HIF PH inhibitors stabilize HIF and stimulate endogenous EPO production, facilitating erythropoiesis and improving iron metabolism in CKD patients. Compared to ESAs, HIF PH inhibitors maintain physiological EPO levels, decrease cardiovascular risks, and reduce need for rescue therapies like transfusions. By coordinating EPO production, iron transport, and hepcidin inhibition, HIF PH inhibitors provide a targeted approach to anemia in CKD.
Presentation given to our fellowship program about diabetic kidney disease.
2022 update discussing SGLT2i, MRA (e.g. finerenone), health economics and beyond
Presentation given to our fellowship program about diabetic kidney disease.
2022 update discussing SGLT2i, MRA (e.g. finerenone), health economics and beyond
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A ppt about contrast nephropathy: basics, risk factors, comparison of preventive strategies.
critical review of POSEIDON trial and brief about PRESERVE trial.
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Although many are still concerned with an ARB–MI paradox, our study of close to 60 000 patients with MI should serve as reassurance that ARBs are not associated with adverse outcomes compared with ACEIs. Potential benefits of ARBs as compared with ACEIs in older women with MI should be further evaluated.
- English version of this lecture is available at: https://youtu.be/_Efu52kZRS4
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Hyertension in patients on regular hemodialysisEhab Ashoor
Everything about hypertension in patients on regular hemodialysis, including management, Resistant hypertension, Intra-dialytic hypertension and Hypertensive urgencies.
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A ppt about contrast nephropathy: basics, risk factors, comparison of preventive strategies.
critical review of POSEIDON trial and brief about PRESERVE trial.
- Recorded videos of the lecture:
English Language version of this lecture is available at: https://youtu.be/-Ynxvhbcl7U
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Although many are still concerned with an ARB–MI paradox, our study of close to 60 000 patients with MI should serve as reassurance that ARBs are not associated with adverse outcomes compared with ACEIs. Potential benefits of ARBs as compared with ACEIs in older women with MI should be further evaluated.
- English version of this lecture is available at: https://youtu.be/_Efu52kZRS4
- Arabic version of this lecture is available at: https://youtu.be/8eGHpjQIy3I
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Hyertension in patients on regular hemodialysisEhab Ashoor
Everything about hypertension in patients on regular hemodialysis, including management, Resistant hypertension, Intra-dialytic hypertension and Hypertensive urgencies.
- English version of this lecture is available at:
https://youtu.be/V3UGzJTwAWw
- Arabic version of this lecture is available at:
https://youtu.be/hGLaUde2ue4
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HIF-1 Gene is transcribed in the nucleus with the help of specific protein .HIF-1 protein with DNA binding activity. Functional HIF transcription factors comprise 2 different subunits, that is, alpha (α) and beta (β). The α subunit, of which there are 3 forms ( HIF-1α, HIF-2α and HIF-3α) out of which HIF-1α and HIF-2α are main, HIF-1α is oxygen sensitive, HIF-1α is expressed in almost all cell types, and transcriptionally upregulates a large number of genes, including those encoding Vascular endothelial growth factor (VEGF), Glucose transporters, Glycolytic pathway enzymes , Insulin-like growth factor-2, Endothelin-1, transferrin, HIF-2 is the primary regulator of EPO production and also plays an important role in enterocyte iron uptake.
HIF-β is continuously transcribed and its mRNA and protein are maintained at constant levels irrespective of oxygen levels, the availability of HIF-α is highly dependent on cellular oxygen levels. Thus, the activity of the HIF transcription factor heterodimer is relatively low under normal tissue oxygen conditions called normaxia however, as cellular oxygen levels decrease called hypoxia, HIF-α concentration increases, making HIF progressively more functionally active.
Hypoxia, its causes, and how hypoxia causes the induction of hypoxia inducible factors to cause angiogenesis in those regions of the body, mechanism of angiogenesis and the role of VEGF in it.
Iron deficiency is an extremely common comorbidity in patients with heart failure, affecting up to 50% of all ambulatory patients. It is associated with reduced exercise capacity and physical well-being and reduced quality of life. Cutoff values have been identified for diagnosing iron deficiency in heart failure with reduced ejection fraction as serum ferritin, <100 μg/l, or ferritin, 100 to 300 μg/l, with transferrin saturation of <20%. Oral iron products have been shown to have little efficacy in heart failure, where the preference is intravenous iron products. Most clinical studies have been performed using ferric carboxymaltose with good efficacy in terms of improvements in 6-min walk test distance, peak oxygen consumption, quality of life, and improvements in New York Heart Association functional class. Data from meta-analyses also suggest beneficial effects for hospitalization rates for heart failure and reduction in cardiovascular mortality rates. A prospective trial to investigate effects on morbidity and mortality is currently ongoing. This paper highlights current knowledge of the pathophysiology of iron deficiency in heart failure, its prevalence and clinical impact, and its possible treatment options
Telehealth Psychology Building Trust with Clients.pptxThe Harvest Clinic
Telehealth psychology is a digital approach that offers psychological services and mental health care to clients remotely, using technologies like video conferencing, phone calls, text messaging, and mobile apps for communication.
Empowering ACOs: Leveraging Quality Management Tools for MIPS and BeyondHealth Catalyst
Join us as we delve into the crucial realm of quality reporting for MSSP (Medicare Shared Savings Program) Accountable Care Organizations (ACOs).
In this session, we will explore how a robust quality management solution can empower your organization to meet regulatory requirements and improve processes for MIPS reporting and internal quality programs. Learn how our MeasureAble application enables compliance and fosters continuous improvement.
Global launch of the Healthy Ageing and Prevention Index 2nd wave – alongside...ILC- UK
The Healthy Ageing and Prevention Index is an online tool created by ILC that ranks countries on six metrics including, life span, health span, work span, income, environmental performance, and happiness. The Index helps us understand how well countries have adapted to longevity and inform decision makers on what must be done to maximise the economic benefits that comes with living well for longer.
Alongside the 77th World Health Assembly in Geneva on 28 May 2024, we launched the second version of our Index, allowing us to track progress and give new insights into what needs to be done to keep populations healthier for longer.
The speakers included:
Professor Orazio Schillaci, Minister of Health, Italy
Dr Hans Groth, Chairman of the Board, World Demographic & Ageing Forum
Professor Ilona Kickbusch, Founder and Chair, Global Health Centre, Geneva Graduate Institute and co-chair, World Health Summit Council
Dr Natasha Azzopardi Muscat, Director, Country Health Policies and Systems Division, World Health Organisation EURO
Dr Marta Lomazzi, Executive Manager, World Federation of Public Health Associations
Dr Shyam Bishen, Head, Centre for Health and Healthcare and Member of the Executive Committee, World Economic Forum
Dr Karin Tegmark Wisell, Director General, Public Health Agency of Sweden
Explore our infographic on 'Essential Metrics for Palliative Care Management' which highlights key performance indicators crucial for enhancing the quality and efficiency of palliative care services.
This visual guide breaks down important metrics across four categories: Patient-Centered Metrics, Care Efficiency Metrics, Quality of Life Metrics, and Staff Metrics. Each section is designed to help healthcare professionals monitor and improve care delivery for patients facing serious illnesses. Understand how to implement these metrics in your palliative care practices for better outcomes and higher satisfaction levels.
Leading the Way in Nephrology: Dr. David Greene's Work with Stem Cells for Ki...Dr. David Greene Arizona
As we watch Dr. Greene's continued efforts and research in Arizona, it's clear that stem cell therapy holds a promising key to unlocking new doors in the treatment of kidney disease. With each study and trial, we step closer to a world where kidney disease is no longer a life sentence but a treatable condition, thanks to pioneers like Dr. David Greene.
The Importance of Community Nursing Care.pdfAD Healthcare
NDIS and Community 24/7 Nursing Care is a specific type of support that may be provided under the NDIS for individuals with complex medical needs who require ongoing nursing care in a community setting, such as their home or a supported accommodation facility.
R3 Stem Cells and Kidney Repair A New Horizon in Nephrology.pptxR3 Stem Cell
R3 Stem Cells and Kidney Repair: A New Horizon in Nephrology" explores groundbreaking advancements in the use of R3 stem cells for kidney disease treatment. This insightful piece delves into the potential of these cells to regenerate damaged kidney tissue, offering new hope for patients and reshaping the future of nephrology.
CHAPTER 1 SEMESTER V PREVENTIVE-PEDIATRICS.pdfSachin Sharma
This content provides an overview of preventive pediatrics. It defines preventive pediatrics as preventing disease and promoting children's physical, mental, and social well-being to achieve positive health. It discusses antenatal, postnatal, and social preventive pediatrics. It also covers various child health programs like immunization, breastfeeding, ICDS, and the roles of organizations like WHO, UNICEF, and nurses in preventive pediatrics.
One of the most developed cities of India, the city of Chennai is the capital of Tamilnadu and many people from different parts of India come here to earn their bread and butter. Being a metropolitan, the city is filled with towering building and beaches but the sad part as with almost every Indian city
Defecation
Normal defecation begins with movement in the left colon, moving stool toward the anus. When stool reaches the rectum, the distention causes relaxation of the internal sphincter and an awareness of the need to defecate. At the time of defecation, the external sphincter relaxes, and abdominal muscles contract, increasing intrarectal pressure and forcing the stool out
The Valsalva maneuver exerts pressure to expel faeces through a voluntary contraction of the abdominal muscles while maintaining forced expiration against a closed airway. Patients with cardiovascular disease, glaucoma, increased intracranial pressure, or a new surgical wound are at greater risk for cardiac dysrhythmias and elevated blood pressure with the Valsalva maneuver and need to avoid straining to pass the stool.
Normal defecation is painless, resulting in passage of soft, formed stool
CONSTIPATION
Constipation is a symptom, not a disease. Improper diet, reduced fluid intake, lack of exercise, and certain medications can cause constipation. For example, patients receiving opiates for pain after surgery often require a stool softener or laxative to prevent constipation. The signs of constipation include infrequent bowel movements (less than every 3 days), difficulty passing stools, excessive straining, inability to defecate at will, and hard feaces
IMPACTION
Fecal impaction results from unrelieved constipation. It is a collection of hardened feces wedged in the rectum that a person cannot expel. In cases of severe impaction the mass extends up into the sigmoid colon.
DIARRHEA
Diarrhea is an increase in the number of stools and the passage of liquid, unformed feces. It is associated with disorders affecting digestion, absorption, and secretion in the GI tract. Intestinal contents pass through the small and large intestine too quickly to allow for the usual absorption of fluid and nutrients. Irritation within the colon results in increased mucus secretion. As a result, feces become watery, and the patient is unable to control the urge to defecate. Normally an anal bag is safe and effective in long-term treatment of patients with fecal incontinence at home, in hospice, or in the hospital. Fecal incontinence is expensive and a potentially dangerous condition in terms of contamination and risk of skin ulceration
HEMORRHOIDS
Hemorrhoids are dilated, engorged veins in the lining of the rectum. They are either external or internal.
FLATULENCE
As gas accumulates in the lumen of the intestines, the bowel wall stretches and distends (flatulence). It is a common cause of abdominal fullness, pain, and cramping. Normally intestinal gas escapes through the mouth (belching) or the anus (passing of flatus)
FECAL INCONTINENCE
Fecal incontinence is the inability to control passage of feces and gas from the anus. Incontinence harms a patient’s body image
PREPARATION AND GIVING OF LAXATIVESACCORDING TO POTTER AND PERRY,
An enema is the instillation of a solution into the rectum and sig
2. PREVALENCE OF ANEMIA IN CKD
The prevalence of anemia (hemoglobin <12 g/dl) is :
47.7% in patients with nondialysis CKD and increases
as CKD progresses
42% of patients with stage 3 CKD
76% in stage 5 CKD.
When compared with patients without anemia (Hb >
12.5 g/dL), patients with anemia (Hb < 10.5 g/dL) had
a 2-fold increased risk of cardiovascular (CV)
hospitalization, a 5-fold increased risk of mortality,
and a 5-fold increased risk of progression to ESRD.
Kidney International Supplements (2017) 7, 157–163;
5. ANEMIA IN CKD
There are 2 key causes underlying the development of anemia in CKD: erythropoietin
(EPO) deficiency and functional iron deficiency (FID).
EPO deficiency : blunted response in EPO production to the degree of anemia.
FID : a combination of impaired iron mobilization from stores and inadequate delivery of
iron to the erythroid marrow in the setting of increased red blood cell (RBC) production
induced by pharmacologic treatment with ESAs.
Absolute iron deficiency : in patients with CKD due to inadequate provision or
absorption of dietary iron and/or blood losses.
Am J Kidney Dis. 69(6):815-826
6.
7. WHY HYPOXIA OCCURS IN CKD
Adequate oxygen is essential for all mammalian organs to fuel various bio-metabolic
processes and to maintain biological homeostasis.
The balance between oxygen consumption and supply is critical especially for kidneys,
which always stay in active metabolic condition and are in high need of oxygen supply.
Hypoxia, insufficient supply of oxygen, has been considered to be closely related to CKD
progression.
The induction of hypoxia during CKD is indeed multifactorial, including increased oxygen
consumption, malfunction of microvasculature, vascular remodeling, anemia associated
impaired oxygen delivery, impaired oxygen diffusion by extracellular matrix (ECM)
accumulation, and mitochondrial abnormality.
12. ERYTHROPOIETIN
• EPO is a proliferation and maturation factor produced in response to tissue hypoxia, as a
result of complex regulatory mechanisms.
• 90% of all EPO produced in the body originates from the kidneys and approximately 10%
is produced by the liver.
• Kidney-derived EPO is produced by cortical
peritubular fibroblasts located near the
proximal tubular cells in the outer medulla
and inner cortex in the kidney. This
production is expanded into the outer
cortex in response to hypoxia and anemia,
a region that is especially susceptible to
hypoxia. Kidney International Supplements (2017) 7, 157–163;
13. ESA AND CHALLENGES WITH ITS USE
• Treatment of anemia related to CKD with
rHuEPO and related products
(erythropoiesis-stimulating agents [ESAs])
increases hemoglobin (Hb) levels, lessens
the need for transfusion, and improves
patient quality of life.
• However, treatment to higher Hb targets
in clinical trials has resulted in higher rates
of access thrombosis, cerebrovascular
events, and cardiovascular events; earlier
requirement for kidney replacement
therapy; and higher mortality.
Kidney International Supplements (2017) 7, 157–163;
Am J Kidney Dis. 69(6):815-826
14. ESA AND CHALLENGES WITH ITS USE
• Analysis suggests high pharmacologic doses of ESAs, rather than the highly achieved
hemoglobin, may mediate harm.
• The circulating levels of EPO required to stimulate erythropoiesis is 7 to 30 mU/ml,
with higher levels required in patients with CKD and ESRD due to shortened red cell
survival.
• The unphysiologic administration of high-dose ESA for anemia of CKD and ESRD can
result in EPO levels as high as 700 mU/ml.
Kidney International Supplements (2017) 7, 157–163;
15. TARGETED APPROACH
An emerging approach to the treatment of EPO deficiency in anemic patients with
CKD is the use of agents that stimulate endogenous EPO production in renal and
nonrenal tissues.
Such a strategy might decrease adverse outcomes by allowing for a more consistent,
although not necessarily continuous, physiologic level of EPO to stimulate RBC
production rather than the high intermittent blood levels that result from
pharmacologic administration of an exogenous ESA.
Am J Kidney Dis. 69(6):815-826
16. HYPOXIA INDUCIBLE FACTOR (HIF)
HIF is a key transcription factor that produces a physiologic response to reduced tissue
oxygen levels by activating the expression of certain genes.
The purpose of this adaptive homeostatic response is to restore oxygen balance and
protect against cellular damage while oxygen levels are being restored.
HIF is a heterodimer with an α and β subunit. The HIF-α subunit joins with the β subunit in
the nucleus and binds to DNA sequences called hypoxia response elements (HREs) and thus
induces the expression target genes.
There are 3 isoforms of the a subunit:HIF-1α, HIF-2α, and HIF-3α, any of which can combine
with the β subunit to induce the expression of different combinations of target genes.
Am J Kidney Dis. 69(6):815-826
17. HOW HIF EPO PATHWAY WORKS
In CKD, EPO production is relatively insufficient because the HIF expression and function in damaged kidneys are
insufficient to respond to their hypoxic condition, which is caused by oxidative stress , inflammation and uremic toxins
Kidney360 August 2020, 1 (8) 855-862; DOI:
https://doi.org/10.34067/KID.000144202
18. HYPOXIA INDUCIBLE FACTOR
The primary means of HIF activity regulation is hydroxylation at 2 proline residues by a
family of HIF-PH enzymes, also known as prolyl hydroxylase domain (PHD) enzymes, of
which there are 3 members: PHD1, PHD2, and PHD3.
PHD2 is the main regulator of HIF activity in normoxia.
HIF-2α is the main subunit involved in upregulating EPO gene expression and iron
transport in hypoxia.
HIF-2α is expressed in peritubular fibroblasts, which are thought to be the primary site of
renal EPO production.
HIF-2α appears to be a key element in the hypoxic response; however, in certain situations,
HIF-1α controls the early response to hypoxia.
Am J Kidney Dis. 69(6):815-826
19. HYPOXIA INDUCIBLE FACTOR
In normoxia, HIF-PH activity leads to
rapid degradation of HIF.
During hypoxia, HIF-PH activity is
suppressed, allowing HIF to accumulate
and directly stimulate endogenous EPO
production, upregulate transferrin
receptor expression, increase iron uptake
by proerythrocytes, and promote
maturation of erythrocytes replete with
Hb. Am J Kidney Dis. 69(6):815-826
20. HYPOXIA INDUCIBLE FACTOR
Oxygen dependent regulation of HIF mainly
involves the degradation of HIF-α subunits, which
starts with hydroxylation of HIF-α by HIF-PH
enzymes.
HIF-PH enzymes require oxygen for their catalytic
activity to regulate HIF. Thus, when oxygen levels
decrease, prolyl hydroxylation does not occur,
which allows HIF-α to dimerize with its partner
HIF-β and accumulate in the nucleus to regulate
HIF target genes. HIF stabilization increases gene
transcription by binding to HREs, thus
upregulating EPO and other genes.
21. HIF ROLE IN ERYTHROPOIESIS
HIF upregulates transferrin, ceruloplasmin, and transferrin receptor 1, the latter facilitating
increased plasma transport of iron to tissues.
HIF-2α boosts intestinal absorption of iron by upregulating duodenal cytochrome b and
divalent metal transporter 1, 2 important genes in iron uptake and export.
EPO production induced by HIF leads to the production by erythroblasts of erythroferrone,
which limits the gene expression of liver hepcidin.
These functions of HIF complement its effect on erythropoiesis by coordinating EPO-
stimulated RBC production with increased available iron
Am J Kidney Dis. 69(6):815-826
26. COMPARED TO ESA....IS IT BETTER?
Although parenteral ESA treatment produces high levels of the ESA in blood, treatment with
HIF-PH inhibitors results in a relatively small increase in EPO blood levels. This may confer a
potential advantage to HIF-PH inhibitors because they lead to endogenous EPO levels close to
the physiologic range and adequately stimulate the high-affinity receptor responsible for
hematopoiesis.
Increases the availability of iron for effective erythropoiesis.
Lowering hepcidin level and beneficial effect on iron metabolism
27. COMPARED TO ESA...IS IT BETTER?
Use of these agents consistently results in dose-related increases in Hb levels, while
decreasing hepcidin and ferritin levels and decreasing TSAT by increasing total iron-binding
capacity.
Potential benefit in EPO resistant patients
Potential blood pressure lowering effect
Potential protection from ischemic events
Potential anti-inflammatory effects
28. TO SUMMERIZE......
Facilitates intestinal iron absorption by promoting the expression of divalent metal
transporter 1 and duodenal cytochrome B
Stimulates erythropoiesis by upregulating endogenous EPO production
Enhances iron uptakes by proerythrocytes by raising the expression transferrin receptor
Propels the recycling of iron in phagocytosed erythrocytes
Improves chronic inflammatory status by elevating erythroferrone and inhibiting hepcidin
Compared to ESAs, comprehensive effect on replenishing endogenous EPO, decreasing
hepcidin, and improving the bioavailability of iron
Reduces the cardiovascular risks by maintaining a physiological elevation of EPO and avoiding
hemoglobin overshoot brought by ESAs.
Reduces rescue therapy like blood transfusion or iv iron need.
29. REFERENCES
1.Nupur Gupta, MD, and Jay B. Wish, MD Hypoxia-Inducible Factor Prolyl Hydroxylase
Inhibitors: A Potential New Treatment for Anemia in Patients With CKD Am J Kidney Dis.
69(6):815-826.
2.DW Coyne et al.: New options for the anemia of CKD Kidney International
Supplements (2017) 7, 157–163
3.https://www.medscape.org/viewarticle/925208_print
4.Joshua M. Kaplan , Neeraj Sharma and Sean Dikdan Hypoxia-Inducible Factor and Its
Role in the Management of Anemia in Chronic Kidney Disease Int. J. Mol. Sci. 2018, 19,
389; doi:10.3390/ijms19020389