This document summarizes key information about chronic kidney disease (CKD) and cardiovascular disease (CVD). It notes that patients with CKD should be considered at the highest risk for CVD. Lower estimated glomerular filtration rate (eGFR) is associated with higher risks of coronary disease and CVD mortality. The risks of all-cause mortality are significantly higher across all levels of eGFR and proteinuria for patients with early diabetic kidney disease compared to those without. Heart failure hospitalization risk increases as kidney function declines. The development of macroalbuminuria in diabetes patients heralds a rapid decline in glomerular filtration rate. Timely protection and maintenance of kidney function can reduce CVD risks.
Managing Heart Failure in Patients on Dialysismagdyelmasry3
•
Heart failure and end-stage kidney disease (ESKD) commonly coexist; 1 comorbidity worsens the prognosis of the other.
•
Although patients with ESKD compose an extremely high-risk population, they have been excluded from landmark clinical trials in heart failure, and there is, thus, a paucity of data regarding the management of heart failure in patients on dialysis.
•
Trial-level evidence is warranted in the future to endorse the efficacy and safety of therapeutic interventions in patients with heart failure and on dialysis. Collaborations between cardiologists and nephrologists are needed to devise an optimal treatment strategy for these patients.
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)
Managing Heart Failure in Patients on Dialysismagdyelmasry3
•
Heart failure and end-stage kidney disease (ESKD) commonly coexist; 1 comorbidity worsens the prognosis of the other.
•
Although patients with ESKD compose an extremely high-risk population, they have been excluded from landmark clinical trials in heart failure, and there is, thus, a paucity of data regarding the management of heart failure in patients on dialysis.
•
Trial-level evidence is warranted in the future to endorse the efficacy and safety of therapeutic interventions in patients with heart failure and on dialysis. Collaborations between cardiologists and nephrologists are needed to devise an optimal treatment strategy for these patients.
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)
Association and prevalence of different comorbidities in hypertension and management with focus guidelines with benefits & choice of different antihypertensives in different comorbidities.
Presentation given to our fellowship program about diabetic kidney disease.
2022 update discussing SGLT2i, MRA (e.g. finerenone), health economics and beyond
Assessment Outcomes Dyslipidaemia in Dialysis PatientAI Publications
Background: Chronic kidney disease is defined as the presence, for more than three months, of changes in the structure or function of the kidneys, secondary to a progressive decline in the number of nephrons, with a consequent deterioration in health resulting from the inability of the kidneys to perform their excretory functions, softener, and metabolism. Chronic kidney disease (CKD) is a clinical condition caused by the progressive and progressive loss of kidney function. Chronic kidney disease is not only implicated by the gradual deterioration of quality of life and life expectancy when it progresses to more advanced stages but also by the increase in cardiovascular morbidity and mortality, which is the leading cause of death in these patients. Aim: This paper aims to assess the outcomes of dyslipidemia in a dialysis patient. Patients and method: In this study, a descriptive cross-sectional study was applied to study the Assessment Outcomes of Dyslipidemia in Dialysis Patients in Iraq from 4th January 2021 to 7th August 2022. Data were collected for 150 patients in different hospitals in Iraq, where the patients were divided into two groups, the first group of patients, which included DIALYSIS PATIENTS, which included 80, and the second group, the control group, which included patients, which include 70 patients. Results and discussions: collected 150 cases distributed according to dialysis patients (80) and controls (70); the most frequent ages in this study ranged from 40-49 years old 34 (42.5%) patients group, 33 (47.14%) control group with a statistical difference of 0.0831. In this study was evaluated the Outcomes of dyslipidemia in a dialysis patient. Imbalances were found in levels of dyslipidemia which LDL 5.12±3.4 of the patients' group, as for the control group 2.1±3.3-HDL 2.43±2.4 of the patients' group, 1.4±1.5 for the control group, TRIGLYCERIDE 1.75±1.8 of patients group, 0.55±0.43 for the control group with A statistically significant relationship were found between dyslipidemia levels and outcomes in the group of patients at P value < 0.05.
Management of CAD in Diabetes the cardiovascular equivalent is challenging.The slides take you from the epidemiology,ADD,and CV benefit and how to manage CAD
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Association and prevalence of different comorbidities in hypertension and management with focus guidelines with benefits & choice of different antihypertensives in different comorbidities.
Presentation given to our fellowship program about diabetic kidney disease.
2022 update discussing SGLT2i, MRA (e.g. finerenone), health economics and beyond
Assessment Outcomes Dyslipidaemia in Dialysis PatientAI Publications
Background: Chronic kidney disease is defined as the presence, for more than three months, of changes in the structure or function of the kidneys, secondary to a progressive decline in the number of nephrons, with a consequent deterioration in health resulting from the inability of the kidneys to perform their excretory functions, softener, and metabolism. Chronic kidney disease (CKD) is a clinical condition caused by the progressive and progressive loss of kidney function. Chronic kidney disease is not only implicated by the gradual deterioration of quality of life and life expectancy when it progresses to more advanced stages but also by the increase in cardiovascular morbidity and mortality, which is the leading cause of death in these patients. Aim: This paper aims to assess the outcomes of dyslipidemia in a dialysis patient. Patients and method: In this study, a descriptive cross-sectional study was applied to study the Assessment Outcomes of Dyslipidemia in Dialysis Patients in Iraq from 4th January 2021 to 7th August 2022. Data were collected for 150 patients in different hospitals in Iraq, where the patients were divided into two groups, the first group of patients, which included DIALYSIS PATIENTS, which included 80, and the second group, the control group, which included patients, which include 70 patients. Results and discussions: collected 150 cases distributed according to dialysis patients (80) and controls (70); the most frequent ages in this study ranged from 40-49 years old 34 (42.5%) patients group, 33 (47.14%) control group with a statistical difference of 0.0831. In this study was evaluated the Outcomes of dyslipidemia in a dialysis patient. Imbalances were found in levels of dyslipidemia which LDL 5.12±3.4 of the patients' group, as for the control group 2.1±3.3-HDL 2.43±2.4 of the patients' group, 1.4±1.5 for the control group, TRIGLYCERIDE 1.75±1.8 of patients group, 0.55±0.43 for the control group with A statistically significant relationship were found between dyslipidemia levels and outcomes in the group of patients at P value < 0.05.
Management of CAD in Diabetes the cardiovascular equivalent is challenging.The slides take you from the epidemiology,ADD,and CV benefit and how to manage CAD
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
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Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
2. Click to add title
2
• CKD and CVD: Accelerated HF, atherosclerosis and arteriosclerosis
Outline
3. Patients with CKD should be considered to be in the highest
risk category, ie, a CHD risk equivalent, for risk factor
management.
• KDOQI Clinical Practice Guidelines for Managing Dyslipidemias in
Chronic Kidney Disease
4. CRM, cardio-renal-metabolic; LV, left ventricular
Adapted from Dzau VJ et al.5
1. Sarafidis PA et al. J Cardiometab Syndr 2006;1:58; 2. Ronco C. Contrib Nephrol 2010;164:33; 3. Banerjee S and Panas R. Hellenic J Cardiol 2017;58:342;
4. Leon BM and Maddox TM. World J Diabetes 2015;6:1246; 5. Dzau VJ et al. Circulation 2006;114:2850
Diseases of the CRM systems share many of
the same risk factors1
4
Progression of interrelated diseases (T2D, CV disease, HF and CKD) can occur due to dysfunction
of the CRM systems, which, in turn, may lead to an increased risk of CV death2–4
= Diabetes and metabolic risk factors
= Kidney disease
= CV disease
PC-TW-102542
Bad metabolic memory
CKD HF CVD
5. Click to add title
5
Worse renal function with higher CAD and CV death
1. PLoS Med. 2007 Sep;4(9):e270. 2. Circulation. 2021 Mar 16;143(11):1157-1172.
Lower eGFR with higher risk of CVD mortality
及時護腎,維持eGFR>75
Lower eGFR with higher risk of coronary disease
及時護腎,維持eGFR>70
Keep GFR as normal as possible!!
6. 6
All-cause mortality risks were significantly higher across all levels
of estimated GFR, proteinuria for early DKD group
Early DKD had higher mortality
across all eGFR levels
Early DKD had higher mortality
across all levels of proteinuria
Wen CP, Chang CH et al. Kidney Int. 2017 Aug;92(2):388-396.
A total of 512,700 subjects were identified; among them, 27,455 (5.4%) had diabetes. One-third of those with
diabetes (9067 or 33.3%) had early DKD. Approximately 50,977 participants (9.9%) had early CKD without diabetes.
~2 fold risk ~2 fold risk
Keep albuminuria as normal as possible, too !!
7. - 7 -
CVD in patients with or without CKD
https://abdominalkey.com/cardiovascular-disease-in-chronic-kidney-disease/#bib15
Chapeter 82, Cardiovascular Disease in Chronic Kidney Disease
「腰子若壞,人生是黑白的;腰子若好,人生是彩色的」
8. Structural and Functional Changes in Human Kidneys
with Healthy Aging
8
JASN October 2017, 28 (10) 2838-2844
9. J Am Soc Nephrol 28: 1023–1039, 2017. doi: 10.1681/ASN.2016060666
Glomerular Hyperfiltration in Diabetes
9
13. High-Protein Diet Is Bad for Kidney Health
• HPD increases the risk of RHF and a rapid renal function decline in the general
population
Nephrol Dial Transplant. 2020 Jan 1;35(1):98-106.
• HPD was significantly associated with a more rapid kidney function
decline in post-MI patients.
Nephrol Dial Transplant . 2020 Jan 1;35(1):106-115.
Mean age~55y/o
14. First-Line therapy is metformin and comprehensive lifestyle
Indicators of high-risk or established
ASCVD, CKD, HF
Consider independently of baseline A1C,
Individualized A1C target, or metformin use
+ASCVD/
Indicators
of high risk
+HF +CKD
Compelling need to
minimize
hypoglycemia
Compelling need to
minimize weight gain
or promote weight
loss
Cost is a
major issue
If A1C above individualized target proceed as below
No
共病考量需先評估病患是否合併有 ASCVD (or high risk),CKD,HF
在治療用藥上,就需要獨立於血糖控制的考量
1
2
Adapted from 2021 ADA guidelines
SGLT2i fits all, esp. for renal
protection!!
15. Click to add title
15
• Prevalence of kidney disease in patients with CVD
Outline
17. Click to add title
17
34% ACS patients suffered from CKD in Taiwan
CKD is defined as eGFR<60
Data from Taiwan Acute Coronary Syndrome Full Spectrum Registry (n=3183); Heart Vessels. 2015 Jul;30(4):441-50.
18. Click to add title
18
45% patients underwent PCI suffered from CKD in Taiwan
CKD was defined as eGFR<60
1394 patients who underwent PCI and 45.3% had CKD; 1676 patients treated with PCI and 45.8% had CKD
1. BMC Cardiovasc Disord. 2017 Sep 11;17(1):242. 2. Sci Rep . 2018 Dec 5;8(1):17673.
19. 2
19
Relative risks of 1-year
preserved RF vs Renal failure Ccr < 60)
Archives of Cardiovascular Disease (2015) 108, 554—562
20. Click to add title
20
CKD had additive effect on adverse long-term outcomes in
patients receiving PCI
CKD is defined as eGFR<60, n=1394
BMC Cardiovasc Disord. 2017 Sep 11;17(1):242.
21. Click to add title
21
CKD is important risk factor for AKI in patients with PCI
11.4倍
Int J Med Sci 2018; 15(5):528-535.
82,186 patients admitted for ACS and receiving
PCI from the Taiwan National Health Insurance
Research
22. 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
23. Click to add title
23
Incidence of heart failure after acute coronary syndromes
Am Heart J. 2013 Mar;165(3):379-85.e2.
Cumulative 1-year HF rates among STEMI, NSTEMI, and UA
24. Click to add title
24
Prevalence of HF in ACS patients with/without CKD
Medicina (Kaunas). 2020 Mar 8;56(3):118.
25. Click to add title
25
Association of renal function and all-cause mortality
in HF patients
All-cause mortality in patients with HF by eGFR
Analysis of 16,740 individual patients with left ventricular ejection fraction <50% from 10 double-blind, placebo-controlled trials
J Am Coll Cardiol. 2019 Dec, 74 (23) 2893–2904.
Death by cause in patients with HF by eGFR
及時護腎,維持eGFR>60
26. Nature Reviews Nephrology volume 15, pages159–175 (2019)
Uraemic cardiomyopathy is characterized by diastolic dysfunction and marked left ventricular
hypertrophy with profound ventricular fibrosis.
Treatments that are effective in other cardiomyopathic conditions such as antihypertensive
drugs improve clinical outcomes in uraemic cardiomyopathy only modestly at best.
27. Click to add title
27
hHF: heart failure hospitalizations
J Am Soc Nephrol. 2015 Mar;26(3):715-22.
HF increases the risk of ESRD
29. 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 ?
31. Levey AS, et al. Kidney Int. 2011;80:17-28
Save kidneys=effective primary and secondary prevention
Macro-DKD needs most intensive cardiorenal protection!!
32.
33. Click to add title
33
• Advantages of canagliflozin on SGLT 1&2 inhibitions
Outline
34. 34
MACE Reduction : Only for Secondary Prevention
Population
www.thelancet.com Published online November 10, 2018
http://dx.doi.org/10.1016/S0140-6736(18)32590-X
The p value for subgroup differences was 0.0501
6.5 7.2 4.2
36. 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.
36
more glucosuria &
natriuresis!!
38. Canagliflozin, dapagliflozin and empagliflozin
for treating type 2 diabetes: Network Meta-analysis 38
Health Technology Assessment, No. 21.2
HbA1c
BW
39. Canagliflozin, dapagliflozin and empagliflozin
for treating type 2 diabetes: Network Meta-analysis 39
Health Technology Assessment, No. 21.2
SBP
41. Prespecified Cox proportional-hazard regression analyses were performed for subgroups of patients with respect to
the primary outcome (first occurrence of death from CV causes, nonfatal MI, or nonfatal stroke). P values signify tests
of homogeneity for between-group differences with no adjustment for multiple testing. The percentages of patients
with a first primary outcome between the randomization date and the date of last follow-up are shown. There were
missing data for BMI in 5 patients in the liraglutide group and 4 in the placebo group and for the duration of diabetes
in 11 patients in the liraglutide group and 8 in the placebo group.
Presented at the American Diabetes Association 76th Scientific Sessions, Session 3-CT-SY24. June 13 2016, New Orleans, LA, USA.
Primary outcome: Subgroup analyses
LEADER trial: 81% CVD
CVD/CKDPrimary cohort with benefit
42. 42
CV risk 33% in DKD patient (stage III)
N Engl J Med 2016;374:311-22. DOI: 10.1056/NEJMoa1603827
43. Renal outcomes from CVOTs
REWIND, LEADER and SUSTAIN 6
*RRT is defined as either dialysis or renal transplantation
CI, confidence interval; eGFR, estimated glomerular filtration rate; ESRD, end stage renal disease
1. Gerstein HC et al. Lancet 2019; 394(10193):131–138; 2. Mann JFE et al. N Engl J Med 2017; 377(9):839–848; 3. Marso et al. N Engl J Med 2016; 375:1834-1844.
REWIND (Dulaglutide)1: Composite renal outcome
Macroalbuminuria, sustained ≥30% decline in eGFR, or new chronic
RRT*
Time from randomisation (years)
0 1 2 3 4 5 6
50
40
30
20
10
0
Cumulative
risk
(%)
HR: 0.85
(95% CI: 0.77; 0.93)
Dulaglutide: 848 events, placebo:
970 events
p=0.0004
Dulaglutide 1.5 mg
Placebo
SUSTAIN 6 (Semaglutide)3: Composite renal outcome
Macroalbuminuria, doubling of serum creatinine
or ESRD
0
2
4
6
8
10
0 8 16 24 32 40 48 56 64 72 80 88 96 104
Semaglutide
Placebo
HR 0.64 (0.46–0.88)
p=0.005
Time from randomisation (weeks)
LEADER (Liraglutide)2: Composite renal outcome
Macroalbuminuria, doubling of serum creatinine, ESRD or renal death
Time since randomisation (months)
Cumulative
risk
(%)
0 6 12 18 24 30 36 42 48 54
0
2
4
6
8
10
Cumulative
risk
(%)
HR: 0.78
95% CI (0.67–0.92)
p=0.003
10
8
6
4
2
0
0 6 12 18 24 30 36 42 48 54
Liraglutide
Placebo
SUSTAIN 6: 83% CVD
REWIND: 30% CVD LEADER: 81% CVD
15% 22% 36%
44. Time to categorical eGFR reduction
Post-hoc pooled analysis of LEADER AND SUSTAIN 6(Macro-DKD got most benefits?)
CI, confidence interval; eGFR, estimated glomerular filtration rate; HR, hazard ratio.
Presented at the 56th European Renal Association - European Dialysis and Transplant Association (ERA-EDTA) Congress, 13–16 June 2019, Budapest, Hungary.
Reduction in
eGFR
Sema/lira
pooled (N)
Placebo pooled
(N)
HR
(95% CI)
p-value
Overall pooled population
30% 791 848 0.92 (0.84; 1.02) 0.1005
40% 378 432 0.86 (0.75; 0.99) 0.0386
50% 185 229 0.80 (0.66; 0.97) 0.0233
57% 121 135 0.89 (0.69; 1.13) 0.3423
eGFR ≥30 to
<60 mL/min/1.73 m2 and
micro-or macroalbuminuria
30% 151 196 0.65 (0.53; 0.81) <0.0001
40% 89 120 0.64 (0.48; 0.84) 0.0013
50% 51 78 0.57 (0.40; 0.81) 0.0017
57% 34 53 0.56 (0.37; 0.87) 0.0093
eGFR
≥60 mL/min/1.73 m2 or
normoalbuminuria
30% 579 591 0.99 (0.88; 1.10) 0.7982
40% 245 270 0.91 (0.76; 1.08) 0.2810
50% 101 118 0.86 (0.66; 1.12) 0.2598
57% 58 61 0.95 (0.67; 1.37) 0.7961
0.2 0.4 0.6 0.8 1 1.2 1.4
Favours placebo
Favours semaglutide/liraglutide
Semaglutide
Liraglutide
49. Effect of SGLT2 inhibitors on cardiovascular, renal and safety outcomes in patients with type 2 diabetes
mellitus and chronic kidney disease: A systematic review and meta-analysis Diabetes
Obes Metab. 2019; 21: 1237– 1250.
53. (31.2%, BP ≥130/80 mm Hg while receiving ≥3 classes of BP-lowering drugs,
including a diuretic)
54. 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?
55. 55
More effective in
symptomatic HF!!
CANVAS: post hoc
Relative risk reduction of CV death and HHF
Diabetologia (2018) 61:2108–2117
62. Click to add title
62
• Save kidneys = effective primary and secondary preventions!!
Outline
63. J Am Soc Nephrol 28: 1023–1039, 2017. doi: 10.1681/ASN.2016060666
Glomerular Hyperfiltration in Diabetes
63
ARB yes/SGLT2i great!!
ARB No! but SGLT2i Yes!
64. N Engl J Med 2001; 345:870-878
Data from the IRMA2 Program BP 153/90
UAE 55 ug/min
Ccr 110 ml/min
65. JASN November 2019, 30 (11) 2229-2242;
Data from the CANVAS Program(65% CVD)
The earlier, the better!!
~3
~1
~1
66.
67. 67
Diabetes Ther. 2020 Dec 18. doi: 10.1007/s13300-020-00953-4. Online ahead of print
Estimated eGFR values used to project the delay in time to dialysis*
by treatment in the CREDENCE trial**
* eGFR of 10 ml/min/1.73 m2
** overlaid with observed data
RENNAL&IDNT
2-3 years
56
68. Renal Safety: CREDENCE
Number of participants
with an event, n
Canagliflozin
(N = 2200)
Placebo
(N = 2197)
Hazard ratio
(95% CI)
All renal-related AEs 290 388 0.71 (0.61–0.82)
Hyperkalemia 151 181 0.80 (0.65–1.00)
Acute kidney injury 86 98 0.85 (0.64–1.13)
Favors Canagliflozin Favors Placebo
0.5 1.0 2.0
Includes all treated participants through 30 days after last dose.
76. First-Line therapy is metformin and comprehensive lifestyle
Indicators of high-risk or established
ASCVD, CKD, HF
Consider independently of baseline A1C,
Individualized A1C target, or metformin use
+ASCVD/
Indicators
of high risk
+HF +CKD
Compelling need to
minimize
hypoglycemia
Compelling need to
minimize weight gain
or promote weight
loss
Cost is a
major issue
If A1C above individualized target proceed as below
No
共病考量需先評估病患是否合併有 ASCVD (or high risk),CKD,HF
在治療用藥上,就需要獨立於血糖控制的考量
1
2
Adapted from 2021 ADA guidelines
Canagliflozin fits all !!