Lupus nephritis update, classification, approach according to guidelines, different case scenarios with stress on algorithmic management of different presentations
Ahmed Yehia
Lupus nephritis update, classification, approach according to guidelines, different case scenarios with stress on algorithmic management of different presentations
Ahmed Yehia
Therapeutic Club on Tauopathy. Its pathophysiology and therapeutic targets. Interactive session held at All India Institute of Medical Sciences, New Delhi - 110029 on 28th October 2017.
Insilico analysis of pkd genes in polycystic kidney disease patientsVeeramuthumariPandia1
The power point tells about the gene polymorphism alters the protein structure. Alteration in protein structure leads to malfunction of gene causes disease. PKD gnes-Polycystin 1 and 2 protein - Polycystic kidney disease.
The current study investigated the immunomodulatory
potential of ethyl acetate soluble supernatant of
Lactobacillus casei (LC-EAS) in vitro. The effect of
LC-EAS on nitric oxide release was analyzed in RAW
264.7 cells, wherein, an inhibition in nitric oxide production
through suppression of inducible nitric oxide synthase
mRNA expression was observed. Evaluation of LC-EAS
on LPS-induced peripheral blood mononuclear cells
showed a down-regulation in TNF-a and IL-6 genes and an
upregulation of IL-10. An inhibition in the protein
expression of NF-kB, ERK1/2 and STAT3 phosphorylation
confirms the immunomodulatory potential of LC-EAS. The
effect of LC-EAS on in vitro intestinal epithelial cells was
investigated using HT-29 human colon adenocarcinoma
cancer cells. LC-EAS exhibited an inhibition of NF-jB and
ERK1/2 phosphorylation, whereas STAT3 phosphorylation
was unregulated. To evaluate the downstream target of
STAT3 upregulation, expression of the intestinal trefoil
factor TFF3 which is a NF-jB regulator and STAT3
downstream target was studied. LC-EAS was observed to
elevate TFF3 mRNA expression. Overall the study shows
that the anti-inflammatory potential of LC-EAS is through
inhibition of NF-kB in different cell types.
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
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.
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
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.
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.
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
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
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.
263778731218 Abortion Clinic /Pills In Harare ,sisternakatoto
263778731218 Abortion Clinic /Pills In Harare ,ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group ABORTION WOMEN’S CLINIC +27730423979 IN women clinic we believe that every woman should be able to make choices in her pregnancy. Our job is to provide compassionate care, safety,affordable and confidential services. That’s why we have won the trust from all generations of women all over the world. we use non surgical method(Abortion pills) to terminate…Dr.LISA +27730423979women Clinic is committed to providing the highest quality of obstetrical and gynecological care to women of all ages. Our dedicated staff aim to treat each patient and her health concerns with compassion and respect.Our dedicated group of receptionists, nurses, and physicians have worked together as a teamof receptionists, nurses, and physicians have worked together as a team wwww.lisywomensclinic.co.za/
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
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
2. Glomerular disease in 2011
Previous studies have hypothesized that BSA can
induce MN and exposure to BSA is common in
the diet and that antibody-BSA immune
complexes can cause MN.
11/50 patients with iMN, but only 2/172 controls,
harbored high-titer serum antibody that
recognized epitopes in BSA not present in human
albumin. 7/11 patients with MN, but no controls,
also had higher than normal serum levels of BSA,
and in four of these patients the cationic BSA
colocalized with the BSA-specific antibody in their
subepithelial immune complex deposits.
Debiec, Ronco et al. N. Engl. J. Med. 364 ,
2101–2110 (2011)
3. Glomerular disease in 2011
This was a landmark study that demonstrated
that exogenous circulating antigens derived from
diet becomes a ―planted antigen‖ to induce MN.
This study raise the possibility that other dietary
antigens may also cause sMN.
Peripheral tolerance is present to protect the
kidney structures from the filtered antigens but
this tolerance fails if the antigen is retained at the
GFB as in the case of the cationic BSA.
The challenge in discovery of other antigens lies
in the search for the best candidates and in
mapping them to the diet andetotherEngl. J. Med. 364 ,
Debiec, Ronco al. N. environmental
4. Glomerular disease in 2011
Plasminogen activator and PAR are a part of the
innate immune mediator of tissue remodeling
during inflammation.
Wei, Reiser et al. made some interesting
observations:
LPS produced by commensal bacteria in the gut,
caused proteinuria in mice by inducing systemic
release of suPAR, which crossed the GFB &
activated podocyte β3 integrin in both native uPAR
+/+ kidneys & transplanted uPAR –/– kidneys.
Nat. Med. 17, 952–960 (2011).
Experimentally sustained secretion of suPAR from
sites outside the kidney induced FSGS.
5. Glomerular disease in 2011
serum suPAR level was significantly elevated in
• this study with primary FSGS (highest in recurrent
patients also provides suggestive evidence
FSGS after Tx).
that FSGS may be an outcome of otherwise
‗clinically silent‘ inflammation from glomerular
In patients in whom FSGS recurred,
lesions showed activated podocyte β3 integrin, &
environmental pathogens.
suPAR removed from serum by Nat. Med. 17, 952–960 (2011).
plasmapheresis
correlated with remission of recurrent FSGS.
• this hypothesis could lead to prophylactic
strategies that manipulate the microbiome to
lessen exposure and secondary damage to as
This was a breakthrough in the study of FSGS
podocytes from these PAMPs. circulating factor
it identified a long-sought-after
that is causative of recurrent FSGS.
This also provides a potential therapeutic target
for treating a disease in which current therapies
6. Glomerular disease in 2011
Gene expression studies in microdissected
human kidneys of patients with diabetic
nephropathy showed a marked up regulation of
• podocyte gene–environment interactions can
target genes of the mTOR pathway, suggesting
drive the progression of diabetic nephropathy. to
that over activation of this pathway in response
the dysregulated nutrient environment of diabetes
• mTOR pathways can be a potential
contributes to the development of diabetic
nephropathy.
therapeutic target to abrogate the progression of
diabetic nephropathy.
mice haploinsufficient for mTORC1 in podocytes
had had experimental diabetic nephropathy
induced with streptozotocin. Intriguingly, the mice
showed significant ameliorationClin.diabetic , 2197–
Godel, Huber et. Al. J.
2209 (2011)
of Invest. 121
nephropathy.
7. Membranous Nephropathy:
Summary Albumin as a putative dietary
Bovine Serum
antigen.
FSGS (recurrent):
Soluble urokinase-type PAR induced by
LPS
Diabetic Nephropathy:
Overactivation of podocyte mTOR pathways
in response to the dysregulated nutrient
environment.
8. Polycystic Kidney Disease in
2011
The main proteins implicated in PKD—polycystin-
1, polycystin-2 and fibrocystin—and in autosomal
Proteasome inhibition increases polycystin-1 2
dominant polycystic liver disease (glucosidase
subunit β and SEC63) functionally interact.
levels and attenuates cystic disease in
Prkcsh-knockout models, thus offering a
Transgenic overexpression of polycystin- 1, but
conceptual therapeutic approach to
not polycystin-2, rescues the renal and hepatic
autosomal dominant polycystic liver disease
and possiblyof tissue-selective Prkcsh-knockout or
phenotype
ADPKD.
Sec63-knockout mice and the renal phenotype of
Pkhd1del 4/del 4 mice.
Fedeles et al. Nat. Genet. 43, 639–647
(2011).
9. Polycystic Kidney Disease in
2011
The vasopressin V2 receptor antagonist,
tolvaptan, inhibits cystogenesis in vitro. Low
concentrations inhibited vasopressin-induced
cAMP production, cell proliferation, Cl secretion &
cyst growth in Reif et al. Am. J. Physiol. Renal Physiol. 301 ,
collagen matrices.
F1005–F1013 (2011).
Tolvaptan also reduced the volume of polycystic
kidneys after 1 week of treatment (3.1%), and
slowed the growth of polycystic kidneys in a 3-
Higashihara et al. CJASN. 6, 2499–2507
year, open-label study of patients with PKD (1.7%
(2011).
vs 5.8% in historical controls).
10. Polycystic Kidney Disease in
2011
Metformin stimulates the energy-sensing molecule
AMP-activated protein kinase (AMPK), inhibits the
activities of AMPK-dependent CFTR & mTOR in
Madin–Darby canine kidney renal epithelial cells, &
attenuates cAMP-dependent growth of these cysts
in collagen matrices & of cysts in metanephric
organ explants, & cystogenesis in constitutive &
inducible Pkd1-knockout mice. Sci. USA 108 , 2462–2467
Takiar et al. Proc. Natl Acad.
(2011).
PPAR-γ agonist pioglitazone inhibits renal and
hepatic cystogenesis in PCK rats by possibly
complementary mechanisms through the
inactivation of MAPK3 & mTOR, & inhibition of
Am. J. Physiol. Renal Physiol. 300 , F465–F474 (2011).
11. Polycystic Kidney Disease in
2011
Karihaloo et al. hypothesized that macrophage
infiltration contributes to the proliferation of cyst-
lining cells and PKD progression. Macrophages
undergo a transition from classically activated, pro
inflammatory cells to alternatively activated cells
that promote epithelial cell proliferation.
They found high concentrations of macrophage
chemoattractant molecules and macrophages in
pkd1-knockout mice.
Macrophage depletion by intra-peritoneal liposomal
clodronate administrationAm. Soc.Nephrol. 22, 1809–1814
J. inhibits epithelial cell
12. Polycystic Kidney Disease in
2011
Three studies have shown marked upregulation of the
signal transducer and transcription activator (STAT)3
in patients with ADPKD and in rodent PKD models.
Proc. Natl Acad. Sci. USA 108 , 7985–
7990 (2011).
Takakura et al. showed that Pyrimethamine, an
inhibitor of STAT3 was found to supress epithelial cell
proliferation & inhibit cystogenesis in pkd1 knockout
mice. Hum. Mol. Genet. 20, 4143–4154 (2011).
Leonhard et al. found that curcumin, a compound
with anti-inflammatory and antiproliferative properties,
reduced STAT3 activation, attenuated cell proliferation
and cystogenesis andJ.delayed renal failure in, F1193–F1202 (20
Am. Physiol. Renal Physiol. 300 an
inducible Pkd1 -knockout model.
13. Novel Therapeutics:
1. Tolvaptan.
2. Metformin.
3. PPAR- γ agonists.
4. Circumin
STAT3 Pathway
5. Pyrimethamine
inhibition
Physiological Understanding:
1. Genetic interactions between the various
implicated genes.
2. Macrophage infiltration contributing to the
cyst growth.
14. AKI in 2011
The source of urinary NGAL seems to be nearly
exclusively from the renal tubule and does not
seem to be released during pre-renal azotemia in
healthy animals. Paragas et al. Nat. Med. 17, 216–222 (2
Plasma NGAL has been known to hasten the
diagnosis of AKI. Srisawat and colleagues
showed that its level also helps predict which
patients with severe acute kidney injury (AKI) will
Kidney Int. 80, 545–552 (2011).
recover renal function.
15. AKI in 2011
Urine output remains an important ‗biomarker‘ of
AKI, and predicts death even in the absence of a
rise in serum creatinine level. The consecutive
hours of oliguria was more sensitive than average
oliguria over fixed periods of time in this study. It
validated the use of u.o. in the AKIN definition of
AKI. Macedo et al. Kidney Int. 80, 760–767
(2011).
Micro RNAs are a new class of AKI biomarkers
that may prove to be important new tools in the
diagnosis and treatment of AKI. Elevated levels of
miR-210, also found to be involved in6, 1540–1546
Lorenzen et al. CJASN molecular
response to stress, predicted mortality.
(2011).
16. 1. Further support to using NGAL as a
diagnostic and prognostic biomarker that
may shape the current practice.
2. Search of newer biomarkers like mRNAs.
3. Further support to the age-old ―urine output
estimation‖.
17. Transplantation in 2011
BENEFIT trial (Phase III results):
686 de novo kidney transplant were randomly
assigned to more-intensive or less-intensive
belatacept regimens or to ciclosporin. All patients
received basiliximab induction therapy, MMF and
corticosteroids. Equivalent rates of graft and
patient survival were noted despite an increased
frequency and severity of early rejection episodes
and increased frequency of PTLD associated with
Vincenti et al. Am. J. Transplant. 10, 535–546
belatacept. (2010).
18. Transplantation in 2011
Graft survival was equivalent across all regimens.
At year 3 post-transplantation, the mean eGFR was
21 ml/min/1.73 m2 higher in the belatacept groups
than in the ciclosporin group.
More importantly, from month 3 through to
month 36, the slope of eGFR in the belatacept
groups averaged 1.1 ml/min/1.73 m2/year versus –
2.0 ml/min/1.73 m2/year with ciclosporin.
Neither a significant increase in acute rejection
episodes nor new cases of PTLD after 18 months
post-transplantation http://dx.doi.org/10.1111/j.1600–
Am. J. Transplant. were observed.
19. Transplantation in 2011
Desensitization protocols are used for
transplantation in sensitized patients but there was
a lack of control groups in many studies.
Montgomery et al. showed in 211 sensitized
patients treated with a desensitization regimen (low
dose IVIG + PP) had better survival than patients
on dialysis or sensitized patients who undergo
compatible transplantation. J. Med. 365 , 318–326 (2011).
N. Engl.
This study however did not give the actual graft
survival or AMR rates and the outcome in deceased
donor sensitized transplantation remains to be
seen.
20. Transplantation in 2011
Recent studies suggest an association between
variants of the apolipoprotein L1 gene ( APOL1 )
and nondiabetic nephropathy among African
Americans. Friedman et al. JASN 22, 2098–2105
(2011).
In a single-center study, kidneys from AA deceased
donors with two APOL1 risk variants were more
likely to fail than kidneys from individuals with one
Reeves-Daniel et al. Am. J. Transplant. 11, 1025–
1030 (2011).
or no APOL1 risk variants.
This points to a biological influence rather than race
underlying transplantation outcomes. The
application of these associations to improve
21. Transplantation in 2011
Increased cold ischemia times of extended
criteria donor kidneys are associated with
delayed graft function, but do not affect graft
survival. Am. J. Transplant. 11, 2657–2664 (2011).
This study is limited by its retrospective nature
and is prone to selection bias, it provides some
impetus to reconsider discard of ECD kidneys
with higher CITs and optimize ECD utilization and
acceptance.
22. Therapeutic advances:
1. Advent of a new, possibly safer alternate to
CNIs in the form of Belatacept.
2. Better trials supporting better outcomes with
desensitization protocols.
3. Absence of difference in graft outcome with
longer CITs
Advances in transplant biology:
1. APOL1 variants in AA affecting outcomes.
2. Identification of factors in some patients which
permits tolerance and independence from
immunosuppressants.
23. Dialysis in 2011
Inflammation is present in majority of patients in
HD .Both factors related to the dialysis procedure
(such as dialysis catheters and quality of
dialysate) and factors unrelated to the dialysis
procedure per se (such as infectious
complications and volume overload).
Catalytic hypothesis: Inflammation was shown
to amplify the risk of death and CV events
associated with high asymmetric dimethylarginine
(ADMA) levels as shown in a study on 225 HD
Tripepi et al. CJASN. 7, 1714–1721 (2011).
patients followed for 13 yrs.
24. Dialysis in 2011
Hung et al. demonstrated in 22 patients that
4 weeks of treatment with a recombinant human
IL- 1 receptor antagonist (anakinra) significantly
reduced mean CRP level (by 53%) and mean IL-
6 level (by 40%), while mean prealbumin level
increased by 23%.
Moreover, the anti-cytokine treatment was well
tolerated and safe.
It is the first study showing that targeted anti-
cytokine treatment decreases inflammation
parameters in this patient group and22, 437–442
J. Am.Soc. Nephrol. long term
studies are needed to study its impact.
(2011).
25. Dialysis in 2011
The SHARP study is the largest randomized
study ever conducted in nephrology and included
9,270 patients randomized to receive either 20
mg simvastatin plus 10 mg ezetimibe daily or
placebo.
Statin Rx was associated with beneficial effects
on major atherosclerotic events in the entire
chronic kidney disease population; the effect is
less pronounced in the subpopulation of dialysis
Lancet 377 , 2181–2192
patients. (2011).
26. Dialysis in 2011
Winkelmayer et al., in a study based on 2.5 million
observations of hemodialysis patients, showed that
the prevalence of atrial fibrillation had increased
threefold from 1992 (3.5%) to 2006 (10.7%).
They also showed that mortality was twice as high
among hemodialysis patients with AF compared to
those without. J. Am. Soc. Nephrol. 22, 349–357 (2011).
In another report, warfarin seemed to increase the
risk if hemorrhagic stroke without lowering the risk
of ischemic stroke. Thus it was concluded that
unless an adequately powered RCT was done, it is
not advisable toCJASN. http://dx.doi.org/10.2215/CJN.04550511.
prescribe warfarin in HD patients
27. 1. Inflammatory markers and detection of atrial
fibrillation should be included in the
assessment of patients on hemodialysis.
2. Statins have a modest but significant benefit
on preventing cardiac events.
3. Warfarin treatment should not advocated in
HD patients till a large RCT shows anything
new.
Editor's Notes
cardiotrophin-like cytokine-1 (CLC-1)
Loss of gluc/SEC 63 expression reduces pc-1 and to a lesser extent pc2 expression, blockes pc-1 translocation to primary cilia, worsens cystic disease in heterogenouspkd ½ +/- mice.