Kidney Disease in Diabetes Mellitus: Cross-Linking between Hyperglycemia, Redox
            Imbalance and Inflammation

Amorim, Rayne Gomes; Guedes, Glaucevane da Silva; Vasconcelos, Sandra Mary de Lima; Santos, Juliana Célia de Farias

doi:10.5935/abc.20190077

Cited by 37 publications

(26 citation statements)

References 79 publications

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“…Centers for Disease Control and Prevention (CDC) reported approximately, 9.4% of American adults have diabetes [ 1 , 2 ]. Diabetes is closely associated with oxidative stress, inflammation, and as a result endothelial dysfunction and cardiovascular complications [ 1 – 3 ]. On the other hand, 15% of US adults are estimated to have chronic kidney disease and 38% of end stage renal disease developed Chronic kidney disease (CKD) as a consequence of diabetes [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Role of Canagliflozin on function of CD34+ve endothelial progenitor cells (EPC) in patients with type 2 diabetes

Nandula

Kundu

Awal

et al. 2021

Cardiovasc Diabetol

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Background Endothelial progenitor cells (EPCs) has been shown to be dysfunctional in both type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) leading to poor regeneration of endothelium and renal perfusion. EPCs have been shown to be a robust cardiovascular disease (CVD) risk indicator. Effect of sodium glucose channel inhibitors (SGLT2i) such as Canagliflozin (CG) on a cellular biomarker such as CD34+ve progenitor cells, which may help predict CVD risk, in patients with T2DM with established CKD has not been explored. Methods This is a pilot study where 29 subjects taking metformin and/or Insulin were enrolled in a 16 week, double blind, randomized placebo matched trial, with a low dose 100 mg CG as the intervention group compared to matched placebo. Type 2 diabetes subjects (30–70 years old), with hemoglobin A1c (HbA1c) of 7–10%, were enrolled. CD34+ve cell number, migratory function, gene expression along with vascular parameters such as arterial stiffness, serum biochemistry pertaining to cardio-metabolic health, resting energy expenditure and body composition were measured. Data were collected at week 0, 8 and 16. A mixed model regression analysis was done and p value less than 0.05 was considered statistically significant. Results A significant expression of CXCR4 receptor with a concomittant increase in migratory function of CD34+ve cells was observed in CG treated group as compared to placebo group. Gene expression analysis of CD34+ve cells showed an increase in expression of antioxidants (superoxide dismutase 2 or SOD2, Catalase and Glutathione Peroxidase or GPX) and notable endothelial markers (PECAM1, VEGF-A, and NOS3). A significant reduction in glucose and HbA1c levels were observed along with improved systolic and diastolic blood pressure in the CG group. A significant increase in adiponectin (p = 0.006) was also noted in treatment group. Urinary exosomal protein leak in urine, examining podocyte health (podocalyxin, Wilm’s tumor and nephrin) showed reduction with CG Conclusion Low dose Canagliflozin has a beneficial effect on CD34+ cell function, serum biochemistry and urinary podocyte specific exosomes in type 2 diabetes.

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Section: Introductionmentioning

confidence: 99%

Role of Canagliflozin on function of CD34+ve endothelial progenitor cells (EPC) in patients with type 2 diabetes

Nandula

Kundu

Awal

et al. 2021

Cardiovasc Diabetol

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“… 5 , 6 , 7 Furthermore, hyperglycaemia is associated with the abnormal activation of several metabolic pathways such as polyol, protein kinase C, the hexosamines pathway, the formation of advanced glycation end products (AGEs), and the activation of NADPH-oxidases and angiotensin II, which can lead to over-induction of oxidative and nitrosative radicals, as well as the stimulation of inflammatory cytokines. 8 …”

Section: Introductionmentioning

confidence: 99%

Comparing the renoprotective effects of the antioxidants melatonin, vitamin D and vitamin E in diabetic rats

Alqasim

Eldin

Hammadi

et al. 2020

Journal of Taibah University Medical Sciences

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Objectives Diabetes mellitus is associated with oxidative stress that leads to inflammation and diabetic nephropathy. This study aimed to determine the possible renoprotective effects of the antioxidants melatonin, vitamin D and vitamin E in diabetic rats. Methods We divided 108 albino rats into 12 groups. G1 group was fed a normal diet and did not receive any medication. G2 to G4 consisted of non-diabetic rats that were treated as follows: G2 with melatonin; G3 with vitamin E; G4 with vitamin D. Groups G5 to G12 consisted of diabetic rats that were treated as follows: G5 received no medication; G6 treated with insulin; G7 treated with melatonin; G8 treated with melatonin and insulin; G9 treated with vitamin E; G10 treated with vitamin E and insulin; G11 treated with vitamin D and G12 treated with vitamin D and insulin. Two months after treatment commenced, histological and biochemical examinations of glucose profile, oxidative stress status, renal function, homocysteine and TNF-α were performed. Results Total antioxidant capacity (TAC) increased significantly in groups G2, 7, 8, 10 and 11. TNF-α significantly increased in G2, but decreased in all other groups. Creatinine increased significantly in groups G5, 6, 7, 8, 9, 11 and 12. In the kidneys of the diabetic rats, thickened capillary basement membrane, diffuse mesangial sclerosis and nodular glomerulosclerosis was observed. Rats treated with melatonin showed marked improvement in these symptoms. However, in those treated with vitamin D and E, thickened capillary basement membrane and mesangial sclerosis was still present. Conclusions Melatonin, administered either with or without insulin had a significant biochemical antioxidant effect and histological renoprotective effect. Conversely, vitamin D and E did not appear to have any effects on the parameters measured.

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“…e downregulation of PGC-1α reduces the amount of mtDNA. Impaired gene expression leads to impaired synthesis of mtETC protein, accumulation of ROS, and continuous accumulation of damage to mtDNA, causing kidney damage [44,45].…”

Section: Mitochondrial Electron Transport Chain and Mtdnamentioning

confidence: 99%

“…The downregulation of PGC-1 α reduces the amount of mtDNA. Impaired gene expression leads to impaired synthesis of mtETC protein, accumulation of ROS, and continuous accumulation of damage to mtDNA, causing kidney damage [ 44 , 45 ]. The DKD model also found that microtubular autophagic vacuoles and mitochondrial fragmentation were reduced under the microscope.…”

Section: Mitochondrial Oxidative Stress and Mtdna In Dkdmentioning

confidence: 99%

Mitochondrial DNA: A New Predictor of Diabetic Kidney Disease

Huang

Chi

Wei

et al. 2020

International Journal of Endocrinology

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Diabetic kidney disease (DKD) is a common cause of end-stage renal disease, and diagnosis and treatment in time can help delay its progress. At present, there are more and more studies on the pathogenesis of DKD; mitochondrial dysfunction plays an important role in DKD. The occurrence and development of DKD is closely related to epigenetic changes and the interaction between mtDNA, ROS, inflammatory factors, and endothelial damage, which continuously aggravates kidney. The change of mtDNA is both the cause of DKD and the result of DKD. It is of great significance to incorporate the change of mtDNA into the monitoring of patients with diabetes. Existing evidence indicates that changes in mtDNA copy number in blood and urine reflect mitochondrial dysfunction and the severity of DKD. However, large-scale, long-term follow-up clinical trials are still needed to determine the threshold range. By the time, mitochondrial-targeted antioxidants will become a new method for the treatment of DKD and other diabetic complications; mtDNA also can be a therapeutic target for them.

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Kidney Disease in Diabetes Mellitus: Cross-Linking between Hyperglycemia, Redox Imbalance and Inflammation

Cited by 37 publications

References 79 publications

Role of Canagliflozin on function of CD34+ve endothelial progenitor cells (EPC) in patients with type 2 diabetes

Role of Canagliflozin on function of CD34+ve endothelial progenitor cells (EPC) in patients with type 2 diabetes

Comparing the renoprotective effects of the antioxidants melatonin, vitamin D and vitamin E in diabetic rats

Mitochondrial DNA: A New Predictor of Diabetic Kidney Disease

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