Renal Protection with SGLT2 Inhibitors: Effects in Acute and Chronic Kidney Disease

Clifford J. Bailey*, Caroline Day, Srikanth Bellary

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

Abstract

Purpose of Review: This review offers a critical narrative evaluation of emerging evidence that sodium-glucose co-transporter-2 (SGLT2) inhibitors exert nephroprotective effects in people with type 2 diabetes. Recent Findings: The SGLT2 inhibitor class of glucose-lowering agents has recently shown beneficial effects to reduce the onset and progression of renal complications in people with and without diabetes. Randomised clinical trials and ‘real world’ observational studies, mostly involving type 2 diabetes patients, have noted that use of an SGLT2 inhibitor can slow the decline in glomerular filtration rate (GFR), reduce the onset of microalbuminuria and slow or reverse the progression of proteinuria. Summary: The nephroprotective effects of SGLT2 inhibitors are class effects observed with each of the approved agents in people with a normal or impaired GFR. These effects are also observed in non-diabetic, lean and normotensive individuals suggesting that the mechanisms extend beyond the glucose-lowering, weight-lowering and blood pressure-lowering effects that accompany their glucosuric action in diabetes patients. A key mechanism is tubuloglomerular feedback in which SGLT2 inhibitors cause more sodium to pass along the nephron: the sodium is sensed by macula cells which act via adenosine to constrict afferent glomerular arterioles, thereby protecting glomeruli by reducing intraglomerular pressure. Other effects of SGLT2 inhibitors improve tubular oxygenation and metabolism and reduce renal inflammation and fibrosis. SGLT2 inhibitors have not increased the risk of urinary tract infections or the risk of acute kidney injury. However, introduction of an SGLT2 inhibitor in patients with a very low GFR is not encouraged due to an initial dip in GFR, and it is prudent to discontinue therapy if there is an acute renal event, hypovolaemia or hypotension.

Original languageEnglish
Pages (from-to)39-52
Number of pages14
JournalCurrent Diabetes Reports
Volume22
Issue number1
DOIs
Publication statusPublished - 3 Feb 2022

Bibliographical note

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Keywords

  • Diabetes Mellitus, Type 2/chemically induced
  • Female
  • Glomerular Filtration Rate
  • Glucose/metabolism
  • Humans
  • Hypoglycemic Agents/therapeutic use
  • Kidney
  • Male
  • Renal Insufficiency, Chronic/drug therapy
  • Sodium/metabolism
  • Sodium-Glucose Transporter 2/metabolism
  • Sodium-Glucose Transporter 2 Inhibitors/pharmacology

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