Clinical, Morphometric and Biochemical Effects on Adiposopathy Associated With the Use of GLP-1RA in CKD (ADIPO-CKD)

December 15, 2025 updated by: Ana Checa-Ros, Cardenal Herrera University

Clinical, Morphometric and Biochemical Effects on Adiposopathy Associated With the Use of GLP-1 Receptor Agonists in Chronic Kidney Disease

Chronic kidney disease (CKD) is the progressive damage to kidney function, associated with an increased risk of cardiovascular diseases, such as stroke or myocardial infarct, particularly in the most severe stages of CKD, in which the patient requires dialysis. Several risk factors are reported for CKD, such as diabetes mellitus, obesity and hypertension. One of the most increasingly recognized risk factors is the fat tissue malfunction, known as adiposopathy. The accumulation of fat tissue around the organs in conditions of obesity or diabetes accelerates the production of pro-inflammatory factors that may worsen the kidney and heart damage. New antidiabetic medications, such as glucagon-like peptide-1 receptor agonists (GLP-1RA), have proven beneficial effects on the kidney and heart due to several mechanisms, including anti-inflammatory actions and a potential action on the fat tissue.

The aim of this study is to assess the link between adiposopathy and CKD, by investigating the changes in adiposopathy measures throughout treatment with GLP-1RA to a sample of patients with CKD.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Chronic kidney disease (CKD) is defined as an irreversible abnormality of kidney structure and/or function lasting for more than three months. CKD is a major global health burden, affecting over 10% of the worldwide population and representing a leading cause of morbidity and mortality. Its progression to end-stage kidney disease (ESKD) drastically increases cardiovascular risk and is associated with a five-year survival rate of only approximately 50%. The principal risk factors for CKD-hypertension, obesity and type 2 diabetes (T2DM) in particular-are intrinsically linked through the dysfunction of fat/adipose tissue (AT), also known as adiposopathy.

Adiposopathy is a key driver of cardiorenal risk in CKD. Evidence from bioimpedance, imaging techniques (CT, MRI), and molecular biology studies confirm that alterations in adipose tissue-including its quantity, distribution (e.g., perirenal, epicardial), radiodensity, and the secretion of pro-inflammatory adipokines-are powerful triggers of cardiorenal damage and mortality in these patients. This understanding frames obesity, T2DM, cardiovascular diseases (CVDs), and CKD as different manifestations of a shared spectrum, now termed adiposity-based chronic disease (ABCD), necessitating an "adipocentric" therapeutic approach.

One hallmark feature of adiposopathy is the reprogramming and increase in size of certain region-specific adipose tissue. Perivisceral adipose tissue plays a pivotal role in adiposity-based chronic diseases as it releases adipokines and cytokines that not only contribute to the systemic pro-inflammatory and oxidative stress processes but may also influence the function of the organs surrounded by this tissue.

GLP-1RA stimulates the receptor for glucagon-like peptide-1 (GLP-1), an incretin-like hormone released in the large intestine that reduces serum glucose concentrations by stimulating the glucose-dependent release of insulin, inhibiting the hypersecretion of glucagon (except in hypoglycemia periods) and promoting satiety. GLP-1RA reduced the incidence of cardiovascular death in patients with T2DM compared with placebo and decreased the incidence of major kidney events, also reducing the progression of kidney dysfunction and the risk of death. In animals, the observed morphological changes generated by GLP-1RA could be underlined by potential actions on adipose tissue remodeling, as these drugs upregulated the expression of AT-browning related genes in perivisceral white adipose tissue from murine models, although the transcriptomic effects from GLP-1RA on the adiposopathy process are still unknown.

Study Type

Observational

Enrollment (Estimated)

250

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Spain
    • Valencia
      • Valencia, Valencia, Spain, 46007
        • Recruiting
        • Vithas Valencia Consuelo
        • Contact:
        • Principal Investigator:
          • Luis D'Marco, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients will be assigned to the different groups according to current treatment criteria:

SGLT2i: patients with CKD and T2DM with an eGFR ≥20ml/min/1.73m2; patients with CKD and eGFR ≥20ml/min/1.73m2, accompanied by an urinary albumin-to-creatinine ratio (ACR) ≥200mg/g; patients with CKD and heart failure, irrespective of level of albuminuria; or subjects with CKD and eGFR 20-45ml/min/1.73m2, with ACR <200mg/g.

GLP-1RA/tirzepatide: In patients with T2D and CKD who have not achieved individualized glycemic targets despite use of metformin and SGLT2i treatment, or who are unable to use those medications.

Other treatments: patients not meeting the criteria to be treated with SGLT2i or GLP-1RA/tirzepatide

Description

Inclusion Criteria:

  • > or = 18 years of age
  • diagnosed with CKD in stages G1, G2, G3a, G3b, and G4, not candidate for dialysis
  • had uncontrolled T2DM, CVDs and/or obesity
  • willing to participate in the study and sign informed consent

Exclusion Criteria:

  • Age <18 years
  • pregnancy
  • CKD in stage G5 or G4 candidate for dialysis
  • neuropsychiatric diseases preventing the patient from understanding the benefits/risks associated with the project
  • refusal to participate and/or consent revocation were considered as exclusion criteria

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
GLP-1RA Cohort
Patients receiving GLP-1RA, mainly semaglutide: weekly administration, subcutaneous form, from 0.25mg (starting dose) to 1mg (maintenance dose) with monthly increase (0.25-0.5-1mg)
Drug: GLP-1 receptor agonist
Semaglutide: weekly subcutaneous administration, starting dose 0.25mg, maintenance dose 1mg
Other Names:
  • liraglutide
  • semaglutide
  • exenatide
  • dulaglutide
Drug: SGLT2 inhibitor
dapagliflozin: oral administration from 5 to 10mg/day
Other Names:
  • dapagliflozin
  • empagliflozin
  • canagliflozin
SGLT2i Cohort
There will also be another comparative group of patients under SGLT2i
Drug: GLP-1 receptor agonist
Semaglutide: weekly subcutaneous administration, starting dose 0.25mg, maintenance dose 1mg
Other Names:
  • liraglutide
  • semaglutide
  • exenatide
  • dulaglutide
Drug: SGLT2 inhibitor
dapagliflozin: oral administration from 5 to 10mg/day
Other Names:
  • dapagliflozin
  • empagliflozin
  • canagliflozin
Other treatments
Patients not under SGLT2i or GLP-1RA/Tirzepatide influence, but receiving other treatments that are part of CKD and diabetes standard care
Dual GIP GLP-1RA
Patients receiving tirzepatide: weekly administration, subcutaneous form, starting dose 2.5mg, maintenance 5mg
Drug: Tirzepatide
subcutaneous injection: starting dose 2.5 mg, maintenance 5mg (weekly administration)
Drug: Other drugs
Patients not under SGLT2i or GLP-1RA influence, but receiving other treatments which are part of CKD standard care: mineralocorticoid receptor agonists, metformin, ACE inhibitors, ARBs...
Other Names:
  • Metformin
  • ACE inhibitors
  • ARBs
  • DPP4i
  • non steroidal mineralocorticoid receptor agonists

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ultrasonography change in perirenal adipose tissue thickness
Time Frame: 16 months
Change in perirenal adipose tissue thickness as measured with ultrasonography
16 months
Change in estimated glomerular filtration rate
Time Frame: 16 months
Change in eGFR as per the CKD-EPI formula
16 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ultrasonographic Change in epicardial adipose tissue thickness
Time Frame: 16 months
Change in epicardial adipose tissue thickness as measured with ultrasonography
16 months
Change in serum leptin levels
Time Frame: 16 months
Serum leptin levels measured with proteomic analysis
16 months
Change in visceral fat area
Time Frame: 16 months
Changes in visceral fat area (cm2) as measured with body composition measures (bioimpedance)
16 months
Ultrasonographic Change in subcutaneous adipose tissue
Time Frame: 16 months
Change in subcutaneous adipose tissue thickness as measured with ultrasonography
16 months
Ultrasonographic Change in preperitoneal adipose tissue thickness
Time Frame: 16 months
Change in preperitoneal adipose tissue thickness as measured with ultrasonography
16 months
Ultrasonographic Change in intrahepatic adipose tissue
Time Frame: 16 months
Change in intrahepatic adipose tissue echogenicity
16 months
Change in subcutaneous fat area
Time Frame: 16 months
Change in subcutaneous fat area (cm2) as measured with bioimpedance
16 months
Changes in muscle mass (kg)
Time Frame: 16 months
Changes in muscle mass as measured with bioimpedance
16 months
Change in serum adiponectin levels
Time Frame: 16 months
Serum adiponectin levels measured with proteomic analysis
16 months
Change in urinary levels of Kidney Injury Molecule-1
Time Frame: 16 months
Change in urinary levels of KIM-1 measured with ELISA, as an early marker of kidney damage
16 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in systemic inflammation markers
Time Frame: 16 months
Change in serum C-reactive protein levels
16 months
Change in systemic inflammation markers
Time Frame: 16 months
Change in serum interleukin-6 levels
16 months
Change in systemic inflammation markers
Time Frame: 16 months
Change in serum tumor necrosis factor-alpha levels
16 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Cardenal Herrera University

Investigators

  • Principal Investigator: Luis D'Marco, MD, PhD, Cardenal Herrera University
  • Principal Investigator: Ana Checa-Ros, MD, PhD, Cardenal Herrera University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 15, 2023

Primary Completion (Estimated)

July 31, 2027

Study Completion (Estimated)

December 31, 2028

Study Registration Dates

First Submitted

December 3, 2025

First Submitted That Met QC Criteria

December 15, 2025

First Posted (Actual)

December 30, 2025

Study Record Updates

Last Update Posted (Actual)

December 30, 2025

Last Update Submitted That Met QC Criteria

December 15, 2025

Last Verified

December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 23/424

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Due to ethical restrictions and in accordance with General Protection Data Regulation, no identifiable patient information will be shared.

Study Data/Documents

  1. Statistical Analysis Plan
  2. Analytic Code

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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