mellitus: a global case–control study in 13 countries. Circulation. 2014;129(9):999–1008.
Stephens JW, Brown KE, Min T. Chronic kidney disease in type 2 diabetes: Implications for managing glycaemic control, cardiovascular and renal risk. Diabetes Obes Metab. 2020 Apr;22 Suppl 1:32–45.
Ni L, Yuan C, Chen G, Zhang C, Wu X. SGLT2i: beyond the glucose-lowering effect. Cardiovasc Diabetol. 2020 Jun;19(1):98.
Liu B, Wang Y, Zhang Y, Yan B. Mechanisms of Protective Effects of SGLT2 Inhibitors in Cardiovascular Disease and Renal Dysfunction. Curr Top Med Chem. 2019;19(20):1818–49.
Nespoux J, Vallon V. Renal effects of SGLT2 inhibitors: an update. Curr Opin Nephrol Hypertens. 2020 Mar;29(2):190–8.
Li H-L, Lip GYH, Feng Q, Fei Y, Tse Y-K, Wu M-Z, et al. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and cardiac arrhythmias: a systematic review and meta-analysis. Cardiovasc Diabetol. 2021 May;20(1):100.
Peng X, Li L, Zhang M, Zhao Q, Wu K, Bai R, et al. Sodium-Glucose Cotransporter 2 Inhibitors Potentially Prevent Atrial Fibrillation by Ameliorating Ion Handling and Mitochondrial Dysfunction. Front Physiol. 2020;11:912.
Verma S, McMurray JJ V. SGLT2 inhibitors and mechanisms of cardiovascular benefit: a state-of-the-art review. Diabetologia. 2018 Oct;61(10):2108–17.
Voors AA, Angermann CE, Teerlink JR, Collins SP, Kosiborod M, Biegus J, et al. The SGLT2 inhibitor empagliflozin in patients hospitalized for acute heart failure: a multinational randomized trial. Nat Med. 2022 Mar;28(3):568–74.
Wanner C, Lachin JM, Inzucchi SE, Fitchett D, Mattheus M, George J, et al. Empagliflozin and Clinical Outcomes in Patients With Type 2 Diabetes Mellitus, Established Cardiovascular Disease, and Chronic Kidney Disease. Circulation. 2018 Jan;137(2):119–29.
Wheeler DC, Stefánsson B V, Jongs N, Chertow GM, Greene T, Hou FF, 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 DAPA-CKD trial. lancet Diabetes Endocrinol. 2021 Jan;9(1):22–31.
Heerspink HJL, Stefánsson B V, Correa-Rotter R, Chertow GM, Greene T, Hou F-F, et al. Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2020 Oct;383(15):1436–46.
Perkovic V, Jardine MJ, Neal B, Bompoint S, Heerspink HJL, Charytan DM, et al. Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy. N Engl J Med. 2019 Jun;380(24):2295–306.
Jongs N, Greene T, Chertow GM, McMurray JJ V, Langkilde AM, Correa-Rotter R, et al. Effect of dapagliflozin on urinary albumin excretion in patients with chronic kidney disease with and without type 2 diabetes: a prespecified analysis from the DAPA-CKD trial. lancet Diabetes Endocrinol. 2021 Nov;9(11):755–66.
Wheeler DC, Stefansson B V, Batiushin M, Bilchenko O, Cherney DZI, Chertow GM, et al. The dapagliflozin and prevention of adverse outcomes in chronic kidney disease (DAPA-CKD) trial: baseline characteristics. Nephrol Dial Transplant Off Publ Eur Dial Transpl Assoc - Eur Ren Assoc. 2020 Oct;35(10):1700–11.
Bhatt DL, Szarek M, Pitt B, Cannon CP, Leiter LA, McGuire DK, et al. Sotagliflozin in Patients with Diabetes and Chronic Kidney Disease. N Engl J Med. 2021 Jan;384(2):129–39.
Agarwal R, Anker SD, Filippatos G, Pitt B, Rossing P, Ruilope LM, et al. Effects of canagliflozin versus finerenone on cardiorenal outcomes: exploratory post hoc analyses from FIDELIO-DKD compared to reported CREDENCE results. Nephrol Dial Transplant Off Publ Eur Dial Transpl Assoc - Eur Ren Assoc. 2022 Jun;37(7):1261–9.
Lytvyn Y, Bjornstad P, Udell JA, Lovshin JA, Cherney DZI. Sodium Glucose Cotransporter-2 Inhibition in Heart Failure: Potential Mechanisms, Clinical Applications, and Summary of Clinical Trials. Circulation. 2017 Oct;136(17):1643–58.
Kluger AY, Tecson KM, Barbin CM, Lee AY, Lerma E V, Rosol ZP, et al. Cardiorenal Outcomes in the CANVAS, DECLARE-TIMI 58, and EMPA-REG OUTCOME Trials: A Systematic Review. Rev Cardiovasc Med. 2018;19(2).
Neuen BL, Young T, Heerspink HJL, Neal B, Perkovic V, Billot L, et al. SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes: a systematic review and meta-analysis. lancet Diabetes Endocrinol. 2019;7(11):845–54.
Tian L, Cai Y, Zheng H, Ai S, Zhou M, Luo Q, et al. Canagliflozin for Prevention of Cardiovascular and Renal
Outcomes in Type2 Diabetes: a Systematic Review and Meta-Analysis of Randomized Controlled Trials. Front Pharmacol. 2021;12:691878.
Toyama T, Neuen BL, Jun M, Ohkuma T, Neal B, Jardine MJ, et al. Effect of SGLT2 inhibitors on cardiovascular, renal and safety outcomes in patients with type 2 diabetes mellitus and chronic kidney disease: a systematic review and meta‐analysis. Diabetes, Obes Metab. 2019;21(5):1237–50.
Layton AT, Vallon V. Renal tubular solute transport and oxygen consumption: insights from computational models. Curr Opin Nephrol Hypertens. 2018;27(5):384–9.
Castellana M, Procino F, Sardone R, Trimboli P, Giannelli G. Generalizability of sodium-glucose co-transporter-2 inhibitors cardiovascular outcome trials to the type 2 diabetes population: a systematic review and meta-analysis. Cardiovasc Diabetol. 2020;19(1):1–10.
Downloads
Published
Issue
Section
License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Licensing
Ninety Nine Publication publishes articles under the Creative Commons Attribution 4.0 International License (CC BY 4.0). This licensing allows for any use of the work, provided the original author(s) and source are credited, thereby facilitating the free exchange and use of research for the advancement of knowledge.
Detailed Licensing Terms
Attribution (BY): Users must give appropriate credit, provide a link to the license, and indicate if changes were made. Users may do so in any reasonable manner, but not in any way that suggests the licensor endorses them or their use.
No Additional Restrictions: Users may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.
