scholarly journals Sodium glucose transporter-2 inhibition has no renoprotective effects on non-diabetic chronic kidney disease

2017 ◽  
Vol 5 (7) ◽  
pp. e13228 ◽  
Author(s):  
Qiuyue Ma ◽  
Stefanie Steiger ◽  
Hans-Joachim Anders
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Glucose Transporter ◽  
Glucose Transporter 2

scholarly journals SGLT2 inhibition requires reconsideration of fundamental paradigms in chronic kidney disease, ‘diabetic nephropathy’, IgA nephropathy and podocytopathies with FSGS lesions

2020 ◽  
Author(s):  
Hans-Joachim Anders ◽  
Anna Julie Peired ◽  
Paola Romagnani
Keyword(s):  
Chronic Kidney Disease ◽  
Diabetic Nephropathy ◽  
Kidney Disease ◽  
Glucose Transporter ◽  
Immunoglobulin A ◽  
Adverse Outcomes ◽  
Glucose Transporter 2 ◽  
Research Activities ◽  
Background Therapy ◽  
Sglt2 Inhibition

Abstract In 2020, the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial first demonstrated that inhibition of the sodium–glucose transporter-2 (SGLT2) with dapagliflozin attenuates the progression of chronic kidney disease (CKD) with proteinuria in patients with or without diabetes at an unprecedented effect size. These results have far-reaching implications for a series of traditional concepts in Nephrology. It now became obvious that CKD with and without diabetes involves a predominant SGLT2-driven pathophysiology compared with the other pathogenic pathways currently under consideration. As SGLT2 inhibition is similarly efficacious in diabetic and non-diabetic CKD with proteinuria, treating CKD rather than ‘diabetic nephropathy’ becomes the central paradigm. Indeed, in older adults with type 2 diabetes, CKD is rather of multifactorial origin. As the DAPA-CKD trial included more patients with immunoglobulin A nephropathy (IgAN) than any of the previous IgAN trials, dual renin-angiotensin/SGLT2 inhibition may become the new standard. The same applies for patients with podocytopathy-related focal segmental glomerulosclerosis lesions. From now on, IgAN and podocytopathy trials without SGLT2 inhibition as background therapy and without glomerular filtration rate decline as primary outcome criterion will be of limited value. These and other potential implications will trigger broad discussions and secondary research activities with conclusions difficult to predict today. However, one is for sure: Nephrology after the DAPA-CKD trial will be not the same as it was before. Finally!

scholarly journals Nephroprotection by SGLT2i in CKD Patients: May It Be Modulated by Low-Protein Plant-Based Diets?

2020 ◽  
Vol 7 ◽  
Author(s):  
Adamasco Cupisti ◽  
Domenico Giannese ◽  
Diego Moriconi ◽  
Claudia D'Alessandro ◽  
Massimo Torreggiani ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Glucose Transporter ◽  
Diabetic Patients ◽  
Protective Effects ◽  
Type 2 Diabetic Patients ◽  
Low Protein ◽  
Glucose Transporter 2 ◽  
Ckd Stage ◽  
Single Nephron ◽  
End Stage

Sodium-glucose-transporter 2 inhibitors (SGLT2i) are a new class of anti-diabetic drugs that in large trials such as CREDENCE have shown also a reduction of glomerular hyperfiltration and albuminuria in type 2 diabetic patients. Hence, the interest toward SGLT2i is focused toward this potential nephroprotective effect, in order to reduce the progression to overt nephropathy, and it seems to be confirmed in the most recent DAPA-CKD trial. This is the reason why the indication for SGLT2i treatment has been extended to chronic kidney disease (CKD) patients with eGFR up to 30 ml/min, namely with CKD stage 1–3. In patients with CKD stage 3 to 5, the most recent KDIGO guidelines recommend low-protein diet and plant-based regimens to delay end-stage kidney disease (ESKD) and improve quality of life. Similarly to SGLT2i, low-protein diets exert renal-protective effects by reducing single nephron hyperfiltration and urinary protein excretion. Beyond the glomerular hemodynamic effects, both protein restriction and SGLT2i are able to restore autophagy and, through these mechanisms, they may exert protective effects on diabetic kidney disease. In this perspective, it is likely that diet may modulate the effect of SGLT2i in CKD patients. Unfortunately, no data are available on the outcomes of the association of SGLT2i and low-protein and/or vegan diets. It is therefore reasonable to investigate whether CKD patients receiving SGLT2i may have further advantages in terms of nephroprotection from the implementation of a low-protein and/or plant-based diet or whether this association does not result in an additive effect, especially in vascular nephropathies.

scholarly journals Kidney Outcomes Associated With SGLT2 Inhibitors Versus Other Glucose-Lowering Drugs in Real-world Clinical Practice: The Japan Chronic Kidney Disease Database

2021 ◽  
Author(s):  
Hajime Nagasu ◽  
Yuichiro Yano ◽  
Hiroshi Kanegae ◽  
Hiddo J.L. Heerspink ◽  
Masaomi Nangaku ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Clinical Practice ◽  
Kidney Disease ◽  
Kidney Function ◽  
Sglt2 Inhibitor ◽  
Sglt2 Inhibitors ◽  
Glucose Lowering ◽  
Glucose Transporter 2 ◽  
Egfr Decline

<b>Objective: </b>Randomized controlled trials have shown kidney protective effects of sodium glucose transporter 2 (SGLT2) inhibitors, and clinical practice databases have suggested that these effects translate to clinical practice. However, long-term efficacy as well as whether the presence or absence of proteinuria and the rate of estimated glomerular filtration rates (eGFR) decline prior to SGLT2 inhibitors initiation modifies treatment efficacy among type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) patients is unknown. <p><b>Research Design and Methods: </b>Using the Japan Chronic Kidney Disease Database (J-CKD-DB), a nationwide multicenter CKD registry, we developed propensity scores for SGLT2 inhibitor initiation, with 1:1 matching with patients who were initiated on other glucose-lowering drugs. The primary outcome included rate of eGFR decline, and the secondary outcomes included a composite outcome of 50% eGFR decline or end-stage kidney disease. </p> <p><b>Results: </b>At baseline, mean age at initiation of the SGLT2 inhibitor (n=1,033) or other glucose-lowering drug (n=1,033) was 64.4 years; mean eGFR was 68.1 mL/min per 1.73 m²; and proteinuria was apparent in 578 (28.0%) of included patients. During follow-up, SGLT2 inhibitor initiation was associated with reduced eGFR decline (difference in slope for SGLT2 inhibitors vs other drugs 0.75 mL/min/1.73 m² per year (0.51 to 1.00). During a mean follow-up of 24 months, 103 c<a>omposite kidney outcomes </a>occurred: 30 (14 events per 1,000 patient-years) among the SGLT2 inhibitors group and 73 (36 events per 1,000 patient-years) among the other drugs group (hazard ratio 0.40, 95% CI 0.26 to 0.61). The benefit provided by SGLT2 inhibitors was consistent irrespective of proteinuria and rate of eGFR decline before initiating SGLT2 inhibitors (p<sub>heterogeneity</sub> ≥0.35). </p> <p><b>Conclusions: </b>The benefits of SGLT2 inhibitors on kidney function as observed in clinical trials translate to patients treated in clinical practice with no evidence that the effects are modified by the underlying rate of kidney function decline or the presence of proteinuria.</p>

scholarly journals Kidney Outcomes Associated With SGLT2 Inhibitors Versus Other Glucose-Lowering Drugs in Real-world Clinical Practice: The Japan Chronic Kidney Disease Database

2021 ◽  
Author(s):  
Hajime Nagasu ◽  
Yuichiro Yano ◽  
Hiroshi Kanegae ◽  
Hiddo J.L. Heerspink ◽  
Masaomi Nangaku ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Clinical Practice ◽  
Kidney Disease ◽  
Kidney Function ◽  
Sglt2 Inhibitor ◽  
Sglt2 Inhibitors ◽  
Glucose Lowering ◽  
Glucose Transporter 2 ◽  
Egfr Decline

<b>Objective: </b>Randomized controlled trials have shown kidney protective effects of sodium glucose transporter 2 (SGLT2) inhibitors, and clinical practice databases have suggested that these effects translate to clinical practice. However, long-term efficacy as well as whether the presence or absence of proteinuria and the rate of estimated glomerular filtration rates (eGFR) decline prior to SGLT2 inhibitors initiation modifies treatment efficacy among type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) patients is unknown. <p><b>Research Design and Methods: </b>Using the Japan Chronic Kidney Disease Database (J-CKD-DB), a nationwide multicenter CKD registry, we developed propensity scores for SGLT2 inhibitor initiation, with 1:1 matching with patients who were initiated on other glucose-lowering drugs. The primary outcome included rate of eGFR decline, and the secondary outcomes included a composite outcome of 50% eGFR decline or end-stage kidney disease. </p> <p><b>Results: </b>At baseline, mean age at initiation of the SGLT2 inhibitor (n=1,033) or other glucose-lowering drug (n=1,033) was 64.4 years; mean eGFR was 68.1 mL/min per 1.73 m²; and proteinuria was apparent in 578 (28.0%) of included patients. During follow-up, SGLT2 inhibitor initiation was associated with reduced eGFR decline (difference in slope for SGLT2 inhibitors vs other drugs 0.75 mL/min/1.73 m² per year (0.51 to 1.00). During a mean follow-up of 24 months, 103 c<a>omposite kidney outcomes </a>occurred: 30 (14 events per 1,000 patient-years) among the SGLT2 inhibitors group and 73 (36 events per 1,000 patient-years) among the other drugs group (hazard ratio 0.40, 95% CI 0.26 to 0.61). The benefit provided by SGLT2 inhibitors was consistent irrespective of proteinuria and rate of eGFR decline before initiating SGLT2 inhibitors (p<sub>heterogeneity</sub> ≥0.35). </p> <p><b>Conclusions: </b>The benefits of SGLT2 inhibitors on kidney function as observed in clinical trials translate to patients treated in clinical practice with no evidence that the effects are modified by the underlying rate of kidney function decline or the presence of proteinuria.</p>

scholarly journals Molecular Biological and Clinical Understanding of the Pathophysiology and Treatments of Hyperuricemia and Its Association with Metabolic Syndrome, Cardiovascular Diseases and Chronic Kidney Disease

2021 ◽  
Vol 22 (17) ◽  
pp. 9221
Author(s):  
Hidekatsu Yanai ◽  
Hiroki Adachi ◽  
Mariko Hakoshima ◽  
Hisayuki Katsuyama
Keyword(s):  
Metabolic Syndrome ◽  
Chronic Kidney Disease ◽  
Cardiovascular Diseases ◽  
Kidney Disease ◽  
Glucose Transporter ◽  
Dominant Role ◽  
Gouty Arthritis ◽  
Renin Angiotensin System ◽  
Renal Diseases ◽  
The Metabolic Syndrome

Uric acid (UA) is synthesized mainly in the liver, intestines, and vascular endothelium as the end product of an exogenous purine from food and endogenously from damaged, dying, and dead cells. The kidney plays a dominant role in UA excretion, and the kidney excretes approximately 70% of daily produced UA; the remaining 30% of UA is excreted from the intestine. When UA production exceeds UA excretion, hyperuricemia occurs. Hyperuricemia is significantly associated with the development and severity of the metabolic syndrome. The increased urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) expression, and glycolytic disturbances due to insulin resistance may be associated with the development of hyperuricemia in metabolic syndrome. Hyperuricemia was previously thought to be simply the cause of gout and gouty arthritis. Further, the hyperuricemia observed in patients with renal diseases was considered to be caused by UA underexcretion due to renal failure, and was not considered as an aggressive treatment target. The evidences obtained by basic science suggests a pathogenic role of hyperuricemia in the development of chronic kidney disease (CKD) and cardiovascular diseases (CVD), by inducing inflammation, endothelial dysfunction, proliferation of vascular smooth muscle cells, and activation of the renin-angiotensin system. Further, clinical evidences suggest that hyperuricemia is associated with the development of CVD and CKD. Further, accumulated data suggested that the UA-lowering treatments slower the progression of such diseases.

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