2354-PUB: Estimating Improvement of TGF Mechanism from Changes of Urinary Glucose and Sodium Excretion by SGLT2 Inhibitors

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 2354-PUB
Author(s):  
CHIZURU WATANABE ◽  
YASUMICHI MORI
Keyword(s):  
Sodium Excretion ◽  
Sglt2 Inhibitors ◽  
Urinary Glucose

scholarly journals Harnessing basic and clinic tools to evaluate SGLT2 inhibitor nephrotoxicity

2017 ◽  
Vol 313 (4) ◽  
pp. F951-F954 ◽  
Author(s):  
Danielle L. Saly ◽  
Mark A. Perazella
Keyword(s):  
Early Stage ◽  
Functional Decline ◽  
Healthcare Providers ◽  
Sglt2 Inhibitor ◽  
Kidney Injury ◽  
Renin Angiotensin System ◽  
Sglt2 Inhibitors ◽  
Diabetic Patients ◽  
Chip Technology ◽  
Urinary Glucose

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a new class of medications that target the transporter that reabsorbs ~90% of glucose in the S1 segment of the proximal convoluted tubule. As a result, SGLT2 inhibition increases urinary glucose excretion, effectively lowering plasma glucose levels. In addition to reducing hemoglobin A1c levels, these drugs also lower body weight, blood pressure, and uric acid levels in Type 2 diabetes mellitus (T2DM) patients. Importantly, empagliflozin has been observed to slow progression of kidney disease and reduce dialysis requirements in T2DM patients. However, the Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS) has collected over 100 cases of acute kidney injury (AKI) for canagloflozin and dapagliflozin since their approval. Of the 101 patients, 96 required hospitalization, 22 required intensive care unit admission, and 15 underwent hemodialysis. The FDA now requires that AKI be listed as a potential side effect of the SGLT2 inhibitors along with cautious prescription of these drugs with other medications, such as renin-angiotensin-system antagonists, diuretics, and NSAIDs. It is unclear, however, whether this FAERS reported “AKI” actually represents structural kidney injury, as randomized, controlled trials of these drugs do not describe AKI as an adverse event despite coprescription with RAS blockers and diuretics. As a result of this FDA warning, diabetic patients with early-stage CKD may not be prescribed an SGLT2 inhibitor for fear of AKI. Thus, it is imperative to ascertain whether the reported AKI represents true structural kidney injury or a functional decline in glomerular filtration rate. We propose using readily available clinical tools with experimental biomarkers of kidney injury and kidney-on-a-chip technology to resolve this question and provide solid evidence about the AKI risk of these drugs for healthcare providers.

scholarly journals Effects of SGLT2 Inhibitors on Kidney and Cardiovascular Function

2020 ◽  
Vol 83 (1) ◽  
Author(s):  
Volker Vallon ◽  
Subodh Verma
Keyword(s):  
Ketone Bodies ◽  
Heart Function ◽  
Oxygen Demand ◽  
Sglt2 Inhibitors ◽  
Annual Review ◽  
Publication Date ◽  
Protective Mechanisms ◽  
Filtration Barrier ◽  
Urinary Glucose ◽  
Resistance To Diuretics

SGLT2 inhibitors are antihyperglycemic drugs that protect kidneys and the heart of patients with or without type 2 diabetes and preserved or reduced kidney function from failing. The involved protective mechanisms include blood glucose–dependent and –independent mechanisms: SGLT2 inhibitors prevent both hyper- and hypoglycemia, with expectedly little net effect on HbA1C. Metabolic adaptations to induced urinary glucose loss include reduced fat mass and more ketone bodies as additional fuel. SGLT2 inhibitors lower glomerular capillary hypertension and hyperfiltration, thereby reducing the physical stress on the filtration barrier, albuminuria, and the oxygen demand for tubular reabsorption. This improves cortical oxygenation, which, together with lesser tubular gluco-toxicity, may preserve tubular function and glomerular filtration rate in the long term. SGLT2 inhibitors may mimic systemic hypoxia and stimulate erythropoiesis, which improves organ oxygen delivery. SGLT2 inhibitors are proximal tubule and osmotic diuretics that reduce volume retention and blood pressure and preserve heart function, potentially in part by overcoming the resistance to diuretics and atrial-natriuretic-peptide and inhibiting Na-H exchangers and sympathetic tone. Expected final online publication date for the Annual Review of Physiology, Volume 83 is February 10, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Multicentre prospective observational study of sodium-glucose cotransporter-2 inhibitor-associated postoperative ketoacidosis: the SAPKA study protocol

BMJ Open ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. e049592
Author(s):  
Hiroyuki Seki ◽  
Norifumi Kuratani ◽  
Toshiya Shiga ◽  
Yudai Iwasaki ◽  
Kanae Karita ◽  
...  
Keyword(s):  
Observational Study ◽  
General Anaesthesia ◽  
Study Protocol ◽  
Prospective Observational Study ◽  
Surgical Stress ◽  
Sglt2 Inhibitor ◽  
Sglt2 Inhibitors ◽  
Sodium Glucose Cotransporter ◽  
Urinary Glucose ◽  
Tract Infections

IntroductionSodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of antihyperglycaemic agents that promote urinary glucose excretion in the renal proximal tubule and have cardio-protective and renal-protective properties. However, there are several safety concerns related to increased risks of hypoglycaemic, urinary tract infections and ketoacidosis. Ketoacidosis is a potentially fatal complication that often presents as euglycaemic ketoacidosis during SGLT2 inhibitor treatment. Furthermore, invasive treatment and related surgical stress may increase the risk of ketogenesis. Therefore, this study aims to clarify the incidence of SGLT2 inhibitor-associated postoperative ketoacidosis (SAPKA) among patients who are receiving SGLT2 inhibitors and undergoing surgery under general anaesthesia.Methods and analysisThis multicentre, prospective, observational study will recruit 750 adult Japanese patients with diabetes who are receiving SGLT2 inhibitors and undergoing surgery under general anaesthesia. Urine samples will be collected on postoperative days 0, 1, 2 and 3. Blood gas analysis will be performed when urine ketone positivity is detected. The incidence of postoperative ketoacidosis will be identified based on urine ketone positivity and a blood pH of ≤7.3. The study will also collect data to identify risk factors for SAPKA.Ethics and disseminationThe study protocol has been approved by the ethics committee of Kyorin University (approval number: 785, 26 October 2020) and local ethical approval will be required at each participating centre. Study findings will be submitted to peer-reviewed journals and abstracts will be submitted to relevant national and international meetings.Trial registration numberUMIN000042795

scholarly journals Natriuretic Effect of Two Weeks of Dapagliflozin Treatment in Patients With Type 2 Diabetes and Preserved Kidney Function During Standardized Sodium Intake: Results of the DAPASALT Trial

2020 ◽  
Author(s):  
Rosalie A. Scholtes ◽  
Marcel H.A. Muskiet ◽  
Michiel .J.B. van Baar ◽  
Anne C. Hesp ◽  
Peter J. Greasley ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Kidney Function ◽  
Plasma Volume ◽  
Sodium Excretion ◽  
Sodium Intake ◽  
Extracellular Volume ◽  
Treatment Change ◽  
Urinary Glucose

<b>Background: </b> <p>Sodium glucose co-transporter 2 (SGLT2) inhibitors reduce risk for heart failure hospitalization, potentially by inducing sodium excretion, osmotic diuresis and plasma volume contraction. Few studies have investigated this hypothesis, but none have assessed cumulative sodium excretion with SGLT2 inhibition during standardized sodium intake in patients with type 2 diabetes. </p> <p><b>Methods: </b></p> <p>DAPASALT (NCT03152084) was a mechanistic, non-randomized, open-label study in patients with type 2 diabetes with preserved kidney function, on a controlled standardized sodium diet (150 mmol/day). It evaluated the effects of dapagliflozin on sodium excretion, 24-hour blood pressure, and extracellular, intracellular and plasma volumes at start of treatment (ST; days 2-4), end of treatment (ET; days_12-14) and at follow-up (FU; days_15-18). </p> <p><b>Results:</b> </p> <p>Fourteen patients were included in the efficacy analysis. Mean [SD] baseline sodium excretion (150 [32] mmol/24-hours), did not significantly change during treatment (change at ST: -7.0 mmol/24-hours [95%CI: -22.4, 8.4]; change at ET 2.1 mmol/24-hours [95%CI: -28.8, 33.0]). Mean (SD) baseline 24-hour systolic blood pressure was 128 (10) mmHg and significantly reduced at ST (-6.1 mmHg [95%CI: -9.1, -3.1]; p<0.001) and ET (-7.2 mmHg [95%CI: -10.0, -4.3]; p<0.001). Dapagliflozin did not significantly alter plasma volume or intracellular volume, while extracellular volume changed at ST (-0.7 L [95%CI: -1.3, 0.1]; p=0.02). As expected, 24-hour urinary glucose excretion significantly increased during dapagliflozin treatment and reversed during FU. </p> <p><b>Conclusions:</b></p> <p>During standardized sodium intake, dapagliflozin reduced blood pressure without clear changes in urinary sodium excretion, suggesting that factors other than natriuresis and volume changes may contribute to the blood-pressure lowering effects. </p>

1097-P: Disposition Index Is a Predictor of Urinary Glucose Excretion in Subjects Treated with SGLT2 Inhibitors

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 1097-P
Author(s):  
KAZUHIKO SAKAGUCHI ◽  
ANNA SO ◽  
JUN ITO ◽  
AKIHIRO KANEKO ◽  
YASUKO MORITA ◽  
...  
Keyword(s):  
Sglt2 Inhibitors ◽  
Disposition Index ◽  
Urinary Glucose Excretion ◽  
Urinary Glucose ◽  
Glucose Excretion
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