Alleviation of Anemia by SGLT2 Inhibitors in Patients with CKD

Packer, Milton

doi:10.2215/cjn.0000000000000362

Cited by 9 publications

(3 citation statements)

References 11 publications

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“…The levels of both hepcidin and ferritin are reduced by SGLT2 inhibitors via inhibitory effects on proinflammatory pathways and enhancing effects on nutrient deprivation signalling, leading to the promotion of iron absorption from the gastrointestinal tract and iron mobilization from both the reticuloendothelial system and intracellular stores. 27,28 These mechanisms might be responsible for the increased erythropoiesis after ipragliflozin treatment initiation in patients with T2DM and CKD. Increase in haemoglobin and haematocrit levels following SGLT2 inhibitor administration may be a surrogate marker for the functional recovery of tubulointerstitial fibroblasts and augmentation of iron utilization.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to the increased EPO production, augmentation of iron utilization may be involved in the increase in haemoglobin and haematocrit levels after initiation of SGLT2 inhibitors. The levels of both hepcidin and ferritin are reduced by SGLT2 inhibitors via inhibitory effects on proinflammatory pathways and enhancing effects on nutrient deprivation signalling, leading to the promotion of iron absorption from the gastrointestinal tract and iron mobilization from both the reticuloendothelial system and intracellular stores 27,28 . These mechanisms might be responsible for the increased erythropoiesis after ipragliflozin treatment initiation in patients with T2DM and CKD.…”

Section: Discussionmentioning

confidence: 99%

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Erythropoiesis and estimated fluid volume regulation following initiation of ipragliflozin treatment in patients with type 2 diabetes mellitus and chronic kidney disease: A post‐hoc analysis of the PROCEED trial

Maruhashi,

Tanaka,

Takahashi

et al. 2024

Diabetes Obesity Metabolism

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AimsTo analyse the changes in erythropoietic and estimated fluid volume parameters after the initiation of ipragliflozin, a sodium‐glucose co‐transporter 2 inhibitor, in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD).MethodsThis was a post‐hoc analysis of the PROCEED trial, which evaluated the effect of 24‐week ipragliflozin treatment on endothelial dysfunction in patients with T2DM and CKD. We evaluated the changes in erythropoietic and estimated fluid volume parameters from baseline to 24 weeks post‐treatment in 53 patients who received ipragliflozin (ipragliflozin group) and 55 patients with T2DM and CKD without sodium‐glucose co‐transporter 2 inhibitors (control group), a full analysis set of the PROCEED trial.ResultsThe increases in haemoglobin [estimated group difference, 0.5 g/dl; 95% confidence interval (CI), 0.3‐0.8; p < .001], haematocrit (estimated group difference, 2.2%; 95% CI, 1.3‐3.1; p < .001) and erythropoietin (estimated log‐transformed group difference, 0.1; 95% CI, 0.01‐0.3; p = .036) were significantly greater in the ipragliflozin group than those in the control group. Ipragliflozin treatment was significantly associated with an increase in erythropoietin, independent of the corresponding change in haemoglobin (β = 0.253, p < .001) or haematocrit (β = 0.278, p < .001). Reductions in estimated plasma volume (estimated group difference, −7.94%; 95% CI, −11.6 to −4.26%; p < .001) and estimated extracellular volume (estimated group difference, −181.6 ml; 95% CI, −275.7 to −87.48 ml; p < .001) were significantly greater in the ipragliflozin group than those in the control group.ConclusionsErythropoiesis was enhanced and estimated fluid volumes were reduced by ipragliflozin in patients with T2DM and CKD.Clinical trialPROCEED trial (registration number: jRCTs071190054).

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Erythropoiesis and estimated fluid volume regulation following initiation of ipragliflozin treatment in patients with type 2 diabetes mellitus and chronic kidney disease: A post‐hoc analysis of the PROCEED trial

Maruhashi,

Tanaka,

Takahashi

et al. 2024

Diabetes Obesity Metabolism

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“…Fifth, our meta-analysis identified that SGLT2is were associated with a lower incidence of anemia. Meanwhile, a newly published article (38) illustrated the possible mechanisms for the alleviation of anemia by SGLT2is. Sixth, our meta-analysis identified that SGLT2is were associated with a lower incidence of back pain, which may be due to the anti-inflammation and anti-oxidative stress activities of SGLT2is.…”

Section: Discussionmentioning

confidence: 99%

A comprehensive meta-analysis on safety outcomes reveals the novel potentials of SGLT2is, especially preventing respiratory diseases

Cai,

Zou,

et al. 2024

Front. Endocrinol.

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Is There a Role for SGLT2 Inhibitors in Patients with End-Stage Kidney Disease?

Siddiqui,

Obi,

Dossabhoy

et al. 2024

Curr Hypertens Rep

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Purpose of Review Chronic kidney disease and end-stage kidney disease (ESKD) are well-established risk factors for cardiovascular disease (CVD), the leading cause of mortality in the dialysis population. Conventional therapies, such as statins, blood pressure control, and renin-angiotensin-aldosterone system blockade, have inadequately addressed this cardiovascular risk, highlighting the unmet need for effective treatment strategies. Sodium–glucose transporter 2 (SGLT2) inhibitors have demonstrated significant renal and cardiovascular benefits among patients with type 2 diabetes, heart failure, or CKD at risk of progression. Unfortunately, efficacy data in dialysis patients is lacking as ESKD was an exclusion criterion for all major clinical trials of SGLT2 inhibitors. This review explores the potential of SGLT2 inhibitors in improving cardiovascular outcomes among patients with ESKD, focusing on their direct cardiac effects. Recent Findings Recent clinical and preclinical studies have shown promising data for the application of SGLT2 inhibitors to the dialysis population. SGLT2 inhibitors may provide cardiovascular benefits to dialysis patients, not only indirectly by preserving the remaining kidney function and improving anemia but also directly by lowering intracellular sodium and calcium levels, reducing inflammation, regulating autophagy, and alleviating oxidative stress and endoplasmic reticulum stress within cardiomyocytes and endothelial cells. Summary This review examines the current clinical evidence and experimental data supporting the use of SGLT2 inhibitors, discusses its potential safety concerns, and outlines ongoing clinical trials in the dialysis population. Further research is needed to evaluate the safety and effectiveness of SGLT2 inhibitor use among patients with ESKD.

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Alleviation of Anemia by SGLT2 Inhibitors in Patients with CKD

Cited by 9 publications

References 11 publications

Erythropoiesis and estimated fluid volume regulation following initiation of ipragliflozin treatment in patients with type 2 diabetes mellitus and chronic kidney disease: A post‐hoc analysis of the PROCEED trial

Erythropoiesis and estimated fluid volume regulation following initiation of ipragliflozin treatment in patients with type 2 diabetes mellitus and chronic kidney disease: A post‐hoc analysis of the PROCEED trial

A comprehensive meta-analysis on safety outcomes reveals the novel potentials of SGLT2is, especially preventing respiratory diseases

Is There a Role for SGLT2 Inhibitors in Patients with End-Stage Kidney Disease?

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