Effects of Sodium-Glucose Co-transporter 2 Inhibition with Empaglifozin on Renal Structure and Function in Non-diabetic Rats with Left Ventricular Dysfunction After Myocardial Infarction.

Abstract:

BACKGROUND:The use of sodium-glucose co-transporter 2 inhibitors (SGLT2i) is currently expanding to cardiovascular risk reduction in non-diabetic subjects, but renal (side-)effects are less well studied in this setting. METHODS:Male non-diabetic Sprague Dawley rats underwent permanent coronary artery ligation to induce MI, or sham surgery. Rats received chow containing empagliflozin (EMPA) (30 mg/kg/day) or control chow. Renal function and electrolyte balance were measured in metabolic cages. Histological and molecular markers of kidney injury, parameters of phosphate homeostasis and bone resorption were also assessed. RESULTS:EMPA resulted in a twofold increase in diuresis, without evidence for plasma volume contraction or impediments in renal function in both sham and MI animals. EMPA increased plasma magnesium levels, while the levels of glucose and other major electrolytes were comparable among the groups. Urinary protein excretion was similar in all treatment groups and no histomorphological alterations were identified in the kidney. Accordingly, molecular markers for cellular injury, fibrosis, inflammation and oxidative stress in renal tissue were comparable between groups. EMPA resulted in a slight increase in circulating phosphate and PTH levels without activating FGF23-Klotho axis in the kidney and bone mineral resorption, measured with CTX-1, was not increased. CONCLUSIONS:EMPA exerts profound diuretic effects without compromising renal structure and function or causing significant electrolyte imbalance in a non-diabetic setting. The slight increase in circulating phosphate and PTH after EMPA treatment was not associated with evidence for increased bone mineral resorption suggesting that EMPA does not affect bone health.

journal_name

Cardiovasc Drugs Ther

authors

Yurista SR,Silljé HHW,van Goor H,Hillebrands JL,Heerspink HJL,de Menezes Montenegro L,Oberdorf-Maass SU,de Boer RA,Westenbrink BD

doi

10.1007/s10557-020-06954-6

subject

Has Abstract

pub_date

2020-06-01 00:00:00

pages

311-321

issue

3

eissn

0920-3206

issn

1573-7241

pii

10.1007/s10557-020-06954-6

journal_volume

34

pub_type

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