Membranoproliferative Glomerulonephritis - PowerPoint PPT Presentation

Loading...

PPT – Membranoproliferative Glomerulonephritis PowerPoint presentation | free to download - id: 3ec6ea-MmFmM



Loading


The Adobe Flash plugin is needed to view this content

Get the plugin now

View by Category
About This Presentation
Title:

Membranoproliferative Glomerulonephritis

Description:

Membranoproliferative Glomerulonephritis AM report Jan 23, 2005 So Yoon Jang MPGN Derived from the characteristic histologic changes by linght microscopy ... – PowerPoint PPT presentation

Number of Views:1605
Avg rating:1.0/5.0
Slides: 30
Provided by: kyu9
Learn more at: http://www.med.unc.edu
Category:

less

Write a Comment
User Comments (0)
Transcript and Presenter's Notes

Title: Membranoproliferative Glomerulonephritis


1
Membranoproliferative Glomerulonephritis
  • AM report
  • Jan 23, 2005
  • So Yoon Jang

2
MPGN
  • Derived from the characteristic histologic
    changes by linght microscopy
  • Mesangiocapillary or lobular glomerulonephritis
  • Form of glomerulonephritis (inflammatory changes
    of glomerular capillaries) caused by an abnormal
    immune response with deposits of immune complex.
    Certain cells in the capillary wall (mesangial
    cells) increase in number and the parts of the
    glomerular membranes change in structure.
  • Persistent and slowly progressive

3
Types of MPGN
  • Type 1 MPGN, most common
  • Type 2 (Dense Deposit disease)
  • Type 3 Mixed features of type I MPGN and
    membranous GN

4
Clinical menifestation
  • Idiopathic form occurs between ages of 8 and 30
  • In childhood, type I and II, frequently
    idiopathic or associated with nephritic factors
  • In adult, usually type I, commonly associated
    with cryoglobulinemia and HCV infection
  • Present with nephrotic range proteinuria or overt
    nephrotic syndrome, diffuse nephritis with
    hematuria, edema, hypertension and renal function
    impairment

5
Hypocomplementemia
  • Type 1
  • Activation of classical pathway normal or low
    C3, low C1, C4 and low CH50
  • Type 2
  • Activation of alternate complement pathway low
    C3, normal C1, C4, low CH50

6
Diagnosis
  • Routine Lab
  • Urine sediment
  • Serological evaluation
  • Biopsy In classical presentation with typical
    serology markers and preserved renal function,
    Biopsy may not be necessary BUT diagnostic biopsy
    is needed to confirm diagnosis and to establish
    activity, chronicity and potential reversibility

7
MPGN Type 1
  • Most common Type
  • Discrete immune deposits in the mesangium and
    subendothelial space, from circulating immune
    complexes, this causes mesangial proliferation
    and extension into the subendothelial zone.
  • Primary idiopathic MPGN is rare, and diagnosis of
    exclusion. Should be evaluated for chronic immune
    complex disease

8
Type I MPGN
  • Thickening of capillary walls,usually global and
    diffuse.
  • There is also hypercellularity. Much of this
    hypercellularity is mesangial proliferation, and
    some of the capillary wall thickening is caused
    by mesangial interposition into the
    subendothelial zone of the capillary loops.

9
Normal Glomeruli
10
Light Microscopy
11
Electron Micrograph
12
Immunofluorescence
13
Type 2
  • 15-35 of total MPGN cases
  • Characterized by a pathognomonic electron-dense
    transformation of GBMs and extensive complement
    deposition
  • Immunofluorescence is positive for C3 but
    negative for immunoglobulins
  • Recurs after renal transplant over 90 cases
  • Most have circulating IgG antibody (C3 nephritic
    factor) that stabilize C3bBb, C3 convertase of
    alternate pathway, resulted continuous C3
    breakdown. low C3
  • Higher hypocomplementemia and worse prognosis

14
Type II MPGN
15
Electron micrography
16
Type 3
  • Similar to type 1 but subepithelial deposits are
    prominent and complex disruption of the GBM
  • Inherited form of type 3 linked to chromosome
    1q32

17
Etiology
  • Primary (idiopathic) vs. Secondary
  • Autoimmune disorders SLE, Sjogrens, Rheumatoid
    arthiritis, hereditary complement deficient state
  • Infections chronic infections rather than
    acute Hep B, Hep C, SBE, ventriculoatrial shunt
    infection, chronic visceral abscess, HIV,
    schistosomiasis, malaria, leprosy.
  • Thrombotic microangiopathies transplant
    glomerulopathy, antiphospholipid antibody
    syndrome, TTP/HUS, scleroderma
  • Others lipodystrophy, CLL, melanoma,
    alpha-1-antitrypsin deficiency, non-Hodgkins,
    renal cell carcinoma
  • Association with HIV in the absence of HCV not
    well known.

18
Severity of disease
  • Renal function
  • Urine protein excretion
  • Histologic features such as necrosis, sclerosis,
    tubular and vascular fibrosis are late in course
    with less reversibility
  • Kidney size (lt9cm) and echogenic on US no
    benefit from disease-specific therapy

19
Hepatitis C induced Type 1MPGN
  • MPGN has been regarded as idiopathic for a long
    time until found out many also have chronic Hep
    C.
  • Strongly associated with cryoglobulinemia but
    mechanism is not well known intraluminal
    precipitates of immune complexes involving the
    cryoglobulins.
  • Incidence varies with location uncommon in
    France and South Africa, common in Japan
  • Commonly presents after 10-15yrs of chronic Hep
    C.
  • Laboratory features HCV antibody, HCV RNA by
    PCR, high concentration of cryoglobulins,
    positive RF and low complement.

20
Treatment
  • Treatment goals include reduction of symptoms,
    prevention of complications, and slowed
    progression of the disorder.
  • Treating secondary causes
  • Idiopathic MPGN - spontaneous improvement in
    lt10, 25-40 maintain renal function, 50-60 to
    ESRD in 10years
  • Corticosteroid more commonly used in children
  • Antiplatelet agents uncertain but showed some
    benefit with ASA and dipyridamole (reduced the
    incidence of progression to ESRD 14 vs. 47 in
    3-5 yrs)
  • Immunosuppressive drugs limited data
  • Dietary adjustments may include restrictions on
    sodium, fluids, protein, or other restrictions as
    appropriate to control high blood pressure,
    swelling, and accumulation of waste products in
    the bloodstream.

21
References
  • Nakopoulou, L. Membranoproliferative
    glomerulonephritis Nephrol Dial transplant
    (2001) 16 suppl 6 71-73
  • Rose, Burton Causes of membranoproliferative
    glomerulonephritis, Treatment of
    membranoproliferative glomerulonephritis Up to
    Date 2006
  • Couser, William. Glomerulonephritis The Lancet
    1999 353 1509-15
  • Curr Opin Nephrol Hypertens, vol 14 (4) 2005 July
    396
  • Rubin and Farber Pathology Lippincott-Raven 3rd
    ed. 1999

22
HIV associated Nephropathy (HIVAN)
23
HIV associated renal disease
  • Collapsing Focal Glomerulosclerosis
  • Drug induced ATN and crystal nephropathy
    (pentamidine, bactrim, acyclovir, indinavir, uric
    acid))
  • HIV associated glomerular disease
  • Interstitial nephritis CMV, drug (bactrim,
    indinaivr, anti-TB med)
  • Papillary necrosis (indinavir)
  • TTP direct endothelial injury
  • ARF from hypovolemia diarrhea, adrenal insuff
    w/ CMV, MAC salt-wasting

24
HIV associated nephropathy
  • 2-10 of HIV pts, predilection for
    African-Americans (12.2 times more likely),
    uncommon in Caucasians and Asians.
  • Most have low CD4 counts lt200 and advanced HIV
  • Mechanism is not well understood but in vitro
    study suggested HIV can infect glomerular
    endothelial cells, mesangial cells and tubular
    cells.
  • Presents with renal insufficiency with heavy
    proteinuria (gt10g), few red or white cells in
    urine sediment and hypoalbuminemia, nl to large
    hyperechogenic kidneys on US. HTN and
    peripheral edema is not common.
  • Rapid decline in renal function due to severe
    glomerular injury and marked damage to the
    tubular cells
  • In histology, tendency to collapse and sclerosis
    of the entire glomerular tuft rather than
    segmental injury.

25
Treatment
  • HAART is strongly recommended rate of
    progression to ESRD down by 38
  • Benefit of corticosteroids or cyclosporine is
    uncertain
  • Ace inhibitor is recommended in qualified
    individual crt lt2.0, absence of hyperkalemia.
    IDSA recommends BP lt130/80
  • RRT dialysis for uremic pt. HD and PD equally
    effective.

26
HIV associated glomerular dz
  • IgA nephropathy
  • Lupus-like GN ( staining for IgG, IgM, C3 and
    c1q) weakly positive ANA and negative dsDNA,
    diffuse and focal proliferative GN
  • Membranous (maybe associated with Hep B)
  • MPGN coinfection with Hep C
  • One case of HIV associated MPGN in the absence of
    Hep C reported Tubuloreticular inclusions with
    no evidence for either cryoglobulinemia or
    cryoglobulin deposits in the kidney
  • Others amyloidosis, cryglobulinemia (hep c),
    concurrent lupus

27
HIV nephropathy
  • absence of capillary loops, the collapse of
    matrix with no adhesions
  • very conspicuous hypertrophied epithelial cells

28
References
  • Lu, Ting-chi HIV associated Nephropathy The Mt
    Sinai Journal of Medicine vol 72 No. 3 May 2005
    193-197
  • Berggren, Ruth HIV associated Renal Disorders
    Recent Insights into Pathogenesis and treatment
    Current HIV/AIDS Reports 2005, 2109-115
  • Rose, Burton Collapsing FGS and other renal
    diseases associated with HIV infection UP to
    Date 2006

29
Mr. J
About PowerShow.com