SGLT-2 inhibitors and nephroprotection: current evidence and future perspectives

Piperidou, Alexia; Loutradis, Charalampos; Sarafidis, Pantelis

doi:10.1038/s41371-020-00393-4

Cited by 38 publications

(28 citation statements)

References 102 publications

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“…It is therefore vital to identify those at higher risk of nephropathy to be able to enhance monitoring and possibly to intervene at an early stage to slow down renal decline. Interventions include intensified glycaemic control; nephroprotective glucose lowering drugs, including glucagon-like peptide 1 receptor antagonists and sodium-glucose cotransporter 2 inhibitors; blood pressure control; and renin-angiotensin system inhibition 14151617. More stringent glycaemic control has been suggested to reduce the development and worsening of nephropathy 13.…”

Section: Discussionmentioning

confidence: 99%

“…Interventions include intensified glycaemic control; nephroprotective glucose lowering drugs, including glucagon-like peptide 1 receptor antagonists and sodium-glucose cotransporter 2 inhibitors; blood pressure control; and renin-angiotensin system inhibition. [14][15][16][17] More stringent glycaemic control has been suggested to reduce the development and worsening of nephropathy. 13 Prediction models will help to estimate the risk of diabetic kidney disease, especially when the models are based on routine clinical markers.…”

Section: Discussionmentioning

confidence: 99%

“…Preventive treatment includes intensified glycaemic control, nephroprotective glucose lowering drugs such as glucagon-like peptide 1 receptor antagonists and sodium-glucose cotransporter 2 inhibitors, blood pressure control, and inhibition of the reninangiotensin system. [14][15][16][17] Moreover, treatment with glucose lowering drugs such as sodium-glucose cotransporter 2 inhibitors has been suggested to prevent the progression of renal disease. 18 Treatment of end stage renal disease comprises renal replacement therapy with dialysis and transplantation.…”

Section: Introductionmentioning

confidence: 99%

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Performance of prediction models for nephropathy in people with type 2 diabetes: systematic review and external validation study

Slieker

Heijden

Siddiqui

et al. 2021

BMJ

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Objectives To identify and assess the quality and accuracy of prognostic models for nephropathy and to validate these models in external cohorts of people with type 2 diabetes. Design Systematic review and external validation. Data sources PubMed and Embase. Eligibility criteria Studies describing the development of a model to predict the risk of nephropathy, applicable to people with type 2 diabetes. Methods Screening, data extraction, and risk of bias assessment were done in duplicate. Eligible models were externally validated in the Hoorn Diabetes Care System (DCS) cohort (n=11 450) for the same outcomes for which they were developed. Risks of nephropathy were calculated and compared with observed risk over 2, 5, and 10 years of follow-up. Model performance was assessed based on intercept adjusted calibration and discrimination (Harrell’s C statistic). Results 41 studies included in the systematic review reported 64 models, 46 of which were developed in a population with diabetes and 18 in the general population including diabetes as a predictor. The predicted outcomes included albuminuria, diabetic kidney disease, chronic kidney disease (general population), and end stage renal disease. The reported apparent discrimination of the 46 models varied considerably across the different predicted outcomes, from 0.60 (95% confidence interval 0.56 to 0.64) to 0.99 (not available) for the models developed in a diabetes population and from 0.59 (not available) to 0.96 (0.95 to 0.97) for the models developed in the general population. Calibration was reported in 31 of the 41 studies, and the models were generally well calibrated. 21 of the 64 retrieved models were externally validated in the Hoorn DCS cohort for predicting risk of albuminuria, diabetic kidney disease, and chronic kidney disease, with considerable variation in performance across prediction horizons and models. For all three outcomes, however, at least two models had C statistics >0.8, indicating excellent discrimination. In a secondary external validation in GoDARTS (Genetics of Diabetes Audit and Research in Tayside Scotland), models developed for diabetic kidney disease outperformed those for chronic kidney disease. Models were generally well calibrated across all three prediction horizons. Conclusions This study identified multiple prediction models to predict albuminuria, diabetic kidney disease, chronic kidney disease, and end stage renal disease. In the external validation, discrimination and calibration for albuminuria, diabetic kidney disease, and chronic kidney disease varied considerably across prediction horizons and models. For each outcome, however, specific models showed good discrimination and calibration across the three prediction horizons, with clinically accessible predictors, making them applicable in a clinical setting. Systematic review registration PROSPERO CRD42020192831.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Performance of prediction models for nephropathy in people with type 2 diabetes: systematic review and external validation study

Slieker

Heijden

Siddiqui

et al. 2021

BMJ

View full text Add to dashboard Cite

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“…This is due to the afferent renal vessels' dilation. SGLT2 are able to restore the tubulo-glomerular feedback, bringing more sodium to the macula densa, reducing the afferent vessels vasodilation, the intraglomerular pressure, and the albuminuria of about 40%, slowing down the kidney damage [51]. Dapagliflozin did not cause electrolyte imbalances in a study comparing it to Gliclazide [52].…”

Section: The Pleiotropic Effects Of Sodium-glucose Cotransporter 2 Inhibitors: Molecular and Pathophysiological Insightsmentioning

confidence: 98%

Sodium-glucose cotransporter 2 inhibitors and heart failure: the best timing for the right patient

et al. 2021

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Sodium-glucose cotransporter 2 inhibitors (SGLT2i), initially born as anti-diabetic drugs, have shown many beneficial effects on the cardiovascular system, in particular against heart failure (HF). HF is a complex and multifaceted disease that requires a comprehensive approach. It should not be considered as a simplistic cardiac disease, but a systemic disease that leads to multisystemic organ failure and death. Exploiting their pleiotropic effects, SGLT2i are a very valid tool for HF treatment. Beyond the indication to reduce HF hospitalization and death risk, in patients with diabetes mellitus at high cardiovascular risk or with established cardiovascular event, SGLT2i administration reported beneficial effects regarding the wide spectrum of HF manifestations and stages, independently by diabetes mellitus presence. Recent evidence focuses on HF rehospitalization, cardiac and all-cause death reduction, as well as symptoms and quality of life improvement, in patients with chronic HF or with a recent HF decompensation episode. Given the recent finding about the SGLT2i usefulness in HF patients, further studies are needed to define the best administration timing to maximize the SGLT2i-derived beneficial effects.

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“…In this 2021 update, it is also noted that the accumulated evidence in the past few years clearly suggests that SGLT2inhibitors have potent nephroprotective properties. In a recent paper published in 2021, Piperidou, Loutradis, and Sarafidis 19 noted that in clinical trials in patients with T2DM, SGLT-2 inhibitors were shown to reduce albuminuria and proteinuria by 30-50 percent and the incidence of composite heard renal outcomes by 40-50 percent.…”

Section: Review Of Antihypertensives For Treating Hypertension In Diabetesmentioning

confidence: 99%

Proteinuria and Hypertension with and without Type 2 Diabetes Mellitus: 2021 Update

2021

SFP

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INTRODUCTION. This 2021 paper is an update of the 2019 version. In this current update, two new items of information added. Firstly, the 2020 Consensus statement of the Taiwan Hypertension Society and the Taiwan Society of Cardiology on HPDM, provided recommendations on additional medications to be considered in uncontrolled morning or night blood pressure (BP) are noted. 9 Secondly, the nephroprotective properties of the SGLT-2 inhibitors are highlighted. 19 Similar to the content of the 2019 version, four related areas are reviewed. They are (1) BP definition and classification; (2) Hypertension diagnosis; (3) Hypertension and proteinuria in non-diabetic patients; and (4) Proteinuria and hypertension in the patient with diabetes. METHODOLOGY. PubMed searches were done for papers to the above four topics published in the last five years (2014 to 2019). These were supplemented by papers from hand searches. RESULTS. For diagnosis of hypertension, the current cut off of 140/90 mmHg can be reduced to 130/80 to improve cardiovascular outcomes and all-cause mortality. Diagnosis of hypertension should not be based on office BP readings alone. Hypertension in older patients should be treated to prevent worse outcomes and should be individualised. In non-diabetic patients, both low grade and microalbuminuria needs to be treated; adequate BP control is needed to prevent cardiovascular outcomes and all-cause mortality. In the diabetic patient, a BP target of less than 140/90 mmHg applies to most patients, but individualisation of the BP goal is important. CONCLUSIONS. Much development in the management of proteinuria and hypertension has taken place in the last five years.

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SGLT-2 inhibitors and nephroprotection: current evidence and future perspectives

Cited by 38 publications

References 102 publications

Performance of prediction models for nephropathy in people with type 2 diabetes: systematic review and external validation study

Performance of prediction models for nephropathy in people with type 2 diabetes: systematic review and external validation study

Sodium-glucose cotransporter 2 inhibitors and heart failure: the best timing for the right patient

Proteinuria and Hypertension with and without Type 2 Diabetes Mellitus: 2021 Update

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