This study aims to investigate whether new glucose-lowering medications, such as SGLT2 inhibitors (e.g., Forxiga/Jardiance) and GLP-1 receptor agonists (e.g., Ozempic), can reduce NETosis in diabetic patients, thereby mitigating secondary complications such as cardiovascular disease and kidney damage. By targeting dysregulated NET formation, the study seeks to establish a link between reduced NETosis and improved clinical outcomes in diabetes.
Additionally, the study will evaluate the effects of immunosuppressive therapies on NETosis in patients with immune-mediated kidney diseases, such as ANCA-associated vasculitis. By correlating NETosis activity with disease progression and treatment response, this research will assess whether reducing NETosis contributes to better management of inflammation and secondary morbidity in these conditions.
Through these evaluations, the study aims to identify potential therapeutic strategies to improve outcomes in both diabetic and chronic kidney disease populations.
Patients who have not previously received SGLT2 inhibitors or GLP-1 receptor agonists.
This part of the study will specifically evaluate immune-mediated kidney disease, such as ANCA-associated vasculitis, and the effects of immunosuppressive therapy on NETosis.
Patients with acute infections, hematologic or oncologic diseases, or positive for HIV or Hepatitis B/C
DM therapy study: - Diabetic patients aged 18 years or older (men and women). * Patients who have not previously received SGLT2 inhibitors or GLP-1 receptor agonists. • Exclusion Criteria: * Patients with conditions affecting NETosis, including autoimmunity, hematologic or oncologic diseases, or positive for HIV or Hepatitis B/C. Chronic kidney disease (CKD) patients :This study will include 50 CKD patients with various etiologies, with a focus on those with immune-mediated kidney diseases, such as ANCA-associated vasculitis. The primary aim is to evaluate the effects of immunosuppressive therapy on NETosis. All patients will be naïve to prior immunosuppressive therapy to ensure the observed effects are directly attributable to the initiation of treatment. • Exclusion Criteria: o Patients with acute infections, hematologic or oncologic diseases, or positive for HIV or Hepatitis B/C
Case-only
Prospective
Not listed
NETosis marker- citrullinated histone H3 (citH3)
* NETosis markers: NET formation will be assessed in sera blood samples across all groups. * Focus on Naïve Patients: Emphasis will be placed on evaluating the initial effects of antiglycemic medications in diabetic patients and the impact of immunosuppressive therapy in CKD patients with immune-mediated diseases. * Samples will be collected at identical intervals and compared among diabetic andCKD, groups to assess differences in NETosis levels over time (controls- only baseline NETosis markers) and in response to treatment. All serum samples will be diluted 1:2 and citrullinated histone H3 (citH3) will be quantified using the Citrullinated Histone H3 ELISA Kit: O.D. (501620; Cayman Chemical, Ann Arbor, USA).
NETosis marker- Myeloperoxidase
Samples will be collected at identical intervals and compared among diabetic andCKD, groups to assess differences in NETosis levels over time (controls- only baseline NETosis markers) and in response to treatment. All serum samples will be diluted 1:2 . MPO measurement will be conducted using Myeloperoxidase ELISA Kit , ng/ml (501410; Cayman Chemical).
NETosis marker- Neutrophil elastase (NE)
Samples will be collected at identical intervals and compared among diabetic andCKD, groups to assess differences in NETosis levels over time (controls- only baseline NETosis markers) and in response to treatment. All serum samples will be diluted 1:2 , and NE measurement will be conducted using Human Neutrophil Elastase ELISA Kit, ng/ml (ab204730; Abcam
NETosis marker: Peptidylarginine deiminase 4-PAD4
Samples will be collected at identical intervals and compared among diabetic andCKD, groups to assess differences in NETosis levels over time (controls- only baseline NETosis markers) and in response to treatment. All serum samples will be diluted 1:2 and PAD4 measurement will be conducted using (PADI4 ELISA Kit, ng/ml (ELH-PADI4, RayBiotech) according to the manufacturer's instructions
Kidney function
1\. Kidney Function * Estimated glomerular filtration rate (eGFR, ml/min) will be measured using CKD-EPI creatinine) equation. * These measures will monitor changes in kidney function over time and will be correlated with NETosis markers assessed prior to and during treatment.
Urine protein/ creatinine ratio
Urine protein/ creatinine ratio w (mg/gr) will be measured. o These measures will monitor changes in kidney function over time and will be correlated with NETosis markers assessed prior to and during treatment
Major adverse cardiovascular events (MACE)
Major adverse cardiovascular events (MACE): Including myocardial infarction, stroke, heart failure and cardiovascular death (present/absent). * Yearly analyses will evaluate the occurrence of these events in relation to NETosis markers
All cause mortality
All-cause mortality: Survival outcomes will be tracked through yearly analyses. * Correlations will be drawn between NETosis markers and mortality rates to understand their predictive value and treatment effects. These secondary outcomes will highlight the association between NETosis and long-term renal and cardiovascular outcomes
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