This document discusses chronic kidney disease (CKD). It defines CKD and notes that risk factors include diabetes, hypertension, glomerulonephritis, smoking, dyslipidemia, and obesity. These conditions can both initiate and promote progression of CKD by damaging kidney structures over time. The document outlines epidemiological data on CKD and provides details on how specific conditions like diabetes and hypertension increase CKD risk and progression. It also examines the role of proteinuria and other factors in contributing to declining kidney function in CKD patients.
Topics Covered:
Basic kidney physiology (just enumeration).
Manifestations of renal impairment.
AKI vs. CRF , definitions, causes and their classifications (in brief) .
Clinical evaluation of a case of renal failure.
indications for renal replacement therapy.
Approach for real-Life patient with renal impairment: group-case discussion.
JNC 8 guideline to Management of HypertensionPranav Sopory
JNC - 8 guidelines to management of Hypertension.
Rencent developments in CKD (Chronic Kidney Disease) and DM (Daibetes Mellitus) management.
Drugs discussed along with doses and side effects.
Compelling indiactions.
2017 AHA/ACC criteria for Hypertension management in brief.
>> Contains animation. Download and view.
Acute kidney injury (AKI) is a potentially life-threatening
syndrome that occurs primarily in hospitalized patients
and frequently complicates the course of critically ill
patient.
Acute Kidney Injury is is (abrupt) reduction in kidney functions as evidence by changed in laboratory values; serum creatinine, blood urea nitrogen(BUN)and urine output
Topics Covered:
Basic kidney physiology (just enumeration).
Manifestations of renal impairment.
AKI vs. CRF , definitions, causes and their classifications (in brief) .
Clinical evaluation of a case of renal failure.
indications for renal replacement therapy.
Approach for real-Life patient with renal impairment: group-case discussion.
JNC 8 guideline to Management of HypertensionPranav Sopory
JNC - 8 guidelines to management of Hypertension.
Rencent developments in CKD (Chronic Kidney Disease) and DM (Daibetes Mellitus) management.
Drugs discussed along with doses and side effects.
Compelling indiactions.
2017 AHA/ACC criteria for Hypertension management in brief.
>> Contains animation. Download and view.
Acute kidney injury (AKI) is a potentially life-threatening
syndrome that occurs primarily in hospitalized patients
and frequently complicates the course of critically ill
patient.
Acute Kidney Injury is is (abrupt) reduction in kidney functions as evidence by changed in laboratory values; serum creatinine, blood urea nitrogen(BUN)and urine output
diabetes was associated with insulin resistant state which affects liver cells.Also fatty liver may be called NAFLA OR NASH may lead to liver cirrhosis and sometimes to hepatocelular carcinoma
Diabetes mellitus is a worldwide epidemic. Its prevalence is on a steep rise and is more pronounced in India making it the ‘diabetes capital of the world’. There is also a parallel increase in the prevalence of diabetic nephropathy and is now the single most common cause of end-stage kidney disease leading to significant morbidity and mortality as well as accounts for a tremendous burden on the health care costs. It is also shown that the presence of diabetes increases the risk and progression of non-diabetic kidney disease.
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!
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.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
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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.
Title: Sense of Taste
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 structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
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.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
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
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
2. Lesson Objectives
Upon completion of the chapter, you will be able to:
List the risk factors for development and progression of chronic
kidney disease (CKD).
Explain the mechanisms associated with progression of CKD.
Develop a therapeutic approach to slow progression of CKD,
including lifestyle modifications and pharmacologic therapies.
Identify complications associated to CKD
Design an appropriate therapeutic approach for specific
consequences associated with CKD.
Monitor and evaluate therapeutic outcomes
List the risk factors for development and progression of chronic
kidney disease (CKD).
Explain the mechanisms associated with progression of CKD.
Develop a therapeutic approach to slow progression of CKD,
including lifestyle modifications and pharmacologic therapies.
Identify complications associated to CKD
Design an appropriate therapeutic approach for specific
consequences associated with CKD.
Monitor and evaluate therapeutic outcomes
3. Case Scenario
A.A, a 41 year-old male, from who has a longstanding history of hypertension
and diabetes and presents JUMC , medical ward with a complaint of pruritis,
lethargy, lower extremity edema, nausea and emesis. He denies any other
medical illnesses.
On physical exam the patient is a well-developed, well-nourished male in
moderate distress. Blood pressure 180/110, pulse 80, respirations 24 and he
was afebrile. Body weight 76.5 kg. Cardiac exam had an S1, S2 and S4. The
remainder of the exam was remarkable for 2+ lower extremity edema and
superficial excoriations of his skin from scratching.
A.A, a 41 year-old male, from who has a longstanding history of hypertension
and diabetes and presents JUMC , medical ward with a complaint of pruritis,
lethargy, lower extremity edema, nausea and emesis. He denies any other
medical illnesses.
On physical exam the patient is a well-developed, well-nourished male in
moderate distress. Blood pressure 180/110, pulse 80, respirations 24 and he
was afebrile. Body weight 76.5 kg. Cardiac exam had an S1, S2 and S4. The
remainder of the exam was remarkable for 2+ lower extremity edema and
superficial excoriations of his skin from scratching.
4. A.A’s Laboratory Data result
Chemistry Result Normal Values Urinalysis
Sodium 133 136-146 mmol/L
PH 6.0
Specific gravity
1.010
Protein 1+
Glucose –Ve
Acetone –ve
Occult blood –ve
Bile -ve
Waxy casts
Potassium 6.2 3.5-5.3 mmol/L
Chloride 100 98-108 mmol/L
Total CO2 15 23-27 mmol/L
BUN 170 7-22 mg/dl
Creatinine 16.0 0.7-1.5 mg/dl
U/S: both shrinked Kidney
PH 6.0
Specific gravity
1.010
Protein 1+
Glucose –Ve
Acetone –ve
Occult blood –ve
Bile -ve
Waxy casts
Creatinine 16.0 0.7-1.5 mg/dl
Glucose 108 70-110 mg/dl
Calcium 7.2 8.9-10.3 mg/dl
Phosphorus 10.5 2.6-6.4 mg/dl
Alkaline
Phosphatase
306 30-110 IU/L
Parathyroid
Hormone
895 10-65 pg/ml
Hemoglobin 8.6 14-17 gm/dl
Hematocrit 27.4 40-54 %
Mean cell
volume
88 85-95 FL
5. 1. “Presents with a complaint of pruritis, lethargy, lower extremity edema, nausea
and emesis." what does the symptoms suggest to you?
2. What does S4 signify? What cardiac findings will you expect to find in a
hypertensive?
3. Is the cause of this patient’s renal failure acute or chronic? How did you arrive at
that conclusion?
4. What are risk factors for his current diagnosis?
5. What is the calculated GFR?
6. Why is the parathyroid hormone elevated?
7. What is the most likely cause of this patient’s anemia?
8. General approach of management??
Viva questions
1. “Presents with a complaint of pruritis, lethargy, lower extremity edema, nausea
and emesis." what does the symptoms suggest to you?
2. What does S4 signify? What cardiac findings will you expect to find in a
hypertensive?
3. Is the cause of this patient’s renal failure acute or chronic? How did you arrive at
that conclusion?
4. What are risk factors for his current diagnosis?
5. What is the calculated GFR?
6. Why is the parathyroid hormone elevated?
7. What is the most likely cause of this patient’s anemia?
8. General approach of management??
6. Introduction: CKD
CKD Defined
Abnormalities in kidney structure or function, present for≥ 3 months
Progressive loss of function over several months to years,
» Characterized by gradual replacement of normal kidney
architecture with parenchymal fibrosis.
The KDIGO classification system based on CGA staging
(Cause, GFR, Albuminuria).
CKD Defined
Abnormalities in kidney structure or function, present for≥ 3 months
Progressive loss of function over several months to years,
» Characterized by gradual replacement of normal kidney
architecture with parenchymal fibrosis.
The KDIGO classification system based on CGA staging
(Cause, GFR, Albuminuria).
KDIGO: Kidney Disease: Improving Global Outcomes
7. Epidemiology
Globally, 8% to 16% of the general population has CKD
1.9 million patients are undergoing renal replacement therapy[RRT].
Prevalence of CKD increases with age: ~30% in >70 years old.
Diabetes and hypertension are also important risk factors for CKD.
In patients with type 2 diabetes, prevalence of 27%.
Among T1DM; 17% to 25% of patients developed diabetic chronic
kidney disease (DCKD) after 30 years.
Globally, 8% to 16% of the general population has CKD
1.9 million patients are undergoing renal replacement therapy[RRT].
Prevalence of CKD increases with age: ~30% in >70 years old.
Diabetes and hypertension are also important risk factors for CKD.
In patients with type 2 diabetes, prevalence of 27%.
Among T1DM; 17% to 25% of patients developed diabetic chronic
kidney disease (DCKD) after 30 years.
10. Susceptibility factors:
Advanced age, reduced kidney mass and low birth weight, family
history, low income, systemic inflammation, dyslipidemia.
Most of them are not amenable to pharmacologic or lifestyle
interventions.
Useful for identifying populations at high risk for CKD.
Etiology/Risk Factors…
Susceptibility factors:
Advanced age, reduced kidney mass and low birth weight, family
history, low income, systemic inflammation, dyslipidemia.
Most of them are not amenable to pharmacologic or lifestyle
interventions.
Useful for identifying populations at high risk for CKD.
11. Initiation Factors:
Conditions that result in direct kidney damage
Modifiable by pharmacologic therapy
DM, Hypertension, Glomerulonephritis: the most common
leading causes of CKD.
DM: a cause for 45% of new ESRD cases in 2010, followed
by HTN (29%), US
Etiology/Risk Factors…
Initiation Factors:
Conditions that result in direct kidney damage
Modifiable by pharmacologic therapy
DM, Hypertension, Glomerulonephritis: the most common
leading causes of CKD.
DM: a cause for 45% of new ESRD cases in 2010, followed
by HTN (29%), US
12. Progression risk factors
Factors associated with further decline in kidney function in patients
who already have kidney damage
Persistence of the underlying initiation factors of CKD (e.g., DM, HTN,
glomerulonephritis)
– Serve as predictors of progressive CKD
Other factors associated with progression
– Factors consequent to the underlying kidney disease, e.g, HTN, proteinuria
– Factors independent of underlying kidney disease, e.g., smoking, obesity
Etiology/Risk Factors…
Progression risk factors
Factors associated with further decline in kidney function in patients
who already have kidney damage
Persistence of the underlying initiation factors of CKD (e.g., DM, HTN,
glomerulonephritis)
– Serve as predictors of progressive CKD
Other factors associated with progression
– Factors consequent to the underlying kidney disease, e.g, HTN, proteinuria
– Factors independent of underlying kidney disease, e.g., smoking, obesity
13. Diabetes
Hyperglycemia: an initiation and progression risk factor for CKD
Without treatment,
~80% of patients with DM-2 and microalbuminuria will develop overt
nephropathy
~50% of those with DM-1, nephropathy, and HTN will develop stage 5 CKD within
10 years.
Lifetime risk of developing CKD
Type 1 DM patients: 40%
Type 2 DM patients: 50%
Greater prevalence of type 2 DM compared to type 1
13
Hyperglycemia: an initiation and progression risk factor for CKD
Without treatment,
~80% of patients with DM-2 and microalbuminuria will develop overt
nephropathy
~50% of those with DM-1, nephropathy, and HTN will develop stage 5 CKD within
10 years.
Lifetime risk of developing CKD
Type 1 DM patients: 40%
Type 2 DM patients: 50%
Greater prevalence of type 2 DM compared to type 1
14. Hypertension
Hypertension: both a cause of CKD and a result of CKD
Early treatment of HTN and achievement of target BP
Slow the rate of progression of CKD
BP goal in CKD is to control at all stages of CKD regardless of the
underlying cause.
Lifetime risk of stage 5 CKD for patients with HTN: 5.6%
Elevated BP increases risk for developing CKD
14
Hypertension: both a cause of CKD and a result of CKD
Early treatment of HTN and achievement of target BP
Slow the rate of progression of CKD
BP goal in CKD is to control at all stages of CKD regardless of the
underlying cause.
Lifetime risk of stage 5 CKD for patients with HTN: 5.6%
Elevated BP increases risk for developing CKD
15. Glomerulonephritis
Glomerulonephritis …..includes a wide variety of lesions caused by
immunologic, vascular, and other idiopathic diseases.
It is the third leading cause of ESRD
Chronic glomerular diseases progress at variable rates
Loss of GFR 1.4 to 9.5 mL/min/year
15
Glomerulonephritis …..includes a wide variety of lesions caused by
immunologic, vascular, and other idiopathic diseases.
It is the third leading cause of ESRD
Chronic glomerular diseases progress at variable rates
Loss of GFR 1.4 to 9.5 mL/min/year
16. Proteinuria
In diabetes with CKD, an albumin excretion rate >30 mg/24 hrs
strongly predicted the development of progression of CKD.
Proteinuria alone may promote progressive loss of nephrons through
direct cellular damage
Filtered proteins are toxic to kidney tubule cells
Albumin, transferrin, complement factors, immunoglobulins,
cytokines, angiotensin II
Presence of proteins in renal tubules activates tubular cells
leads to ed production of inflammatory and vasoactive
cytokines such as endothelin (potent VC)
16
In diabetes with CKD, an albumin excretion rate >30 mg/24 hrs
strongly predicted the development of progression of CKD.
Proteinuria alone may promote progressive loss of nephrons through
direct cellular damage
Filtered proteins are toxic to kidney tubule cells
Albumin, transferrin, complement factors, immunoglobulins,
cytokines, angiotensin II
Presence of proteins in renal tubules activates tubular cells
leads to ed production of inflammatory and vasoactive
cytokines such as endothelin (potent VC)
17. Proteinuria is also associated with the activation of complement
components on the apical membrane of proximal tubules
Intratubular complement activation may be the key mechanism of
damage in the progressive proteinuric nephropathies
Interstitial scarring
Progressive loss of structural nephron units
Reduction in GFR
Proteinuria…
17
Proteinuria is also associated with the activation of complement
components on the apical membrane of proximal tubules
Intratubular complement activation may be the key mechanism of
damage in the progressive proteinuric nephropathies
Interstitial scarring
Progressive loss of structural nephron units
Reduction in GFR
18. Smoking
Smoking is associated with ….
Acute reduction in GFR
Increase in urinary albumin excretion, HR, and BP, likely
secondary to nicotine exposure
May promote initiation & progression of CKD in DM patients
Smoking has been associated with ….
Diagnosis of CKD in those with HTN
Development of stage 5 CKD
18
Smoking is associated with ….
Acute reduction in GFR
Increase in urinary albumin excretion, HR, and BP, likely
secondary to nicotine exposure
May promote initiation & progression of CKD in DM patients
Smoking has been associated with ….
Diagnosis of CKD in those with HTN
Development of stage 5 CKD
19. Dyslipidemia
CKD with/without nephrotic syndrome is frequently accompanied by
abnormalities in lipoprotein metabolism.
In patients with CKD and proteinuria >3 g/day, the major lipid
abnormalities are:
Elevation of plasma total and LDL cholesterol
Low HDL cholesterol (<35 mg/dL)
Elevated triglycerides (>200 mg/dL)
Lipid abnormality treatment may slow CKD progression
Treatment of proteinuria resolves the hyperlipidemia in most patients
with nephrotic syndrome.
19
CKD with/without nephrotic syndrome is frequently accompanied by
abnormalities in lipoprotein metabolism.
In patients with CKD and proteinuria >3 g/day, the major lipid
abnormalities are:
Elevation of plasma total and LDL cholesterol
Low HDL cholesterol (<35 mg/dL)
Elevated triglycerides (>200 mg/dL)
Lipid abnormality treatment may slow CKD progression
Treatment of proteinuria resolves the hyperlipidemia in most patients
with nephrotic syndrome.
20. Obesity***
Studies demonstrate increased risk of stage 5 CKD in overweight
and obese subjects
BMI ≥25 kg/m2 associated with 3-fold increase in CKD risk.
Obesity (BMI ≥30 kg/m2)associated with 3- to 4 fold increased
in CKD risk
Weight reduction as part of the treatment of progressive kidney
disease is suggested.
20
Studies demonstrate increased risk of stage 5 CKD in overweight
and obese subjects
BMI ≥25 kg/m2 associated with 3-fold increase in CKD risk.
Obesity (BMI ≥30 kg/m2)associated with 3- to 4 fold increased
in CKD risk
Weight reduction as part of the treatment of progressive kidney
disease is suggested.
***a major risk factor for essential hypertension, diabetes, and other
comorbid conditions
Puts more strain on the kidneys
21. Bottom line
Clinical Factors
Diabetes
Hypertension
Obesity
Autoimmune
diseases
Systemic
infections
Urinary tract
infections
Urinary stones
Lower urinary
tract obstruction
Neoplasia
Family history of
CKD
Recovery from
acute kidney
injury
Reduction in
kidney mass
Exposure to
certain drugs
Low birth weight
Sociodemographic Factors
Older age
Exposure to certain chemical and
environmental conditions
Low income/education
Diabetes
Hypertension
Obesity
Autoimmune
diseases
Systemic
infections
Urinary tract
infections
Urinary stones
Lower urinary
tract obstruction
Neoplasia
Family history of
CKD
Recovery from
acute kidney
injury
Reduction in
kidney mass
Exposure to
certain drugs
Low birth weight
Older age
Exposure to certain chemical and
environmental conditions
Low income/education
22. Pathophysiology
Precise mechanism of kidney damage dependent on the etiology
of the disease.
Heterogeneous causes
Diabetic nephropathy: glomerular mesangial expansion
Hypertensive nephrosclerosis: kidney's arterioles have arteriolar
hyalinosis
Polycystic kidney disease: renal cysts develop
Precise mechanism of kidney damage dependent on the etiology
of the disease.
Heterogeneous causes
Diabetic nephropathy: glomerular mesangial expansion
Hypertensive nephrosclerosis: kidney's arterioles have arteriolar
hyalinosis
Polycystic kidney disease: renal cysts develop
23. Key elements of the pathway to ESRD:
Loss of nephrons mass,
Glomerular capillary hypertension,
Proteinuria.
Pathophysiology…
Key elements of the pathway to ESRD:
Loss of nephrons mass,
Glomerular capillary hypertension,
Proteinuria.
24. Exposure to initiation risk factors can result in loss of nephrons mass
The remaining nephrons hypertrophy to compensate for the loss of nephrons mass
and kidney function
Compensatory hypertrophy may be adaptive
Over time, hypertrophy may lead to intraglomerular hypertension
Possibly mediated by angiotensin II
High intraglomerular capillary pressure impairs the size-selective function of
the glomerular permeability barrier
Resulting in increased urinary excretion of albumin and proteinuria
Pathophysiology…
Exposure to initiation risk factors can result in loss of nephrons mass
The remaining nephrons hypertrophy to compensate for the loss of nephrons mass
and kidney function
Compensatory hypertrophy may be adaptive
Over time, hypertrophy may lead to intraglomerular hypertension
Possibly mediated by angiotensin II
High intraglomerular capillary pressure impairs the size-selective function of
the glomerular permeability barrier
Resulting in increased urinary excretion of albumin and proteinuria
28. GFR Categorya GFR (mL/min2 [mL/s/]) Terms
1 >90 (>0.87) Normal or high
2 60–89 (0.58–0.86) Mildly decreased
3a 45–59 (0.43–0.57) Mildly to moderately
decreased
CKD Stages Based on KDIGO Classification
Mildly to moderately
decreased
3b 30–44 (0.29–0.42) Moderately to severely
decreased
4 15–29 (0.14–0.28) Severely decreased
5 <15 (<0.14) Kidney failure
aTo meet criteria for CKD there must be a significant reduction in GFR (categories 3a-5) or there must
also be evidence of kidney damage (categories 1 and 2) for 3 months or greater.
CKD can be present with normal/near normal GFR if other markers of kidney disease are
present
29. Prognosis of CKD
Dependent on the following factors:
Cause of kidney disease;
GFR at time of diagnosis;
Degree of albuminuria;
Presence of other comorbid conditions.
End-stage renal disease (ESRD) GFR <15 mL/min/: need chronic
dialysis or kidney transplantation
Dependent on the following factors:
Cause of kidney disease;
GFR at time of diagnosis;
Degree of albuminuria;
Presence of other comorbid conditions.
End-stage renal disease (ESRD) GFR <15 mL/min/: need chronic
dialysis or kidney transplantation
30. Clinical Pictures and Assessment
Often asymptomatic
Symptoms
Fatigue, weakness, shortness of breath, mental confusion, nausea and
vomiting, bleeding, and loss of appetite, itching, cold intolerance, and
peripheral neuropathies.
Signs
Edema, weight gain (from accumulation of fluid), changes in urine
output (volume and consistency), “foaming” of urine (indicative of
proteinuria), and abdominal distension.
Often asymptomatic
Symptoms
Fatigue, weakness, shortness of breath, mental confusion, nausea and
vomiting, bleeding, and loss of appetite, itching, cold intolerance, and
peripheral neuropathies.
Signs
Edema, weight gain (from accumulation of fluid), changes in urine
output (volume and consistency), “foaming” of urine (indicative of
proteinuria), and abdominal distension.
31. …Assessment
Laboratory Tests
Decreased: eGFR, bicarbonate (metabolic acidosis), Hb/hematocrit (Hct) (anemia),
transferrin saturation (TSat) and/or ferritin (iron deficiency; note: ferritin may be
increased due to inflammatory conditions), vitamin D levels, albumin (malnutrition),
glucose (may result from decreased degradation of insulin with impaired kidney function
or poor oral intake), and calcium (in early stages of CKD).
Increased: Serum creatinine, blood urea nitrogen, potassium, phosphorus, PTH, FGF-23,
ACR, PCR blood pressure (hypertension is a common cause and result of CKD), glucose
(uncontrolled diabetes is a cause of CKD), low-density lipoprotein (LDL) and
triglycerides, and calcium (more likely in CKD 5).
Other: May be hemoccult-positive if GI bleeding occurs secondary to uremia.
Decreased: eGFR, bicarbonate (metabolic acidosis), Hb/hematocrit (Hct) (anemia),
transferrin saturation (TSat) and/or ferritin (iron deficiency; note: ferritin may be
increased due to inflammatory conditions), vitamin D levels, albumin (malnutrition),
glucose (may result from decreased degradation of insulin with impaired kidney function
or poor oral intake), and calcium (in early stages of CKD).
Increased: Serum creatinine, blood urea nitrogen, potassium, phosphorus, PTH, FGF-23,
ACR, PCR blood pressure (hypertension is a common cause and result of CKD), glucose
(uncontrolled diabetes is a cause of CKD), low-density lipoprotein (LDL) and
triglycerides, and calcium (more likely in CKD 5).
Other: May be hemoccult-positive if GI bleeding occurs secondary to uremia.
Fibroblast growth factor 23
32. Urine sediment abnormalities (hematuria, red blood cell and white blood cell casts, renal
tubular epithelial cells)
Pathologic abnormalities indicating glomerular, vascular, tubulointerstitial disease, or
cystic and congenital diseases
Structural abnormalities such as polycystic kidneys, renal masses, renal artery stenosis,
cortical scarring due to infarcts and pyelonephritis, or small kidneys (common in more
severe CKD) detected by imaging studies (eg, ultrasound, computed tomography,
magnetic resonance imaging, angiography)
Other Diagnostic Tests
…Assessment
Urine sediment abnormalities (hematuria, red blood cell and white blood cell casts, renal
tubular epithelial cells)
Pathologic abnormalities indicating glomerular, vascular, tubulointerstitial disease, or
cystic and congenital diseases
Structural abnormalities such as polycystic kidneys, renal masses, renal artery stenosis,
cortical scarring due to infarcts and pyelonephritis, or small kidneys (common in more
severe CKD) detected by imaging studies (eg, ultrasound, computed tomography,
magnetic resonance imaging, angiography)
CKD stages 3, 4, 5 require additional workup
Anemia, CV disease, metabolic bone disease, malnutrition, fluid & electrolyte, disorders
33. Treatment of CKD
General
Identify the presence and causes of secondary complications
and comorbid conditions.
Interprofessional approach
Dietary education, and social/financial concerns.
Comprehensive medication management (CMM) /Drug-dosing
General
Identify the presence and causes of secondary complications
and comorbid conditions.
Interprofessional approach
Dietary education, and social/financial concerns.
Comprehensive medication management (CMM) /Drug-dosing
34. Desired Outcome
Delay or prevent progression of the disease
Minimizing the development or severity of associated complications.
Plan for RRT(HD or PD) starting from CKD
Sustain and improve, if possible, the patient’s quality of life [CKD 5]
Prevent adverse outcomes by aggressively managing complications of
CKD.
Delay or prevent progression of the disease
Minimizing the development or severity of associated complications.
Plan for RRT(HD or PD) starting from CKD
Sustain and improve, if possible, the patient’s quality of life [CKD 5]
Prevent adverse outcomes by aggressively managing complications of
CKD.
35. Non-pharmacologic management
Diet
Protein restriction to 0.8 g/kg/day in eGFR <30 mL/min(i.e,
CKD 4).
Decreasing sodium intake <2 g or 90 mEq (mmol)/day
(corresponding to 5 g NaCl)
Smoking Cessation, Exercise, and Weight Loss
Diet
Protein restriction to 0.8 g/kg/day in eGFR <30 mL/min(i.e,
CKD 4).
Decreasing sodium intake <2 g or 90 mEq (mmol)/day
(corresponding to 5 g NaCl)
Smoking Cessation, Exercise, and Weight Loss
36. Pharmacologic management
Proteinuria
Initiate ACEIs/ARBs
DCKD: ACEI/ARB 1st line therapy [urine albumin excretion is in
category A2 or greater (ACR between 30-300 mg/g)]
Increase dose until albuminuria is reduced by 30% to 50% or side
effects [e.g. >30% decrease in eGFR or elevation in serum potassium
occur]
ACEI + ARB ??
ACEI/ARB+ Aldosterone antagonist??
Proteinuria
Initiate ACEIs/ARBs
DCKD: ACEI/ARB 1st line therapy [urine albumin excretion is in
category A2 or greater (ACR between 30-300 mg/g)]
Increase dose until albuminuria is reduced by 30% to 50% or side
effects [e.g. >30% decrease in eGFR or elevation in serum potassium
occur]
ACEI + ARB ??
ACEI/ARB+ Aldosterone antagonist??
DCKD: Diabetic CKD
37. Dihydropyridine CCBs do not appear to have any beneficial effects
beyond those attributable to reducing BP.
Nondihydropyridine agents (diltiazem and verapamil]:yielded beneficial
effects on proteinuria, although not as profoundly as ACEIs.
2nd antiproteinuric drugs [ACEI/ARB is contraindicated/not tolerated]
Suppress of glomerular hypertrophy,
Inhibit of platelet aggregation, and
Decrease in salt accumulation.
Pharmacologic management…
Dihydropyridine CCBs do not appear to have any beneficial effects
beyond those attributable to reducing BP.
Nondihydropyridine agents (diltiazem and verapamil]:yielded beneficial
effects on proteinuria, although not as profoundly as ACEIs.
2nd antiproteinuric drugs [ACEI/ARB is contraindicated/not tolerated]
Suppress of glomerular hypertrophy,
Inhibit of platelet aggregation, and
Decrease in salt accumulation.
38. Hypertension
Recommended BP goals based on the degree of albuminuria and
the choice of antihypertensive agent.
KDIGO: ≤140/90 mm Hg for those with category A1 albuminuria.
Category ≥A2 albuminuria :≤ 130/80 mm Hg
Subjects with proteinuria greater than 300 mg/day did benefit
from the lower blood pressure target.
1st line: ACEI/ARB,, if not at goal, add diuretic(s)
Recommended BP goals based on the degree of albuminuria and
the choice of antihypertensive agent.
KDIGO: ≤140/90 mm Hg for those with category A1 albuminuria.
Category ≥A2 albuminuria :≤ 130/80 mm Hg
Subjects with proteinuria greater than 300 mg/day did benefit
from the lower blood pressure target.
1st line: ACEI/ARB,, if not at goal, add diuretic(s)
42. Diabetes
Patients with DM should be screened annually for CKD
Start at the time of diagnosis of T2DM
5 years after the diagnosis of T1DM
Reduction of proteinuria and achievement of desired BP & HbA1c [7%]
CKD 3 and 4 are at higher risk of developing hypoglycemia
Reduction in metabolism of insulin by the kidney as GFR declines.
Require reduced doses of oral or injectable hypoglycemic agents
Metformin:
Continued: eGFR ≥45 mL/min; Reviewed: eGFR 30 to 44 mL/min,
Discontinued: eGFR <30 mL/min
Patients with DM should be screened annually for CKD
Start at the time of diagnosis of T2DM
5 years after the diagnosis of T1DM
Reduction of proteinuria and achievement of desired BP & HbA1c [7%]
CKD 3 and 4 are at higher risk of developing hypoglycemia
Reduction in metabolism of insulin by the kidney as GFR declines.
Require reduced doses of oral or injectable hypoglycemic agents
Metformin:
Continued: eGFR ≥45 mL/min; Reviewed: eGFR 30 to 44 mL/min,
Discontinued: eGFR <30 mL/min
44. Recommendations
Nonpharmacologic
Exercise 30 minutes five times per week [1D]
Weight loss if BMI >25 kg/m2 [1D]
Smoking cessation [1D]
Alcohol: Two standard drinks per day for men and one standard drink per day for women[2D]
If hypertension: Low-sodium diet (<2 g/day, <90 mmol/day) [1C]
Pharmacologic
Adjust medication doses for kidney function [1A]
Seek pharmacist or medical advice before using over-the-counter medicines or nutritional protein
supplements [1B]
Herbal medicines are not recommended [1B]
Temporarily discontinue potentially nephrotoxic/renally excreted drugs if eGFR <60 mL/min/1.73
m2 in patients who are acutely unwell or hypovolemic (eg, metformin, RAAS blockers, diuretics,
NSAIDs/COX II inhibitors, lithium, digoxin) [1C]
Vaccines:
Influenza yearly [1B]
Pneumococcal vaccine if eGFR <30 mL/min/1.73 m2, nephrotic syndrome, diabetes, or receiving
immunosuppression. Single booster dose at year 5 [1B]
Hepatitis B vaccine if eGFR <30 mL/min/1.73 m2 and risk of progression of CKD [1B]
ASA suggested for patients at risk for atherosclerotic events unless there is an increased bleeding
risk [2B]
Avoid oral phosphate-containing bowel preparations in people with a GFR <60 mL/min/1.73
m2 (<0.58 mL/s/m2) or in those known to be at risk of phosphate nephropathy [1A]
Pharmacologic
Adjust medication doses for kidney function [1A]
Seek pharmacist or medical advice before using over-the-counter medicines or nutritional protein
supplements [1B]
Herbal medicines are not recommended [1B]
Temporarily discontinue potentially nephrotoxic/renally excreted drugs if eGFR <60 mL/min/1.73
m2 in patients who are acutely unwell or hypovolemic (eg, metformin, RAAS blockers, diuretics,
NSAIDs/COX II inhibitors, lithium, digoxin) [1C]
Vaccines:
Influenza yearly [1B]
Pneumococcal vaccine if eGFR <30 mL/min/1.73 m2, nephrotic syndrome, diabetes, or receiving
immunosuppression. Single booster dose at year 5 [1B]
Hepatitis B vaccine if eGFR <30 mL/min/1.73 m2 and risk of progression of CKD [1B]
ASA suggested for patients at risk for atherosclerotic events unless there is an increased bleeding
risk [2B]
Avoid oral phosphate-containing bowel preparations in people with a GFR <60 mL/min/1.73
m2 (<0.58 mL/s/m2) or in those known to be at risk of phosphate nephropathy [1A]
1=recommended; 2= suggested;; A=high quality, B=Moderate, C= Low; D= Very low
45. Monitor and evaluate
Effectiveness and safety
Monitor for HTN, DM, others related conditions
Clinical signs and symptoms
48. Complications of CKD
Frequent complications of advanced CKD:
Altered sodium and water balance,
Hyperkalemia, metabolic acidosis, anemia,
CKD-related mineral and bone disorder (CKD-MBD),
Cardiovascular disease (CVD).
Frequent complications of advanced CKD:
Altered sodium and water balance,
Hyperkalemia, metabolic acidosis, anemia,
CKD-related mineral and bone disorder (CKD-MBD),
Cardiovascular disease (CVD).
49. Other Complications of CKD
Organ System or
Complication Clinical Manifestations
Amyloidosis Accumulation of β2-microglobulin
Carpal tunnel syndrome
Blood and immune
disorders
Bleeding diathesis
Impaired cell-mediated immunity
Lymphopenia
Platelet dysfunction
Endocrine Hypoglycemic episodes (result of decreased
degradation of insulin by the kidney)
GI Nausea, vomiting, anorexia (from uremia)
Delayed gastric emptying
Gastroesophageal reflux
GI bleeding
Protein–energy wasting Malnutrition
Neurologic Peripheral neuropathies
Restless leg syndrome
Uremic encephalopathy
Uremic pruritus Generalized itching predominantlyof back, face, and
extremity used for vascular access, but may affect any
area
May be more severe during or immediately after
hemodialysis
Organ System or
Complication Clinical Manifestations
Amyloidosis Accumulation of β2-microglobulin
Carpal tunnel syndrome
Blood and immune
disorders
Bleeding diathesis
Impaired cell-mediated immunity
Lymphopenia
Platelet dysfunction
Endocrine Hypoglycemic episodes (result of decreased
degradation of insulin by the kidney)
GI Nausea, vomiting, anorexia (from uremia)
Delayed gastric emptying
Gastroesophageal reflux
GI bleeding
Protein–energy wasting Malnutrition
Neurologic Peripheral neuropathies
Restless leg syndrome
Uremic encephalopathy
Uremic pruritus Generalized itching predominantlyof back, face, and
extremity used for vascular access, but may affect any
area
May be more severe during or immediately after
hemodialysis
50. Anemia of CKD
Primary cause: decrease in production of erythropoietin.
Normochromic -normocytic anemia.
Iron deficiency is also common in advanced kidney disease (i.e, CKD
4 and 5):
Decreased GI absorption of iron
Inflammation, Frequent blood testing,
Blood loss from hemodialysis (HD),
Increased iron demands from erythropoiesis stimulating agent
(ESA) therapy.
leading cause of resistance to ESAs and the reason frequent iron supplementation is necessary.
Primary cause: decrease in production of erythropoietin.
Normochromic -normocytic anemia.
Iron deficiency is also common in advanced kidney disease (i.e, CKD
4 and 5):
Decreased GI absorption of iron
Inflammation, Frequent blood testing,
Blood loss from hemodialysis (HD),
Increased iron demands from erythropoiesis stimulating agent
(ESA) therapy.
leading cause of resistance to ESAs and the reason frequent iron supplementation is necessary.
51. Additional factors contributing to the development of anemia of
CKD:
Decreased red cell life span (from the normal of 120 days to
approximately 60 days in individuals with CKD 5D),
Effects of accumulation of uremic toxins and inflammatory
cytokines,
vitamin B12 and folate deficiencies.
Anemia of CKD…
Additional factors contributing to the development of anemia of
CKD:
Decreased red cell life span (from the normal of 120 days to
approximately 60 days in individuals with CKD 5D),
Effects of accumulation of uremic toxins and inflammatory
cytokines,
vitamin B12 and folate deficiencies.
52. Sign & sxs of anemia:
Fatigue, shortness of breath, cold intolerance, chest pain, tingling in
the extremities, tachycardia, headaches, and general malaise.
CBC: Hb concentrations [<13 g/dL for male & <12 g/dL for females]
Annually in CKD 3,
biannually in CKD 4-5, and
At least every 3 months in CKD 5 patients.
Iron status; Tsat, serum ferritin
Vitamin B12 or folate, Guaiac test
Anemia of CKD…Dx
Sign & sxs of anemia:
Fatigue, shortness of breath, cold intolerance, chest pain, tingling in
the extremities, tachycardia, headaches, and general malaise.
CBC: Hb concentrations [<13 g/dL for male & <12 g/dL for females]
Annually in CKD 3,
biannually in CKD 4-5, and
At least every 3 months in CKD 5 patients.
Iron status; Tsat, serum ferritin
Vitamin B12 or folate, Guaiac test
53. Note: The risk of mortality and CV events is higher in CKD patients treated
to higher Hb target values with an ESA.
KDOQI suggest:
Hb range of 11 to 12 g/dL for all CKD patients.
TSat of greater than 20% (>0.20
Serum ferritin
> 100 ng/mL for CKD patients not requiring HD
> 200 ng/mL for CKD 5HD patients.
Anemia of CKD…Rx
Note: The risk of mortality and CV events is higher in CKD patients treated
to higher Hb target values with an ESA.
KDOQI suggest:
Hb range of 11 to 12 g/dL for all CKD patients.
TSat of greater than 20% (>0.20
Serum ferritin
> 100 ng/mL for CKD patients not requiring HD
> 200 ng/mL for CKD 5HD patients.
54. Higher risk of dialysis access thrombosis and uncontrolled blood pressure
in the higher Hb.
Almost twofold increase in the risk of stroke (5%)
High-dose ESA use was associated with greater risk of death.
Non-pharmacologic Therapy
Dietary intake of iron, folate and B12
Anemia of CKD…Rx…
Higher risk of dialysis access thrombosis and uncontrolled blood pressure
in the higher Hb.
Almost twofold increase in the risk of stroke (5%)
High-dose ESA use was associated with greater risk of death.
Non-pharmacologic Therapy
Dietary intake of iron, folate and B12
55. Anemia of CKD: Pharmacologic Rx
Iron Supplementation
Provide the elemental iron required for production of Hb.
Warranted in individuals with a TSat < 30% (<0.30) and a ferritin < 500
ng/mL in whom an increase in Hb or a decrease in ESA dose is desired.
Oral preparations: ferrous salts (ferrous sulfate, ferrous fumarate,
and ferrous gluconate), polysaccharide iron complex, and carbonyl
iron.
Differ in terms of the amount of elemental iron: ferrous sulfate
(20%), ferrous gluconate (12%), ferrous fumarate (33%), iron
polysaccharide (100%), and carbonyl iron (100%).
Iron Supplementation
Provide the elemental iron required for production of Hb.
Warranted in individuals with a TSat < 30% (<0.30) and a ferritin < 500
ng/mL in whom an increase in Hb or a decrease in ESA dose is desired.
Oral preparations: ferrous salts (ferrous sulfate, ferrous fumarate,
and ferrous gluconate), polysaccharide iron complex, and carbonyl
iron.
Differ in terms of the amount of elemental iron: ferrous sulfate
(20%), ferrous gluconate (12%), ferrous fumarate (33%), iron
polysaccharide (100%), and carbonyl iron (100%).
Oral absorption??
56. IV iron preparations are colloids
To correct absolute iron deficiency, especially if they are receiving
an ESA.
Improves the responsiveness to ESA therapy & lower doses can be
used to maintain the target Hb in HD patients
In patients with CKD 5HD GI absorption of iron is often inadequate
Thus the IV route is preferred for almost all HD patients.
If oral therapy is initiated a 1- to 3-month trial is recommended to assess
response.
Anemia of CKD: Pharmacologic Rx…
IV iron preparations are colloids
To correct absolute iron deficiency, especially if they are receiving
an ESA.
Improves the responsiveness to ESA therapy & lower doses can be
used to maintain the target Hb in HD patients
In patients with CKD 5HD GI absorption of iron is often inadequate
Thus the IV route is preferred for almost all HD patients.
If oral therapy is initiated a 1- to 3-month trial is recommended to assess
response.
57. Iron dosing
Oral therapy:
200 mg of elemental iron per day
1- to 3-month trial in the non-HD CKD prior to initiating IV therapy.
For the HD population: IV preferred
1-g course of IV iron (in divided doses) recommended.
Typical repletion dosing regimens for IV iron:
100 mg as iron sucrose over 10 dialysis sessions or
125 mg of sodium ferric gluconate over 8 dialysis sessions.
Oral therapy:
200 mg of elemental iron per day
1- to 3-month trial in the non-HD CKD prior to initiating IV therapy.
For the HD population: IV preferred
1-g course of IV iron (in divided doses) recommended.
Typical repletion dosing regimens for IV iron:
100 mg as iron sucrose over 10 dialysis sessions or
125 mg of sodium ferric gluconate over 8 dialysis sessions.
Test dose needed for IV iron (iron dextran)
58. Algorithm for iron therapy in
management of anemia
of CKD
ESA, erythropoiesis-stimulating
agent; Hb, hemoglobin; TSat,
transferrin saturation; ND-CKD, non-
dialysis CKD patients; PD-
CKD, peritoneal dialysis patients;
HD-CKD, hemodialysis patients.)
59. Iron Adverse Effects
Primarily GI in nature and include constipation, nausea, and
abdominal cramping; more likely as the dose is escalated.
IV iron: hypotension, dizziness, dyspnea, headaches, lower back
pain, arthralgia, syncope, and arthritis, anaphylaxisanaphylaxis 0.60.6% to 0.7%% to 0.7%
So, decrease the dose or rate of infusion
Primarily GI in nature and include constipation, nausea, and
abdominal cramping; more likely as the dose is escalated.
IV iron: hypotension, dizziness, dyspnea, headaches, lower back
pain, arthralgia, syncope, and arthritis, anaphylaxisanaphylaxis 0.60.6% to 0.7%% to 0.7%
60. Iron Drug Interactions
Iron absorption is decreased by
Other elements (eg, calcium in calcium-containing phosphate
binders),
Medications that increase the pH of the GI tract such as PPIs and
H2As , and antibiotics [doxycycline and tetracycline].
Iron also decreases absorption of other drugs such as antibiotics
(fluoroquinolones, doxycycline)
Iron absorption is decreased by
Other elements (eg, calcium in calcium-containing phosphate
binders),
Medications that increase the pH of the GI tract such as PPIs and
H2As , and antibiotics [doxycycline and tetracycline].
Iron also decreases absorption of other drugs such as antibiotics
(fluoroquinolones, doxycycline)
61. Erythropoiesis-Stimulating Agent Therapy
Are recombinant erythropoietin with similar amino acid sequence.
Darbepoetin alfa = long t1/2
Epoetin alfa
Administered by either IV or SubQ route.
Don’t make dosing changes too soon
Are recombinant erythropoietin with similar amino acid sequence.
Darbepoetin alfa = long t1/2
Epoetin alfa
Administered by either IV or SubQ route.
Don’t make dosing changes too soon
Hb continues to increase until the life span of the cells stimulated by ESA therapy is reached
(mean 2 months; range 1-4 months in patients with ESRD)
62. ESA’s Efficacy:
Respond to ESA therapy in a dose-related fashion.
Most common causes of therapeutic resistance:
Erythropoiesis-Stimulating Agent Therapy
ESA’s Efficacy:
Respond to ESA therapy in a dose-related fashion.
Most common causes of therapeutic resistance:
63. ESA Adverse Effects
Hypertension, Hypertensive encephalopathy.
Don’t be used in those with uncontrolled blood pressure.
Seizures: within 3months of initiation
Thrombosis of the HD vascular access site and other thromboembolic
events esp. in higher hemoglobin [>13 g/dL]
ESAs are not indicated in patients receiving myelosuppressive
chemotherapy when the anticipated outcome is cure.
Hypertension, Hypertensive encephalopathy.
Don’t be used in those with uncontrolled blood pressure.
Seizures: within 3months of initiation
Thrombosis of the HD vascular access site and other thromboembolic
events esp. in higher hemoglobin [>13 g/dL]
ESAs are not indicated in patients receiving myelosuppressive
chemotherapy when the anticipated outcome is cure.
64. ESA dosing and administration
Hb levels should be monitored at least monthly (weekly may be
preferred) until stable and then monthly thereafter.
Dose adjustments should be made based on Hb response
An acceptable rate of increase in Hb is 1 to 2 g/dL/month.
25% increase in dose if Hb not increased by 1 g/dL after 4 weeks.
25% decrease in dose if Hb increased >1 g/dL in a 2-week
Hb levels should be monitored at least monthly (weekly may be
preferred) until stable and then monthly thereafter.
Dose adjustments should be made based on Hb response
An acceptable rate of increase in Hb is 1 to 2 g/dL/month.
25% increase in dose if Hb not increased by 1 g/dL after 4 weeks.
25% decrease in dose if Hb increased >1 g/dL in a 2-week
66. KDIGO ESA use recommendation
ND-CKD CKD 5HD and CKD 5PD Pediatric CKD
ESA initiation If Hb <10 g/dL (<100 g/L; <6.21
mmol/L). Consider rate of fall of Hb,
prior response to iron, risk of needing a
transfusion, risk of ESA therapy, and
presence of anemia symptoms before
initiating an ESA. [2C]
Do not initiate if Hb ≥10 g/dL (≥100
g/L; ≥6.21 mmol/L). [2D]
Use ESAs to avoid drop in Hb to <9
g/dL (<90 g/L; <5.59 mmol/L) by
starting an ESA when Hb is between
9 and 10 g/dL (90 and 100 g/L; 5.59
and 6.21 mmol/L). [2B]
Selection of Hb concentration at which to
initiate ESA therapy should include
consideration of potential benefits (eg,
improvement in QOL, school attendance,
avoidance of blood transfusions) and
potential harms. [2D]
If Hb <10 g/dL (<100 g/L; <6.21
mmol/L). Consider rate of fall of Hb,
prior response to iron, risk of needing a
transfusion, risk of ESA therapy, and
presence of anemia symptoms before
initiating an ESA. [2C]
Do not initiate if Hb ≥10 g/dL (≥100
g/L; ≥6.21 mmol/L). [2D]
Hb level Do not use ESAs
to intentionally increase Hb above 13
g/dL (130 g/L, 8.07 mmol/L). [1A]
Do not use ESAs to maintain Hb above
11.5 g/dL (115 g/L; 7.14 mmol/L). [2C]
Do not use ESAs
to intentionally increase Hb above 13
g/dL (130 g/L, 8.07 mmol/L). [1A]
Do not use ESAs to maintain Hb
above 11.5 g/dL (115 g/L; 7.14
mmol/L). [2C]
Suggest Hb range of 11-12 g/dL (110-120
g/L, 6.83-7.45 mmol/L). [2D]
Iron initiationb If TSat is ≤30% (≤0.30) and ferritin is
≤500 ng/mL (μg/L; ≤1,120 pmol/L).
[2C]
If TSat is ≤30% (≤0.30) and ferritin is
≤500 ng/mL (μg/L; ≤1,120 pmol/L).
[2C]
If TSat is ≤20% (≤0.20) and ferritin is
≤100 ng/mL (μg/L; ≤225 pmol/L). [1D]
CKD, chronic kidney disease; ESA, erythropoiesis
stimulating agent; Hb, hemoglobin; ND-CKD, non-
dialysis CKD patients; QOL, quality of life; TSat,
transferrin saturation.
Serum ferritin is an acute-phase reactant-use
clinical judgment when above 500 ng/mL
68. Transfusions
Red blood cell transfusions carry many risks
Should only be used in select situations, such as
Acute management of symptomatic anemia,
Following significant acute blood loss
Red blood cell transfusions carry many risks
Should only be used in select situations, such as
Acute management of symptomatic anemia,
Following significant acute blood loss
69. Evaluation of Therapeutic Outcomes
Iron status at least every 3 months if on stable ESA regimen.
Iron status every month:
Hb levels :
Iron status at least every 3 months if on stable ESA regimen.
Iron status every month:
Hb levels :
70. CKD-Related Mineral and Bone Disorder
Include abnormalities in PTH, Ca, P, Vit. D, fibroblast growth factor-
23 (FGF-23), bone turnover, as well as soft-tissue calcifications.
The pathophysiology of CKD-MBD is complex.
Include abnormalities in PTH, Ca, P, Vit. D, fibroblast growth factor-
23 (FGF-23), bone turnover, as well as soft-tissue calcifications.
The pathophysiology of CKD-MBD is complex.
71. Pathophysiology of CKD-MBD
(Ca, calcium; FGF-23, fibroblast growth factor-23; PTH,
parathyroid hormone.) aFGF-23 also increases in
response to 1,25-dihydroxyvitamin D3.
72. The abnormalities of CKD-MBD lead to alterations in structural integrity
of bone and other associated consequences.
Continuous high rate of production of PTH by the parathyroid glands
promotes parathyroid hyperplasia.
Bone abnormalities are almost universal in dialysis patients and
observed in the majority of those with CKD 3-5.
Osteitis fibrosa cystica (high bone turnover disease): Most common
Osteomalacia (low bone turnover disease), disease.
CKD-MBD
The abnormalities of CKD-MBD lead to alterations in structural integrity
of bone and other associated consequences.
Continuous high rate of production of PTH by the parathyroid glands
promotes parathyroid hyperplasia.
Bone abnormalities are almost universal in dialysis patients and
observed in the majority of those with CKD 3-5.
Osteitis fibrosa cystica (high bone turnover disease): Most common
Osteomalacia (low bone turnover disease), disease.
Characterized by areas of peritrabecular fibrosis.
Its result in bone marrow fibrosis and decreased erythropoiesis
73. Vitamin D metabolism
DBP, vitamin D binding protein; NVD, nutritional
vitamin D; VDRs, vitamin D receptors.)
74. Dx of CKD-MBD
Alterations in serum phosphorus, calcium, PTH, and 25(OH)D.
Evaluation of bone architecture
Gold standard: bone biopsy for histologic analysis[very invasive]
Other: based on patient presentation
Alterations in serum phosphorus, calcium, PTH, and 25(OH)D.
Evaluation of bone architecture
Gold standard: bone biopsy for histologic analysis[very invasive]
Other: based on patient presentation
75. Goal of therapy:
Normalize” the biochemical parameters
Prevent bone manifestations, CV and extravascular calcifications,
and the associated morbidity and mortality
Management of PTH, phosphorus, and calcium is important.
Combination of dietary intervention, phosphate-binding
medications, vitamin D, and calcimimetic therapy (for ESRD patients).
Rx of CKD-MBD
Goal of therapy:
Normalize” the biochemical parameters
Prevent bone manifestations, CV and extravascular calcifications,
and the associated morbidity and mortality
Management of PTH, phosphorus, and calcium is important.
Combination of dietary intervention, phosphate-binding
medications, vitamin D, and calcimimetic therapy (for ESRD patients).
76. CKD-MBD… Non-pharmacologic RX
Dietary phosphorus restriction:
To manage hyperphosphatemia
Should be initiated for most patients with CKD 3-5.
Phosphorus restriction to 800 to 1,000 mg/day
Parathyroidectomy: therapeutic option
Persistently elevated PTH associated with hypercalcemia and/or
hyperphosphatemia [refractory to medical therapy]
Dietary phosphorus restriction:
To manage hyperphosphatemia
Should be initiated for most patients with CKD 3-5.
Phosphorus restriction to 800 to 1,000 mg/day
Parathyroidectomy: therapeutic option
Persistently elevated PTH associated with hypercalcemia and/or
hyperphosphatemia [refractory to medical therapy]
When PTH >800 pg/mL
77. Phosphate-Binding Agents
Especially for those with ESRD; to limit GI absorption and
thereby control serum phosphorus.
Includes: elemental calcium, iron, and lanthanum-containing
compounds, and the non-elemental agent [sevelamer]
Vitamin D Therapy
Calcimimetics: Cinacalcet acts by increasing the sensitivity of the
calcium-sensing receptor.
CKD-MBD… Pharmacologic RX
Phosphate-Binding Agents
Especially for those with ESRD; to limit GI absorption and
thereby control serum phosphorus.
Includes: elemental calcium, iron, and lanthanum-containing
compounds, and the non-elemental agent [sevelamer]
Vitamin D Therapy
Calcimimetics: Cinacalcet acts by increasing the sensitivity of the
calcium-sensing receptor.
78. Cardiovascular Complications of CKD
(AFIB, atrial fibrillation; AMI, acute myocardial infarction; ASHD, atherosclerotic heart disease;
CHF, congestive heart failure; CKD, chronic kidney disease; CVA/TIA, cerebrovascular
accident/transient ischemic attack; CVD, cardiovascular disease; PAD, peripheral arterial
disease; SCA/VA, sudden cardiac arrest and ventricular arrhythmias.)
Read on management of
specific CV disorders among
CKD patients
Read on management of
specific CV disorders among
CKD patients
ACEI/ARBs
Aspirin
Statin
79. Management of Dyslipidemia in CKD
Dyslipidemia Goal Initial Therapy Modification in
Therapya Alternativea
TG ≥500
mg/dL
TG<500
mg/dL
TLC TLC + fibrate
or niacin
Fibrate or niacin
LDL 100–129
mg/dL
LDL <100
mg/dL
TLC TLC + low-
dose statin
Bile acid
sequestrant
or niacin
LDL 100–129
mg/dL
LDL <100
mg/dL
TLC + low-
dose statin
Bile acid
sequestrant
or niacin
LDL ≥130
mg/dL
LDL <100
mg/dL
TLC + low-
dose statin
TLC +
maximum-
dose statin
Bile acid
sequestrant
or niacin
TG ≥200
mg/dL and non-
HDL
≥130mg/dL
Non-HDL <130
mg/dL
TLC + low-
dose statin
TLC +
maximum-
dose statin
Fibrate or niacin
aDosing of selected agents by class: fibrate (gemfibrozil 600 mg twice daily); niacin (1.5–3 g/day of immediate-release
product); statin (simvastatin 10–40 mg/day if GFR<30 mL/min [<0.50 mL/s], 20–80 mg/day if GFR >30 mL/min [>0.50
mL/s]); bile acid sequestrant (cholestyramine 4–16 g/day).