Clinical, Morphometric and Biochemical Effects on Adiposopathy Associated With the Use of GLP-1RA in CKD
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: GLP-1 receptor agonist, SGLT2 inhibitor, Tirzepatide, Other drugs.
- Who it may be relevant to
- Registry conditions: Chronic Kidney Disease stage3, Chronic Kidney Disease stage4, Chronic Kidney Disease Stage 1, Chronic Kidney Disease Stage 2. Basic parameters: 18 years — 90 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Spain
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
Clinical, Morphometric and Biochemical Effects on Adiposopathy Associated With the Use of GLP-1 Receptor Agonists in Chronic Kidney Disease
Overview
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.
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.
Interventions
- Drug GLP-1 receptor agonist
Semaglutide: weekly subcutaneous administration, starting dose 0.25mg, maintenance dose 1mg - Drug SGLT2 inhibitor
dapagliflozin: oral administration from 5 to 10mg/day - 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...
Primary outcome measures
- Ultrasonography change in perirenal adipose tissue thickness [Time frame: 16 months]
- Change in estimated glomerular filtration rate [Time frame: 16 months]
Secondary outcome measures (10)
- Ultrasonographic Change in epicardial adipose tissue thickness [Time frame: 16 months]
- Change in serum leptin levels [Time frame: 16 months]
- Change in visceral fat area [Time frame: 16 months]
- Ultrasonographic Change in subcutaneous adipose tissue [Time frame: 16 months]
- Ultrasonographic Change in preperitoneal adipose tissue thickness [Time frame: 16 months]
- Ultrasonographic Change in intrahepatic adipose tissue [Time frame: 16 months]
- Change in subcutaneous fat area [Time frame: 16 months]
- Changes in muscle mass (kg) [Time frame: 16 months]
- Change in serum adiponectin levels [Time frame: 16 months]
- Change in urinary levels of Kidney Injury Molecule-1 [Time frame: 16 months]
Eligibility criteria
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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Observational model
- Cohort
Study locations
Spain · 1 center
- Vithas Valencia Consuelo — Valencia
Publications
- Zhao L, Li W, Zhang P, Wang D, Yang L, Yuan G. Liraglutide induced browning of visceral white adipose through regulation of miRNAs in high-fat-diet-induced obese mice. Endocrine. 2024 Jul;85(1):222-232. doi: 10.1007/s12020-024-03734-2. Epub 2024 Feb 20. PMID 38378894
- Ying Y, Zhu H, Liang Z, Ma X, Li S. GLP1 protects cardiomyocytes from palmitate-induced apoptosis via Akt/GSK3b/b-catenin pathway. J Mol Endocrinol. 2015 Dec;55(3):245-62. doi: 10.1530/JME-15-0155. Epub 2015 Sep 18. PMID 26386043
- Carraro-Lacroix LR, Malnic G, Girardi AC. Regulation of Na+/H+ exchanger NHE3 by glucagon-like peptide 1 receptor agonist exendin-4 in renal proximal tubule cells. Am J Physiol Renal Physiol. 2009 Dec;297(6):F1647-55. doi: 10.1152/ajprenal.00082.2009. Epub 2009 Sep 23. PMID 19776173
- Perkovic V, Tuttle KR, Rossing P, Mahaffey KW, Mann JFE, Bakris G, Baeres FMM, Idorn T, Bosch-Traberg H, Lausvig NL, Pratley R; FLOW Trial Committees and Investigators. Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes. N Engl J Med. 2024 Jul 11;391(2):109-121. doi: 10.1056/NEJMoa2403347. Epub 2024 May 24. PMID 38785209
- Giugliano D, Maiorino MI, Bellastella G, Longo M, Chiodini P, Esposito K. GLP-1 receptor agonists for prevention of cardiorenal outcomes in type 2 diabetes: An updated meta-analysis including the REWIND and PIONEER 6 trials. Diabetes Obes Metab. 2019 Nov;21(11):2576-2580. doi: 10.1111/dom.13847. Epub 2019 Aug 28. PMID 31373167
- D'Marco L, Puchades MJ, Panizo N, Romero-Parra M, Gandia L, Gimenez-Civera E, Perez-Bernat E, Gonzalez-Rico M, Gorriz JL. Cardiorenal Fat: A Cardiovascular Risk Factor With Implications in Chronic Kidney Disease. Front Med (Lausanne). 2021 May 25;8:640814. doi: 10.3389/fmed.2021.640814. eCollection 2021. PMID 34113631
- Ku E, Lee BJ, Wei J, Weir MR. Hypertension in CKD: Core Curriculum 2019. Am J Kidney Dis. 2019 Jul;74(1):120-131. doi: 10.1053/j.ajkd.2018.12.044. Epub 2019 Mar 19. PMID 30898362
- Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract. 2010 Jan;87(1):4-14. doi: 10.1016/j.diabres.2009.10.007. Epub 2009 Nov 6. PMID 19896746
Identifiers
NCT: NCT07309094 · 23/424