SGLT2i relieve proteinuria in diabetic nephropathy patients potentially by inhibiting renal oxidative stress rather than through AGEs pathway
© 2024. The Author(s)..
AIMS: To estimate the effects of the sodium-glucose cotransporter 2 inhibitor (SGLT2i) on proteinuria and oxidative stress expression in type 2 diabetes patients.
MATERIALS AND METHODS: 68 patients with type 2 diabetes mellitus (T2DM) were divided into three groups according urinary albumin-to-creatinine ratio (UACR), including T2DM with non-albuminuria group (UACR < 30 mg/g), T2DM with microalbuminuria group (30 ≤ UACR ≤ 300 mg/g), T2DM with macroalbuminuria group (UACR>300 mg/g). They all received SGLT2 inhibitors (SGLT2i) treatment for 12 weeks. The expression of advanced glycation end products (AGEs) in plasma and 8-hydroxy-2-deoxyguanosine (8-OHdG) in urine were measured as indications of oxidative stress. The 24-hour urine samples were collected to measure the concentration of proteinuria and 8-OHdG before and after 12 weeks SGLT2i treatment. Plasma renin activity (PRA), angiotensin II (Ang II) and Aldosterone (ALD) were measured to evaluate renin angiotensin aldosterone system (RASS) levels.
RESULTS: After 12 weeks SGLT2 inhibitors treatment, the median values of 24-hour proteinuria decreased in macroalbuminuria compared to baseline (970 vs. 821 mg/d, P = 0.006). The median values of AGEs and 8-OHdG decreased in microalbuminuria and macroalbuminuria groups when compared to baseline, AGEs (777 vs. 136 ug/ml, P = 0.003) and (755 vs. 210 ug/ml, P = 0.001), 8-OHdG (8.00 vs. 1.88 ng/ml, P = 0.001) and (11.18 vs. 1.90 ng/ml, P < 0.001), respectively. Partial correlations showed that 8-OHdG were relevant to the baseline 24-h proteinuria (r = 0.389, p = 0.001), the reduction of OHdG (Δ8-OHdG) were positively correlated with the decrease of 24-h proteinuria (Δ24-h proteinuria) after 12 weeks of SGLT2i treatment (r = 0.283, P = 0.031). There was no significant correlation between 24-h proteinuria and AGEs in baseline (r = -0.059, p = 0.640) as well as between ΔAGEs and Δ24-h proteinuria (r = 0.022, p = 0.872) after12 weeks of SGLT2i treatment in T2DM patients.
CONCLUSIONS: SGLT2i may reduce proteinuria in diabetic nephropathy patients, potentially by inhibiting renal oxidative stress, but not through the AGEs pathway and does not induce RAAS activation.
TRIAL REGISTRATION: This clinical trial was registered on 15/10/2019, in ClinicalTrials.gov, and the registry number is NCT04127084.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:16 |
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| Enthalten in: |
Diabetology & metabolic syndrome - 16(2024), 1 vom: 16. Feb., Seite 46 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zeng, Xiao-Chun [VerfasserIn] |
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| Links: |
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| Themen: |
8-OHdG |
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| Anmerkungen: |
Date Revised 19.02.2024 published: Electronic ClinicalTrials.gov: NCT04127084 Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1186/s13098-024-01280-5 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM368559173 |
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| 245 | 1 | 0 | |a SGLT2i relieve proteinuria in diabetic nephropathy patients potentially by inhibiting renal oxidative stress rather than through AGEs pathway |
| 264 | 1 | |c 2024 | |
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| 500 | |a Date Revised 19.02.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT04127084 | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a © 2024. The Author(s). | ||
| 520 | |a AIMS: To estimate the effects of the sodium-glucose cotransporter 2 inhibitor (SGLT2i) on proteinuria and oxidative stress expression in type 2 diabetes patients | ||
| 520 | |a MATERIALS AND METHODS: 68 patients with type 2 diabetes mellitus (T2DM) were divided into three groups according urinary albumin-to-creatinine ratio (UACR), including T2DM with non-albuminuria group (UACR < 30 mg/g), T2DM with microalbuminuria group (30 ≤ UACR ≤ 300 mg/g), T2DM with macroalbuminuria group (UACR>300 mg/g). They all received SGLT2 inhibitors (SGLT2i) treatment for 12 weeks. The expression of advanced glycation end products (AGEs) in plasma and 8-hydroxy-2-deoxyguanosine (8-OHdG) in urine were measured as indications of oxidative stress. The 24-hour urine samples were collected to measure the concentration of proteinuria and 8-OHdG before and after 12 weeks SGLT2i treatment. Plasma renin activity (PRA), angiotensin II (Ang II) and Aldosterone (ALD) were measured to evaluate renin angiotensin aldosterone system (RASS) levels | ||
| 520 | |a RESULTS: After 12 weeks SGLT2 inhibitors treatment, the median values of 24-hour proteinuria decreased in macroalbuminuria compared to baseline (970 vs. 821 mg/d, P = 0.006). The median values of AGEs and 8-OHdG decreased in microalbuminuria and macroalbuminuria groups when compared to baseline, AGEs (777 vs. 136 ug/ml, P = 0.003) and (755 vs. 210 ug/ml, P = 0.001), 8-OHdG (8.00 vs. 1.88 ng/ml, P = 0.001) and (11.18 vs. 1.90 ng/ml, P < 0.001), respectively. Partial correlations showed that 8-OHdG were relevant to the baseline 24-h proteinuria (r = 0.389, p = 0.001), the reduction of OHdG (Δ8-OHdG) were positively correlated with the decrease of 24-h proteinuria (Δ24-h proteinuria) after 12 weeks of SGLT2i treatment (r = 0.283, P = 0.031). There was no significant correlation between 24-h proteinuria and AGEs in baseline (r = -0.059, p = 0.640) as well as between ΔAGEs and Δ24-h proteinuria (r = 0.022, p = 0.872) after12 weeks of SGLT2i treatment in T2DM patients | ||
| 520 | |a CONCLUSIONS: SGLT2i may reduce proteinuria in diabetic nephropathy patients, potentially by inhibiting renal oxidative stress, but not through the AGEs pathway and does not induce RAAS activation | ||
| 520 | |a TRIAL REGISTRATION: This clinical trial was registered on 15/10/2019, in ClinicalTrials.gov, and the registry number is NCT04127084 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a 8-OHdG | |
| 650 | 4 | |a AGEs | |
| 650 | 4 | |a Diabetic nephropathy | |
| 650 | 4 | |a Oxidative stress | |
| 650 | 4 | |a Proteinuria | |
| 650 | 4 | |a SGLT2i | |
| 700 | 1 | |a Tian, Yuan |e verfasserin |4 aut | |
| 700 | 1 | |a Liang, Xian-Ming |e verfasserin |4 aut | |
| 700 | 1 | |a Wu, Xiao-Bin |e verfasserin |4 aut | |
| 700 | 1 | |a Yao, Chun-Meng |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Xiao-Min |e verfasserin |4 aut | |
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