Effects of sodium glucose co-transporter 2 inhibitors on the kidney

Natalia de Albuquerque Rocha, Ian J Neeland, Peter A. McCullough, Robert D Toto, Darren K McGuire

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Sodium–glucose cotransporter 2 inhibitors are antihyperglycaemic medications with an emerging evidence base for cardiovascular and kidney disease risk reduction. Sodium–glucose cotransporter 2 inhibitors medications lower plasma glucose by inhibiting glucose reabsorption in the proximal tubule of the kidney independent of insulin. Furthermore, they reduce intraglomerular pressure by restoring tubuloglomerular feedback. Large cardiovascular outcome trials of both empagliflozin and canagliflozin have consistently shown beneficial kidney effects that go beyond glycaemic control, such as reducing risk for incident nephropathy and progression of chronic kidney disease. The mechanisms by which sodium–glucose cotransporter 2 inhibitors improve kidney outcomes are not clear. Proposed hypotheses underpinning the kidney benefits include kidney-specific effects such as decreased intraglomerular pressure, activation of angiotensin-(1-7) and the Mas receptor leading to decreased inflammation, decrease in overall kidney oxygen consumption, rise in erythropoietin levels, inhibition of the renal sodium–hydrogen exchanger and secondary kidney effects related to improvements in HbA1c and blood pressure. This review will focus on describing the mechanisms of action of sodium–glucose cotransporter 2 inhibitors in the kidney, clinical efficacy data on their use in patients with chronic kidney disease, postulated physiologic underpinnings of kidney protection observed with sodium–glucose cotransporter 2 inhibitors and the promise and potential pitfalls for their use in patients with chronic kidney disease.

Original languageEnglish (US)
JournalDiabetes and Vascular Disease Research
DOIs
StateAccepted/In press - Jun 1 2018

Keywords

  • canagliflozin
  • chronic kidney disease
  • empagliflozin
  • kidney
  • Sodium–glucose cotransporter 2 inhibitors
  • sodium–glucose cotransporter 2 inhibitors
  • type 2 diabetes mellitus

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Cardiology and Cardiovascular Medicine

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