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.
> 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
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
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
Cohort
Prospective
GLP-1 receptor agonist
DrugSemaglutide: weekly subcutaneous administration, starting dose 0.25mg, maintenance dose 1mg
SGLT2 inhibitor
Drugdapagliflozin: oral administration from 5 to 10mg/day
Tirzepatide
Drugsubcutaneous injection: starting dose 2.5 mg, maintenance 5mg (weekly administration)
Other drugs
DrugPatients 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...
Ultrasonography change in perirenal adipose tissue thickness
Change in perirenal adipose tissue thickness as measured with ultrasonography
Change in estimated glomerular filtration rate
Change in eGFR as per the CKD-EPI formula
Ultrasonographic Change in epicardial adipose tissue thickness
Change in epicardial adipose tissue thickness as measured with ultrasonography
Change in serum leptin levels
Serum leptin levels measured with proteomic analysis
Change in visceral fat area
Changes in visceral fat area (cm2) as measured with body composition measures (bioimpedance)
Ultrasonographic Change in subcutaneous adipose tissue
Change in subcutaneous adipose tissue thickness as measured with ultrasonography
Change in systemic inflammation markers
Change in serum C-reactive protein levels
Change in systemic inflammation markers
Change in serum interleukin-6 levels
Change in systemic inflammation markers
Change in serum tumor necrosis factor-alpha levels
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