scholarly journals Impact of sodium–glucose cotransporter 2 inhibitors on renal function in participants with type 2 diabetes and chronic kidney disease with normoalbuminuria

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Akinobu Nakamura ◽  
Hideaki Miyoshi ◽  
Hiraku Kameda ◽  
Kumiko Yamashita ◽  
Yoshio Kurihara
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Sglt2 Inhibitor ◽  
Sglt2 Inhibitors ◽  
Creatinine Ratio ◽  
Sodium Glucose Cotransporter ◽  
Clinical Records

Abstract Background We compared the effects of sodium–glucose cotransporter 2 (SGLT2) inhibitors on renal function in participants with type 2 diabetes and chronic kidney disease (CKD) classified by degree of albuminuria. Methods A retrospective review of the clinical records of Japanese participants with type 2 diabetes (age > 20 years; SGLT2 inhibitor treatment > 2 years; estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2) was conducted. Based on the urinary albumin-to-creatinine ratio (UACR) or urinary protein-to-creatinine ratio (UPCR) at the start of SGLT2 inhibitor administration, participants were categorized into three groups: normoalbuminuria (A1; UACR < 30 mg/g Cr or UPCR < 0.15 g/g Cr), microalbuminuria (A2; UACR 30 to < 300 mg/g Cr or UPCR 0.15 to < 0.50 g/g Cr), and macroalbuminuria (A3; UACR ≥ 300 mg/g Cr or UPCR ≥ 0.50 g/g Cr). The study outcome was a comparison of the rates of change in renal function evaluated by eGFR at 2 years after starting SGLT2 inhibitor among the three groups. Results A total of 87 participants (40 females, 47 males) were categorized into three groups: A1 (n = 46), A2 (n = 25), and A3 (n = 16). eGFR was similarly decreased at 2 years before starting SGLT2 inhibitor in all three groups. However, the decline in eGFR was ameliorated at 2 years after starting SGLT2 inhibitor, and eGFR was rather increased in the A1 and A2 groups. Interestingly, the rate of change in eGFR at 2 years after starting SGLT2 inhibitor in the A1 group was significantly higher than that in the A3 group. Conclusions These results demonstrate that more favorable effects of SGLT2 inhibitors on renal function were observed in participants with type 2 diabetes and CKD with normoalbuminuria compared with those with macroalbuminuria. Trial registration UMIN-CTR: UMIN000035263. Registered 15 December 2018

scholarly journals Initial dip predicts renal protective effects after the administration of sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes and chronic kidney disease with normoalbuminuria

2020 ◽  
Author(s):  
Kiyohiko Takahashi ◽  
Akinobu Nakamura ◽  
Sho Furusawa ◽  
Kei Yokozeki ◽  
Hajime Sugawara ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Control Group ◽  
Creatinine Ratio ◽  
Sodium Glucose Cotransporter ◽  
Initial Dip ◽  
Clinical Records

Abstract Background: We investigated the renoprotective effects of sodium-glucose cotransporter 2 inhibitors (SGLT2is) on renal function in patients with type 2 diabetes and chronic kidney disease (CKD) with normoalbuminuria. Methods: A retrospective review of clinical records of Japanese participants with type 2 diabetes and CKD (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m 2 ) with normoalbuminuria (urine albumin to creatinine ratio < 30 mg/g Cr and/or urinary protein to creatinine ratio < 150 mg/g Cr) was conducted. Participants were categorized into two groups depending on whether they had started using SGLT2is. The main study outcome was a comparison of the change in renal function evaluated by eGFR after 1 year (ΔeGFR + 1 y) between the two groups. Then, we identified predictors that were associated with the outcome. Results: Among the 48 participants, 21 were treated with SGLT2is (SGLT2 group) and 25 were treated with other antidiabetic medications (control group). Although eGFR was significantly decreased at 1 year in the control group, the decline in eGFR was not observed in the SGLT2 group. The change in eGFR was significantly greater in the SGLT2 group than in the control group (ΔeGFR + 1 year, -4.0 [-7.7 to -0.3] mL/min/1.73 m 2 in the control group, 0.9 [-3.9 to 5.7] mL/min/1.73 m 2 in the SGLT2 group; P = 0.0231). Additionally, multiple linear regression analysis showed that an initial dip was an independent factor associated with the worsening of renal function in the SGLT2 group. Conclusions: Although more favorable effects of SGLT2is on renal function were observed in patients with type 2 diabetes and CKD with normoalbuminuria, the higher initial dip was a possible marker of worsening renal function after the initiation of SGLT2is.

scholarly journals The Effect of Long-term Sodium-glucose Cotransporter 2 Inhibitor Treatment on Renal Function in the Patients with Type 2 Diabetes

2020 ◽  
Vol 95 (4) ◽  
pp. 236-243
Author(s):  
Jong Ha Baek ◽  
Tae Jung Oh ◽  
Ju-Young Moon ◽  
Taehee Kim ◽  
Seung Hyu Ko ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Renal Function ◽  
Kidney Disease ◽  
Sglt2 Inhibitor ◽  
Sglt2 Inhibitors ◽  
Renal Outcomes ◽  
Sodium Glucose Cotransporter ◽  
Inhibitor Treatment

Chronic kidney disease is developed commonly in type 2 diabetes mellitus (T2DM) and is the most common cause of end-stage renal disease and related cardiovascular complications. Meanwhile, despite the current standard of care including optimized glucose control and the use of single-agent blockade of the renin-angiotensin-aldosterone system (RAAS), patients with T2DM remain at increased risk for death and complications from cardiorenal causes. The recent studies using sodium-glucose cotransporter 2 (SGLT2) inhibitors have shown not only glucose lowering effect, but also a reduction in blood pressure, weight loss, and a lowering cardiovascular risk. Regarding renal outcomes, the use of SGLT2 inhibitor slows the progression of kidney disease compared to placebo when added to standard care. However, concern has been raised that currently available SGLT2 inhibitors in Korea may be also associated with improved renal outcomes with long-term treatment. As a result, we aimed to evaluate the effect of long-term SGLT2 inhibitor treatment on renal function in the patients with T2DM using meta-analysis. (Korean J Med 2020;95:236-243)

scholarly journals Roles of sodium-glucose cotransporter 2 of mesangial cells in diabetic kidney disease

2021 ◽  
Author(s):  
Masanori Wakisaka ◽  
Kuniyuki Nakamura ◽  
Toshiaki Nakano ◽  
Takanari Kitazono
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Nephropathy ◽  
Kidney Disease ◽  
Mesangial Cells ◽  
Sglt2 Inhibitor ◽  
Sglt2 Inhibitors ◽  
Urine Sodium ◽  
Sodium Glucose Cotransporter ◽  
Urine Sodium Excretion

Abstract We have been studying the presence of sodium-glucose cotransporter 2 (SGLT2) in mesangial cells and pericytes since 1992. Recent large placebo-controlled studies of SGLT2 inhibitors in patients with type 2 diabetes mellitus have reported desirable effects of the inhibitors on the diabetic kidney and the diabetic heart. Most studies have indicated that these effects of SGLT2 inhibitors could be mediated by the tubuloglomerular feedback (TGF) system. However, a recent study about urine sodium excretion in the presence of an SGLT2 inhibitor did not show any increases in urine sodium excretion. A very small dose of an SGLT2 inhibitor did not inhibit SGLT2 at the S1 segment of proximal tubules. Moreover, SGLT2 inhibition protects against progression in chronic kidney disease with and without type 2 diabetes. In these circumstances, the TGF hypothesis involves several theoretical concerns that must be clarified. The presence of SGLT2 in mesangial cells seems to be very important for diabetic nephropathy. We now propose a novel mechanism by which the desirable effects of SGLT2 inhibitors on diabetic nephropathy are derived from the direct effect on SGLT2 expressed in mesangial cells.

scholarly journals Sodium-glucose cotransporter 2 inhibitor effects on cardiovascular outcomes in chronic kidney disease

2020 ◽  
Vol 35 (Supplement_1) ◽  
pp. i43-i47 ◽  
Author(s):  
Oshini Shivakumar ◽  
Naveed Sattar ◽  
David C Wheeler
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Major Adverse Cardiovascular Event ◽  
Sglt2 Inhibitors ◽  
Adverse Cardiovascular Event ◽  
Sodium Glucose Cotransporter ◽  
Patients With Heart Failure

Abstract Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce cardiovascular events, specifically those related to heart failure in patients with type 2 diabetes. Reductions in major adverse cardiovascular event (MACE) outcomes are also observed, but confined largely to patients who have prior cardiovascular disease. Cardiovascular outcome benefits extend to patients with type 2 diabetes and reduced estimated glomerular filtration (eGFR) rate down to 30 mL/min/1.73 m2 and to patients with heart failure but without diabetes. Ongoing trials are exploring whether patients with chronic kidney disease (CKD) but without diabetes will gain similar benefits from this class of agents. Although some safety concerns have emerged, it seems likely that SGLT2 inhibitors will be used more widely in CKD patients to reduce their cardiovascular risk.

scholarly journals Sodium-Glucose Cotransporter-2 Inhibitors in Nephrology Practice: A Narrative Review

2020 ◽  
Vol 7 ◽  
pp. 205435812093570
Author(s):  
Lisa Dubrofsky ◽  
Anand Srivastava ◽  
David Z. Cherney
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Clinical Practice ◽  
Kidney Disease ◽  
Primary Care Physicians ◽  
Real Life ◽  
Atherosclerotic Cardiovascular Disease ◽  
Specific Patient ◽  
Sodium Glucose Cotransporter

Purpose of the review: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are recommended for eligible patients with type 2 diabetes for the secondary prevention of adverse cardiovascular and kidney disease outcomes. Patients with type 2 diabetes and albuminuric chronic kidney disease, a history of atherosclerotic cardiovascular disease, and/or heart failure with reduced ejection fraction should be assessed for the use of these therapies. Sources of information: The sources include published clinical trials with SGLT2is, with a focus on cardiovascular safety studies and kidney protection trials. Methods: Information was gathered via a review of relevant literature and clinical practice guidelines, incorporated with real-life clinical experience. Key findings: Clinicians prescribing these agents must be familiar with the benefits of SGLT2is on cardiovascular and renal endpoints, and with adverse effects of SGLT2is, including mycotic genital infections and diabetic ketoacidosis. Primary care physicians and specialists should know how to adjust antihypertensive, antiglycemic, and diuretic agents. With the results of completed cardiovascular outcome trials and the Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy trial, nephrologists specifically have a unique opportunity to impact the safe, effective, and equitable implementation of SGLT2is into clinical practice. Limitations: Further work is needed in specific patient subgroups, including patients with chronic kidney disease stages IV and V, patients with kidney disease but lower levels of albuminuria, and in patients without diabetes.

Cardiovascular Outcomes With the Use of Sodium-Glucose Cotransporter-2 Inhibitors in Patients With Type 2 Diabetes and Chronic Kidney Disease

2020 ◽  
Vol 28 (3) ◽  
pp. 116-124 ◽  
Author(s):  
Aaqib H. Malik ◽  
Srikanth Yandrapalli ◽  
Michael Goldberg ◽  
Diwakar Jain ◽  
William H. Frishman ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Cardiovascular Outcomes ◽  
Sodium Glucose Cotransporter
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