This document provides information on membranoproliferative glomerulonephritis (MPGN), including its classification, pathogenesis, clinical presentation, pathology, and treatment. MPGN is classified based on immunofluorescence and electron microscopy findings. It can be immune-mediated via immune complex deposition or complement-mediated via dysregulation of the alternative complement pathway. On pathology, it is characterized by thickened glomerular basement membranes, mesangial hypercellularity, and endocapillary proliferation. Clinical presentation varies from asymptomatic to nephrotic syndrome or renal failure.
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lupus nephritis is a autoimmune disease, commonly seen in adult and child and the medical or nursing care is also very important for this type of disease condition.
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download link : https://www.dropbox.com/s/xc0fpdul47g1gu8/IgA%20Nephropathy.ppt?m
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lupus nephritis is a autoimmune disease, commonly seen in adult and child and the medical or nursing care is also very important for this type of disease condition.
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Rapidly progressive glomerulonephritis in childrenNishatTasnim46
Rapidly progressive or crescentic glomerulonephritis is a medical emergency and diagnostic challenge in paediatric population. There is a significant risk of development of complications such as CKD in the long term. This seminar was prepared to increase knowledge about early diagnosis and management of this condition in a tertiary level hospital.
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.
Factory Supply Best Quality Pmk Oil CAS 28578–16–7 PMK Powder in Stockrebeccabio
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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
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
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
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
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
These lecture slides, by Dr Sidra Arshad, offer a quick overview of 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 leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
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. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
- 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
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
2. MPGN
§ Pattern of glomerular injury on renal biopsy
§ Thickening of GBM
§ Mesangial hypercellularity
§ Endocapillary proliferation
§ Double-contour along glomerular capillary walls
§ Lobulation glomerulonephritis
3. MPGN : Epidemiology
§ 2–10% of all cases of GN confirmed by renal
biopsy.
§ Common age group 8-16 yr
§ 5th leading cause of ESRD among primary
glomerular diseases
§ ‘idiopathic’ MPGN is more commonly seen in
pediatric age than older adults.
Nat. Rev. Nephrol. 11, 14–22 (2015)
19. Mixed cryoglobulinemia
§ Acute nephritic syndrome
§ Hematuria
§ Nephritic range proteinuria
§ Renal insufficiency (50%)
§ Hypertension (80%)
§ Low C3, C4, and C1q with reductions
in C4 > C3 level
•Polyclonal IgG and monoclonal IgM kappa
rheumatoid factor directed against the Fc
portion of IgG
•❖ Circulating anti-HCV antibodies
•❖ Polyclonal IgG anti-HCV antibodies
•within the cryoprecipitate
•❖ HCV RNA in the plasma and the
cryoprecipitate
20. Cryoglobulinemic MPGN
§ Amorphous eosinophilic
PAS- positive
intraluminal thrombi
(cryoglobulins)
§ Thickening of the GBM
with double-contoured
GBMs
§ Cellular proliferation,
including massive
exudation of monocytes
21. Immunofluorescence microscopy
§ Both IgM as well as IgG with C3 and frequently C1q in the
distribution of subendothelial and mesangial deposits and the
intracapillary “thrombi
24. Clinical presentation
§ Most commonly presents in childhood but can occur
at any age.
§ Clinical presentation and course are extremely
variable :
§ From benign and slowly to rapidly progressive.
§ Asymptomatic hematuria and proteinuria,AGN,
nephrotic syndrome, CKD or RPGN.
§ Varied clinical presentation is caused by
§ Different pathogenesis
§ Timing of biopsy relative to clinical course.
N Engl J Med 2012;366:1119-31.
25. Clinical presentation
§ In early disease, kidney biopsy shows :
§ Proliferative lesion : nephritic phenotype
§ Crescentic lesion : RPGN
§ In advanced disease, kidney biopsy shows :
§ Both repair and sclerosis : nephrotic phenotype
§ Classic MPGN : both nephritonephrotic phenotype.
N Engl J Med 2012;366:1119-31.
26. Pathogenesis
§ Two primary mechanisms have been described :
§ Immune complex deposition (immune complex-
mediated)
§ Activation of complement via classical pathway
§ Typically : mildly decreased serum C3 and low C4
§ Dysregulation and persistent activation of alternative
pathway (complement-mediated)
§ usually low C3 and normal C4 levels (80% of cases )
§ normal serum C3 is not excluded complement-
mediated MPGN
N Engl J Med 2012;366:1119-31.
28. N Engl J Med 2012;366:1119-31.
Pathogenesis : immune mediated MPGN
29. Pathology
§ Key characteristic histologic changes:
§ Thickened GBM :
§ deposition of IC and/or complement factors
§ interposition of mesangial cell and other cellular
between GBM and the endothelial cell à new
basement membrane formation.
§ Increased mesangial and endocapillary cellularity à
often leading to lobular appearance of glomerular
tuft.
Fundamental of Renal Pathology, Section II, Chapter 2, Page 31,32
31. MPGN type 1 : LM pathology
§ Mesagial proliferation
§ Increased mesangial matrix
§ Endocapillary proliferation
§ Diffuse global capillary wall thickening
§ Mesangial interposition
§ Doubing or replication of GBM
“Lobular glomerulonephritis”
32. MPGN type 1 : LM pathology
§ Mesangial interposition
§ Doubing or replication of GBM
33. MPGN type 1 : IF pathology
§ Segmental, coarsely
granular-to-globular
or elongated
capillary wall IgG
deposits
§ Less granular and
less symmetrical than
MN
34. MPGN type 1 : EM findings
Mesangial interposition
Subendothelial electrondense deposits
Tram track sign
36. § Very small number of children and
young adults
§ Clinical similar MPGN type I
§ low C3 levels and absence of C3
nephritic factor
§ EM: subendothelial and subepithelial
EDD
Brenner&Rector’s: The Kidney 10th Edition
MPGN type III
(Burkholder, And Strife And Anders Variants)
37. Some Key Pathology to differentiate
Primary VS Secondary MPGN
§ IF :
§ HCV
§ IgM, IgG, C3, kappa and lambda
§ IgG may not be present
§ C1q is typically negative
§ Monoclonal gammopathy
§ monotypic kappa or lambda light-chain
§ Autoimmune diseases : "full house" pattern
38. § Tubuloreticular structures in endothelial cells lupus
nephritis
§ Fingerprint pattern associated with cryoprecipitates
is seen in mixed cryoglobulinemia
Some Key Pathology to differentiate
Primary VS Secondary MPGN
40. Novel Classificationof MPGN
IMMUNOFLUORESCENCE FINDING
IgG + C3
± IgM , C1q
C3 alone or dominant
Immune mediated MPGN
Complement mediated MPGN
(C3 Glomerulopathy)
ELECTROMICROSCOPE FINDING
Subendothel
ail +
Mesangail
deposit
Highly EDD
intramembranous
(Lamina densa) and
mesangial ± Bowman c,
MPGN type 1
Subendothelail and
Mesangail deposit
± Subepithelial or
Intramembranous
deposit
MPGN type 3 DDD
EDD subendothelial /
mesangial ±
subepithelium ,
Bowman c,TBM
C3 GN
Burkholder
Variant
Strife
Variant
W/U 2nd cause : Chr
infection , autoimmune ,
monoclonal gammopathy
Familial form C3 GN
Adapted from N Engl J Med 2012;366:1119-31
Kidney International (2016) 89, 278–288.
Nat. Rev. Nephrol. 11, 14–22 (2015)
LM compatible with MPGN pattern
No IgG, No C3
Chronic TMA
APS
Radiation nephritis
Paraproteinemia
(Fibrillary GN)
Transplant
glomerulopathy
PIGN
Collagen III
glomerlulopathy
C1Q nephropathy
C3 Nef
41. § less common than IC-mediated MPGN
§ results from dysregulation of alternative
complement pathway (AP) à persistent activation
§ C3 are usually low and C4 are normal
N Engl J Med 2012;366:1119-31.
Complement mediated MPGN
43. Pathogenesis
§ Important dysregulation of AP :
§ C3 nephritic factors (C3Nefs)
§ absence of circulating factor H
§ presence of a circulating inhibitor of factor H
§ mutation in gene encoding C3 : Lysine 224,
§ Polymorphism :Tyr 402His allele variant
(impaired factor H regulation of C3 convertase)
Brenner&Rector’s: The Kidney 9th Edition
45. Complement-mediated MPGN
§ In many patients, complement abnormalities does not
develop MPGN, suggests that
§ genetic risk factors are not enough to trigger the
disease
§ additional ‘hit(s)’ are required
§ Activate complement and overwhelm the
regulatory mechanism resulting in high levels of
complement factors then deposited in glomeruli.
Nephrol Dial Transplant (2012) 27: 4288–4294
46. Dense deposit disease
§ Clinical Features
§ 1/3 of patients : nephrotic syndrome
§ 1/4 of patients : nephritic syndrome
§ Mild HT
§ > 50% Renal dysfunction
§ more common in adults than in children
§ Onset is preceded by acute URI , with high ASO
titers in 20-40%.
§ 80 - 90% low C3 levels
§ Depressed C4 levels “uncommon”
§ Syndrome of acquired partial lipodystrophy
Brenner&Rector’s: The Kidney 10th Edition
47. Acquired partial lipodystrophy
- loss of fat from face, neck, upper limbs, trunk and anterior thighs.
- accumulation of excess fat in hips and other regions of lower limbs
48. Ocular drusen in DDD
§ Mild visual field
§ Color defects
§ Prolonged dark adaptation
§ mottled retinal pigmentation
(drusen bodies)
§ Indocyanine green
angiography dense deposits in
ciliary basement membrane
and choroidal
neovascularization
Brenner&Rector’s: The Kidney 10th Edition
49. Dense deposit disease
§ Prognosis is worse than type I
§ Clinical remissions <5%
§ Worse in adults than in children
§ 50% turn to ESRD in 10 years from the onset
Brenner&Rector’s: The Kidney 10th Edition
51. Light microscopy
§ Both DDD and C3GN
§ Typical MPGN patern
§ ⬆ mesangial matrix and cell
§ GBM thickening with double contour
§ Glomerular lobulation
§ Some cases infiltration of macrophages or
neutrophils. Similar to postinfectious GN
§ Crescent formation may be present
52. § In a series of 69 patients with DDD, the incidence
of di erent histologic patterns was
§ membranoproliferative (25%)
§ mesangioproliferative (45%)
§ crescentic (18%)
§ acute proliferative and exudative (12%)
Light microscopy
N Engl J Med 2012;366:1119-31.
53. DDD, LM finding
DDD, capillary walls appear rigid, thickened, and with a more intensely PAS,
also observed with trichrome (sometimes fuchsinophilic) (arrows).
In some cases there is slight cellularity increase and in others it can be mesangial
54. C3
§ Negative staining for Ig
§ Capillary wall staining is
linear or bilinear
§ bandlike staining for C3
§ ring-shaped mesangial
deposits that
correspond to dense
deposits in EM
C3DDD: Immunofluorescence
Fundamental of Renal Pathology, Section II, Chapter 2,
55. DDD: Electronmicroscope
§ DDD shows typical osmiophilic , highly densed
electron deposition in glomerular basement
membrane (Ribbon like)
§ EDD can be seen in Mesangium , Bowman capsule
and tubular basement membranes.
Fundamental of Renal Pathology, Section II, Chapter 2
56. Dense ribbon like appearance of subendothelial and inramembranous material
57. Dense Deposit disease : EDD of GBM and mesangial area
Sausage shaped, wavy or Ribbon-like
Deposits are seen in Bowman capsule and TBM
61. C3 Glomerulonephritis
§ 27% nephrotic syndrome
§ 65% microhematuria
§ 30% elevated blood pressure.
§ Rate of progression to ESRD in C3GN patients was
similar to that in patients with DDD.
Comprehensive Clinical Nephrology 5th Edition
62. C3 Glomerulonephritis
§ Has been reported in
§ association with monoclonal gammopathies
§ anti-factor H activity
§ Inherited disease :
§ mutations in CFHR5 gene (CFHR5
nephropathy)
Nat. Rev. Nephrol. 8, 634–642 (2012)
64. C3GN : IF
widespread staining of capillary walls and
focal granular mesangial staining.
C3
65. C3GN : EM
complex pattern of thickening of GBM with intramembranous electron-dense material.
Similar deposits are also seen in the mesangium
66. CFHR5 nephropathy
§ Familial form of C3GN, autosomal dominant
§ Described in Cypriot origin
§ Mutation in gene that encodes complement factor-H-
related protein 5 (CFHR5).
§ compete with factor H on surfaces such as the GBM
and
§ interfere factor H to inhibit alternative pathway
activation
Nat. Rev. Nephrol. 8, 634–642 (2012)
67. CFHR5 nephropathy
§ Clinical :
§ Hematuria (90%)
§ Proteinuria (38%)
§ often episodes of synpharyngitic haematuria
§ Men > Women to develop CKD (80 vs 21%) and
ESRD (78 vs 4 %)
Nat. Rev. Nephrol. 8, 634–642 (2012)
68. Novel Classificationof MPGN
IMMUNOFLUORESCENCE FINDING
IgG + C3
± IgM , C1q
C3 alone or dominant
Immune mediated MPGN
Complement mediated MPGN
(C3 Glomerulopathy)
ELECTROMICROSCOPE FINDING
Subendothel
ail +
Mesangail
deposit
Highly EDD
intramembranous
(Lamina densa) and
mesangial ± Bowman c,
MPGN type 1
Subendothelail and
Mesangail deposit
± Subepithelial or
Intramembranous
deposit
MPGN type 3 DDD
EDD subendothelial /
mesangial ±
subepithelium ,
Bowman c,TBM
C3 GN
Burkholder
Variant
Strife
Variant
W/U 2nd cause : Chr
infection , autoimmune ,
monoclonal gammopathy
Familial form C3 GN
Adapted from N Engl J Med 2012;366:1119-31
Kidney International (2016) 89, 278–288.
Nat. Rev. Nephrol. 11, 14–22 (2015)
LM compatible with MPGN pattern
No IgG, No C3
Chronic TMA
APS
Radiation nephritis
Paraproteinemia
(Fibrillary GN)
Transplant
glomerulopathy
PIGN
Collagen III
glomerlulopathy
C1Q nephropathy
C3 Nef
69. MPGN without immunoglobulin
or complement deposition
§ In TMA resulting from injury to endothelial cells.
§ In the acute phase : endothelial swelling, and
fibrin thrombi in the glomerular capillaries,
mesangiolysis
§ In reparative and chronic phase : remodeling of
glomerular capillary wall à double-contour
formation.
N Engl J Med 2012;366:1119-31.
70. TMA
Nat. Rev. Nephrol. 11, 14–22 (2015)
Early changes : endothelial swelling and lifting from basement membrane,
with relatively electronlucent flocculent material filling the space
Over time : new layers of basement membrane form beneath the endothelium giving rise to the hallmark double contours.
71. Treatment of Primary MPGN
§ Idiopathic MPGN is now an uncommon condition.
§ The few RCTs of treatment of idiopathic MPGN in
children and adults have given inconsistent and
largely inconclusive results .
§ Many of the reported trials have weak experimental
design or are underpowered, and the evidence base
underlying the recommendations for treatment of
§ “idiopathic” MPGN is very weak.
N Engl J Med 2012;366:1119-31.
72. Treatment
§ Evaluate for underlying diseases before considering
a specific treatment regimen (Not Graded).
§ For idiopathic MPGN :
§ If accompanied by nephrotic syndrome AND
progressive decline of kidney function receive
§ oral cyclophosphamide/MMF plus low-dose
alternate-day/daily corticosteroids with initial
therapy limited to less than 6 months. (2D)
74. Corticosteroid
§ No systematic evaluation of glucocorticoid therapy
for idiopathic MPGN in adults.
§ Retrospective studies showed no clear benefit.
75.
76.
77.
78. Cyclophosphamide
• RCT (n=59)
• Compare
•Combination
•Cyclophosphamide 1.5-2.0 mg/dl
•Coumadin keep PT 2-2.5 times
•Dipyridamole start 25 mg qid full dose 100 mg qid
•No specific therapy
83. Eculizumab
§ anti-C5 monoclonal antibody à inhibits C5
activation
§ MPGN due to a genetic mutation in complement-
regulating proteins may benefit that inhibit
formation of MAC.
§ elevated serum levels of MAC more likely to
response with eculizumab.
N Engl J Med 2012;366:1119-31.