This document discusses gaps in the current definitions and management of chronic kidney disease-mineral and bone disorder (CKD-MBD). It notes that while CKD-MBD is now defined more broadly than just renal osteodystrophy, clinical definitions are still lacking. Guidelines for phosphorus management need clarification on organic vs. inorganic phosphorus and dialysate calcium guidelines could be more precise. Role of magnesium and biomarkers like alkaline phosphatase are underexplored. PTH assays and their relationship to bone remodeling is also in need of better definition. Overall, this highlights several areas where CKD-MBD understanding and treatment could be improved.
Diagnosis, Evaluation, Prevention and Treatment of CKD-MBDAbdullah Ansari
Introduction and definition of CKD–MBD
Diagnosis of CKD–MBD: biochemical abnormalities
Diagnosis of CKD–MBD: bone
Diagnosis of CKD–MBD: vascular calcification
Treatment of CKD–MBD targeted at serum phosphorus and serum calcium
Treatment of abnormal PTH levels in CKD–MBD
Treatment of bone with bisphosphonates, other osteoporosis medications and growth hormone
Evaluation and treatment of kidney transplant bone disease
Diagnosis, Evaluation, Prevention and Treatment of CKD-MBDAbdullah Ansari
Introduction and definition of CKD–MBD
Diagnosis of CKD–MBD: biochemical abnormalities
Diagnosis of CKD–MBD: bone
Diagnosis of CKD–MBD: vascular calcification
Treatment of CKD–MBD targeted at serum phosphorus and serum calcium
Treatment of abnormal PTH levels in CKD–MBD
Treatment of bone with bisphosphonates, other osteoporosis medications and growth hormone
Evaluation and treatment of kidney transplant bone disease
- Recorded videos of this lecture:
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Presentation given to our fellowship program about diabetic kidney disease.
2022 update discussing SGLT2i, MRA (e.g. finerenone), health economics and beyond
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
Insights from the FIGARO-DKD and FIDELIO-DKD trials - Dr. GawadNephroTube - Dr.Gawad
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- Recorded videos of this lecture:
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Presentation given to our fellowship program about diabetic kidney disease.
2022 update discussing SGLT2i, MRA (e.g. finerenone), health economics and beyond
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
Insights from the FIGARO-DKD and FIDELIO-DKD trials - Dr. GawadNephroTube - Dr.Gawad
- Recorded videos of this lecture:
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Background: Chronic kidney disease affects one in five adults ≥65 years old, over half of whom develop secondary hyperparathyroidism. In observational studies, secondary hyperparathyroidism is associated with low bone mineral density and excess vascular calcification, presumably leading to surplus fractures, more cardiovascular events and shortened lifespan. Several bioactive vitamin D analogs are FDA approved to treat secondary hyperparathyroidism and published algorithms direct their clinical use. However, whether such therapy improves patient outcomes is uncertain. The purpose of this review is to summarize evidence derived from clinical trials describing the benefits of treating secondary hyperparathyroidism in patients with Pre-dialysis chronic kidney disease.
Methods: We performed a systematic review of the literature to identify trials using bioactive vitamin D (calcitriol, alfacalcidol, paricalcitol and doxercalciferol) to treat secondary hyperparathyroidism in chronic kidney disease patients. We focused on changes in bone mineral density, fractures, falls, vascular events and lifespan, resulting from treatment of secondary hyperparathyroidism.
Update on the 18th International Conference on Co-morbidities and Adverse Drug Reactions in HIV
Daniel Lee, M.D.
January 20th, 2017
UCSD HIV & Global Health Rounds
Current treatments for postmenopausal osteoporosis
suffer from side effects. Safe and natural milk
proteins, ribonuclease, and lactoferrin promote formation
of new capillaries and bone formation.
Previous year question on osteoporosis based on neet pg, usmle, plab and fmge...Abhishek Gupta
Revision with a Master Quiz of 38 questions based on NEET PG Sample Questions on Osteoporosis from Previous Year NEET PG Online Exams.
http://medicoapps.org
Hyperphosphatemia in CKD patients; The Magnitude of The Problem - Prof. Alaa ...MNDU net
Hyperphosphatemia in CKD patients; The Magnitude of The Problem
Prof. Alaa Sabry - Professor of Nephrology
Mansoura Nephrology and Dialysis Unit (MNDU) Course
Sample size and how to calculate it
- Why sample size is important
- Alpha and beta errors
- Main outcome and Effect size
- Practical examples using Means-Proportions-Correlation- Confidence Interval
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
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
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
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.
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Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
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
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
- 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
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.
4. Definition of CKD-MBD
A systemic disorder of mineral and bone metabolism due
to CKD manifested by either one or a combination of the
following:
– Abnormalities of calcium, phosphorus, PTH, or vitamin D metabolism
– Abnormalities in bone turnover, mineralization, volume, linear growth, or
strength
– Vascular or other soft tissue calcification
• Moe et al Kidney International June 2006
5. Standardization of Terms
• The term renal osteodystrophy (ROD)
should be used exclusively to define the bone
pathology associated with CKD.
• The clinical, biochemical, and imaging
abnormalities should be defined more broadly
as a clinical entity or syndrome called Chronic
Kidney Disease-Mineral and Bone Disorder
(CKD-MBD).
6. A Framework for Classification of CKD-MBD
Type*
Laboratory
Abnormalities
Bone Disease
Calcification of
Vascular or Other
Soft Tissue
L + - -
LB + + -
LC + - +
LBC + + +
* L = laboratory abnormalities (of calcium, phosphorus, PTH,
alkaline phosphatase or vitamin D metabolism); B = bone disease
(abnormalities in bone turnover, mineralization, volume, linear
growth, or strength); C = calcification of vascular or other soft
tissue.
•Kidney International June 2006
21. The percentage of hyperphosphatemia
was 50% and iPTH > 300 pg/mL was
also 50%.
Elevated iPTH levels showed a
significant association with increased
hyperphosphatemia
26. Biopsy of bone and the microscopic analysis of undercalcified sections after
double tetracycline labeling provide definitive and quantitative diagnosis of
renal bone disease.25 To standardize reports on bone histology, the Kidney
Disease:
Improving Global Outcomes (KDIGO) CKD-MBD work group proposed the
TMV classification, an assessment of turnover (T), mineralization (M), and bone
volume (V).1 Bone mineralization is assessed by the administration of two
different tetracyclines spaced apart (e.g., tetracycline 500 mg three times daily
for 2 days, followed by a 10-day interval, then demeclocycline 300 mg three
times daily for 3 days) and biopsy 4 days later; the quantitation of bone
mineralization rate is achieved by measuring the distance between the two
fluorescent tetracycline bands.
29. Phosphorus
• Fasting or postprandial
• Organic and non organic
• Ph binders
• Protein and fish phosphorous
30. Fasting or
postprandial
Fasting and postprandial
measurements of serum
phosphorus (A), fractional
excretion of phosphorus (B), FGF-
23 (C), serum calcium (D),
fractional excretion of calcium (E),
and PTH (F) after meal 1 in healthy
volunteers (○) and patients with
CKD (▪). Time 0 represents the
fasting measurements.
Isakova et al., JASN 2008
31. Fasting and postprandial
measurements of serum
phosphorus (A), fractional
excretion of phosphorus (B), FGF-
23 (C), serum calcium (D),
fractional excretion of calcium (E),
and PTH (F) after meal 1 in healthy
volunteers (○) and patients with
CKD (▪). Time 0 represents the
fasting measurements.
Isakova et al., JASN 2008
35. Comparison: 2017 vs 2009
• New 4.1.8: In patients with CKD
G3a-G5D, we suggest limiting
dietary phosphate intake in the
treatment of
hyperphosphatemia alone or in
combination with other
treatments. (2D)
• It is reasonable to consider
phosphate source (e.g., animal,
vegetable, additives) in making
dietary recommendations. (Not
Graded)
• Old 4.1.7: In patients with
CKD G3a–G5D, we
suggest limiting dietary
phosphate intake in the
treatment of
hyperphosphatemia
alone or in combination
with other treatments
(2D).
44. Comparison: 2017 vs 2009
• New 4.1.4: In patients with CKD
G5D, we suggest using a
dialysate calcium concentration
between 1.25 and 1.50 mmol/l
(2.5 and 3.0 mEq/l) (2C).
• Old 4.1.3: In patients with CKD
G5D, we suggest using a
dialysate calcium concentration
between 1.25 and 1.50 mmol/l
(2.5 and 3.0 mEq/l) (2D).
50. From: Magnesium and outcomes in patients with chronic kidney disease: focus on vascular calcification, atherosclerosis an
survival
Clin Kidney J. 2012;
53. A growing body of evidence from in vitro investigations, animal models
and both observational as well as interventional clinical studies point to
the possibility that low magnesium levels are associated with vascular
calcification.
Moreover, several observational studies suggest a relationship between
increased serum magnesium concentrations and better survival rates for
patients receiving long-term dialysis treatment.
59. From: Outcome predictability of serum alkaline phosphatase in men with pre-dialysis CKD
Nephrol Dial Transplant. 2010;25(9):3003-3011. doi:10.1093/ndt/gfq144
Nephrol Dial Transplant | Published by Oxford University Press on behalf of ERA-EDTA 2010. All rights reserved. For
Permissions, please e-mail: journals.permissions@oxfordjournals.orgOxford University Press
High levels of BAP were strongly
associated with short-term
mortality in dialysis patients,
suggesting BAP as an important
biomarker of bone and mineral
disorder in dialysis patients.
62. Table 3. Results of baseline multivariate Cox regression and competing risk regression
analysis for all-cause mortality in Beijing maintenance hemodialysis patients (n = 8530).
Li D, Zhang L, Zuo L, Jin CG, Li WG, et al. (2017) Association of CKD-MBD Markers with All-Cause Mortality in Prevalent
Hemodialysis Patients: A Cohort Study in Beijing. PLOS ONE 12(1): e0168537. https://doi.org/10.1371/journal.pone.0168537
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0168537
63. Fig 1. Kaplan-Meier curves for the five groups categorized by different iPTH level.
Li D, Zhang L, Zuo L, Jin CG, Li WG, et al. (2017) Association of CKD-MBD Markers with All-Cause Mortality in Prevalent
Hemodialysis Patients: A Cohort Study in Beijing. PLOS ONE 12(1): e0168537. https://doi.org/10.1371/journal.pone.0168537
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0168537
67. The third-generation bio-
intact parathyroid hormone
(PTH) (1–84) assay was
designed to overcome
problems associated with
the detection of C-terminal
fragments by the second-
generation intact PTH assay
71. Bisphosphonates
• CKD–MBD KDIGO guidelines,
• in patients with CKD stages 1–2 with OP and/or high risk of fracture, treatment as for
the general population is suggested (guideline 4.3.1, evidence 1A).
• In patients with CKD stage 3 with PTH in the normal range and OP and/or high risk of
fracture, treatment as for the general population is again suggested (guideline 4.3.2,
evidence 2B).
• On the other hand, in patients with CKD stage 3 with biochemical abnormalities of CKD–
MBD and low BMD and/or fragility fractures, it is suggested that treatment choices
should take into account the magnitude and reversibility of the biochemical
abnormalities and the progression of CKD, with consideration of a bone biopsy
(guideline 4.3.3, evidence 2D).
• Oral bisphosphonates are also indicated in order to reduce bone loss in
glucocorticoid- or transplant-induced OP
• FDA advises against the use of bisphosphonates in patients with a
GFR <30 ml/min/1.73 m2
• The scarce clinical evidence of efficacy and safety of bisphosphonates in stage
4–5 CKD make it difficult to make any definite recommendations.
73. Denosumab
• DMab also to be effective in reducing fracture risk and increasing
BMD after 36 months of follow-up in subjects receiving DMAb or
placebo.
• However, other studies have shown that DMab may induce significant
hypocalcemia, especially in CKD and hemodialysis patients with
underlying high-turnover bone disease due to secondary
hyperparathyroidism or metastatic bone disease
Nishikawa ,. Et alClinical Interventions in Aging, 2016
74. Teriparatide
• Compared with placebo, teriparatide was found
to significantly increase lumbar spine and
femoral neck BMD within each renal function
subgroup.
• A recent post-hoc analysis of a postmarketing
surveillance study that included elderly female
Japanese patients with OP who were at high risk
of fracture (82% had a previous fracture) and
stage 4 or 5 CKD and had been receiving
subcutaneous teriparatide 20 μg daily for up to
24 months revealed that teriparatide appeared
to be effective by increasing BMD and
procollagen type 1 N-terminal propeptide
Nishikawa ,. Et alClinical Interventions in Aging, 2016
75. Romosozumab
• Humanized monoclonal antibody against sclerostin—an inhibitor of
the Wnt and bone morphogenic protein signaling pathways—which
stimulates bone formation.
• Anti-sclerostin antibody treatment was found to be helpful in
improving bone properties in experimental models of progressive
renal osteodystrophy but only when the PTH levels were low
Moe SM, et al. J Bone Miner Res, 2015
76. Osteoporosis
Nephrologists should probably not ignore any longer fracture risk
assessment, especially in patients with additional risk factors for osteoporosis
if results will impact treatment decisions.
However, although different therapeutic agents have been shown to reduce
the risk of fracture in CKD patients with low BMD, specific prospective
studies, with or without bone biopsies, in CKD are urgently needed.
77. Thus, although this study is an important addition to the literature, we still need prospective
observational studies to determine whether measurement of BMD by DXA also predicts
fractures in patients with CKD stages 4 and 5, with overt biochemical manifestations of CKD-
MBD.
81. • CKD-MBD is a systemic disorder that has significant clinical
implications.
• Treatment of CKD-MBD in children requires special consideration in
order to maximize growth, optimize skeletal health, and prevent
cardiovascular disease.
82. Growth in children
• After correcting all metabolic abnormalities that can worsen growth
status such as metabolic acidosis, anemia, CKD–MBD and
malnutrition in pediatric patients with mild-to-moderate renal
insufficiency.
• The use of supraphysiological doses of recombinant human GH
(rhGH) has been proved to be safe and effective in increasing growth
and final adult height.
83. Why would we need vit D
1- to replenish vit D YES
2- to increase Ca levels
3- to control PTH
4- Skeletal effects
5- other
CVD, Mortality, and morbidly
84. 4.2.2.
In adult patients with CKD Stages 3a-5 not on dialysis,
we suggest calcitriol and vitamin D analogs not be
routinely used. (2C)
It is reasonable to reserve the use of calcitriol and
vitamin D analogs for patients with CKD Stages 4-5
with severe and progressive hyperparathyroidism. (Not
Graded)
86. Management of clinical presentations of CKD-MBD:
• Bone pains
• Muscle pain and weakness
• Skeletal deformities
• Pseudogout
• Calcefic periartheritis
• Vascular calcification
• Fractures.
• Tendon rupture
• Pruritus
• Calciphelaxis
87. Conclusion
• We are missing Large RCT establishing solid endpoints
like, Fractures, calcification, mortality, and quality of
life.
• Attention to ALP, MG and difference in PTH assays.
• Clear guidelines regarding all aspects of CKD-MBD
• Biopsy when indicated
• Reconsider using Magnesium salts alone and as
phosphate binder.
88.
89.
90.
91.
92.
93.
94. • ferric citrate was generally well tolerated and adverse
events were consistent with its known safety profile.
The most commonly reported adverse events in the
Phase 3 study were diarrhea (21%), constipation
(19%), discolored feces (15%), nausea (11%),
abdominal pain (6%), and hyperkalemia (7%)
Keryx Biopharmaceuticals Inc.’s
95. What are the key considerations in phosphate
binder treatment?
96. What are the key considerations in phosphate
binder treatment?
• Data from three observational studies (Isakova et al
study, DOPPS, and COSMOS, and Study) have shown a
survival benefit associated with the early
administration of phosphate binders.
Isakova , et al. JASN 2009;20:388-396.
Lopes AA, et al (DOPPS):Am J Kidney Dis 2012
Cannata-Andia JB COSMOS study. 49th ERA-EDTA Congress; 2012.
97. Stratified HRs for mortality in the unmatched subcohort (n = 8610) comparing patients who
began treatment with phosphorus binders during the first 90 d on hemodialysis versus those
who were not treated during the first 90 d.
Isakova T et al. JASN 2009;20:388-396
98. Parameter HR 95% CI P
Intention-to-treat analyses
a
no adjustment 0.58 0.52 to 0.66 <0.0001
multivariable-adjusted
b
0.70 0.62 to 0.79 <0.0001
vitamin D–adjusted
c
0.70 0.62 to 0.79 <0.0001
facility-specific SMR–
stratified
d
0.71 0.62 to 0.81 <0.0001
As-treated analyses
e
no adjustment 0.70 0.61 to 0.78 <0.0001
multivariable-adjusted
b
0.82 0.72 to 0.93 0.001
vitamin D–adjusted
c
0.82 0.72 to 0.93 0.002
facility-specific SMR–
stratified
d
0.71 0.63 to 0.81 <0.0001
25% reduction in the risk of death compared with those who did not receive phosphate binders (HR: 0.75;
95% CI: 0.68–0.83); in models adjusted for nutritional factors, a 12% lower risk of death was reported
Lopes AA, et al (DOPPS):Am J Kidney Dis 2012
DOPPS study
99. • Third study data from 6321 patients on hemodialysis included in the
COSMOS study also indicate that the use of phosphate binders,
either alone or in combination regimens, was associated with a
significantly lower risk of all-cause mortality.
Cannata-Andia JB COSMOS study. 49th ERA-EDTA Congress; 2012.
101. Ca Vs Sevelamer
• In clinical practice, calcium containing PB, and sevelamer
hydrochloride are currently the two most commonly used phosphate
binders.
• Previous studies comparing them suggested that they are equally
effective.
QUNIBI et al. (CARE Study). Kidney Int 2004
102. Phosphate Binders in Moderate CKD
Block G et al. J Am Soc Nephrol. 2012;23:1407-1415.
ACTIVE PLACEBO PLACEBOLANTHANUM SEVELAMER CALCIUM
103. Ca Vs Sevelamer
• CARE study; the only prospective, randomized,
double-blind study comparing the only two FDA-
approved phosphate binders,
• Calcium-based binders have been shown to be more
effective in reducing serum phosphate levels than
sevelamer hydrochloride
•
QUNIBI et al. (CARE Study). Kidney Int 2004
106. Care study
CONCLUSION
• the superiority of calcium acetate over sevelamer
hydrochloride for achieving the target levels of serum
phosphorus and Ca P product recommended by K/DOQI
guidelines.
• Moreover, calcium acetate appears to be the more cost-
effective choice as first-line treatment for hyperphosphatemia
in patients with ESRD on maintenance dialysis.
WAJEHY QUNIBI and CHARLES R NOLAN ,Kidney International (2004)
107. Ca Vs Sevelamer
• In other study, in a prospective 42-month study
including 1347 haemodialysis patients, those
prescribed sevelamer HCl had a higher mortality risk
compared with those prescribed calcium carbonate
(HR: 1.46; 95% CI: 1.1–1.9).
Jean G, et al., Hemodial Int 2011
108. Effects of sevelamer and calcium on coronary artery calcification in patients new to hemodialysis
GEOFFREY A BLOCK, et al., Kidney International (2005)
Median coronary artery calcium score.
109. Ca Vs Sevelamer
• In BLOCK, et al study , CV mortality in the sevelamer group was ten
times lower than that in the calcium carbonate group (P < 0.001).
• A significant reduction in all-cause mortality, though not in non-CV
mortality, was also noted in the sevelamer group.
BLOCK, et al., Kidney International (2005)
112. Suki WN, et al . Effects of sevelamer and calcium-based phosphate binders on mortality in hemodialysis patients.
Kidney Int 2007
113.
114. Ca Vs Sevelamer
• A Cochrane review and meta-analysis of studies including patients
with CKD stages 3–5D according to KDOQI guidelines indicated that
sevelamer significantly decreases end-of-treatment serum phosphate
levels compared with placebo, although comparisons of reduction in
serum phosphate with calcium-based binders favored the latter
group.
Navaneethan SD, et al., Database Syst Rev 2011
115.
116.
117. Comparison: 2017 vs 2009
• New 4.1.5: In patients with CKD
G3a-G5D, decisions about
phosphate-lowering treatment
should be based on
progressively or persistently
elevated serum phosphate (Not
Graded).
• Old 4.1.5: In patients with CKD
G3a–G5 (2D) and G5D (2B), we
suggest using phosphate-
binding agents in the treatment
of hyperphosphatemia.
• It is reasonable that the choice
of phosphate binder takes into
account CKD stage, presence of
other components of CKD-MBD,
concomitant therapies, and side
effect profile (Not Graded).
118. Comparison: 2017 vs 2009
• New 4.1.6: In adult patients with CKD
G3a-G5D receiving phosphate-
lowering treatment, we suggest
restricting the dose of calcium-based
phosphate binders (2B).
• Old 4.1.5: In patients with CKD G3a–
G5D and hyperphosphatemia, we
recommend restricting the dose of
calcium-based phosphate binders
and/or the dose of calcitriol or
vitamin D analog in the presence of
persistent or recurrent hypercalcemia
(1B).
• In patients with CKD G3a–G5D and
hyperphosphatemia, we suggest
restricting the dose of calcium-based
phosphate binders in the presence of
arterial calcification (2C) and/or
adynamic bone disease (2C) and/or if
serum PTH levels are persistently low
(2C).
119. Phosphate Binders and Mortality
All-Cause Mortality Dialysis Inception
Di Iorio B et al. Clin J Am Soc Nephrol 2012;7:487-493
120. Sevelamer vs. Calcium
Di Iorio B et al. Am J Kidney Dis. 2013;62:771-778
Arrythmias Cardiovascular Mortality