Sodium glucose cotransporter 2 and the diabetic kidney

Komala, Muralikrishna Gangadharan; Panchapakesan, Usha; Pollock, Carol; Mather, Amanda

doi:10.1097/mnh.0b013e32835a17ae

Cited by 58 publications

(49 citation statements)

References 46 publications

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“…Interestingly, SGLT2 inhibitors also have renal hemodynamic effects, including reducing glomerular hyperfiltration (11), as well as inhibitory effects on the inflammatory and fibrotic responses of proximal tubular cells to hyperglycemia (12). The SGLT2 is localized to the proximal tubule and is responsible for ;90% of the reabsorption of the glucose filtered by the kidney.…”

mentioning

confidence: 99%

“…Several review articles, primarily in nephrological journals (11,12,(17)(18)(19)(20), have considered the potential nephroprotective effects of SGLT2 inhibitors. The present review will emphasize considerations for the diabetologist, especially in discussion of the use and limitations of SGLT2 inhibitors in improving glucose control in patients with chronic kidney disease (CKD).…”

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confidence: 99%

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SGLT2 Inhibitors and the Diabetic Kidney

et al. 2016

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Diabetic nephropathy (DN) is the most common cause of end-stage renal disease worldwide. Blood glucose and blood pressure control reduce the risk of developing this complication; however, once DN is established, it is only possible to slow progression. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, the most recent glucose-lowering oral agents, may have the potential to exert nephroprotection not only through improving glycemic control but also through glucose-independent effects, such as blood pressure-lowering and direct renal effects. It is important to consider, however, that in patients with impaired renal function, given their mode of action, SGLT2 inhibitors are less effective in lowering blood glucose. In patients with high cardiovascular risk, the SGLT2 inhibitor empagliflozin lowered the rate of cardiovascular events, especially cardiovascular death, and substantially reduced important renal outcomes. Such benefits on DN could derive from effects beyond glycemia. Glomerular hyperfiltration is a potential risk factor for DN. In addition to the activation of the renin-angiotensin-aldosterone system, renal tubular factors, including SGLT2, contribute to glomerular hyperfiltration in diabetes. SGLT2 inhibitors reduce sodium reabsorption in the proximal tubule, causing, through tubuloglomerular feedback, afferent arteriole vasoconstriction and reduction in hyperfiltration. Experimental studies showed that SGLT2 inhibitors reduced hyperfiltration and decreased inflammatory and fibrotic responses of proximal tubular cells. SGLT2 inhibitors reduced glomerular hyperfiltration in patients with type 1 diabetes, and in patients with type 2 diabetes, they caused transient acute reductions in glomerular filtration rate, followed by a progressive recovery and stabilization of renal function. Interestingly, recent studies consistently demonstrated a reduction in albuminuria. Although these data are promising, only dedicated renal outcome trials will clarify whether SGLT2 inhibitors, in addition to their glycemic and blood pressure benefits, may provide nephroprotective effects.Diabetes is a worldwide growing public health problem with high risks of severe microvascular and macrovascular complications. Diabetic nephropathy (DN) is a major burden among the chronic complications of diabetes, given that it affects ;30% of patients with diabetes. Indeed, DN is the most common cause of end-stage renal disease in the U.S. (1) and worldwide. Known risk factors for DN include hyperglycemia, hypertension, dyslipidemia, smoking, and obesity as well as ethnic, familial, and genetic predispositions (2). Key clinical trials have demonstrated that early interventions, especially those aimed at primary prevention, are by far more effective and that it is only possible to slow progression once DN is established (2). Thus, large intervention trials on the impact of long-term intensified glucose control on chronic diabetes complications, both in type 1 and type 2 diabetes (2-6), have documented the critical role of glycemic control i...

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SGLT2 Inhibitors and the Diabetic Kidney

et al. 2016

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“…Animal studies have demonstrated that SGLT2 inhibitors decrease glomerular inflammation and fibrosis, and reduce albuminuria. 32 The results of an extension of the EMPA-REG OUTCOME trial demonstrated that empagliflozin had favourable renal outcomes in patients with severe renal impairment and diabetes, and this could encourage broader use of such drugs in patients with diabetic nephropathy in the future. 34 The most common side-effects of SGLT2 inhibitors are polyuria and increased risk of bacterial and fungal genitourinary infections.…”

Section: Sglt2 Inhibitorsmentioning

confidence: 99%

“…They act by reducing glucose and sodium reabsorption in the proximal tubule, causing tubuloglomerular feedback, afferent arteriole vasoconstriction and reduction in hyperfiltration. 32,33 In patients with type 2 diabetes, they give rise to a transient reduction in eGFR. Animal studies have demonstrated that SGLT2 inhibitors decrease glomerular inflammation and fibrosis, and reduce albuminuria.…”

Section: Sglt2 Inhibitorsmentioning

confidence: 99%

Managing diabetes in the presence of renal impairment

Goodchild¹,

Chowdhury²

2017

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“…Adenosine triggers vasoconstriction of the afferent arteriole with reduction of intraglomerular pressure [49][50][51]. In addition, reduced glucose passage across the proximal tubular cells may lead to decreased oxidative stress, inflammation, and tubuleinterstitial fibrosis [52].…”

Section: Dapagliflozin In Special Populationsmentioning

confidence: 99%

A consensus statement for the clinical use of the renal sodium-glucose co-transporter-2 inhibitor dapagliflozin in patients with type 2 diabetes mellitus

Avogaro

Giaccari

Fioretto

et al. 2017

Expert Review of Clinical Pharmacology

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Introduction: The present review developed a clinical consensus based on a Delphi method on Dapagliflozin, a selective inhibitor of the renal sodium-glucose co-transporter-2 (SGLT2-I) in the treatment of patients with Type 2 diabetes mellitus. Areas covered: Panel members, using a 5-point scale, were asked to rate 9 statements on pharmakodinamic, mode of action on glycaemic and extra-glycaemic effects, and safety of dapaglifozin, Members also aimed to identify the patient most susceptible to the treatment with dapagliflozin . Expert commentary: Dapagliflozin is effective in lowering the plasma glucose concentration with a good safety profile. Dapagliflozin can be utilized in combination with all other antihyperglycaemic agents at all stages of the disease: however, a reduced GFR limits its efficacy. As for the other drugs of the class, Dapagliflozin positively modifies other risk factors for CV disease: these effects will be tested in the so far largest cardiovascular outcome trial for the SGLT2 inhibitors so far, the DECLARE trial, which will communicate whether this class of drugs will be disease-modifier in patients with type 2 diabetes also in primary prevention.

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Sodium glucose cotransporter 2 and the diabetic kidney

Cited by 58 publications

References 46 publications

SGLT2 Inhibitors and the Diabetic Kidney

SGLT2 Inhibitors and the Diabetic Kidney

Managing diabetes in the presence of renal impairment

A consensus statement for the clinical use of the renal sodium-glucose co-transporter-2 inhibitor dapagliflozin in patients with type 2 diabetes mellitus

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