The document discusses antibody-mediated rejection in kidney transplantation. It notes that antibody-mediated rejection is associated with donor-specific antibodies, involves complement activation and endothelial injury, and is characterized by peritubular capillary C4d staining. Current therapeutic approaches aim to reduce antibodies and inhibit complement activation through treatments like plasma exchange, low-dose IVIG, high-dose IVIG, and rituximab. High-dose IVIG specifically works to inhibit C3 convertase and absorb complement activation fragments.
Basics of kidney_transplant and donor_recepient evaluationJosephN7
This contains basic information on kidney transplant, benefits of transplant , donor_recepient evaluation, immunosuppressive drugs and risk factors
for update on my new presentations follow and leave a comment on any topic.
follow me on social media for related content (IG "mulebajoseph" and Pinterest "Joseph N Muleba" twitter "joseph n muleba"
Basics of kidney_transplant and donor_recepient evaluationJosephN7
This contains basic information on kidney transplant, benefits of transplant , donor_recepient evaluation, immunosuppressive drugs and risk factors
for update on my new presentations follow and leave a comment on any topic.
follow me on social media for related content (IG "mulebajoseph" and Pinterest "Joseph N Muleba" twitter "joseph n muleba"
1-3. Electrolyte disorders: diagnosis and management. Tatyana Nastausheva (rus)KidneyOrgRu
IPNA-ESPN teaching course "Pediatric nephrology: Evidence-based statements and open questions", Moscow, Russia, October 22-24, 2013.
Symposium 1: WATER & ELECTROLYTE DISTURBANCES IN CHILDREN WITH CKD
By Dr. Usama Ragab, Zagazig Faculty of Medicine
PSC incidence ranges from 0.5 to 1.25 cases/100 000.
The prevalence of the disease ranges between six and 20 cases/100 000.
Men are more likely to be affected (70%).
Prevalence of PSC may be increased in first degree relatives of PSC patients
Chronic Liver Disease in pediatric: a case presentation and discussionDr Abdalla M. Gamal
A presentation from a tutorial about an interesting case that came to the Pediatric Department of Sebha Medical Center and was imaged by the Radiology Department.
The tutorial was a joint effort between Dr Zeinab Salem Ali (from Pediatric Department) and me (from Radiology Department). In her slides, Dr Zeinab presented the case history, examination, investigations, differential diagnosis and discussed the clinical presentation, investigations and management for chronic liver diseases in pediatric patients.In my slides, I discussed the definition, etiology, natural history of this condition and explained the role of imaging in its diagnosis.
These are my slides after some modifications. I added an aknowlegement page to illustrate Dr Zeinab effort and to thank Dr Khaled Aljasem from Pediatric Department for his effort in revising the original presentations and the constructive feedback he provided which improved the quality of the presented material. Then I added a summary for the parts Dr Zeinab has presented to make this powerpoint presentation complete.
This presentation was presented by Dr Zeinab Salem (from Pediatric Department) and me in a joint tutorial between Pediatric Department and Radiology Department of Sebha Medical Center.
Всемирный день почки 2016 в НИКИ им. академика Ю.Е. ВельтищеваKidneyOrgRu
9 марта 2016 г в конференц-зале Научно-Исследовательского Клинического Института имени академика Ю.Е. Вельтищева проведено праздничное мероприятие, посвященное Всемирному Дню Почки, который отмечается во всем мире с 2006 года по инициативе Международного Общества Нефрологов (http://www.worldkidneyday.org). Впервые в этом году Всемирный День Почки был посвящен детям с акцентом на ранней профилактике развития заболеваний почек.
Сотрудники отделения наследственных и приобретенных болезней почек представили для детей презентации об истории проведения праздника, распространенности заболеваний почек с рекомендациями здорового образа жизни для сохранения функций почек.
Было организовано праздничное веселое интерактивное представление для детей с участием Центра детского и юношеского творчества "Бибирево", театра-студии «Рампа», танцевально-акробатических студий «Овация» и «Альфа». Все дети получили праздничные подарки с символом Всемирного Дня Почки.
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.
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
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.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of the physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar lead (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
6. Describe the flow of current around the heart during the cardiac cycle
7. Discuss the placement and polarity of the leads of electrocardiograph
8. Describe the normal electrocardiograms recorded from the limb leads and explain the physiological basis of the different records that are obtained
9. Define mean electrical vector (axis) of the heart and give the normal range
10. Define the mean QRS vector
11. Describe the axes of leads (hexagonal reference system)
12. Comprehend the vectorial analysis of the normal ECG
13. Determine the mean electrical axis of the ventricular QRS and appreciate the mean axis deviation
14. Explain the concepts of current of injury, J point, and their significance
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
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!
Best Ayurvedic medicine for Gas and IndigestionSwastikAyurveda
Here is the updated list of Top Best Ayurvedic medicine for Gas and Indigestion and those are Gas-O-Go Syp for Dyspepsia | Lavizyme Syrup for Acidity | Yumzyme Hepatoprotective Capsules etc
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/
Adv. biopharm. APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMSAkankshaAshtankar
MIP 201T & MPH 202T
ADVANCED BIOPHARMACEUTICS & PHARMACOKINETICS : UNIT 5
APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMS By - AKANKSHA ASHTANKAR
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. The very first kidney transplantation in humans
has been performed in
A.
B.
C.
D.
E.
Mumbai, India, 1915
Chicago, USA, 1912
Moskow, Russia, 1909
Lyon, France, 1906
London, UK, 1903
5. The first kidney transplantation in humans has
been performed in
A.
B.
C.
D.
E.
Mumbai, India, 1915
Chicago, USA, 1912
Moskow, Russia, 1909
Lyon, France, 1906
London, UK, 1903
6. What is the lower age limit for kidney Tx?
A.
B.
C.
D.
E.
Birth
6 months
1 year
2 years
3 years
7. Indication for kidney transplantation
Children with irreversible renal failure
Minimal age: 6 to 12 mos
Minimal BW: 5 to 10 kg
According to local
experience & guidelines
Relative contraindications
ABO incompatibility
Malignancy within the previous 12 months
Active viral infection: HIV, VHB, VHC
Active systemic disease: HUS, SLE, RPGN, vasculites, etc.
Multiorgan failure, severe brain damage, etc.
8. Options according to age at start of RRT
Age
PD
HD
Tx
Premature baby – Birth – 6 mos – 12 mos – 18 mos – 2 yrs
9. Transplantation
6 mos – 5.4 kg
RRT options
1st yr of life
Hemodialysis
5 mos – 4.8 kg
Peritoneal dialysis
1000 g
11. What is the lower age limit for kidney Tx?
A.
B.
C.
D.
E.
Birth
6 months
1 year
2 years
3 years
12. What is the part of pediatrics among all kidney Tx?
A.
B.
C.
D.
E.
1%
2.5%
5%
7.5%
10%
13. Kidney transplantation activity in Europe
Cochat Comprehensive Pediatric Nephrology 2008
Country
Total Nb of Tx
Tx in children (%)
Croatia
109
4 (3.66%)
Czech Republic
427
15 (3.51%)
France
2423
81 (3.34%)
Germany
2478
117 (4.72%)
Israel
94
21 (22.3%)
Italy
1746
58 (3.32%)
Lithuania
63
2 (3.17%)
Netherlands
420
14 (3.33%)
Norway
256
9 (3.51%)
Poland
1067
38 (3.56%)
Spain
2057
68 (3.31%)
Sweden
372
13 (3.49%)
Turkey
665
59 (8.87%)
UK
1516
128 (8.44%)
67
3 (4.47%)
Serbia
Average
% Tx in
children
4.5 %
14. What is the part of pediatrics among all kidney Tx?
A.
B.
C.
D.
E.
1%
2.5%
5%
7.5%
10%
15. What is the main cause of ESRD in children < 5 yrs?
A.
B.
C.
D.
E.
CAKUT
Steroid resistant nephrotic syndrome
Inherited renal diseases
Hemolytic uremic syndrome
Chronic pyelonephritis
17. What is the main cause of ESRD in children < 5 yrs?
A.
B.
C.
D.
E.
CAKUT
Steroid resistant nephrotic syndrome
Inherited renal diseases
Hemolytic uremic syndrome
Chronic pyelonephritis
18. What are the 2 critically important outcomes in
kidney Tx?
A.
B.
C.
D.
E.
Patient survival
Blood pressure
Graft survival
Acute rejection
Graft function
19. Hospices Civils de Lyon & Université Claude-Bernard Lyon 1
ERA-EDTA ERBP in press
20. What are the 2 critically important outcomes in
kidney Tx?
A.
B.
C.
D.
E.
Patient survival
Blood pressure
Graft survival
Acute rejection
Graft function
21. Preemptive kidney Tx
A.
B.
C.
D.
E.
Is used for an average 25% of the pediatric population
Is associated with a greater risk of nonadherence
Can be proposed irrespective of the primary disease
Provides the same survival than in dialysis children
Relies on local facilities
22. % Preemptive Tx in Europe
Cochat Comprehensive Pediatric Nephrology 2008
Sweden
Norway
Netherlands
USA
UK
Spain
Croatia
France
Germany
Turkey
Czech Rep
Israel
Serbia
0
10
20
30
40
50
24. The best option for RRT in children is preemptive Tx
Dialysis should be limited to those children who cannot benefit from preemptive Tx
Advantages
Avoids dialysis (school attendance, social and family life)
Avoids vascular/peritoneal access
Better results than non-preemptive Tx
Cost effectiveness
Drawbacks
Timing for putting the patient on the waiting list?
Increased risk of non-adherence?
25.
26. Preemptive kidney Tx
A.
B.
C.
D.
E.
Involves an average 25% of the pediatric population
Is associated with a greater risk of nonadherence
Can be proposed irrespective of the primary disease
Provides the same survival than in dialysis children
Relies on local facilities
27. In Europe, the average rate of living donation for
children is
A.
B.
C.
D.
E.
15%
20%
25%
30%
40%
28. % Living (related) donors in pediatric kidney Tx
Cochat Comprehensive Pediatric Nephrology 2008
100
80
60
40
20
Sw USA
itz
er
la n
d
Tu
rk
ey
S
Sc erb
ia
an
di
na
via
lan
ds
he
r
UK
Ne
t
ae
l
Isr
Sp
ain
Po
lan
d
Fr
an
c
Ge e
rm
an
y
Cr
oa
t ia
Cz
e
ch
Re
p
0
29. In Europe, the rate of living donation for children is
A.
B.
C.
D.
E.
15%
20%
25%
30%
40%
30. In the post-operative period after cadaver Tx,
A.
B.
C.
D.
E.
The use of 20% mannitol is recommended
The use of dopamine at ‘renal’ dose enhances diuresis
Urinary bladder catheter can be removed after 3 days
IV wide-spectrum antibiotics should be given for 1 week
A 2-week strict isolation period is mandatory
31. Hospices Civils de Lyon & Université Claude-Bernard Lyon 1
ERA-EDTA ERBP in press
32. In the post-operative period after cadaver Tx,
A.
B.
C.
D.
E.
The use of 20% mannitol is recommended
The use of dopamine at ‘renal’ dose enhances diuresis
Urinary bladder catheter can be removed after 3 days
Antibiotic prophylaxis should be given for 1 week
A 2-week strict isolation period is mandatory
33. The current rate of acute rejection in kidney Tx is:
A.
B.
C.
D.
E.
3%
13%
23%
33%
43%
34. Hospices Civils de Lyon & Université Claude-Bernard Lyon 1
N
Transplants with
TheatissueRejection
of ARE
Least 1
N
%
N
%
11519
All Transplants
%
100.0
5846
100.0
5673
100.0
5256
45.6
2388
40.9
EXHIBIT 4.1A
FREQUENCY OF ACUTE REJECTIONS
6263
54.4
3458
59.2
1987-2010
NAPRTCS 2010
2868
50.6
Transplantation
Number of Acute Rejections
0
1
2
3
>4
Transplants with
All Transplants
at Least 1 Rejection
Transplants withEra
by Transplant
at Least 1 Rejection
1987-1990
Number of Acute Rejections
1991-1994
0
1995-1998
1
1999-2002
2
2003-2006
3
2007-2010
>4
2805
49.4
2715
23.6
1289
22.1
1426
25.1
1253
10.9
597
10.2
656
11.6
Total
653
*
5.7
263
4.5
Living Donor
390
6.9
Deceased Donor
635
N
5.5
%
239
N
4.1
%
396
N
7.0
%
11519
100.0
5846
100.0
5673
100.0
5256
1509/2127
45.6
70.9
2388
593/908
40.9
65.3
2868
916/1219
50.6
75.1
1463/2413
6263
1126/2473
2715
653/2046
1253
394/1621
653
111/839
635
60.6
54.4
45.5
23.6
31.9
10.9
24.3
5.7
13.2
5.5
668/1198
3458
571/1362
1289
359/1239
597
163/808
263
34/331
239
55.8
59.2
41.9
22.1
29.0
10.2
20.2
4.5
10.3
4.1
795/1215
2805
555/1111
1426
294/807
656
231/813
390
77/508
396
65.4
49.4
50.0
25.1
36.4
11.6
28.4
6.9
15.2
7.0
Transplants with
at Least 1 Rejection
Total with known Era source (84 additional transplants have unknown donor source).
by Transplant donor
*
1987-1990
1509/2127
70.9
593/908
65.3
916/1219
75.1
1991-1994
NAPRTCS 2010
1463/2413
60.6
668/1198
55.8
795/1215
65.4
1995-1998
1126/2473
45.5
571/1362
41.9
555/1111
50.0
35. The current rate of acute rejection in kidney Tx is:
A.
B.
C.
D.
E.
3%
13%
23%
33%
43%
36. In children, the main cause of graft failure is:
A.
B.
C.
D.
E.
Vascular thrombosis
Recurrence of the primary disease
Acute rejection
Chronic rejection
PTLD
38. In children, the main cause of graft failure is:
A.
B.
C.
D.
E.
Vascular thrombosis
Recurrence of the primary disease
Acute rejection
Chronic rejection (high rate of non-adherence)
PTLD
39. In children, the risk of metabolic syndrome at 1 yr
post-Tx is:
A.
B.
C.
D.
E.
5 to 10%
15 to 20%
25 to 30%
35 to 40%
45 to 50%
40. Hospices Civils de Lyon & Université Claude-Bernard Lyon 1
Metabolic syndrome in children after renal Tx
Reversal of metabolic abnormalities depends on post-Tx GFR
But immunosuppressive drugs cause metabolic abnormalities
Atherosclerotic dyslipidemia
Insulin resistance
Risk of new-onset diabetes after Tx
Prevalence in children 1 year post-Tx: 35 to 40% (mostly de novo)
Major role of glucocorticoids
Falls to 5% in the absence of steroids
Greater risk of
Lower graft survival
Lower GFR
Left ventricular hypertrophy
Litwin Pediatr Nephrol 2013
41. In children, the risk of metabolic syndrome at 1 yr
post-Tx is:
A.
B.
C.
D.
E.
5 to 10%
15 to 20%
25 to 30%
35 to 40% with steroid-based immunsuppression
45 to 50%
42. In children, the risk of metabolic syndrome at 1 yr
post-Tx is:
A.
B.
C.
D.
E.
5 to 10% without corticosteroids
15 to 20%
25 to 30%
35 to 40%
45 to 50%
43. Antibody-mediated rejection
A.
B.
C.
D.
E.
Is associated with serum donor-specific antibodies
Can be treated by high-dose methylprednisolone
Involves complement activation and endothelial injury
Is characterized by peritubular capillary C4d staining
Has better outcomes than cellular acute rejection
44. Humoral [antibody-mediated] rejection
Diagnosis
Circulating anti-HLA Ab
Protocol biopsy (C4d)
Graft dysfunction
Post Tx anti-HLA antibodies
DSA, donor specific antibodies
Blood transfusion
Pregnancy
Retransplantation
DR matching
46. Hospices Civils de Lyon & Université Claude-Bernard Lyon 1
Impact of donor-specific anti-HLA antibodies
FO
CUS O RENAL TRANSPLANTATIO
N
N
2005 Banff clasCAN as an entity
se definition of
ocesses that lead
hy.25
Complement activation
FO US O RENAL TRANSPLANTATIO
C
N
N
for this point of view grew and in the 2005 Banff clas-
Circulating sification of renal allograft pathology, CAN as an entity
Antibody-targeting
DSAs
therapies and
was eliminated in favor of a more precise definition of
the cellular and/or humoral rejection processes thathigh-dose IVIG
lead
Circulating
DSAs
to interstitial fibrosis and tubular atrophy.25
or ABMR
Complement activation
Acceleration
of arteriosclerosis
Antibody-targeting
therapies and
high-dose IVIG
Current therapeutic approaches for ABMR
Acceleration
of arteriosclerosis
MR are aimed at
Endothelial injur y
Current therapeutic approaches for ABMR are aimed at
Endothelial injur y
antibody reduction and the inhibition of complement
of complement
activation and injury. The available therapies include
erapies include
plasma exchange with low-dose IVIG, high-dose IVIG
and rituximab for antibody reduction, and high-dose
high-dose IVIG
IVIG for complement inhibition.
The activity of
2
and high-dose
high-dose IVIG includes the inhibition of C3 convertase and the ability to absorb complement activation
Figure 4 | DSA-mediated acceleration of arteriosclerosis. The presence of DSAs is
The activity of
fragments (such as C3a, C5a and C4b). Other, more
associated with acceleration of arteriosclerosis after transplantation. This
n of C3 converspecific, inhibitors of complement (such as eculizumab,
phenomenon is observed in patients with either preformed/ persisting or de novo
DSAs. The use of prophylactic anti-CD20 antibodies combined with high-dose IVIG
an anti-C5 antibody) and inhibitors of C1 are likely to
ment activation
is associated presence of DSAs is
Figure 4 | DSA-mediated acceleration of arteriosclerosis. Thewith lower grade arteriosclerosis 1 year after transplantation.
show benefit in the prevention and treatment of ABMR.
33
Abbreviations: DSAs, donor-specific
Human acceleration of kidney transplantation are
trials of these drugs in arteriosclerosis after transplantation. This anti-HLA antibodies; IVIG, intravenous
). Other, more
associated with
immunoglobulin.
now underway.
h as eculizumab,
phenomenonAis observedABO-incompatible transplantation
in patients with either preformed/ persisting or de novo
study of human
published in 2012 showed anti-CD20 antibodies combined
DSAs. The2012;of prophylactic that patients who received Conclusions with high-dose IVIG
use Everly Transplantation 2013
Loupy Nat
C1 are likely to Rev Nephrol
12
32,34
33
75
76–78
75
B-cell depletion with rituximab as an induction agent
The increasing recognition of the frequency and diversity
is associated with lower grade arteriosclerosis 1 year after transplantation.
47. Antibody-mediated rejection
A.
B.
C.
D.
E.
Is associated with serum donor-specific antibodies
Can be treated by high-dose methylprednisolone
Involves complement activation and endothelial injury
Is characterized by peritubular capillary C4d staining
Has better outcomes than cellular acute rejection
48. In children, these diseases have a 80 to 100% risk
of recurrence in the renal graft
A.
B.
C.
D.
E.
Focal segmental glomerulosclerosis
Atypical HUS with factor H mutation
Primary hyperoxaluria type 1
Lupus nephritis
MPGN type 2
49. Recurrent renal diseases: an overview
Recurrence of the full primary renal disease
High risk of graft loss
Low risk of graft loss
Late risk of graft loss
Primary hyperoxaluria type 1
IgA nephropathy
Type 1 diabetes
Steroid resistant NS / FSGS
Lupus nephritis
Sickle cell disease
Atypical HUS
ANCA-associated GN
Membranoproliferative GN
Membranous nephropathy
Recurrence of specific features
Alloimmunization
Urinary tract malformations
Nephrin, Podocin
Alport syndrome
Posterior urethral valves
Different from recurrence
De novo renal diseases
Specific deposits
Membranous GN, TMA
Cystinosis, Fabry
50. Recurrence rate after the 1st renal Tx
Primary disease
Recurrence rate (%)
Graft loss to recurrence (%)
14-50 (average 30)
40-60
Atypical HUS
17 (MCP) – 90 (CFH-CFI)
10 (MCP) – 85 (CFH-CFI)
Typical HUS
0-1
0-1
MPGN type 1
30-77
17-50
MPGN type 2
66-100
25-61
Lupus nephritis
0-30
0-5
IgAN (Berger disease)
32-60
3-7
Henoch Shönlein nephritis
31-100
8-10
Primary hyperoxaluria type 1
90-100
80-100
SRNS/FSGS
Cochat Current Pediatr Rep 2013
51. Hospices Civils de Lyon & Université Claude-Bernard Lyon 1
Graft survival according to primary disease
van Stralen Nephrol Dial Transplant 2013
54. One third are genetic Another third will recur post-Tx
55. Treatment options for recurrent FSGS
High-dose iv CsA
Plasmapheresis/immunoadsorption
With or without iv CsA
With or without cyclophosphamide instead of MMF/Aza
Rituximab?
59. Eculizumab blocks terminal complement pathway
Ag-Ab complexes
Constitutive
Microorganisms
Lectin
Classical
Alternative
Terminal
Proximal
Microorganisms
C3
C5a
Eculizumab binds with high affinity to
C5
C3a
C3b
C5
Eculizumab
Terminal complement activity is
blocked
Proximal functions of complement
remain intact
C5b
C5b-9
Weak anaphylatoxin
Immune complex and apoptotic
body clearance
Microbial opsonization
Figueroa Clin Microbiol Rev 1991 - Walport N Engl J Med 2001
60. In children, these diseases have a 80 to 100% risk
of recurrence in the renal graft
A.
B.
C.
D.
E.
Focal segmental glomerulosclerosis
Atypical HUS with factor H mutation
Primary hyperoxaluria type 1
Lupus nephritis
MPGN type 2
61. In pediatric kidney Tx, the risk of malignancy is:
A.
B.
C.
D.
E.
Quite null
1 to 3% at 3 yrs
4 to 5% at 3 yrs
5 to 7% at 3 yrs
7 to 9% at 3 yrs
62. Hospices Civils de Lyon & Université Claude-Bernard Lyon 1
The issue of malignancies
NAPRTCS 2010
Transplantation
POST TRANSPLANT MALIGNANCY RATE
By Transplant Era
1 Year
3 Year
%
SE
%
SE
1987 – 1990
0.68
0.20
1.05
0.25
1991 – 1994
1.03
0.22
1.41
0.26
1995 – 1998
1.73
0.28
2.88
0.37
1999 – 2002
1.85
0.32
2.96
0.43
2003 - 2010
0.74
0.20
1.13
0.28
While substantial temporal improvements have been observed in graft failure, rejection and
other endpoints, similar trends for malignancy rates were not observed, although the most
recent cohort suggests that there has been some improvement.
NAPRTCS 2010
63. In pediatric kidney Tx, the risk of malignancy is:
A.
B.
C.
D.
E.
Quite null
1 to 3% at 3 yrs
4 to 5% at 3 yrs
5 to 7% at 3 yrs
7 to 9% at 3 yrs
64. In children with a functioning renal graft, growth
A.
B.
C.
D.
E.
Returns to normal velocity
Is retarded in 10 to 20% of patients
Depends on steroid exposure
Depends on GFR
Can be improved by the use of rhGH
67. In children with a functioning renal graft, growth
A.
B.
C.
D.
E.
Returns to normal velocity
Is retarded in 10 to 20% of patients
Depends on steroid exposure
Depends on GFR
Can be improved by the use of rhGH, if licenced