scholarly journals Glycemic control by the SGLT2 inhibitor empagliflozin decreases aortic stiffness, renal resistivity index and kidney injury

2018 ◽  
Vol 17 (1) ◽  
Author(s):  
Annayya R. Aroor ◽  
Nitin A. Das ◽  
Andrea J. Carpenter ◽  
Javad Habibi ◽  
Guanghong Jia ◽  
...  
2017 ◽  
Vol 313 (4) ◽  
pp. F951-F954 ◽  
Author(s):  
Danielle L. Saly ◽  
Mark A. Perazella

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.


2021 ◽  
Vol 22 (9) ◽  
pp. 4374
Author(s):  
Tomoaki Takata ◽  
Hajime Isomoto

Diabetes mellitus is a major cause of chronic kidney disease and end-stage renal disease. However, the management of chronic kidney disease, particularly diabetes, requires vast improvements. Recently, sodium-glucose cotransporter-2 (SGLT2) inhibitors, originally developed for the treatment of diabetes, have been shown to protect against kidney injury via glycemic control, as well as various other mechanisms, including blood pressure and hemodynamic regulation, protection from lipotoxicity, and uric acid control. As such, regulation of these mechanisms is recommended as an effective multidisciplinary approach for the treatment of diabetic patients with kidney disease. Thus, SGLT2 inhibitors are expected to become key drugs for treating diabetic kidney disease. This review summarizes the recent clinical evidence pertaining to SGLT2 inhibitors as well as the mechanisms underlying their renoprotective effects. Hence, the information contained herein will advance the current understanding regarding the pleiotropic effects of SGLT2 inhibitors, while promoting future research in the field.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A331-A331
Author(s):  
Matthew J Budoff ◽  
Timothy M E Davis ◽  
Alexandra G Palmer ◽  
Robert Frederich ◽  
David E Lawrence ◽  
...  

Abstract Introduction: Ertugliflozin (ERTU), a sodium-glucose cotransporter 2 (SGLT2) inhibitor, is approved as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus (T2DM). Aim: As a pre-specified sub-study of the Phase 3 VERTIS CV trial (NCT01986881), the efficacy and safety of ERTU were assessed in patients with T2DM and established atherosclerotic cardiovascular disease (ASCVD) inadequately controlled with metformin and sulfonylurea (SU). Methods: Patients with T2DM, established ASCVD, and HbA1c 7.0–10.5% on stable metformin (≥1500 mg/day) and SU doses as defined per protocol were randomized to once-daily ERTU (5 mg or 15 mg) or placebo. The primary sub-study objectives were to assess the effect of ERTU on HbA1c compared with placebo and to evaluate safety and tolerability during 18-week follow-up. Key secondary endpoints included proportion of patients achieving HbA1c <7%, fasting plasma glucose (FPG), body weight, and systolic blood pressure. Changes from baseline at Week 18 for continuous efficacy endpoints were assessed using a constrained longitudinal data analysis model. Results: Of the 8246 patients enrolled in the VERTIS CV trial, 330 patients were eligible for this sub-study (ERTU 5 mg, n=100; ERTU 15 mg, n=113; placebo, n=117). Patients had a mean (SD) age of 63.2 (8.4) years, T2DM duration 11.4 (7.4) years, estimated glomerular filtration rate 83.5 (17.8) mL/min/1.73 m2, and HbA1c 8.3% (1.0) (67.4 [10.6] mmol/mol). At Week 18, ERTU 5 mg and 15 mg were each associated with a significantly greater least squares mean (95% CI) HbA1c reduction from baseline versus placebo; the placebo-adjusted differences for ERTU 5 mg and 15 mg were –0.7% (–0.9, –0.4) and –0.8% (–1.0, –0.5), respectively (P<0.001). A higher proportion of patients in each ERTU group achieved HbA1c <7% relative to placebo (P<0.001). ERTU significantly reduced FPG and body weight (P<0.001, for each dose versus placebo), but not systolic blood pressure. Adverse events were reported in 48.0%, 54.9%, and 47.0% of patients in the ERTU 5 mg, 15 mg, and placebo groups, respectively. Genital mycotic infections were experienced by significantly higher proportions of male patients who received ERTU 5 mg and 15 mg (4.2% and 4.8%, respectively) versus placebo (0.0%; P≤0.05) and by a numerically, but not significantly, higher proportion of female patients who received ERTU 15 mg (10.3%) compared with placebo (3.8%) (P=0.36). The incidences of symptomatic hypoglycemia were 11.0% (5 mg), 12.4% (15 mg), and 7.7% (placebo), and of severe hypoglycemia 2.0% (5 mg), 1.8% (15 mg), and 0.9% (placebo). Conclusion: Among patients with T2DM and ASCVD, ERTU (5 mg and 15 mg) added to metformin and SU for 18 weeks improved glycemic control (HbA1c and FPG) and reduced body weight, and was generally well tolerated with a safety profile consistent with the SGLT2 inhibitor class.


2021 ◽  
Vol 15 (3) ◽  
pp. 225-228
Author(s):  
Aline de Sousa Alves ◽  
Fernanda Vieira Henrique ◽  
Sabrina Barros Araújo ◽  
Dayanny de Sousa Alencar ◽  
Higina Moreira Melo ◽  
...  

This study aimed to evaluate the renal function of six bitches of various breeds and ages, with open pyometra, attended in the Small Animal Medical Clinic sector of the Veterinary Hospital from Federal University of Campina Grande, through the measurement of laboratory tests: urea and creatinine serum, dosage of the urinary Protein-Creatinine Ratio (PCR), urinary gamma-glutamyltransferase (GGT) and determination of the renal resistivity index (RI). The levels of urea and creatinine were elevated in 16.6% (1/6) of the female dogs; the urinary protein-creatinine ratio was increased in 66.6% (4/6), while the urinary gamma-glutamyltransferase value was elevated in 50% (3/6). The renal resistivity index was increased in the right and left kidneys by 66.6% (4/6) of bitches, with no statistical difference between them. It was concluded that the renal resistivity index was a practical and effective method to assist in the diagnosis of acute kidney injury, along with other early markers, such as PCR and urinary GGT.


2009 ◽  
Vol 609 (1-3) ◽  
pp. 148-154 ◽  
Author(s):  
Yoshikazu Fujimori ◽  
Kenji Katsuno ◽  
Kazuma Ojima ◽  
Ikumi Nakashima ◽  
Shigeru Nakano ◽  
...  

2020 ◽  
Vol 76 (1) ◽  
pp. 144-147 ◽  
Author(s):  
Gautam Phadke ◽  
Amit Kaushal ◽  
Dean R. Tolan ◽  
Kai Hahn ◽  
Thomas Jensen ◽  
...  

2020 ◽  
Vol 318 (4) ◽  
pp. F1017-F1029 ◽  
Author(s):  
Judit Hodrea ◽  
Dora B. Balogh ◽  
Adam Hosszu ◽  
Lilla Lenart ◽  
Balazs Besztercei ◽  
...  

Diabetic kidney disease is a worldwide epidemic, and therapies are incomplete. Clinical data suggest that improved renal outcomes by Na+-glucose cotransporter 2 inhibitor (SGLT2i) are partly beyond their antihyperglycemic effects; however, the mechanisms are still elusive. Here, we investigated the effect of the SGLT2i dapagliflozin (DAPA) in the prevention of elevated O-GlcNAcylation and tubular hypoxia as contributors of renal fibrosis. Type 1 diabetes was induced by streptozotocin in adult male Wistar rats. After the onset of diabetes, rats were treated for 6 wk with DAPA or DAPA combined with losartan (LOS). The effect of hyperglycemia was tested in HK-2 cells kept under normal or high glucose conditions. To test the effect of hypoxia, cells were kept in 1% O2 for 2 h. Cells were treated with DAPA or DAPA combined with LOS. DAPA slowed the loss of renal function, mitigated renal tubular injury markers (kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin), and reduced tubulointerstitial fibrosis. DAPA diminished high glucose-induced protein O-GlcNAcylation and moderated the tubular response to hypoxia through the hypoxia-inducible factor pathway. DAPA alone was as effective as combined treatment with LOS in all outcome parameters. These data highlight the role of ameliorated O-GlcNAcylation and diminished tubular hypoxia as important benefits of SGLT2i treatment. Our results support the link between glucose toxicity, tubular hypoxia, and fibrosis, a vicious trio that could be targeted by SGLT2i in kidney diseases of other origins as well.


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