Effect of Empagliflozin on Urinary Excretion of Adenosine and Osteocyte Function in Patients With Chronic Kidney Disease
Status:
Recruiting
Trial end date:
2021-08-31
Target enrollment:
Participant gender:
Summary
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are the newest class of orally drugs for
the treatment of type 2 diabetes. These drugs decrease plasma glucose levels by inhibiting
its reabsorption in the proximal tubules of the kidney. They have an attractive clinical
efficacy profile, including glycemic control, weight loss, and lowering blood pressure. SGLT2
inhibitors have also been reported to reduce the risk of severe adverse cardiovascular events
and progression of diabetic kidney disease. SGLT2 is expressed in the kidney, while its
expression in other tissues is most likely negligible or absent.
SGLT2 dilates the supply vessels to the glomerulus thereby promoting hyperfiltration. In
animal models SGLT2 has been shown to reduce the excretion of macular dense adenosine, which
may contribute to the excessive glomerular filtration rate as a result of vasodilation of the
afferent vessels. Adenosine, unlike other vascular regions, increases the tension in the
walls of the vessels supplying blood to the glomerulus. The role of adenosine in humans in
this regard is poorly defined, although treatment with empagliflozin has recently been shown
to increase the urinary excretion of adenosine in type 1 diabetic patients with controlled
hyperglycemia. Our working hypothesis is that the SGLT2 inhibitor empagliflozin may reduce
the hyperfiltration of residual nephrons by increasing adenosine production, which affects
the contraction of the afferent arterioles, and this effect occurs in various types of
nephropathy.
In addition, it has been described that SGLT2 inhibitors may affect individual parameters of
calcium-phosphate metabolism, leading to changes in bone mineral density and an increase in
bone resorption marker SGLT2 inhibitors also stimulate renal, proximal phosphate
reabsorption. Increased phosphate reabsorption triggers the secretion of fibroblast growth
factor 23 (FGF23). FGF23 inhibits the production of 1,25-dihydroxyvitamin D (the biologically
active form of vitamin D), which reduces the absorption of calcium from the gastrointestinal
tract, thereby stimulating the secretion of parathyroid hormone (PTH). In the conducted
studies, it was found that SGLT2 inhibitors increase the concentration of serum phosphorus,
FGF23 in the plasma and PTH in the plasma, while lowering the level of 1,25-dihydroxyvitamin
D.