Renal Effects of Sodium-Glucose Co-Transporter Inhibitors

Thomson, Scott C.; Vallon, Volker

doi:10.1016/j.amjmed.2019.08.005

Cited by 8 publications

(6 citation statements)

References 45 publications

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“…Currently, DKD natural history has been changed by advances in pharmacological tools, especially due to sodium-glucose cotransporter-2 (SGLT2) inhibition by gliflozins addition to the standard treatment [ 18 ]. Specifically, gliflozins preserve kidney function through hemodynamic reestablishment, preventing hyperfiltration and restoration of tubule-glomerular feedback [ 19 ]. However, the association of pharmacological interventions with improvements in the life style (diet, exercise, weight control, and quitting smoking) is able to slow disease progression, yet not recovering either lost tissue, function, or both [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Potential of Mesenchymal Stem Cells in a Pre-Clinical Model of Diabetic Kidney Disease and Obesity

Sávio-Silva

Soinski-Sousa

Simplício-Filho

et al. 2021

IJMS

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Diabetic kidney disease (DKD) is a worldwide microvascular complication of type 2 diabetes mellitus (T2DM). From several pathological mechanisms involved in T2DM-DKD, we focused on mitochondria damage induced by hyperglycemia-driven reactive species oxygen (ROS) accumulation and verified whether mesenchymal stem cells (MSCs) anti-oxidative, anti-apoptotic, autophagy modulation, and pro-mitochondria homeostasis therapeutic potential curtailed T2DM-DKD progression. For that purpose, we grew immortalized glomerular mesangial cells (GMCs) in hyper glucose media containing hydrogen peroxide. MSCs prevented these cells from apoptosis-induced cell death, ROS accumulation, and mitochondria membrane potential impairment. Additionally, MSCs recovered GMCs’ biogenesis and mitophagy-related gene expression that were downregulated by stress media. In BTBRob/ob mice, a robust model of T2DM-DKD and obesity, MSC therapy (1 × 106 cells, two doses 4-weeks apart, intra-peritoneal route) led to functional and structural kidney improvement in a time-dependent manner. Therefore, MSC-treated animals exhibited lower levels of urinary albumin-to-creatinine ratio, less mesangial expansion, higher number of podocytes, up-regulation of mitochondria-related survival genes, a decrease in autophagy hyper-activation, and a potential decrease in cleaved-caspase 3 expression. Collectively, these novel findings have important implications for the advancement of cell therapy and provide insights into cellular and molecular mechanisms of MSC-based therapy in T2DM-DKD setting.

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Section: Discussionmentioning

confidence: 99%

Therapeutic Potential of Mesenchymal Stem Cells in a Pre-Clinical Model of Diabetic Kidney Disease and Obesity

Sávio-Silva

Soinski-Sousa

Simplício-Filho

et al. 2021

IJMS

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“…Blood pressure also needs to be well regulated, including use of renin angiotensin-aldosterone system (RAAS) inhibitors when complications appear [ 34 , 35 ]. Recently, SGLT-2-inhibitors have shown promising results in preventing renal complications in large randomized trials of patients with T2D [ 36 ]. Indications also exist in T1D patients; these agents might have specific renal protective effects in addition to the HbA1c-lowering effect.…”

Section: Discussionmentioning

confidence: 99%

Renal Complications and Duration of Diabetes: An International Comparison in Persons with Type 1 Diabetes

et al. 2021

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Introduction: Renal complications are both a marker of previous suboptimal glycaemic control and a major risk factor for cardiovascular disease in persons with type 1 diabetes (T1D). The aim of the study was to evaluate the prevalence of renal complications in persons with T1D in four geographical regions. Methods: Nationwide registry data from Austria/Germany, Sweden and the US were used to estimate the prevalence of renal complications from January 2016 until September 2018.Chronic kidney disease (CKD) and albuminuria in the study population and each registry were analysed by diabetes duration. Risk factors for renal complications were described by registry. Results: In the total cohort of 78.926 adults with T1D, mean age was 44.4 ± 18.43 years and mean diabetes duration was 21.6 ± 22 years. Mean estimated glomerular filtration rate (eGFR) was 94.0 ± 31.45 ml/min, 13.0% had microalbuminuria and 3.9% had macroalbuminuria. Mean age, diabetes duration, use of insulin pumps and continuous glucose monitoring, as well as presence of albuminuria, varied between registries. Albuminuria was present in approximately 10% of persons with diabetes

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“…SGLT1 is located on the lumina of the small intestine with smaller amounts in other parts of the gastrointestinal tract of humans [34,35] . SGLT1 in the gut transports glucose and galactose from the gut lumen across the gut wall [34] . SGLT1 is also located in the late proximal tubule of the nephrons of the kidney.…”

Section: Location and Mechanism Of The Sglt Receptorsmentioning

confidence: 99%

Sodium Glucose Cotransporter-2 Inhibitors: An Overview from Evolution to Clinical Implications

Ravi,

Balasubramaniam,

Dhingra

et al. 2024

IJPS

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The rise in comorbid conditions with type 2 diabetes requires novel drug targets which benefits not only in glycaemic management but provide beneficial effects to other co-existing conditions too. One such drug available in market is the sodium glucose cotransport-2 inhibitor which is known for its pleiotropic effects. Keyword based comprehensive search was made in PubMed, Scopus and Google Scholar. Critical appraisal of all the collected literature was done and the key findings were used. The novel class of oral anti-diabetics act by reducing hyperglycaemia by rising urinary glucose excretion independently of insulin secretion or action. Clinical trials have shown its effects not only in controlling glycaemic levels but other effects such as reducing hypertension, providing cardiovascular benefits and positive renal outcomes too. Despite the positive outcomes, a segment of adverse effects such as lower limb amputations, risk of genital infections has set as drawbacks to bringing the drug into extensive clinical practice. This review provides an overview of the current evidence available so far on the therapeutic potential of the sodium glucose cotransporter-2 inhibitors for the treatment of type 2 diabetes mellitus and suggests the use of drug into practice to obtain evidences at a large level.

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Renal Effects of Sodium-Glucose Co-Transporter Inhibitors

Cited by 8 publications

References 45 publications

Therapeutic Potential of Mesenchymal Stem Cells in a Pre-Clinical Model of Diabetic Kidney Disease and Obesity

Therapeutic Potential of Mesenchymal Stem Cells in a Pre-Clinical Model of Diabetic Kidney Disease and Obesity

Renal Complications and Duration of Diabetes: An International Comparison in Persons with Type 1 Diabetes

Sodium Glucose Cotransporter-2 Inhibitors: An Overview from Evolution to Clinical Implications

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