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SGLT-2 inhibitors and nephroprotection: current evidence and future perspectives

Journal of Human Hypertension volume 35, pages 12–25 (2021)Cite this article

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Abstract

Chronic kidney disease (CKD) is a major public health issue and an independent risk factor for cardiovascular and all-cause mortality. Diabetic kidney disease develops in 30–50% of diabetic patients and it is the leading cause of end-stage renal disease in the Western world. Strict blood pressure control and renin-angiotensin system (RAS) blocker use are the cornerstones of CKD treatment; however, their application in everyday clinical practice is not always ideal and in many patients CKD progression still occurs. Accumulated evidence in the past few years clearly suggests that sodium-glucose co-transporter-2 (SGLT-2) inhibitors present potent nephroprotective properties. In clinical trials in patients with type 2 diabetes mellitus, these agents were shown to reduce albuminuria and proteinuria by 30–50% and the incidence of composite hard renal outcomes by 40–50%. Furthermore, their mechanism of action appears rather solid, as they interfere with the major mechanism of proteinuric CKD progression, i.e., glomerular hypertension and hyperfiltration. The present review summarizes the current evidence from human trials on the effects of SGLT-2 inhibitors on nephroprotection and discusses their position in everyday clinical practice.

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Fig. 1: Weighted mean difference in change in UACR (mg/g).
Fig. 2: Possible mechanism for nephroprotection offered by SGLT-2 inhibitors in diabetic kidney disease.

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Authors and Affiliations

  1. Department of Nephrology, Hippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece

    Alexia Piperidou, Charalampos Loutradis & Pantelis Sarafidis

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  1. Alexia Piperidou
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  2. Charalampos Loutradis
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  3. Pantelis Sarafidis
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Correspondence to Pantelis Sarafidis.

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AP have not any financial or other relationships, which might lead to a conflict of interest regarding this paper. CL received scholarship from the Hellenic Society for Medical Education. PS is an advisor/speaker to Amgen, Astra Zeneca, Bayer, Boehringer Ingelheim, Elpen Pharmaceuticals, Genesis Pharma, Menarini, Innovis Pharma, Winmedica and has received research support for an Investigator-Initiated Study from Astra Zeneca.

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Piperidou, A., Loutradis, C. & Sarafidis, P. SGLT-2 inhibitors and nephroprotection: current evidence and future perspectives. J Hum Hypertens 35, 12–25 (2021). https://doi.org/10.1038/s41371-020-00393-4

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