Effect of Empagliflozin on Urinary Excretion of Adenosine and Osteocyte Function in Patients With Chronic Kidney Disease

Sponsor
Medical University of Lodz
Study ID
NCT04961931
Status
Unknown

Conditions

  • Chronic Kidney Disease stage3

Eligibility Criteria

Sex
ALL
Age
18 Years - 70 Years
Healthy Volunteers
Accepted

Interventions

  • Empagliflozin 10 MG — DRUG
    After qualifying for the study all subjects received oral empagliflozin 10 mg once daily for 7 days.

Study Details

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.

Key Dates

Start date
Jan 1, 2019
Status verified
Jul 2021
Primary completion
Aug 31, 2021
Completion
Aug 31, 2021

Study Design

Enrollment
45 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION

Arms

  • Other: diabetes group
    After qualifying for the study subjects with diabetes and chornic kidney disease received oral empagliflozin 10 mg once daily for 7 days.
  • Other: non-diabetes group
    After qualifying for the study subjects with chronic kidney disease without diabetes received oral empagliflozin 10 mg once daily for 7 days.
  • Other: control
    After qualifying for the study healthy subjects received oral empagliflozin 10 mg once daily for 7 days.

Primary Outcome Measure

albuminuria [ Time Frame: 7 days ]

Central Contacts