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

NCT04961931 | Unknown

• 1 other identifier: EMPA - 1 - AMZ
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Chronic Kidney Disease stage3

Keywords

SGLT2 inhibitors; adenosine; calcium-phosphate metabolism; chronic kidney disease; diabetes; non-diabetes; albuminuria

Outcome Measures

Primary Outcomes (12)

• albuminuria

  ratio of albumin to creatinine in urine in mg/g

  7 days

• serum calcium concentration

  serum calcium level in mmol/l

  7 days

• urine calcium concentration

  level of calcium in urine in mmol/l

  7 days

• urine adenosine

  adenosine in urine in µmol/mmol creatinine

  7 days

• urine phosphorus concetration

  serum phosphorus level in mmol/l

  7 days

• serum Fibroblast growth factor 23 concentration

  serum Fibroblast growth factor 23 level in pg/ml

  7 days

• serum parathormone concentration

  serum parathormone level in pg/ml

  7 days

• serum Klotho concentration

  serum Klotho level in ng/ml

  7 days

• serum Bone alkaline phosphatase concentration

  serum Bone alkaline phosphatase level in µg/l

  7 days

• serum 1,25(OH)2D concentration

  serum 1,25(OH)2D level in pg/ml

  7 days

• serum sclerostin concentration

  serum sclerostin level in pmol/l

  7 days

• urine phosphorus concetration

  phosphorus in urine in mmol/l

  7 days

Study Arms (3)

diabetes group

OTHER

After qualifying for the study subjects with diabetes and chornic kidney disease received oral empagliflozin 10 mg once daily for 7 days.

Drug: Empagliflozin 10 MG

non-diabetes group

OTHER

After qualifying for the study subjects with chronic kidney disease without diabetes received oral empagliflozin 10 mg once daily for 7 days.

Drug: Empagliflozin 10 MG

control

OTHER

After qualifying for the study healthy subjects received oral empagliflozin 10 mg once daily for 7 days.

Drug: Empagliflozin 10 MG

Interventions

Empagliflozin 10 MG DRUG

After qualifying for the study all subjects received oral empagliflozin 10 mg once daily for 7 days.

Also known as: Jardiance

control; diabetes group; non-diabetes group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• type 2 diabetes complicated by diabetic nephropathy (first group), non-diabetic nephropathy (second group) or healthy subjects
• Angiotensin-converting enzyme inhibitor or antagonists of angiotensin receptor blockers in the stable dose for the 4 months
• age 18 - 70 years
• stable clinical condition for the last 3 months
• GFR 25-60 ml / min / 1.73 m2
• proteinuria 0.5-3 g / day

You may not qualify if:

• diabetes mellitus other than t.2
• have taken SGLT2 inhibitors in the last 4 weeks or have ever had an intolerance to SGLT2 inhibitors in the past
• acute kidney damage
• systolic blood pressure \<90 mmHg
• Cancer
• acute inflammation
• liver failure
• heart failure\> 2. NYHA grade
• pregnancy
• patients with impaired consciousness and testers with insufficient management in the past.

Sponsors & Collaborators

• Medical University of Lodz: lead

Study Sites (1)

Department of Nephrology, Hypertension and Kidney Transplantation

Lodz, 90-153, Poland

RECRUITING

MeSH Terms

Conditions

Renal Insufficiency, Chronic; Diabetes Mellitus; Albuminuria

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Proteinuria; Urination Disorders; Urological Manifestations; Signs and Symptoms

Study Officials

• Ireneusz Staroń

  Medical University of Lodz

  STUDY CHAIR

Central Study Contacts

Michał Nowicki, Prof

CONTACT

+48 42 201 4400; nefro@wp.pl

Anna Masajtis-Zagajewska, PhD

CONTACT

+48 606 558 005; anna.masajtis-zagajewska@umed.lodz.pl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: The study will be prospective, interventional and will be conducted in two parallel groups selected on the basis of clinical diagnosis (diabetic nephropathy or other chronic nephropathies).

Study Record Dates

• First Submitted: June 30, 2021
• First Posted: July 14, 2021
• Study Start: January 1, 2019
• Primary Completion: August 31, 2021
• Study Completion: August 31, 2021
• Last Updated: July 14, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

PL (1)