Geriatric Nephrology (changes in renal physiology, Chronic Kidney Disease, Advanced Care Planning for the elderly patients with CKD, pharmacotherapy of common medical problems in the older individual with chronic kidney disease)
Journal Club about the Phase 2 study of Selonsertib in Diabetic Kidney Disease to Our Division on 12/9/19.
Also an intro about the Phase 3 study (MOSAIC) we will be launching before the end of the year
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)
A limited presentation about a) age related renal functional changes b) management of CKD, including advance care planning and transplantation referral c) management of potentially risky drugs in the elderly with CKD (NOACs)
Journal Club about the Phase 2 study of Selonsertib in Diabetic Kidney Disease to Our Division on 12/9/19.
Also an intro about the Phase 3 study (MOSAIC) we will be launching before the end of the year
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)
A limited presentation about a) age related renal functional changes b) management of CKD, including advance care planning and transplantation referral c) management of potentially risky drugs in the elderly with CKD (NOACs)
SGLT2 Inhibitor therapy has opened up an exciting avenue for the Physicians to manage the patients with CKD . The slide set highlights the major trials on the drug showing remarkable benefits.
New Therapeutics in Diabetic Kidney Disease
Conjoint Meeting of the Iraqi Society of Nephrology and Renal Transplantation and The Iraqi Diabetes Association.
SGLT2 Inhibitor therapy has opened up an exciting avenue for the Physicians to manage the patients with CKD . The slide set highlights the major trials on the drug showing remarkable benefits.
New Therapeutics in Diabetic Kidney Disease
Conjoint Meeting of the Iraqi Society of Nephrology and Renal Transplantation and The Iraqi Diabetes Association.
This was a review of different guidelines on lupus nephritis from ACR, EULAR, and KDIGO. Goal is appreciate similarities and differences between the different guidelines.
Introduction to Chronic Kidney Disease epidemiology, diagnosis, treatment of complications and system issues (e.g. interface between nephrology and primary care, specialty referrals) for medical students
Cardiometabolic Benefits of Renal Diabetes and Obesity MedicationsChristos Argyropoulos
Presentation I gave to UW's ECHO program on 9/21/22 about the cardiorenal protection afforded by SGLT2i/GLP1 Receptor Agonists and Non-steroidal MRAs (finerenone)
Presentation given to our fellowship program about diabetic kidney disease.
2022 update discussing SGLT2i, MRA (e.g. finerenone), health economics and beyond
Survival analysis is an important method for analysis time to event data for biomedical and reliability applications. It is often done with semiparametric methods e.g. the Cox proportional hazards model. In this presentation I discuss an alternative parametric approach to survival analysis that can overcome some of the limitations of the Cox model and provide additional flexibility to the modeler. This approach may also be justified from a Bayesian perspective and the connection is shown as well. Simulations and case studies that illustrate the flexibility of the GAM approach for survival analysis and its equivalent performance to existing methods for survival data are discussed in the text.
The material presented herein are based on two publications:
1) Argyropoulos C, Unruh ML. Analysis of time to event outcomes in randomized controlled trials by generalized additive models. PLoS One. 2015 Apr 23;10(4):e0123784. doi: 10.1371/journal.pone.0123784. PMID: 25906075; PMCID: PMC4408032.
2)Bologa CG, Pankratz VS, Unruh ML, Roumelioti ME, Shah V, Shaffi SK, Arzhan S, Cook J, Argyropoulos C. High performance implementation of the hierarchical likelihood for generalized linear mixed models: an application to estimate the potassium reference range in massive electronic health records datasets. BMC Med Res Methodol. 2021 Jul 24;21(1):151. doi: 10.1186/s12874-021-01318-6. PMID: 34303362; PMCID: PMC8310602.
Heavily based on a presentation I gave for the CMS 2020 National Quality Forum. Emphasis is on dialysis (particularly home dialysis). Discusses regulatory framework, medical devices used to render the services and outcomes of studies performed to day
Effects of Sodium Glucose contransporter (SGLT2) inhibition on renal outcomes in patients with (diabetic) chronic kidney disease.
Presentation given during the East by Southwest, Annual Update in Nephrology, September 17th 2017, Santa Fe, NM
http://medicine.unm.edu/academic-divisions/nephrology/east-by-southwest.html
Correcting bias and variation in small RNA sequencing for optimal (microRNA) ...Christos Argyropoulos
Presentation given about the Generalized Additive Model Location, Scale and Shape (GAMLSS) methodology for the analysis of small RNA sequencing data and the potential of microRNAs as biomarkers for kidney and cardiometabolic diseases
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
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
- 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
Factory Supply Best Quality Pmk Oil CAS 28578–16–7 PMK Powder in Stockrebeccabio
Factory Supply Best Quality Pmk Oil CAS 28578–16–7 PMK Powder in Stock
Telegram: bmksupplier
signal: +85264872720
threema: TUD4A6YC
You can contact me on Telegram or Threema
Communicate promptly and reply
Free of customs clearance, Double Clearance 100% pass delivery to USA, Canada, Spain, Germany, Netherland, Poland, Italy, Sweden, UK, Czech Republic, Australia, Mexico, Russia, Ukraine, Kazakhstan.Door to door service
Hot Selling Organic intermediates
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
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.
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.
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.
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
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
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
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
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
Triangles of Neck and Clinical Correlation by Dr. RIG.pptx
The aging kidney and what we should (not?) do about it
1. The aging kidney and what
we should (not?) do about
it
Christos Argyropoulos MD PhD FASN
Division of Nephrology
University of New Mexico
2. Learning Objectives
• Physiological changes in renal function and renal
function tests with aging
• Evaluation and management of chronic kidney
disease in the older adult
• Management of common medical problems and
drug dosing in renal functional impairment
(including patients on dialysis)
4. Filtration
Reabsorption
Secretion
Fluid and electrolyte
homeostasis
Endocrine function (renin,
erythropoietin, activation of
25(OH)D to the active 1,25
(OH)2D
Metabolic function
(gluconeogenesis, drug
metabolism and insulin)
All renal physiology in one slide:
The kidney functions to maintain balance
5. Renal Filtration Declines With Age(but
we disagree about the rate)
~ 8 ml/min (~10%) per
decade after the age of 40
Longitudinal Studies tell a
more complex story
• B(altimore)LSA:
• 0.95 ml/min/yr
• 36% will not decline
• B(ronx)LAS:
• Minimal change over time in male pts
over 6 yrs
• FDA Registrational Trial Data
Am J Kidney Dis. 2003 Jan;41(1):1-12.
J Am Geriatr Soc. 1985 Apr;33(4):278-85.
J Am Geriatr Soc. 1995 Apr;43(4):412-4.
Biopharm Drug Dispos. 2015 Dec;36(9):613-21
6. Tubular Function Age Related
Changes
• Failure to conserve sodium under salt deprivation
(risk for prerenal AKI/ARF)
• Renal Acidosis Type IV (hyperkalemia)
• Maximal Concentrating Capacity Diminishes
• Nocturia
• Dehydration
• Hypernatremia
• Maximal Diluting Capacity Diminishes
• Hyponatremia when fluid challenged
Kidney Int. 2008 Sep;74(6):710-20.
7. Endocrine Function Age Related
Changes
• Levels of EPO will slightly increase with age
• However anemic elderly patients have lower levels than
anemic young ones (esp in iron deficiency)
• Lower levels of calcitriol (osteoporosis AND falls)
• Calcitriol supplementation reduced falls by ~50%
• Insulin Clearance Declines
• Insulin Resistance Increases
Kidney Int. 2008 Sep;74(6):710-20.
8. Age Related Changes In Renal
Vascular Function
• Renal Vasodilation more dependent on
• Prostaglandins
• Nitric Oxide
9. Age-Related Structural Changes
• Glomerulosclerosis
• 5% (<40) vs 30% (>80)
• Consider pathological
when % > (age/2) -10
• Arteriosclerosis
• Intimal fibrosis (similar
to DM or HTN)
• Interstitial Fibrosis
• Kidney weight declines
and Cortex thins
Kidney Int. 2008 Sep;74(6):710-20.
12. We try to keep kidney disease
simple in the clinical chemistry lab
•Test of renal function:
•estimated glomerular filtration rate
•Test of renal damage:
•“protein” in the urine
13. GFR is equal to the sum of the filtration rates in all of
the functioning nephrons.
GFR is not routinely measured in clinical settings.
Estimation of the GFR (eGFR) gives a rough measure of
the number of functioning nephrons:
Formula based on age, gender, race, creatinine (+/-
cystatin, beta-trace protein, beta 2 microglobulin)
Various formulas in use (Cockroft-Gault, MDRD, CKD-EPI)
What is the glomerular filtration rate (GFR)?
14. A typical “normal” reference range of
0.6–1.2 mg/dL listed on many lab reports does not
account for muscle mass, age, gender,
and race.
A 28-year-old African American man with serum
creatinine of 1.2 has an eGFR > 60.
A 78-year-old white woman with serum creatinine of
1.2 has an eGFR of 43.
“Normal” serum creatinine
may not be normal
15. A fistful of eGFR formulas
Int Urol Nephrol (2017) 49:1979–1988
16. Do not use with:
− Rapidly changing creatinine levels
Example: acute kidney injury
− Extremes in muscle mass, body size, or altered diet patterns
− Medications that interfere with the measurement of serum
creatinine
− Not all estimating equations are created equal
Not all estimating equations are created equal
− MDRD is “blind” above 60 ml/min/1.73m2
Creatinine-based estimates of kidney
function have limitations
17. Performance of eGFR equations in the
elderly (> 70 years old)
Int Urol Nephrol (2017) 49:1979–1988
The Berlin equations seem to work
somewhat better than MDRD/CKD-Epi
18. Cystatin – C v.s. Creatinine
• Cystatin – C is a “novel”
measure of renal
function
• Estimating equations
have been developed to
use Cys-C alone or with
SCr
• These equations do not
always agree !
19. Cystatin OR the Combination of Cystatin C
and Creatinine may be better ways to
assess renal function in the Elderly
Int Urol Nephrol (2017) 49:1979–1988
20. Proteinuria/Albuminuria
• Marker of kidney damage that independently predicts
cardiovascular disease.
• It is in the definition of stage 1 and stage 2 CKD.
• Controversial whether isolated microalbuminuria always
represents kidney disease or whether it could reflect
endothelial dysfunction without kidney damage.
21. Dipstick
− Semi-quantitative, screening only
Affected by urine concentration, highly variable
− Detection of urine albumin > 300 mg/day
(1+ approximates albumin excretion of 30 mg/day)
Urine protein/creatinine ratio
‒ All proteins, not just albumin (myeloma/CIN)
Urine albumin-to-creatinine ratio (UACR)
‒ Quantifies urine albumin
− Steps toward standardization currently in progress
− Standard for public health, clinical care, and research
Use which urine test?
22. Definition of Albuminuria
Method Normal
Micro-
albuminuria
Overt/Macro-
albuminuria
24 hour excretion <30 mg/day 30-300 mg/day >300 mg/day
Timed urine specimen <20 g/min 20-200 g/min >200 g/min
Spot-urine albumin
specific dipstick
(screening)
<3 mg/dl >3 mg/dl N/A
Spot urine albumin/
creatinine ratio (ADA)
< 30 mg/g 30-300 mg/g >300 mg/g
Spot urine albumin/
creatinine ratio (gender
specific) (K/DOQI)
<17 mg/g (men)
<25 mg/g (women)
17-250 (men)
25-355 (women)
>250 (men)
>355 (women)
K/DOQI and ADA
25. Screening for CKD
1. Guidelines disagree (ACP/USPSTF vs ASN)
2. One will find low eGFR in the elderly if one looks
for it
3. Consensus is that patients with diabetes should
be screened (eGFR/albuminuria) but ?? older
people (>60 y/o) or those with hypertension
4. Cost-effectiveness of screening largely dependent
on the health care system
26. Adverse Outcomes Associated With
eGFR : Death and Dialysis
Adv Chronic Kidney Dis. 2016 Jan;23(1):8-11
J Am Soc Nephrol. 2007 Oct;18(10):2758-65.
28. CKD Checklist for PCPs
• Slowing Progression
• BP < 140/90
• HBA1c ≤ 7% within 6 mos
• Annual screen for proteinuria
• On ACEi/ARB if DM or microalb
> 30mg/g
• Smoking cessation
• Discuss avoidance of
NSAIDs/nephrotoxins
• LDL < 100 within the last year
• 5 year pneumovax
• Yearly flu
• Tx of Complications
• CBC, iron studies within the
year
• Ca, P, PTH (q 6 mo if eGFR <
60, q 3 mo if eGFR < 30)
• Nephrology Referral
• GFR < 30
• Persistent proteinuria despite
ACEi
• Persistent hyperK
• Resistant HTN (≥4 meds)
• ↓GFR by 30% (“certain drop”)
irrespective of eGFR
• Unclear etiology of CKD
• Anemia requiring ESAs
• ↑ P, PTH
CJASN 9:1526-1535, 2014
30. Outcomes of the elderly patient
receiving renal replacement
Kidney Int. 2012 Aug;82(3):261-9.
31. Choice of Initial Dialysis Modality
Kidney Int. 2012 Aug;82(3):261-9.
Kidney Int Rep (2017) 2, 645–653;
32. Shared Decision Making and
Conservative Management of CKD
Rosansky et al. BMC Nephrology (2017) 18:200
33. When to Discuss Dialysis And When
Not in your >75 year old patient
Rosansky et al. BMC Nephrology (2017) 18:200
ΔeGFR
ml/min/1.73m2
Low
Comorbidity
High
Comorbidity
< 3 Conservative Conservative
3-5 Dialysis Conservative
> 5 Dialysis SDM
AKI Dialysis Conservative
35. Referral for Renal Transplant
Kidney Int. 2012 Aug;82(3):261-9.
Kidney Int Rep (2017) 2, 645–653;
Appropriateness of renal transplant referral
• Require estimated survival > 5 years
• Variability in expected survival very
high in the elderly (poor models)
• Wait-list times routinely exceed 6 years
• Clinical score developed to guide
referral of older patients
• Shared decision making between
patient, family, nephrologist and
transplant center
• An option for the “healthy” old patient
Time required for cumulative survival after kidney
transplantation to exceed cumulative survival on
the waiting list, by age group
36. Advance Care Planning (ACP) in CKD
and ESRD
Intervention Flow Chart Improving ACP in CKD / ESRD
Clinical Kidney Journal, Volume 10, Issue 1, 1 February 2017,
Pages 68–73
38. Drug Dosing Considerations
• Renal impairment may alter both
pharmacodynamics and pharmacokinetics
• MOST DRUGS HAVE NEVER BE TESTED IN
CKD POPULATIONS
• There is a higher risk for Adverse Drug
Reactions as a result of renal functional
impairment AND comorbidities AND age in
CKD patients
39. Cockroft Gault ≠ MDRD for drug dosing
Ann Pharmacother 2012;46:1174-87
For patients with advanced age, low weight, and modestly elevated serum
creatinine, further work is needed before the MDRD equations can replace the CG
equation for dose adjustment in the labeling.
42. Alternatives to warfarin that are licensed for
use without Therapeutic Drug Monitoring
− Rivaroxaban (Xarelto) : Xa inhibitor
− Apixaban (Eliquis): Xa inhibitor
− Dabigatran (Pradaxa): DRI
They are removed by the kidneys
Safety signals for older individuals with renal
impairment
Dialytic clearance substantial only for dabigatran
Novel Oral AntiCoagulants (NOACs) in CKD
43. Safety of NOACs in CKD (major or
clinically relevant bleeding)
eGFR(50-79) eGFR(30-49)
Canadian Journal of Cardiology 30 (2014) 888- 897
44. Efficacy of NOACs in mild CKD
(eGFR 50-79)
Stroke VTE or VTE related death
Canadian Journal of Cardiology 30 (2014) 888- 897
45. Efficacy of NOACs in moderate CKD
(eGFR 30-49)
Stroke VTE or VTE related death
Canadian Journal of Cardiology 30 (2014) 888- 897
46. NOACs – Dosing Recommendations
• Apixaban 2.5 mg- 10mg BID (depending on indication)
• 2.5 mg BID if one of the following (Wt<60 kgr, age>80), SCr > 1.5 mg/dl
• Dabigatran 150 mg BID
• 75 mg BID if CrCl 15-30 ml/min
• Rivaroxaban 10 -20 mg QD (depending on indication)
• VTE prophylaxis (use w caution for ClCr 30-50, avoid for ClCr < 30)
• Afib: 20mg/d (ClCr > 50), 15 mg/d (15-50 ml/min, avoid for ClCr <15)
• NOACs not recommended for non dialysis dependent CKD
stage V (ClCr < 15)
• In patients on dialysis may only use Apixaban:
• 5 mg po BID unless one of the following (Wt<60 kgr, age>80): use 2.5
mg bid
50. Renal function has a substantial
effect on dosing of SGLT2i
eGFR range Canagliflozin Dapagliflozin Empagliflozin
>60
ml/min/1.73m2
100-300 mg/d 5-10 mg/d 10-25 mg/d
45-60
ml/min/1.73m2
Not to exceed
100 mg/d
Do not initiate 10-25 mg/d
<45
ml/min/1.73m2
Do not initiate Do not initiate Do not initiate
<30
ml/min/1.73m2
Contraindicated Contraindicated Do not initiate
Adjustments
during therapy
Not recommended
when eGFR
declines
persistently below
45 ml/min/1.73m2
Not recommended
when eGFR
declines
persistently
between 30-60
ml/min/1.73m2
Discontinue if eGFR
persistently falls
below 45
ml/min/1.73m2
51. There are NO randomized
controlled trials in this
population
Many studies find U shaped
curves, with mortality
worse when A1c<6% or
>8%
Existing guidelines:
− Let A1c rise to >7%
− Many nephrologists will
tolerate 7-9%
What is the target for glycemic control in
ESRD?
Ricks et al., Diabetes 61(30):
708–715, 2012).
52. Dose: To prevent hypoglycemia, insulin may have to be reduced
by 50% when the eGFR<10 (many patients are firmly on their
way to dialysis by then)
Timing: a single study suggests lowering basal insulin by 25% on
the day after dialysis to provent hypoglycemia
Titration: In insulin-naïve dialysis patients start at 10-12 units
Many nephrologists consider insulin based regimens the
treatment of choice for patients with DM and ESRD
Treatment of Diabetes in Dialysis: Insulin
Nephrol Dial Transplant (2016) 31 (1): 8-15. DOI: https://doi.org/10.1093/ndt/gfv258
53. Sulfonylureas: glipizide is the agent of choice
Meglitinides:
− repaglinide is >90% metabolized by the liver
− Start at 0.5 mg po tid with meals
− May be used as monotherapy in ESRD
Biguanides (metformin): no-no
Thiazolidinedione (pioglitazone):
− Overall low risk of hypoglycemia
− As monotherapy may reduce A1c by 0.5-1% in ESRD
− Pioglitazone may be associated with impr survival
Treatment of Diabetes in Dialysis: Non-insulin agents I
54. DPP4:
− Lina(gliptin) is the only one that is cleared by the liver (no dose
adjustment): 5 mg po daily
− Sita: 25mg/day (irrespective of timing of dialysis)
Similar efficacy to glipizide with less severe hypoglycemia in a double blind, RCT
− Saxa 2.5 mg/day (give after dialysis – removes 25%)
− Alo: 6.25 mg/day
GLP-1 (exenatide, liraglutide): not recommended in patients on
dialysis
Alpha-glucosidase inhibitors: not recommended in patients on
dialysis
Amylin analog (pramalintide): renal clearance – not recommended
SGLT2 inhibitors: cannot be used
Treatment of Diabetes in Dialysis: Non-insulin agents II
Am J Kidney Dis. 2013 Apr;61(4):579-87. doi: 10.1053/j.ajkd.2012.11.043
55. Summary and Unresolved Issues
• Changes in renal physiology imply that one should be very
cautious when:
• Giving fluids
• Restricting fluids
• Adding and dose adjusting meds
• The prevalence of CKD = “low eGFR” is high in older patients
• Variability of outcomes in this population is very high
• If one chooses conservative rather than dialytic management,
frequent clinic visits are essential to manage complications of
CKD
• A multi-disciplinary approach and SDM is essential
Editor's Notes
Describing the kidney as just a filter is a bit too simplistic. It's probably more accurate to describe the kidney as an organ which functions to maintain internal balance, to maintain the composition of the blood within narrow physiologic ranges. The kidney is able to do this through a sequential process of filtration by the glomerulus, followed by modification of the filtrate by tubular reabsorption of water and other substances, as well as active tubular secretion into the urine. The result is urine which is highly concentrated with substances that the body needs to eliminate and conservation of substances which it needs.
What is the glomerular filtration rate? As we described earlier the kidney is made up of a million filtering units called nephrons. The nephrons tend to be damaged and lost one by one. We can estimate how many nephrons are working by assessing how well the kidney is filtering and comparing that level to a normal filtration rate.
We don't routinely measure GFR in the clinical setting. Actual measurement is generally a research procedure. We are able to estimate GFR from serum creatinine, and that reflects the number of functioning nephrons.
Because creatinine reflects muscle mass which varies, by age, gender, and race, the “normal” serum creatinine may not be normal for many people. Clinical labs list a normal reference range, usually between 0.6 and 1.2 milligrams per deciliter, but this does not account for muscle mass, age, gender, or race. Thus, a serum creatinine of 1.2 in a 28-year-old African American man reflects an estimated GFR that's greater than 60. However, the same serum creatinine value in a 78-year-old white woman reflects significantly reduced estimated GFR of 43.
Creatinine-based estimates of kidney function, including the MDRD equation, have significant limitations. They cannot be used when creatinine is not stable or when the creatinine level is changing, such as occurs in acute kidney injury or in many patients who are sick and hospitalized. In these situations the estimated GFR will give an inaccurate reflection of kidney function.
In addition, for people who have either greatly increased muscle mass or greatly decreased muscle mass as occurs in cachexia, eGFR will inaccurately reflect their kidney function because the creatinine will be increased or decreased based on muscle mass rather than changes in kidney function. There are medications which interfere with the measurement of serum creatinine as well.
Much of the confusion about urine albumin relates to the many different tests that are available to measure in one way or another urine albumin or urine protein. There are dipsticks. All dipsticks are what we call semi-quantitative, which means that they will give you a reflection of the concentration of albumin in the urine but are affected by how concentrated or dilute the urine is.
The urine protein-to-creatinine ratio will give you an estimate of total protein excretion. However, total protein/creatinine is less reproducible because total urine protein includes many different substances. It's not a test that is standardized or, in fact, could be standardized.
So, that leaves us with the urine albumin-to-creatinine ratio, which is not perfect but, again, is probably our best way of estimating 24-hour excretion of urine albumin.
Not only are there changes in insulin sensitivity and catabolism, but the kidney is the site of metabolism of many oral agents as well. As a result, medications may need to be discontinued or adjusted as CKD progresses.