Renoprotective effects of canagliflozin, a sodium glucose cotransporter 2 inhibitor, in type 2 diabetes patients with chronic kidney disease: A randomized open-label prospective trial

Takashima, Hiroyuki; Yoshida, Yoshinori; Nagura, Chinami; Furukawa, T.; Tei, Ritsukou; Maruyama, Takashi; Maruyama, Noriaki; Abe, Masanori

doi:10.1177/1479164118782872

Cited by 45 publications

(52 citation statements)

References 12 publications

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“…Canagliflozin compared with glimepiride slowed the progression of renal disease over 2 years in patients with T2DM together with reductions in albuminuria and declines in eGFR independently of its glycaemic effects [137]. These renoprotective effects of canagliflozin were confirmed in a 1-year open-label study of Japanese T2DM patients with CKD, which also showed a reduction in tubulointerstitial markers [138]. The large-scale ongoing prospective Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) compares the efficacy and safety of canagliflozin vs. placebo in preventing clinically important kidney and CV outcomes (primary outcome is a composite of ESRD, doubling of serum creatinine and renal or CV death) in patients with T2DM and established CKD [139].…”

Section: Sglt2 Inhibitorsmentioning

confidence: 80%

Effects of glucose-lowering agents on surrogate endpoints and hard clinical renal outcomes in patients with type 2 diabetes

Scheen

2019

Diabetes & Metabolism

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Section: Sglt2 Inhibitorsmentioning

confidence: 80%

Effects of glucose-lowering agents on surrogate endpoints and hard clinical renal outcomes in patients with type 2 diabetes

Scheen

2019

Diabetes & Metabolism

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“…32 Canagliflozin could prevent the progression of tubulointerstitial damage, since urinary L-FABP, NAG, and β 2 MG levels were reported to be reduced by canagliflozin treatment. 33 Taken together, the increase in hematocrit during SGLT2 inhibitor therapy may indicate an improvement of hypoxia and oxidative stress in the tubulointerstitial region of the renal cortex, as well as the recovery of EPO production by interstitial fibroblast-like cells. However, the precise sequence of events starting from enhanced glycosuria to oxygen availability and stimulation of EPO production needs to be elucidated.…”

Section: Discussionmentioning

confidence: 93%

Canagliflozin Improves Erythropoiesis in Diabetes Patients with Anemia of Chronic Kidney Disease

Maruyama

Takashima

Oguma

et al. 2019

Diabetes Technology & Therapeutics

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Background: We evaluated the erythropoietic effects of canagliflozin, a sodium-glucose cotransporter 2 inhibitor, in type 2 diabetes patients with anemia of chronic kidney disease.Methods: Nine diabetes patients were enrolled and administered 100 mg canagliflozin once a day for 12 weeks. The patients received fixed doses of conventional antidiabetic drugs and renin-angiotensin system inhibitors for 8 weeks before enrollment; these drugs were continued during the study. Endpoints were changes in erythropoiesis parameters, including erythrocyte and reticulocyte count, hemoglobin, hematocrit, and serum erythropoietin (EPO) concentration from baseline to 12 weeks. All variables were measured every 2 weeks.Results: Serum EPO concentration increased by 38 [15–62]% (P = 0.043) between baseline and 2 and 4 weeks. Reticulocyte count transiently increased at 2 weeks. Erythropoiesis occurred after 2 weeks of canagliflozin treatment. Erythrocyte count (from 386 ± 36 × 104/μL to 421 ± 36 × 104/μL; P = 0.0009), hemoglobin (from 11.8 ± 0.6 g/dL to 12.9 ± 1.1 g/dL; P = 0.0049), and hematocrit (from 37.1 ± 2.3% to 40.4 ± 3.2%; P = 0.002) increased from baseline to study completion. Although there were no significant changes in transferrin saturation, serum ferritin levels were decreased (P = 0.003).Conclusions: Canagliflozin treatment led to an improvement in erythropoiesis in patients with impaired kidney function. The effect on erythropoiesis appeared to be due to an EPO production-mediated mechanism and might be independent of glycemic control; however, further studies are needed to clarify this since the present study had a small sample size and no comparator group.

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“…The role of SGLT2i on modulating RAAS is controversial; studies by Yoshimoto et al reported no significant RAAS activation [ 75 ]. Furthermore, SGLT2i also potentiates reduction in albuminuria in diabetic kidney disease by reducing intra-glomerular pressure and podocyte stabilization [ 20 , 43 , 76 , 77 ].…”

Section: Proposed Renoprotective Mechanisms Of Sglt2imentioning

confidence: 99%

SGLT2 Inhibitors and Kidney Outcomes in Patients with Chronic Kidney Disease

Kanduri

Kovvuru

Hansrivijit

et al. 2020

JCM

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Globally, diabetes mellitus is a leading cause of kidney disease, with a critical percent of patients approaching end-stage kidney disease. In the current era, sodium-glucose co-transporter 2 inhibitors (SGLT2i) have emerged as phenomenal agents in halting the progression of kidney disease. Positive effects of SGLT2i are centered on multiple mechanisms, including glycosuric effects, tubule—glomerular feedback, antioxidant, anti-fibrotic, natriuretic, and reduction in cortical hypoxia, alteration in energy metabolism. Concurrently, multiple kidney and cardiovascular outcome studies have reported remarkable advantages of SGLT2i including mortality benefits. Additionally, the superiority of combination therapies (SGLT2I along with metformin/DDP-4 Inhibitors) in treatment-naïve diabetic patients is further looked into with potential signal towards glycemic and blood pressure control. Reported promising results initiate a gateway for future research targeting kidney outcomes with combination therapies as an initial approach. In the current paper, we summarize leading cardiovascular and kidney outcome trials in patients with type 2 diabetes, the role of SGLT2i in non-diabetic proteinuric kidney disease, and the potential mechanisms of action of SGLT2i with special focus on combination therapy as an initial therapeutic approach in treatment-naïve diabetic patients.

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Renoprotective effects of canagliflozin, a sodium glucose cotransporter 2 inhibitor, in type 2 diabetes patients with chronic kidney disease: A randomized open-label prospective trial

Abstract: Canagliflozin was associated with slower progression of kidney disease and reduction in albuminuria and tubulointerstitial markers in diabetes patients with CKD.

Cited by 45 publications

References 12 publications

Effects of glucose-lowering agents on surrogate endpoints and hard clinical renal outcomes in patients with type 2 diabetes

Effects of glucose-lowering agents on surrogate endpoints and hard clinical renal outcomes in patients with type 2 diabetes

Canagliflozin Improves Erythropoiesis in Diabetes Patients with Anemia of Chronic Kidney Disease

SGLT2 Inhibitors and Kidney Outcomes in Patients with Chronic Kidney Disease

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