- The document discusses the burden of diabetic kidney disease and the benefits of SGLT2 inhibitors (SGLT2i).
- It notes that progression of diabetic kidney disease depends on glomerular blood pressure and that SGLT2i lower intraglomerular pressure through their mechanisms of action.
- Clinical trials show that SGLT2i provide renal benefits including postponing end-stage renal disease and that earlier treatment provides longer-term protection of kidney function.
This document summarizes the treatment of hypertension from the perspectives of primary care and metabolic departments. It discusses:
1) Treatment of hypertension in primary care is similar to specialist centers, with some minor differences in related checks and tests.
2) The metabolic department treats diseases like diabetes and its complications, and chronic kidney disease.
3) Current guidelines recommend treating hypertension according to disease status, with a focus on RAS inhibitors as first-line drugs due to their protective effects on organs like the brain, heart and kidneys.
SGLT2 inhibitors for the prevention of kidney failure in patients with type 2...Brendon Neuen
SGLT2 inhibitors were found to reduce major kidney outcomes in patients with type 2 diabetes based on a systematic review and meta-analysis of four major trials. The analysis found that SGLT2 inhibitors reduced the risk of dialysis, transplant or renal death by 33%, end-stage kidney disease by 35%, substantial loss of kidney function or end-stage kidney disease by 42%, substantial loss of kidney function or cardiovascular or renal death by 29%, and acute kidney injury by 25% compared to placebo. The kidney protective effects were consistent across various subgroups including those with and without albuminuria and those with and without blockade of the renin-angiotensin system.
New Approaches To The Treatment Of Hyperphosphataemia (CRF)Andre Garcia
The document discusses new approaches to treating hyperphosphataemia in patients with kidney disease. It summarizes findings from several studies that show disorders of mineral metabolism like hyperphosphatemia are associated with increased risks of cardiovascular disease and mortality in dialysis patients. One study found that treatment with the phosphate binder lanthanum carbonate was more effective at controlling serum phosphate levels and reducing the calcium-phosphate product compared to calcium-based binders, with fewer hypercalcemia side effects.
This document discusses sodium glucose cotransporter-2 inhibitors (SGLT2i) across the spectrum of renal diseases. It begins with an overview of renal glucose handling and the role of the SGLT2 channel. It then reviews the rationale for SGLT2 inhibition in diabetic and non-diabetic kidney diseases and basic SGLT2i pharmacology. Finally, it examines clinical outcomes data from trials demonstrating the cardiovascular, renal, and heart failure benefits of SGLT2is across levels of renal function and in diabetic and non-diabetic patients.
Ponencia realizada por el Dr. José Ramón González-Juanatey del Hospital Clínico Universitario de Santiago de Compostela en la sesión 'Diabetes 2021. Cardiólogos y endocrinólogos: ¿matrimonio o divorcio?' del 13 de mayo de 2021
Hypertension and Diabetic Kidney Disease Progression Hypertension and Diabe...MedicineAndHealthUSA
Hypertension and diabetic kidney disease progression are linked, and reducing proteinuria is key to slowing kidney disease. The document discusses how conditions like hypertension and diabetes that cause kidney damage have increased in the US population. Landmark trials found that lowering blood pressure and proteinuria reduced kidney disease progression and cardiovascular risks. Initial therapy for kidney or diabetes patients should be an ACE inhibitor or ARB to target blood pressure under 130/80 mmHg.
Gpc manejo de enfermedades glomerulares-kdigo-2021WilliamBarrera34
This document provides clinical practice guidelines for the management of glomerular diseases published by KDIGO (Kidney Disease: Improving Global Outcomes) in 2021. It includes 11 chapters covering various glomerular diseases and recommendations for their evaluation and treatment. Key recommendations are presented in figures and tables throughout. Evaluation of evidence and grading of recommendations follows standardized processes. The guidelines aim to provide an evidence-based framework to guide clinical decision-making for glomerular diseases.
This document summarizes the treatment of hypertension from the perspectives of primary care and metabolic departments. It discusses:
1) Treatment of hypertension in primary care is similar to specialist centers, with some minor differences in related checks and tests.
2) The metabolic department treats diseases like diabetes and its complications, and chronic kidney disease.
3) Current guidelines recommend treating hypertension according to disease status, with a focus on RAS inhibitors as first-line drugs due to their protective effects on organs like the brain, heart and kidneys.
SGLT2 inhibitors for the prevention of kidney failure in patients with type 2...Brendon Neuen
SGLT2 inhibitors were found to reduce major kidney outcomes in patients with type 2 diabetes based on a systematic review and meta-analysis of four major trials. The analysis found that SGLT2 inhibitors reduced the risk of dialysis, transplant or renal death by 33%, end-stage kidney disease by 35%, substantial loss of kidney function or end-stage kidney disease by 42%, substantial loss of kidney function or cardiovascular or renal death by 29%, and acute kidney injury by 25% compared to placebo. The kidney protective effects were consistent across various subgroups including those with and without albuminuria and those with and without blockade of the renin-angiotensin system.
New Approaches To The Treatment Of Hyperphosphataemia (CRF)Andre Garcia
The document discusses new approaches to treating hyperphosphataemia in patients with kidney disease. It summarizes findings from several studies that show disorders of mineral metabolism like hyperphosphatemia are associated with increased risks of cardiovascular disease and mortality in dialysis patients. One study found that treatment with the phosphate binder lanthanum carbonate was more effective at controlling serum phosphate levels and reducing the calcium-phosphate product compared to calcium-based binders, with fewer hypercalcemia side effects.
This document discusses sodium glucose cotransporter-2 inhibitors (SGLT2i) across the spectrum of renal diseases. It begins with an overview of renal glucose handling and the role of the SGLT2 channel. It then reviews the rationale for SGLT2 inhibition in diabetic and non-diabetic kidney diseases and basic SGLT2i pharmacology. Finally, it examines clinical outcomes data from trials demonstrating the cardiovascular, renal, and heart failure benefits of SGLT2is across levels of renal function and in diabetic and non-diabetic patients.
Ponencia realizada por el Dr. José Ramón González-Juanatey del Hospital Clínico Universitario de Santiago de Compostela en la sesión 'Diabetes 2021. Cardiólogos y endocrinólogos: ¿matrimonio o divorcio?' del 13 de mayo de 2021
Hypertension and Diabetic Kidney Disease Progression Hypertension and Diabe...MedicineAndHealthUSA
Hypertension and diabetic kidney disease progression are linked, and reducing proteinuria is key to slowing kidney disease. The document discusses how conditions like hypertension and diabetes that cause kidney damage have increased in the US population. Landmark trials found that lowering blood pressure and proteinuria reduced kidney disease progression and cardiovascular risks. Initial therapy for kidney or diabetes patients should be an ACE inhibitor or ARB to target blood pressure under 130/80 mmHg.
Gpc manejo de enfermedades glomerulares-kdigo-2021WilliamBarrera34
This document provides clinical practice guidelines for the management of glomerular diseases published by KDIGO (Kidney Disease: Improving Global Outcomes) in 2021. It includes 11 chapters covering various glomerular diseases and recommendations for their evaluation and treatment. Key recommendations are presented in figures and tables throughout. Evaluation of evidence and grading of recommendations follows standardized processes. The guidelines aim to provide an evidence-based framework to guide clinical decision-making for glomerular diseases.
A limited presentation about a) age related renal functional changes b) management of CKD, including advance care planning and transplantation referral c) management of potentially risky drugs in the elderly with CKD (NOACs)
1) The document discusses a Phase 3 clinical trial investigating the effects of the ASK1 inhibitor selonsertib (SEL) in patients with diabetic kidney disease (DKD).
2) The trial did not meet its primary endpoint of a 50% improvement in eGFR from baseline to week 48. However, exploratory analyses found SEL induced acute but reversible eGFR declines followed by stabilization or improvement in eGFR slope over time.
3) Adverse events including acute kidney injury and fluid overload were similar between SEL and placebo groups. The study was limited by its short duration and data issues from two sites.
SGLT2 Inhibitor therapy has opened up an exciting avenue for the Physicians to manage the patients with CKD . The slide set highlights the major trials on the drug showing remarkable benefits.
1) The document summarizes the results of a large clinical trial testing the fixed-dose combination drug Preterax (perindopril and indapamide) for the treatment of type 2 diabetes patients.
2) The trial found that Preterax reduced the risk of cardiovascular mortality by 18%, total mortality by 14%, and the combined outcome of major macrovascular or microvascular events by 9% compared to placebo.
3) The beneficial effects of Preterax were consistent across patient subgroups and backgrounds in ancillary treatments.
Ponencia realizada por el Dr. Eduard Montanya Mias del Hospital Universitari de Bellvitge (Barcelona). Director Científico CIBERDEM en la sesión 'Diabetes 2021. Cardiólogos y endocrinólogos: ¿matrimonio o divorcio?' del 13 de mayo de 2021
1. Diabetic nephropathy is a leading cause of end-stage renal disease. It is defined by progressive albuminuria coupled with increasing blood pressure and declining kidney function.
2. The prevalence and incidence of diabetic nephropathy is increasing worldwide due to rising rates of diabetes. Optimizing blood glucose and blood pressure control can reduce the risk or slow the progression of nephropathy.
3. Standard treatment involves angiotensin-converting enzyme inhibitors or angiotensin receptor blockers to control blood pressure and slow kidney function decline, though current therapies only slow progression and do not halt it. Additional research is still needed to develop more effective treatments.
This document provides guidelines for the evaluation and management of chronic kidney disease (CKD) developed by the Kidney Disease: Improving Global Outcomes (KDIGO) organization. It defines CKD and staging systems based on glomerular filtration rate and albuminuria levels. The guidelines provide recommendations on screening and diagnosis of CKD, predicting progression, managing risk factors and complications, and referral to specialists. CKD is a major global public health problem, and these evidence-based guidelines aim to aid healthcare providers in delivering optimal care to patients with CKD.
The document discusses biomarkers for detecting acute kidney injury (AKI). It notes that serum creatinine is currently used but is not an early indicator. Newer biomarkers like NGAL can detect AKI earlier, within 2 hours after an event instead of 1-2 days with creatinine. Having early biomarkers could allow for improved understanding, earlier treatment and better outcomes for AKI patients. The document reviews studies on NGAL for detecting AKI in settings like cardiac surgery, contrast-induced nephropathy, sepsis, and kidney transplantation.
Pentoxyfilline in Diabetic Renal Disease and Renal TransplantationChristos Argyropoulos
Pentoxifylline may reduce proteinuria in patients with diabetic kidney disease, according to a meta-analysis of 10 randomized controlled trials. The analysis found that pentoxifylline led to a statistically significant decline in proteinuria compared to standard renin-angiotensin system blockade alone, with an effect size similar to full-dose ACE inhibitors. However, the included studies had small sample sizes and short durations. Pentoxifylline did not significantly affect glomerular filtration rate, blood pressure, or adverse effects. Larger and longer term studies are still needed to determine if pentoxifylline can delay kidney function decline in diabetic kidney disease.
Slidedeck of the presentation I gave during the East by Southwest conference, co-organized by the Division of Nephrology (UNM) and the Renal and Electrolyte Division (UPMC)
SGLT-2 inhibitors have shown promising cardiovascular and renal benefits:
1) Trials have found SGLT-2 inhibitors reduce the risk of cardiovascular death in patients with type 2 diabetes and established cardiovascular disease, as well as reducing heart failure hospitalizations in those with diabetes and cardiovascular risk factors.
2) Studies also show SGLT-2 inhibitors improve outcomes for patients with heart failure with reduced ejection fraction, reducing rates of heart failure hospitalization and mortality regardless of diabetes status or background heart failure therapies.
3) SGLT-2 inhibitors were also found to reduce the risk of renal death or progression to end-stage kidney disease in patients with type 2 diabetes and macroalbuminuria.
Ngal ,cystatin c versus creatinine clearence asMoustafa Rezk
This document discusses biomarkers for acute kidney injury (AKI), specifically NGAL and cystatin C. It provides background on the definition and classification of AKI, limitations of creatinine as a biomarker, and the need for earlier detection. It summarizes studies showing NGAL and cystatin C can increase within hours after cardiac surgery or injury, earlier than rises in creatinine. These biomarkers may allow for earlier diagnosis and intervention to prevent further kidney damage.
Diabetic kidney disease, also known as diabetic nephropathy, is a complication of diabetes that affects the kidneys. It is characterized by persistent albuminuria, declining kidney function, and elevated blood pressure. Strict control of blood glucose and blood pressure can help prevent and slow the progression of diabetic kidney disease. Current treatments include ACE inhibitors, ARBs, SGLT2 inhibitors, and GLP-1 agonists, which have shown benefits in reducing proteinuria, slowing kidney function decline, and preventing cardiovascular disease in patients. Diabetic kidney disease remains a leading cause of chronic kidney disease and end-stage renal disease worldwide.
This document provides guidelines for the detection, prevention and management of kidney disease in people with diabetes. It aims to standardize screening approaches and improve diagnosis and management to reduce progression to end-stage renal disease. Key points covered include definitions of microalbuminuria and nephropathy, prevalence of chronic kidney disease in diabetes populations, screening recommendations including annual urine testing for albumin/protein starting at age 12, and the relationship between reduced kidney function and mortality risk. The goal is a collaborative approach between primary care, diabetes specialists and nephrology to manage renal complications of diabetes.
a-comprehensive-approach-to-kidney-disease-and-hypertension by HazwanMohd Hanafi
This document discusses kidney disease and hypertension. It begins by outlining the key functions of the kidneys, including regulating blood pressure through the renin-angiotensin-aldosterone system. It then examines the causes and classifications of acute and chronic kidney disease. Chronic kidney disease is a growing problem due to its asymptomatic nature in early stages. The document reviews factors that can damage the kidneys and lead to reduced glomerular filtration rate. It also discusses how chronic kidney disease and reduced kidney function are linked to increased risk of cardiovascular disease, anemia, and bone disease like renal osteodystrophy. Hypertension is both a common cause and complication of chronic kidney disease. Tight blood pressure control is important to slow
The document discusses the history and development of dialysis for treating acute renal failure. It describes how Dr. Haas invented the first dialysis machine for humans in 1928 but all 6 of his initial patients died. Dr. Kolff then created the second human dialysis machine in 1943 and was able to successfully treat his first patient. The document also examines biomarkers like KIM-1 and NGAL that can help diagnose acute kidney injury earlier than creatinine. It analyzes the RIFLE criteria for classifying the severity of acute renal failure.
This document summarizes the background and qualifications of Dr. Gwei-Bian Gao, a cardiologist and diabetes specialist. It lists his medical education, areas of specialty training, positions held at major hospitals, awards for diabetes care quality, and current practice at Muh-Kang Clinic in Kaohsiung, Taiwan. The clinic focuses on cardiology, pulmonology, endocrinology, and diabetes management. Recent clinical trials show that SGLT2 inhibitors can protect cardiac and renal function in patients with type 2 diabetes.
This document summarizes a presentation on the benefits of SGLT2 inhibitors (SGLT2i) for patients with diabetes and kidney disease. It discusses how SGLT2i lower intraglomerular pressure and protect the kidneys by reducing hyperfiltration. Clinical trials show SGLT2i slow the progression of kidney disease and reduce cardiovascular risks compared to other treatments like ACE inhibitors or ARBs alone. The document concludes SGLT2i provide renal and cardiovascular benefits and are an important new treatment for preserving kidney function in patients with diabetes.
This document discusses diabetic kidney disease (DKD). It provides information on the epidemiology, clinical presentation, pathogenesis, standard of care, and pharmacological interventions to reduce cardiorenal risk in patients with type 2 diabetes. Regarding standard of care, it outlines glycemic and blood pressure targets, the use of RAAS inhibitors and statins, and glucose-lowering medications. It then discusses how SGLT2 inhibitors have shown benefits in reducing cardiovascular, renal, and heart failure outcomes as well as slowing kidney disease progression in patients with DKD and type 2 diabetes.
A limited presentation about a) age related renal functional changes b) management of CKD, including advance care planning and transplantation referral c) management of potentially risky drugs in the elderly with CKD (NOACs)
1) The document discusses a Phase 3 clinical trial investigating the effects of the ASK1 inhibitor selonsertib (SEL) in patients with diabetic kidney disease (DKD).
2) The trial did not meet its primary endpoint of a 50% improvement in eGFR from baseline to week 48. However, exploratory analyses found SEL induced acute but reversible eGFR declines followed by stabilization or improvement in eGFR slope over time.
3) Adverse events including acute kidney injury and fluid overload were similar between SEL and placebo groups. The study was limited by its short duration and data issues from two sites.
SGLT2 Inhibitor therapy has opened up an exciting avenue for the Physicians to manage the patients with CKD . The slide set highlights the major trials on the drug showing remarkable benefits.
1) The document summarizes the results of a large clinical trial testing the fixed-dose combination drug Preterax (perindopril and indapamide) for the treatment of type 2 diabetes patients.
2) The trial found that Preterax reduced the risk of cardiovascular mortality by 18%, total mortality by 14%, and the combined outcome of major macrovascular or microvascular events by 9% compared to placebo.
3) The beneficial effects of Preterax were consistent across patient subgroups and backgrounds in ancillary treatments.
Ponencia realizada por el Dr. Eduard Montanya Mias del Hospital Universitari de Bellvitge (Barcelona). Director Científico CIBERDEM en la sesión 'Diabetes 2021. Cardiólogos y endocrinólogos: ¿matrimonio o divorcio?' del 13 de mayo de 2021
1. Diabetic nephropathy is a leading cause of end-stage renal disease. It is defined by progressive albuminuria coupled with increasing blood pressure and declining kidney function.
2. The prevalence and incidence of diabetic nephropathy is increasing worldwide due to rising rates of diabetes. Optimizing blood glucose and blood pressure control can reduce the risk or slow the progression of nephropathy.
3. Standard treatment involves angiotensin-converting enzyme inhibitors or angiotensin receptor blockers to control blood pressure and slow kidney function decline, though current therapies only slow progression and do not halt it. Additional research is still needed to develop more effective treatments.
This document provides guidelines for the evaluation and management of chronic kidney disease (CKD) developed by the Kidney Disease: Improving Global Outcomes (KDIGO) organization. It defines CKD and staging systems based on glomerular filtration rate and albuminuria levels. The guidelines provide recommendations on screening and diagnosis of CKD, predicting progression, managing risk factors and complications, and referral to specialists. CKD is a major global public health problem, and these evidence-based guidelines aim to aid healthcare providers in delivering optimal care to patients with CKD.
The document discusses biomarkers for detecting acute kidney injury (AKI). It notes that serum creatinine is currently used but is not an early indicator. Newer biomarkers like NGAL can detect AKI earlier, within 2 hours after an event instead of 1-2 days with creatinine. Having early biomarkers could allow for improved understanding, earlier treatment and better outcomes for AKI patients. The document reviews studies on NGAL for detecting AKI in settings like cardiac surgery, contrast-induced nephropathy, sepsis, and kidney transplantation.
Pentoxyfilline in Diabetic Renal Disease and Renal TransplantationChristos Argyropoulos
Pentoxifylline may reduce proteinuria in patients with diabetic kidney disease, according to a meta-analysis of 10 randomized controlled trials. The analysis found that pentoxifylline led to a statistically significant decline in proteinuria compared to standard renin-angiotensin system blockade alone, with an effect size similar to full-dose ACE inhibitors. However, the included studies had small sample sizes and short durations. Pentoxifylline did not significantly affect glomerular filtration rate, blood pressure, or adverse effects. Larger and longer term studies are still needed to determine if pentoxifylline can delay kidney function decline in diabetic kidney disease.
Slidedeck of the presentation I gave during the East by Southwest conference, co-organized by the Division of Nephrology (UNM) and the Renal and Electrolyte Division (UPMC)
SGLT-2 inhibitors have shown promising cardiovascular and renal benefits:
1) Trials have found SGLT-2 inhibitors reduce the risk of cardiovascular death in patients with type 2 diabetes and established cardiovascular disease, as well as reducing heart failure hospitalizations in those with diabetes and cardiovascular risk factors.
2) Studies also show SGLT-2 inhibitors improve outcomes for patients with heart failure with reduced ejection fraction, reducing rates of heart failure hospitalization and mortality regardless of diabetes status or background heart failure therapies.
3) SGLT-2 inhibitors were also found to reduce the risk of renal death or progression to end-stage kidney disease in patients with type 2 diabetes and macroalbuminuria.
Ngal ,cystatin c versus creatinine clearence asMoustafa Rezk
This document discusses biomarkers for acute kidney injury (AKI), specifically NGAL and cystatin C. It provides background on the definition and classification of AKI, limitations of creatinine as a biomarker, and the need for earlier detection. It summarizes studies showing NGAL and cystatin C can increase within hours after cardiac surgery or injury, earlier than rises in creatinine. These biomarkers may allow for earlier diagnosis and intervention to prevent further kidney damage.
Diabetic kidney disease, also known as diabetic nephropathy, is a complication of diabetes that affects the kidneys. It is characterized by persistent albuminuria, declining kidney function, and elevated blood pressure. Strict control of blood glucose and blood pressure can help prevent and slow the progression of diabetic kidney disease. Current treatments include ACE inhibitors, ARBs, SGLT2 inhibitors, and GLP-1 agonists, which have shown benefits in reducing proteinuria, slowing kidney function decline, and preventing cardiovascular disease in patients. Diabetic kidney disease remains a leading cause of chronic kidney disease and end-stage renal disease worldwide.
This document provides guidelines for the detection, prevention and management of kidney disease in people with diabetes. It aims to standardize screening approaches and improve diagnosis and management to reduce progression to end-stage renal disease. Key points covered include definitions of microalbuminuria and nephropathy, prevalence of chronic kidney disease in diabetes populations, screening recommendations including annual urine testing for albumin/protein starting at age 12, and the relationship between reduced kidney function and mortality risk. The goal is a collaborative approach between primary care, diabetes specialists and nephrology to manage renal complications of diabetes.
a-comprehensive-approach-to-kidney-disease-and-hypertension by HazwanMohd Hanafi
This document discusses kidney disease and hypertension. It begins by outlining the key functions of the kidneys, including regulating blood pressure through the renin-angiotensin-aldosterone system. It then examines the causes and classifications of acute and chronic kidney disease. Chronic kidney disease is a growing problem due to its asymptomatic nature in early stages. The document reviews factors that can damage the kidneys and lead to reduced glomerular filtration rate. It also discusses how chronic kidney disease and reduced kidney function are linked to increased risk of cardiovascular disease, anemia, and bone disease like renal osteodystrophy. Hypertension is both a common cause and complication of chronic kidney disease. Tight blood pressure control is important to slow
The document discusses the history and development of dialysis for treating acute renal failure. It describes how Dr. Haas invented the first dialysis machine for humans in 1928 but all 6 of his initial patients died. Dr. Kolff then created the second human dialysis machine in 1943 and was able to successfully treat his first patient. The document also examines biomarkers like KIM-1 and NGAL that can help diagnose acute kidney injury earlier than creatinine. It analyzes the RIFLE criteria for classifying the severity of acute renal failure.
This document summarizes the background and qualifications of Dr. Gwei-Bian Gao, a cardiologist and diabetes specialist. It lists his medical education, areas of specialty training, positions held at major hospitals, awards for diabetes care quality, and current practice at Muh-Kang Clinic in Kaohsiung, Taiwan. The clinic focuses on cardiology, pulmonology, endocrinology, and diabetes management. Recent clinical trials show that SGLT2 inhibitors can protect cardiac and renal function in patients with type 2 diabetes.
This document summarizes a presentation on the benefits of SGLT2 inhibitors (SGLT2i) for patients with diabetes and kidney disease. It discusses how SGLT2i lower intraglomerular pressure and protect the kidneys by reducing hyperfiltration. Clinical trials show SGLT2i slow the progression of kidney disease and reduce cardiovascular risks compared to other treatments like ACE inhibitors or ARBs alone. The document concludes SGLT2i provide renal and cardiovascular benefits and are an important new treatment for preserving kidney function in patients with diabetes.
This document discusses diabetic kidney disease (DKD). It provides information on the epidemiology, clinical presentation, pathogenesis, standard of care, and pharmacological interventions to reduce cardiorenal risk in patients with type 2 diabetes. Regarding standard of care, it outlines glycemic and blood pressure targets, the use of RAAS inhibitors and statins, and glucose-lowering medications. It then discusses how SGLT2 inhibitors have shown benefits in reducing cardiovascular, renal, and heart failure outcomes as well as slowing kidney disease progression in patients with DKD and type 2 diabetes.
Three cases of acute myocardial infarction are presented. All three patients had type 2 diabetes and other cardiovascular risk factors like hypertension and dyslipidemia. They presented with chest pain and ST-segment changes on electrocardiogram. All underwent emergency cardiac catheterization and had stents placed in obstructed coronary arteries. Strict control of blood sugar, blood pressure, and lipids is emphasized going forward to prevent further cardiovascular complications. The role of SGLT2 inhibitors in cardiovascular and renal protection for patients with diabetes is also discussed.
The EMPA-KIDNEY trial aims to evaluate whether empagliflozin can benefit patients with chronic kidney disease (CKD) and cardiovascular disease outcomes in patients with or without diabetes. The trial plans to enroll approximately 6,000 patients with CKD at risk of kidney disease progression, defined as an eGFR of 20-45 mL/min/1.73 m2 or an eGFR of 45-90 mL/min/1.73 m2 with albuminuria above 200 mg/g. Patients will be randomly assigned to receive empagliflozin 10 mg daily or placebo daily in addition to standard of care. The primary outcome is a composite of cardiovascular death, end-stage kidney disease,
The EMPA-KIDNEY trial aims to evaluate whether empagliflozin can benefit patients with chronic kidney disease (CKD) and cardiovascular disease outcomes in patients with or without diabetes. The trial plans to enroll approximately 6,000 patients with CKD at risk of progression and randomly assign them to receive empagliflozin or placebo in addition to standard of care. The primary outcome is a composite of cardiovascular death, end-stage kidney disease, or sustained decline in kidney function. Key secondary outcomes include hospitalization for heart failure or cardiovascular death, all-cause hospitalization, and all-cause mortality. The estimated trial completion is in 2022 and will provide important data on the efficacy of empagliflo
1) The document discusses the double burden of diabetes and chronic kidney disease (CKD) in India. Over 50% of patients with type 2 diabetes in one study had CKD as defined by reduced eGFR or albuminuria.
2) Microalbuminuria is an early marker of kidney dysfunction in patients with diabetes. Higher levels of microalbuminuria are associated with poorer glycemic control and longer duration of diabetes.
3) The CARMELINA trial evaluated the cardiovascular and kidney safety of linagliptin versus placebo in patients with type 2 diabetes at high cardiovascular risk but relatively early in their disease. Linagliptin demonstrated kidney safety and reduced the risk of microvascular outcomes.
The document summarizes emerging concepts around SGLT2 inhibitors and renal outcomes. It discusses the mechanism of action of SGLT2 inhibitors including reducing glucose reabsorption and increasing sodium delivery to the macula densa. A key trial on the SGLT2 inhibitor dapagliflozin showed it reduced the composite of sustained ≥50% eGFR decline, end-stage kidney disease, or renal or cardiovascular death by 39% compared to placebo in patients with chronic kidney disease. Updated guidelines now recommend SGLT2 inhibitors to reduce renal and cardiovascular risk in patients with chronic kidney disease based on these renal protection benefits shown in clinical trials.
Management of coronary disease in diabetes - Is it different?Dr Vivek Baliga
The management of diabetes and coronary artery disease go hand in hand. This presentation by Dr Vivek talks on whether it varies from usual management.
The document provides guidance from NICE on testing and managing chronic kidney disease (CKD) and diabetic kidney disease. It recommends testing people with diabetes, hypertension, cardiovascular disease or a family history of CKD to check for renal disease. It advises measuring estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (ACR) annually. Abnormal results should be confirmed with a repeat test. The guidance outlines treatment targets for blood pressure and referral criteria for nephrology assessment. It discusses the rationale for the guidelines, including evidence that angiotensin-converting enzyme inhibitors (ACEi) can slow CKD progression independently of blood pressure lowering.
This document discusses the clinical profile and efficacy of the combination drug GLYXAMBI, which contains empagliflozin and linagliptin. It summarizes clinical trial results showing that GLYXAMBI provides significant reductions in HbA1c and body weight compared to the individual components alone in patients with type 2 diabetes. Guidelines from major diabetes organizations have been updated to recommend SGLT2 inhibitors like empagliflozin and GLP-1 receptor agonists to reduce cardiovascular risk based on positive cardiovascular outcomes trial results.
La insulinoterapia es un arte y actualmente contamos con nuevas formulaciones y otras en proceso de investigación y aprobación. Ponencia presentada en las jornadas del benemérito H2M.
Cardiometabolic Benefits of Renal Diabetes and Obesity MedicationsChristos Argyropoulos
1. This document summarizes a presentation on pharmacological interventions to reduce cardiorenal risk in patients with diabetes mellitus type 2 (DM2) and chronic kidney disease (CKD).
2. It discusses using urine albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) to diagnose diabetic kidney disease (DKD) and stratify cardiovascular risk.
3. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) were shown to reduce cardiovascular, renal, and heart failure outcomes, while mineralocorticoid receptor antagonists (MRAs) like finerenone improved proteinuria and cardiorenal outcomes.
Travel vaccination in Manchester offers comprehensive immunization services for individuals planning international trips. Expert healthcare providers administer vaccines tailored to your destination, ensuring you stay protected against various diseases. Conveniently located clinics and flexible appointment options make it easy to get the necessary shots before your journey. Stay healthy and travel with confidence by getting vaccinated in Manchester. Visit us: www.nxhealthcare.co.uk
low birth weight presentation. Low birth weight (LBW) infant is defined as the one whose birth weight is less than 2500g irrespective of their gestational age. Premature birth and low birth weight(LBW) is still a serious problem in newborn. Causing high morbidity and mortality rate worldwide. The nursing care provide to low birth weight babies is crucial in promoting their overall health and development. Through careful assessment, diagnosis,, planning, and evaluation plays a vital role in ensuring these vulnerable infants receive the specialize care they need. In India every third of the infant weight less than 2500g.
Birth period, socioeconomical status, nutritional and intrauterine environment are the factors influencing low birth weight
Nano-gold for Cancer Therapy chemistry investigatory projectSIVAVINAYAKPK
chemistry investigatory project
The development of nanogold-based cancer therapy could revolutionize oncology by providing a more targeted, less invasive treatment option. This project contributes to the growing body of research aimed at harnessing nanotechnology for medical applications, paving the way for future clinical trials and potential commercial applications.
Cancer remains one of the leading causes of death worldwide, prompting the need for innovative treatment methods. Nanotechnology offers promising new approaches, including the use of gold nanoparticles (nanogold) for targeted cancer therapy. Nanogold particles possess unique physical and chemical properties that make them suitable for drug delivery, imaging, and photothermal therapy.
Histololgy of Female Reproductive System.pptxAyeshaZaid1
Dive into an in-depth exploration of the histological structure of female reproductive system with this comprehensive lecture. Presented by Dr. Ayesha Irfan, Assistant Professor of Anatomy, this presentation covers the Gross anatomy and functional histology of the female reproductive organs. Ideal for students, educators, and anyone interested in medical science, this lecture provides clear explanations, detailed diagrams, and valuable insights into female reproductive system. Enhance your knowledge and understanding of this essential aspect of human biology.
10 Benefits an EPCR Software should Bring to EMS Organizations Traumasoft LLC
The benefits of an ePCR solution should extend to the whole EMS organization, not just certain groups of people or certain departments. It should provide more than just a form for entering and a database for storing information. It should also include a workflow of how information is communicated, used and stored across the entire organization.
5-hydroxytryptamine or 5-HT or Serotonin is a neurotransmitter that serves a range of roles in the human body. It is sometimes referred to as the happy chemical since it promotes overall well-being and happiness.
It is mostly found in the brain, intestines, and blood platelets.
5-HT is utilised to transport messages between nerve cells, is known to be involved in smooth muscle contraction, and adds to overall well-being and pleasure, among other benefits. 5-HT regulates the body's sleep-wake cycles and internal clock by acting as a precursor to melatonin.
It is hypothesised to regulate hunger, emotions, motor, cognitive, and autonomic processes.
Co-Chairs, Val J. Lowe, MD, and Cyrus A. Raji, MD, PhD, prepared useful Practice Aids pertaining to Alzheimer’s disease for this CME/AAPA activity titled “Alzheimer’s Disease Case Conference: Gearing Up for the Expanding Role of Neuroradiology in Diagnosis and Treatment.” For the full presentation, downloadable Practice Aids, and complete CME/AAPA information, and to apply for credit, please visit us at https://bit.ly/3PvVY25. CME/AAPA credit will be available until June 28, 2025.
8 Surprising Reasons To Meditate 40 Minutes A Day That Can Change Your Life.pptxHolistified Wellness
We’re talking about Vedic Meditation, a form of meditation that has been around for at least 5,000 years. Back then, the people who lived in the Indus Valley, now known as India and Pakistan, practised meditation as a fundamental part of daily life. This knowledge that has given us yoga and Ayurveda, was known as Veda, hence the name Vedic. And though there are some written records, the practice has been passed down verbally from generation to generation.
Kosmoderma Academy, a leading institution in the field of dermatology and aesthetics, offers comprehensive courses in cosmetology and trichology. Our specialized courses on PRP (Hair), DR+Growth Factor, GFC, and Qr678 are designed to equip practitioners with advanced skills and knowledge to excel in hair restoration and growth treatments.
Breast cancer: Post menopausal endocrine therapyDr. Sumit KUMAR
Breast cancer in postmenopausal women with hormone receptor-positive (HR+) status is a common and complex condition that necessitates a multifaceted approach to management. HR+ breast cancer means that the cancer cells grow in response to hormones such as estrogen and progesterone. This subtype is prevalent among postmenopausal women and typically exhibits a more indolent course compared to other forms of breast cancer, which allows for a variety of treatment options.
Diagnosis and Staging
The diagnosis of HR+ breast cancer begins with clinical evaluation, imaging, and biopsy. Imaging modalities such as mammography, ultrasound, and MRI help in assessing the extent of the disease. Histopathological examination and immunohistochemical staining of the biopsy sample confirm the diagnosis and hormone receptor status by identifying the presence of estrogen receptors (ER) and progesterone receptors (PR) on the tumor cells.
Staging involves determining the size of the tumor (T), the involvement of regional lymph nodes (N), and the presence of distant metastasis (M). The American Joint Committee on Cancer (AJCC) staging system is commonly used. Accurate staging is critical as it guides treatment decisions.
Treatment Options
Endocrine Therapy
Endocrine therapy is the cornerstone of treatment for HR+ breast cancer in postmenopausal women. The primary goal is to reduce the levels of estrogen or block its effects on cancer cells. Commonly used agents include:
Selective Estrogen Receptor Modulators (SERMs): Tamoxifen is a SERM that binds to estrogen receptors, blocking estrogen from stimulating breast cancer cells. It is effective but may have side effects such as increased risk of endometrial cancer and thromboembolic events.
Aromatase Inhibitors (AIs): These drugs, including anastrozole, letrozole, and exemestane, lower estrogen levels by inhibiting the aromatase enzyme, which converts androgens to estrogen in peripheral tissues. AIs are generally preferred in postmenopausal women due to their efficacy and safety profile compared to tamoxifen.
Selective Estrogen Receptor Downregulators (SERDs): Fulvestrant is a SERD that degrades estrogen receptors and is used in cases where resistance to other endocrine therapies develops.
Combination Therapies
Combining endocrine therapy with other treatments enhances efficacy. Examples include:
Endocrine Therapy with CDK4/6 Inhibitors: Palbociclib, ribociclib, and abemaciclib are CDK4/6 inhibitors that, when combined with endocrine therapy, significantly improve progression-free survival in advanced HR+ breast cancer.
Endocrine Therapy with mTOR Inhibitors: Everolimus, an mTOR inhibitor, can be added to endocrine therapy for patients who have developed resistance to aromatase inhibitors.
Chemotherapy
Chemotherapy is generally reserved for patients with high-risk features, such as large tumor size, high-grade histology, or extensive lymph node involvement. Regimens often include anthracyclines and taxanes.
2. • The burden of diabetic kidney disease (DKD) and the
coming era of SGLT2i
• Progression of DKD: glomerular blood pressure
matters!!
• Renal benefits of SGLT-2i: a wonder drug
• CVOTs of SGLT2i: The earlier, the longer, the better
but never too late!!
• Why Canagliflozin? : beneficial add-on effects of
GLP-1
2
Outline
3. 0
500,000
1,000,000
1,500,000
2,000,000
2007
2008
2009
2010
2011
2012
2013
2014
2015
2016
DM pt >60 yr
Estimated 2017 DM patients by IDF2
Prevalence of Diabetes In Past 10 years1 (2007-2016)
Patients (n)
1. 衛生福利部國民健署歷年統計2.International Diabetes Federation, 2015Diabetes Atlas. https://www.idf.org/e-library/epidemiology-research/diabetes-atlas/13-diabetes-atlas-seventhedition.html.
56%
51%
How BIG is Diabetes in Taiwan ?
What is the proportion of elderly age ?
4. 4
Diabetic kidney disease, we face today in Taiwan
~78,000 hemodialysis patients in Taiwan in 2017
49.3% are diabetic patients
1. 2017 Annual Report on Kidney Disease in Taiwan. http://www.tsn.org.tw/UI/L/TWRD/ebook_2017%E5%B9%B4%E5%A0%B1.pdf
2. Am J Kidney Dis. 2018 Jun;71(6):884-895.
3. Acta Nephrologica 2009; 23: 90-95
30-40% of patients with diabetes develop
diabetic nephropathy.
In Taiwan, about 39.7% of patients
with type 2 diabetes have diabetic
nephropathy
6. Nephrol Dial Transplant (2008) 23: 3977–3982
Nephrology 22, Suppl. 4 (2017) 3–8
2017 Annual Report on Kidney Disease in Taiwan.
ESRD
The era of SGLT2i: Renal endpoint postponded!!
腎臟終點出現在生命終點之前!!
7. Development of Macroalbuminuria Heralds Rapid Decline in
Glomerular Filtration in Type II Diabetes
-50
-40
-30
-20
-10
0
1 1.5 2 2.5 3 3.5 4
Time years
Change
in
GFR
ml/min
Microalbuminuria
Macroalbuminuria
Nelson RG. et al NEJM, 1996
10ml/min/yr
SLOW PROGRESSION
Or Compensation ?
8. 20
25
30
35
40
Losartan -4.29 ml/min/year
P=0.002
Placebo
-5.05 ml/min/year
-1.55 ml/min
-2.28 ml/min
P=0.031
Estimated
GFR
(ml/min)
0 6 12 18 24 30 36 42
Time (month)
RENAAL: Relationship between initial eGFR change and
subsequent long-term renal function decline
Holtkamp et al. Kid Int 2011
Residual renal risk is still high by using RAS blockade!!
sCr doubling 25%
ESRD 28% 100% macro DKD
0.76
9. .
Zhang Z et al. JASN 2005;16:1775-1780
2x Cr, ESRD, or death
RENAAL Study
NNT
82
30
24
14
10. The Greater Changes in eGFR; the Better Protection from ARB
10 Kidney Int. 2011 Aug;80(3):282-7
RENAAL trial
2020 ADA--------
An ACEi or ARB, at the
maximum tolerated
dose indicated for BP
treatment, is
recommended for HTN
in pts with DM and
UACR>300 mg/g
11. For training purposes only.
Dulaglutide has received positive opinion from the CHMP; however, there is no guarantee it will receive regulatory approval and become commercially available in your affiliate.
Levey AS, et al. Kidney Int. 2011;80:17-28
CV-renal outcome in CKD:
Each ml GFR counts in macro!!
1. Rennal & IDNT: 100% macro
2. Empareg-outcome: 11% macro with egfr>60 ml/min可保護的腎絲球較多!!
3. Credence 100% macro, mean egfr 56可保護的腎絲球較少,但延緩崩壞!
4. Dapa-CKD: 90% macro with 11% egfr>60 ml/min(1+2)
12. Mechanistic concept of the effects of RAS and SGLT-2 inhibition
on intraglomerular pressure.
CKJ: Clinical Kidney Journal 11(6):749-761
16. Cox regression analyses in patients treated with ≥1 dose of study drug. Interaction p-value is for test of homogeneity of treatment group difference between subgroups with no adjustment for
multiple tests. Data for patients who did not have an event were censored on the last day they were known to be free of the outcome. Albuminuric DKD defined as UACR >300 mg/g with
any eGFR [CKD-EPI]; non-albuminuric DKD group defined as eGFR <60 ml/min/1.73 m2 and UACR ≤300 mg/g; all others group defined as eGFR ≥60 ml/min/1.73 m2 or UACR ≤300 mg/g.
CV, cardiovascular; DKD, diabetic kidney disease; eGFR, estimated glomerular filtration rate; HHF, hospitalisation for heart failure; UACR; urinary albumin-to-creatinine ratio.
16
Empagliflozin Placebo Hazard ratio
(95% CI)
Hazard ratio
(95% CI)
Interaction
p-value
n event/N % n event/N %
CV death
All patients 172/4687 3.7 137/2333 5.9 0.62 (0.49, 0.77)
0.2567
Albuminuric DKD 42/509 8.3 36/260 13.8 0.54 (0.35, 0.85)
Non-albuminuric DKD 47/850 5.5 29/440 6.6 0.86 (0.54, 1.37)
All others 82/3276 2.5 72/1617 4.5 0.55 (0.40, 0.76)
HHF
All patients 126/4687 2.7 95/2333 4.1 0.65 (0.50, 0.85)
0.7087
Albuminuric DKD 32/509 6.3 24/260 9.2 0.58 (0.34, 0.99)
Non-albuminuric DKD 31/850 3.6 29/440 6.6 0.57 (0.34, 0.95)
All others 62/3276 1.9 42/1617 2.6 0.72 (0.49, 1.07)
All-cause hospitalisation
All patients 1725/4687 36.8 925/2333 39.6 0.89 (0.82, 0.96)
0.3408
Albuminuric DKD 237/509 46.6 139/260 53.5 0.77 (0.62, 0.94)
Non-albuminuric DKD 373/850 43.9 208/440 47.3 0.88 (0.74, 1.05)
All others 1093/3276 33.4 575/1617 35.6 0.91 (0.82, 1.01)
0.25 0.5 1 2
CV outcomes in patients with albuminuric vs non-albuminuric DKD vs all
others
Favours empagliflozin Favours placebo
18
90
50
NNT
26
250
166
20. Intraglomerular blood pressure is derived from
Systemic blood pressure
Afferent arteriole tone
Efferent arteriole tone
N Engl J Med 2017; 377:1765-1776
SGLT2i
RAAS blockade
21. • The burden of diabetic kidney disease (DKD) and the
era of SGLT2i has come
• Progression of DKD/CKD: glomerular blood pressure
matters!!
• Renal benefits of SGLT-2i: a wonder drug
• CVOTs of SGLT2i: The earlier, the longer, the better
but never too late!!
• Why Canagliflozin? : beneficial add-on effects of
GLP-1
21
Outline
22. eGFR over 192 weeks
22
Mixed model repeated measures analysis using all data from patients treated with ≥1 dose of study drug
(modified intent-to-treat approach). eGFR by Chronic Kidney Disease Epidemiology Collaboration formula.
eGFR, estimated glomerular filtration rate.
80% pts with ACEI/ARB; eGFR >30 ml/min; 100% CVD
N Engl J Med 2016; 375:323-334
Slope= 5.9ml/min
Slope= 1.14 ml/min
RENAAL 0.76/yr
及早,快速累積腎臟保護紅利是關鍵!!
4.76
23. Natural history of diabetic nephropathy
Functional Hyperfiltration Microalbuminuria, hypertension Albuminuira, declining GFR
Vora JP, et al. In: Johnson RJ, Feehally J, eds. Comprehensive Clinical Nephrology. New York: Mosby; 2000.
Urinary
protein
excretion
(mg/d)
Years
Glomerular
filtration
rate
(GFR)
(mL/min)
0
150
100
50
5 10 15 20 25
Incipient diabetic
nephropathy
Pre Overt diabetic
nephropathy
End-stage
renal disease
1 2 3 4 5
200
1000
5000
20
Urinary protein excretion
GFR
SGLT2i
SGLT2i?
26. For training purposes only.
Dulaglutide has received positive opinion from the CHMP; however, there is no guarantee it will receive regulatory approval and become commercially available in your affiliate.
JASN April 2017, 28 (4) 1023-1039
Silent loss
Save diabetic kidneys: The earlier, the better!!
Single nephron protection!!
SGLT2i
28. Am J Kidney Dis. 2016;67(3):483-498
SGLT2i
Uremic toxin
29. Diabetes 2013 Oct; 62(10): 3324-3328.
SGLT2i works in non-DM, too!!
Why?
30. • The burden of diabetic kidney disease (DKD) and the
era of SGLT2i has come
• Progression of DKD/CKD: glomerular blood pressure
matters!!
• Renal benefits of SGLT-2i: a wonder drug
• CVOTs of SGLT2i: The earlier, the longer, the better
but never too late!!
• Why Canagliflozin? : beneficial add-on effects of
GLP-1
30
Outline
31. The hidden beauty of SGLT2i !!
31
Reduce glucose reabsorption
by SGLT2 inhibition
Reduce intraglomerular
pressure
Reduce tubular
workload
Reduce renal
inflammation
35. 35
A surrogate marker for
1. Recovery from reversible
tubulointerstitial injury!!
2. Preserved GFR and EF make
hemoconcentration possible!!
36. • The burden of diabetic kidney disease (DKD) and the
era of SGLT2i has come
• Progression of DKD/CKD: glomerular blood pressure
matters!!
• Renal benefits of SGLT-2i: a wonder drug
• CVOTs of SGLT2i: The earlier, the longer, the better
but never too late!!
• Why Canagliflozin? : beneficial add-on effects of
GLP-1
36
Outline
37. CV(HF!!) and Renal protection start soon after Na-Glu excretion !!
(albuminuria)
N Engl J Med 2016; 375:323-334
38. 38
Data are reported for week 6 in CANVAS and week 13 in CANVAS-R.
Circulation. 2018;138:1537–1550.
Data From the CANVAS Program
80% pts with ACEI/ARB; mean eGFR =77 ml/min; median UACR 12.4 mg/g
The earlier, the better
1.47
1.09
1.05
1.35
39. 39
Am J Nephrol. 2018 Jan; 46(6): 462–472. April 14, 2019 DOI: 10.1056/NEJMoa1811744
(<60ml/min 60%)
(macro 100%)
40. 252 required dialysis or transplantation or died of kidney disease
Lancet Diabetes Endocrinol. 2019 Nov;7(11):845-854.
Canaglu 對最高腎風險的族群帶來有效保護!!
44. Hazard ratio
(95% CI) P value
Primary composite outcome 0.70 (0.59–0.82) 0.00001
Doubling of serum creatinine 0.60 (0.48–0.76) <0.001
ESKD 0.68 (0.54–0.86) 0.002
eGFR <15 mL/min/1.73 m2
0.60 (0.45–0.80) –
Dialysis initiated or kidney transplantation 0.74 (0.55–1.00) –
Renal death 0.39 (0.08–2.03) –
CV death 0.78 (0.61–1.00) 0.0502
CV death or hospitalization for heart failure 0.69 (0.57–0.83) <0.001
CV death, MI, or stroke 0.80 (0.67–0.95) 0.01
Hospitalization for heart failure 0.61 (0.47–0.80) <0.001
ESKD, doubling of serum creatinine, or renal death 0.66 (0.53–0.81) <0.001
Summary of Key Renal and CV Outcomes
Favors Canagliflozin Favors Placebo
0.25 0.5 1.0 2.0 4.0
Baseline SBP 140mmHg; 100% Macro, 60% GFR<60 ml/min and 50% CVD
(risk is as high as 100% CVD population??)
45. Primary Outcome: Benefits in eGFR 30 to <45 Subgroup
Hazard ratio
(95% CI)
Interaction
P value
Screening eGFR 0.11
30 to <45 mL/min/1.73 m2 0.75 (0.59–0.95)
45 to <60 mL/min/1.73 m2 0.52 (0.38–0.72)
60 to <90 mL/min/1.73 m2 0.82 (0.60–1.12)
Favors Canagliflozin Favors Placebo
0.25 0.5 1.0 2.0 4.0
16
NNT in patients with eGFR 30 to <45 mL/min/1.73 m2
再爛的腎臟還是會有好的腎絲球
Single nephron protection!!
Never too late for Cana!!
46. JASN 31: 1128–1139, 2020
14.3 M
11.2 M
8.7 M
A Secondary Analysis of the CREDENCE Randomized
Trial
40%
48. 48
Diabetes Ther. 2020 Dec 18. doi: 10.1007/s13300-020-00953-4. Online ahead of print
Estimated eGFR values used to projectthe delay in time to dialysis*
by treatment in the CREDENCEtrial**
* eGFR of 10 ml/min/1.73 m2
** overlaid with observed data
53. Long-term Decline in GFR is Correlated
With Poor Control of Blood Pressure:
9 Studies on Nephropathy Progression
–14
–12
–10
–8
–6
–4
–2
0
95 97 99 101 103 105 107 109 111 113 115 117 119
MAP (mmHg)
GFR
(ml/min/yr)
(mmHg)
Untreated HTN
140/90
130/85
Graph: (Bakris GL. J Clin Hypertens. 1999)
Trials: (Parving HH, et al. Br Med J. 1989) (Viberti GC, et al. JAMA. 1993) (Klaur S, et al. N Engl J Med. 1993*) (Herbert L, et al.
Kidney Int. 1994) (Lebovitz H, et al. Kidney Int. 1994) (Moschio G, et al. N Engl J Med. 1996*) (Bakris GL, et al. Kidney
Int. 1996) (Bakris GL, et al. Hypertension. 1997) (GISEN Group, Lancet. 1997)
121
*Trials marked by * are non-diabetic renal disease patients.
125/75 mmHg
if proteinuria
>1g/day
+SGLT2i
Untreated HTN and DM
54. • The burden of diabetic kidney disease (DKD) and the
era of SGLT2i has come
• Progression of DKD/CKD: glomerular blood pressure
matters!!
• Renal benefits of SGLT-2i: a wonder drug
• CVOTs of SGLT2i: The earlier, the longer, the better
but never too late!!
• Why Canagliflozin? : beneficial add-on effects of
GLP-1
54
Outline
55. Structure and selectivity profiles for SGLT2 over
SGLT1
Empagliflozin
Canagliflozin
Dapagliflozin
Selectivity
SGLT-1 : SGLT-2
1:2500
1:1200
1:160
Singh AK et al. Indian J Endocrinol Metab. 2015 Nov-Dec;19(6):722-30.
55
more natriuresis!!
57. Canagliflozin, dapagliflozin and empagliflozin
for treating type 2 diabetes: Network Meta-analysis 57
Health Technology Assessment, No. 21.2
HbA1c
BW
58. Canagliflozin, dapagliflozin and empagliflozin
for treating type 2 diabetes: Network Meta-analysis 58
Health Technology Assessment, No. 21.2
SBP
64. 64
KDIGO 2020 CLINICAL PRACTICE GUIDELINE FOR DM MANAGEMENT IN CKD
Kidney International (2020) 98, S1–S115
65. GLP-1a/DPP4i: seal glue
+
SGLT2i+ARB/ACEi: wrench
to decrease the flow and
pressure
In macroalbuminuria
Complementary effect!!
Broken pipe needs wrench and seal glue!
CREDENCE pts!!
66. 心衰竭病史、巨量蛋白尿、eGFR<60增加hHF相對風險2-4倍
n X2 Adjusted
Hazard Ratio
95% Confidence
Intervals
P
Previous heart failure 1986 231.99 4.18 3.48-5.02 <0.01
Albumin/creatinine ratio >33.9 mg/mmol 1638 119.26 3.66 2.90-4.62 <0.01
Albumin/creatinine ratio 3.4 to ≤33.9 mg/mmol 4426 35.77 1.89 1.54-2.34 <0.01
Estimated glomerular filtration rate ≤60 mL/min 4602 49.86 2.00 1.65-2.42 <0.01
Age ≥75y 2192 24.92 1.70 1.38-2.09 <0.01
Previous myocardial infarction 5933 15.62 1.47 1.21-1.78 <0.01
Non-Hispanic 12327 10.71 1.56 1.20-2.04 <0.01
Established cardiovascualr disease 12344 8.81 1.64 1.18-2.28 <0.01
Saxagliptin 7916 7.77 1.29 1.08-1.54 0.01
Female 5205 6.93 0.76 0.62-0.93 0.01
Dyslipidemia 11213 4.63 1.27 1.02-1.59 0.03
Circulation 2014; 130: 1579-1588
Risk Factors for hHF in the Overall SAVOR-TIMI 53 Population
67. J Am Coll Cardiol. 2018, 71 (11 Supplement) A921.
PRIOR HEART FAILURE (HF) HOSPITALIZATION AND 30-DAY AND 1-YEAR
OUTCOMES IN PATIENTS WITH HF AND PRESERVED EF
27% 33%
68. Due to the progressive nature of HF, patients cannot be perceived as
‘stable’
Mortality
Cardiac
function
and
Quality
of life Decompensation/
hospitalization
Chronic decline1
Disease progression
1. Adapted from Gheorghiade et al. Am J Cardiol 2005;96:11G–17G; 2. Ahmed et al. Am Heart J 2006;151:444–50; 3. Gheorghiade and Pang. J Am Coll Cardiol
2009;53:557–73; 4. Holland et al. J Card Fail 2010;16:150–6; 5. Muntwyler et al. Eur Heart J 2002;23:1861–6
Frequency of decompensation and risk of mortality increase,1–5 with acute events and
sudden death occurring at any time
Canagliflozin?
69. 69
More effective in
symptomatic HF!!
CANVAS: post hoc
Relative risk reduction of CV death and HHF
Diabetologia (2018) 61:2108–2117
80. Effect on eGFR (CANVAS vs CREDENCE)
80
Mean eGFR 76 ml/min
Mean ACR 12mg/gCr
Mean eGFR 56 ml/min
Mean ACR 923 mg/gCr
Secondary renal outcomes of the
CANVAS/CANVAS R study
CREDENCE study
N Engl J Med 2017; 377:644-657; 21. N Engl J Med 2019; 380:2295-2306; CAN-20200324.No2
The earlier, the better Never too late
85. No. at risk
Placebo 2197 2169 2131 2065 1766 1177 658 182
Canagliflozin 2200 2163 2118 2071 1788 1228 667 202
Lower Extremity Amputation
0
5
10
15
20
25
0 26 52 78 104 130 156 182
Months since randomization
63 participants
70 participants
Hazard ratio, 1.11 (95% CI, 0.79–1.56)
Participants
with
an
event
(%)
6 12 18 24 30 36 42
Placebo
Canagliflozin
Includes all treated patients through the end of the trial.
NS
86. 0
5
10
15
20
25
0 26 52 78 104 130 156 182
Months since randomization
Fracture
68 participants
67 participants
No. at risk
Placebo 2197 2166 2128 2061 1769 1178 656 176
Canagliflozin 2200 2171 2121 2074 1785 1225 668 200
Hazard ratio, 0.98 (95% CI, 0.70–1.37)
Participants
with
an
event
(%)
6 12 18 24 30 36 42
Placebo
Canagliflozin
Includes all treated patients through the end of the trial.
NS
87. Safety by Diabetes Status
aSafety outcomes reported in participants on and off treatment; bSurgical or spontaneous/non-surgical amputation, excluding amputation due to trauma; cBased on pre-defined list of preferred
terms; dAE with the following criteria confirmed by the investigator: i) symptoms of severe impairment in consciousness or behaviour, ii) need of external assistance, iii) intervention to treat
hypoglycemia, iv) prompt recovery of acute symptoms following the intervention.
AE = adverse event; T2D = type 2 diabetes;
Wheeler D. Presented at: ASN – Kidney Week 2020; October 22 – October 25, 2020.
Safety outcomesa, %
With T2D Without T2D
Dapagliflozin
(n=1453)
Placebo
(n=1450)
Dapagliflozin
(n=696)
Placebo
(n=699)
Discontinuation due to AE 5.6 6.5 5.2 4.1
Any serious AE 33.2 38.8 21.6 23.9
AE of interest
Amputationb
Any definite or probable
diabetic ketoacidosis
Fracturec HR=1.29
Renal related adverse eventc
Major hypoglycemiad
Volume depletionc
2.4
0
4.5
8.3
1.0
6.3
2.6
0.1
3.5
10.2
1.9
4.9
0
0
2.9
4.9
0
5.0
0.1
0
2.6
5.7
0
2.7
For reactive use only. This slide includes information for the purpose of scientific medical exchange only. AstraZeneca has no intention to promote its drugs outside of it approved indications.
DAPA-CKD: