The Potential Roles of Osmotic and Nonosmotic Sodium Handling in Mediating the Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Heart Failure

Autor: Peter J. Greasley, Petter Bjornstad, Anna Maria Langkilde, David C. Wheeler, Glenn M. Chertow, Daniël H. van Raalte, Hiddo J.L. Heerspink
Přispěvatelé: Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Groningen Kidney Center (GKC)
Rok vydání: 2021
Předmět:
Zdroj: JOURNAL OF CARDIAC FAILURE, 27(12), 1447-1455. Churchill Livingstone
Bjornstad, P, Greasley, P J, Wheeler, D C, Chertow, G M, Langkilde, A M, Heerspink, H J L & van Raalte, D H 2021, ' The Potential Roles of Osmotic and Nonosmotic Sodium Handling in Mediating the Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Heart Failure ', Journal of Cardiac Failure, vol. 27, no. 12, pp. 1447-1455 . https://doi.org/10.1016/j.cardfail.2021.07.003
Journal of cardiac failure
ISSN: 1071-9164
Popis: Concomitant type 2 diabetes and chronic kidney disease increases the risk of heart failure. Recent studies demonstrate beneficial effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors on chronic kidney disease progression and heart failure hospitalization in patients with and without diabetes. In addition to inhibiting glucose reabsorption, SGLT2 inhibitors decrease proximal tubular sodium reabsorption, possibly leading to transient natriuresis. We review the hypothesis that SGLT2 inhibitor’s natriuretic and osmotic diuretic effects mediate their cardioprotective effects. The degree to which these benefits are related to changes in sodium, independent of the kidney, is currently unknown. Aside from effects on osmotically active sodium, we explore the intriguing possibility that SGLT2 inhibitors could also modulate nonosmotic sodium storage. This alternative hypothesis is based on emerging literature that challenges the traditional 2-compartment model of sodium balance to provide support for a 3-compartment model that includes the binding of sodium to glycosaminoglycans, such as those in muscles and skin. This recent research on nonosmotic sodium storage, as well as direct cardiac effects of SGLT2 inhibitors, provides possibilities for other ways in which SGLT2 inhibitors might mitigate heart failure risk. Overall, we review the effects of SGLT2 inhibitors on sodium balance and sensitivity, cardiac tissue, interstitial fluid and plasma volume, and nonosmotic sodium storage.
Lay summary SGLT2 inhibitors have cardiovascular benefits that include HF outcomes in patients with and without diabetes. Because the underlying mechanisms are only partly explained by improvements in BP, body weight, or glucose control, other mechanisms have been proposed. We focus here on a central role for effects on sodium as underlying the positive benefits of SGLT2 inhibitors in HF. We explore the new (although still unconfirmed) idea that SGLT2 inhibitors exert some of their positive effects by affecting nonosmotic sodium (ie, sodium bound to muscles and skin and not dissolved in the blood). SGLT2 inhibitors have emerged as a class of drugs, previously prescribed for patients with T2D, that have in more recent years been shown to have substantial heart and kidney clinical benefits in patients with and without T2D.The degree to which these benefits are related to kidney-independent changes in sodium homeostasis is currently unknown.A better understanding of the nonosmotic mechanisms underpinning the benefits of SGLT2 inhibition on HF (with reduced or preserved left ventricular ejection fraction) may allow researchers to assess the effects of SGLT2 inhibitors in combination with other treatments that affect sodium balance.
Databáze: OpenAIRE
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