Anti-GBM disease is a rare form of rapidly progressive glomerulonephritis caused by antibodies against the glomerular basement membrane. It presents with lung hemorrhage, renal failure, and linear IgG deposits along the glomerular basement membrane on biopsy. The disease is treated with plasma exchange and immunosuppression to remove antibodies, with the goal of preventing permanent kidney damage and failure. Prognosis depends on early diagnosis and treatment, with the most important factor being the level of anti-GBM antibodies at time of treatment.
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Update on Patterns of Study in ANCA Associated Vasculitis presented at regional Northern Ireland Nephrology Meeting with Dr David Jayne as guest speaker..
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Goodpasture syndrome (GPS) also known as Goodpasture’s disease is a rare autoimmune disease in which antibodies attack the basement membrane in lungs and kidneys, leading to bleeding from the lungs and to kidney failure
Some forms of the disease involve just the lung or the kidney, most times, both.
Men are eight times more likely to be affected than women. The disease most commonly occurs in early adulthood.
Update on Patterns of Study in ANCA Associated Vasculitis presented at regional Northern Ireland Nephrology Meeting with Dr David Jayne as guest speaker..
- English version of this lecture is available at:
https://youtu.be/XRD-QqGFP18
- Arabic version of this lecture is available at:
https://youtu.be/c9PoavAtNKM
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Goodpasture syndrome (GPS) also known as Goodpasture’s disease is a rare autoimmune disease in which antibodies attack the basement membrane in lungs and kidneys, leading to bleeding from the lungs and to kidney failure
Some forms of the disease involve just the lung or the kidney, most times, both.
Men are eight times more likely to be affected than women. The disease most commonly occurs in early adulthood.
On March 23, 2016, Prof. Henning Müller (HES-SO Valais-Wallis and Martinos Center) presented Medical image analysis and big data evaluation infrastructures at Stanford medicine.
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ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
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The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
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.
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
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
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- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
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
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
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TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
3. Epidemiology
Acute GN due to anti-GBM antibody disease is
rare, estimated in <1 per million
<20% of RPGN cases
Bimodal distribution young males (3rd decade)
and older females (6th decade) most typical
Disease limited to the kidney more common in
older patients
Less common in blacks, likely due to HLA antigen
differences
4. Nomenclature
Goodpasture’s Syndrome
• Used to describe clinical findings of GN and
pulmonary hemorrhage
Goodpasture’s Disease
• Triad of proliferative GN (usually crescentic),
pulmonary hemorrhage, anti-GBM antibodies
Anti-GBM Disease
• Anti-GBM antibodies + GN
5. Chelsea Naval Hospital
Circa 1918
Dr. Ernest Goodpasture
1955
Vanderbilt Laboratory
1919—looking at pathologic
features of influenza in the lung
patient with systemic disease
and pulmonary + renal involvement
6. A lesson in history…
1919: Goodpasture described the case of an 18-yo man
who died with lung hemorrhage and acute GN
1958: Clinical picture of pulmonary renal syndrome
described by Stanton and Tage and named after Dr.
Goodpasture
Anti-GBM antibodies discovered in 1967
• Lerner, et al. conducted famous studies with antibodies eluted
from the serum of Goodpasture’s patients transferred to
monkeys who developed proliferative GN
7. Table 1 Differential Diagnosis in Patients Presenting Clinically
with Pulmonary-Renal Syndrome
- NECROTIZING SMALL-VESSEL VASCULITIS
* PR3- and MPO-ANCA associated (MPA, WG, CSS)
* Anti-GBM disease
* Other vasculitides (Henoch-Schönlein purpura, SLE, cryoglobulinemia, drug
induced)
- CATASTROPHIC ANTI-PHOSPHOLIPID SYNDROME
- RENAL FAILURE WITH VOLUME OVERLOAD / CARDIAC FAILURE
* Chronic/acute glomerulonephritis, diabetes
* Atherosclerosis/hypertensive nephrosclerosis
* Microangiopathic renal failure/hemolytic uremic syndrome
- RENAL FAILURE ASSOCIATED WITH PULMONARY INFECTION
* Legionella, mycoplasma, streptococcus
* Hemorrhagic fever with renal syndrome (eg, Hantavirus)
- ENDOCARDITIS
- SIRS/SEPSIS WITH MULTIORGAN FAILURE
- CARDIOVASCULAR (eg, renal artery stenosis) Sanders, et al. 2011
8. Pathogenesis
Antibodies directed against an antigen
intrinsic to the GBM
• Antibodies may precede clinical signs by
weeks or months
• Typically IgG1 or IgG3 antibodies
• Principal target is the NC1 domain of
the alpha-3 chain of type IV collagen
9. Varied Presentations of Anti-GBM
Disease
In anti-GBM disease the pulmonary hemorrhage
may precede, occur concurrently with, or follow the
glomerular involvement
Some patients with anti-GBM antibodies and GN
and hence “anti-GBM” disease never experience
pulmonary involvement and thus do not have true
“Goodpasture’s syndrome.” (perhaps 60%)
Typical presentation is relatively acute renal failure
with urinalysis showing proteinuria and a nephritic
sediment
• Typically not nephrotic range proteinuria
• Dysmorphic RBCs, WBCs, red cell and granular casts
10. Clinical Presentation
Systemic complaints typically absent
• Malaise, weight loss, fever, arthralgia
• May suggest concurrent vasculitis
Relatively mild degree of renal involvement
may be more common than previously
thought
• Retrospective analysis in Australia found 36%
(5/14) had previous findings of hematuria and/or
proteinuria with normal creatinine
11. Antibodies bind tightly and
rapidly to the GBM, which
has been demonstrated in
passive transfer experiments
in which antibody obtained
from the plasma of patients
with the disorder are infused
into animals.
Titers of antibodies directed against
the N-terminus of the NC1 domain
correlate directly with renal survival.
Hellmark, et al. Kidney International, 1999.
12. Subendothelial deposits of circulating immune complexes most
common, with subepithelial deposits rarely seen.
13. Anti-GBM autoantibodies react with epitopes on the
noncollagenous domain of the α-3 and -5 chains of type IV
collagen.
The antigenic epitope has been localized between amino
acids 198 and 237 of the terminal region of the α-3 chain.
The α-3 chain of type IV collagen is found predominantly in
the GBM and alveolar capillary basement membranes,
which correlates with the limited distribution of disease
involvement in Goodpasture’s syndrome
Cryptic epitope??
14. Pathogenesis: Antigen Structure
The alpha-3 chain forms a triple helix with
alpha 4/5 chains, combining with another
triple helix to form a hexamer
The antibodies DO NOT BIND the intact
hexamer, binding only when it dissociates
In vivo studies indicate that the alpha 3
epitopes are sequestered under normal
circumstances (hidden) and become
exposed due to some disruption of the
GBM
15. Pathogenesis: Autoreactive T Cells
T cell infiltrates typically found on biopsy
T cell proliferative response found with
exposure to α-3 IV NC1 domain (serum from
patients with anti-GBM)
Regulatory T cells (CD4/25+) that counter
the effects of autoreactive cells reduce the
severity of lesions in murine anti-GBM GN
Correlation found between number of
autoreactive T cells and disease activity
16. Role of epidermal
growth factor?
constitutively expressed
in the kidney, activation
linked with RPGN
In RPGN there is an accumulation of CD4 T cells and macrophages in the tuft, proliferation of endogenous
glomerular cells, development of cellularcrescents that result from capillary damage and leakage of plasma
proteins into Bowman’s space. Crescents consist of fibrous material and proliferating
cells arising from the parietal epithelium and podocytes as well as infilatrating macrophages and fibroblasts.
17. Antigenic Triggers
Smoking
Exposure to hydrocarbons
Lithotripsy
Pulmonary Infections
Secondary GN process
Degradation by reactive oxygen species
Damage to the GBM revealing the epitope?
Damage to alveolar capillaries allowing
circulating antibody to interact?
18. Genetic Susceptibility
Patients with HLA-DR15 and DR4
appear to be at increased risk
• Association with DR15 confirmed in Chinese
and Japanese studies
• Molecular analysis has revealed a particular 6
amino acid motif common to both that may
confer susceptibility
DR1 and DR7 appear to be at lesser
risk
19. Diagnosis
Pulmonary hemorrhage can be seen
with other acute nephritides
• SLE, ANCA+ vasculitis, patients with
pulmonary edema
Diagnosis requires demonstration of
anti-GBM antibodies in serum or kidney
Renal biopsy should be done unless
there is a contraindication
20. Renal Biopsy
Light microscopy typically shows crescentic
glomerulonephritis
Immunofluorescence demonstrates
pathognomonic findings of linear IgG
deposition along the capillaries and
occasionally distal tubules (occasionally IgA or
IgM)
Linear IgG staining can be seen in 2 other
disorders:
• Diabetic Nephropathy
• Fibrillary Glomerulonephritis
**staining typically not as strong as with anti-GBM
22. FIGURE 32-21 Anti–glomerular basement membrane disease
(Goodpasture’s syndrome). There is diffuse crescentic
glomerulonephritis with large circumferential cellular crescents and
severe compression of the glomerular tuft (periodic acid–Schiff, ×80).
Brenner and Rector’s The Kidney
23. FIGURE 32-22 Anti–glomerular basement membrane disease
(Goodpasture’s syndrome). Immunofluorescence photomicrograph
showing linear glomerular basement membrane deposits of
immunoglobulin G. Some of the glomerular basement membranes are
discontinuous, indicating sites of rupture (×800).
Brenner and Rector’s The Kidney
24. Serologic Testing
Indirect Immunofluorescence
• Requires an experienced renal pathologist
• Fluorescein-labeled anti-human IgG added to
incubation of the patient’s serum with normal renal
tissue
ELISA serum assay for anti-GBM antibodies
• Specificity can be confirmed by Western blot
• Sensitivity varies by kit (63% to almost 100%)
• False negatives in Alport syndrome patients
25. Antineutrophil Cytoplasm
Antibodies
Should be tested in any patient with acute GN with
or without pulmonary findings
• 10-38% of patients with anti-GBM also ANCA+ (usually
MPO)
Low levels of ANCA may be detectable years before
production of anti-GBM antibody and onset of
symptoms
Clinically relevant because patients with ANCA may
have more treatable disease than anti-GBM + only
• Tailor long-term management to vasculitis treatment
• These patients may have relapses of systemic vasculitis
26. Retrospective military analysis of 30 patients who
ultimately developed anti-GBM disease:
Looked back 30 years at stored serum samples obtained at the time
of enlistment and every other year after
Patients diagnosed with anti-GBM and healthy controls were identified
from the military database
Compared with matched controls, a greater number of patients with
anti-GBM disease had PR3-ANCA and MPO-ANCA levels detected in
multiple serum samples obtained in the years prior to clinical disease
82% versus 14% control for PR3-ANCA
72% versus 27% control for MPO-ANCA
In all cases, ANCA were detected in earlier samples than anti-GBM
antibodies that were detected months prior to onset of symptoms (but
not years).
Mechanism of ANCA in disease pathogenesis not clear.
Olson, et al. J Am Soc Nephrol, 2011.
27. Treatment
Plasmapheresis + Prednisone
+ Cyclophosphamide
• Plasmapheresis removes
circulating anti-GBM
antibodies and complement
• Immunosuppression
minimizes new antibody
formation
40-45% will benefit by not
progressing to ESRD or death
when treated with this
combination
• Recovery more likely in non-
oliguric patients
• Patients on dialysis or with
100% crescents on renal
biopsy unlikely to respond to
treatment
28. To pherese or not to pherese?
1 randomized trial evaluated outcomes among 17 patients
prednisone and cyclophosphamide alone or with plasmapheresis
• 2/8 patients with plasmapheresis progressed to ESRD compared
with 6/9 in the immunosuppression group
• % crescents on initial renal biopsy and entry plasma creatinine
correlated better with outcomes
• Patients with creatinine <3 and <30% crescents did well
• Creatinine >4 and severe crescentic involvement did not
Typically recommended based on 2 factors:
• improved morbidity and mortality in the era of plasmapheresis
when compared to historic rates
• The “common sense” argument of greater reduction of disease
consequences with rapid removal of anti-GBM antibody
Johnson, et al. Medicine, 1985.
29. Plasmapheresis
Typically daily or alternate day 4-liter exchanges for 2-3 weeks
Albumin given as replacement fluid
1-2 units of FFP at the end of the procedure should be
substituted for albumin if recent hemorrhage or biopsy to
reverse depletion of coagulation factors by pheresis
Monitor for metabolic alkalosis with FFP administration
Recheck antibody titers after regimen, may need to continue
for another 2-3 weeks
30. Immunosuppressants
Methylprednisolone 15-30 mg/kg to
a max of 1000 mg IV for 3 doses
• Followed by daily oral prednisone (max
60-80 mg per day)
Oral cyclophosphamide 2 mg/kg per
day initial dosing
• Not to exceed 100 mg/day in those
patients > 60 years due to toxicity
31. Treatment Duration
Optimal timing unknown, may take 6-9 months
for cessation of antibody formation
Maintenance therapy with prednsione and
azathioprine typically given after remission
induced
• Some use 3 months of prednisone and
cyclophosphamide therapy if titers negative
• Anti-GBM antibody levels should be monitored every 1-2
weeks
Patients presenting with dialysis-dependant renal
failure must weigh risks of treatment
32. Treatment: Patient Selection
Retrospective review of 71
Plasma Patient Renal
patients treated with the Creatinine Survival Survival
typical triad @ 1 year @ 1 year
Among 42 patients with
<5.7mg/dL
100% 95%
pulmonary hemorrhage,
bleeding resolved in 90%
>5.7mg/dL
No urgent
83% 82%
Dialysis
All patients with crescents Requiring
urgent 65% 8%
in all glomeruli on biopsy
dialysis
required long-term dialysis
Levy, et al. Ann Intern Med, 2001
33. Treatment: Patient Selection
Recommendations are to treat with pheresis +
immunosuppression in the following situations:
• Pulmonary hemorrhage, regardless of renal involvement
• Patients with renal involvement NOT requiring
immediate RRT
• Most patients with less severe disease (30-50%
crescents) although they may do well with
methylprednisolone followed by oral prednisone
**Some consider a short trial of combination therapy in
patients with very acute disease, younger patients,
patients with ANCA+ and clinical signs of vasculitis
(purpura, arthralgias) as they may recover function.
Levy, et al. Ann Intern Med, 2001
34. Complications of Therapy
Infection
• May be exacerbated by plasmapheresis and require IVIG
infusion
• High dose steroids multiple adverse effects
Cyclophosphamide-related
• Increased risk of PJP
• Amenorrhea
• Bladder toxicity (cystitis, bladder CA)
35. Novel Therapy
Suppression of T Cell involvement via blockade of
CD28-B7 (co-stimlatory pathyway for T cell
activation)
• Fusion protein CTLA41g evaluated in rat model of anti-
GBM
• Development of crescentic GN completely prevented
• No human studies done yet
36. Prognosis
In general, patients who survive the first year with
intact renal function do well
Survival (patient and renal) closely correlates with
degree of renal impairment at diagnosis
Few requiring immediate dialysis recover renal
function
Relapses uncommon 2% in a single center study,
clinically more common with ANCA+ patients
Higher rate of recurrence in smokers
37. Post-Transplantation Disease
Occurs in 5-10% of renal transplants in patients with
underlying hereditary nephritis (Alport Syndrome)
Commonly have abnormality in the alpha-5 type IV
collagen chain
• May also have alpha-3 or alpha-4 mutation
• Defective organization of alpha 3,4,5 chains in the GBM
leads to altered Goodpasture antigen in the alpha 3 chain
• Altered antigen not recognized by the GBM antibody
• Donor kidney has normal antigen, which elicits an immune
response against the “new” antigen in the transplanted
kidney
• Alloantibody produced recognizes a different epitope than
the autoantibody in Goodpasture’s disease
38. References:
Levy JB, Turner AN, Rees AJ, et al. Long term outcome of
anti-glomerular basement membrane antibody disease
treated with plasma exchange and immunosuppressants.
Ann Intern Med. 2001;134(11):1033.
Taal: Brenner and Rector’s The Kidney, 9th Ed. Chapter 32:
Secondary Glomerular Diseases. 2012:1224-1226
www.unckidneycenter.org
www.uptodate.com
*Pathogenesis and diagnosis of anti-GBM antibody
(Goodpasture’s) disease
*Treatment of anti-GBM antibody (Goodpasture’s) disease