4) Acute Glomerulonephritis and rapid progressive glomerulonephritis Flashcards
what are the classification for acute glomerulonephritis ?
acute post infection glomerulonephritis :
- post strep GN +
- GN of infective endocarditis
- shunt nephritis
acute glomerulonephritis with systemic disorders :
> SLE (lupus nephritis in another topic)
> henoch scholein purpura (systemic form of IgA nephropathy) +
> microscopic polyangitis and other vasculitis disorders +
> wegner granulomatosis +
> Good pasture’s syndrome + ( anti glomerular basement membrane antibody mediated glomerulonephritis AntiGBM)
what is the classification rapidly progressive glomerulonephritis ?
type 1 : anti glomerular basement membrane antibody - good pasture syndrome
type 2 - immune complex mediates glomerulonephritis :
membranoprolifertive neuropathy
henoch scholen purpura
lupus nephritis
post strep GN
Type III: glomerulonephritis associated with vasculitis (pauci GN)
ANCA associated crescentic glomerulonephritis = wegner
= microscopic polyangitis
= eosinophilic granulomatosis / shrug strauss syndrome
what are the proliferative glomerulonephritis in acute and rapidly progressive glomerulonephritis ? ££££££££££££££££££££££££££££££££££££££££££££££££££££££££££££££££££££££££££££££££££££££££££££££££££££££££££££
rapidly progressive glomerulonephritis
membranoproliferative glomerulonephritis
post infectious glomerulonephritis
post strep GN most commonly seen in
children of 3–12 years and patients > 60 years of age
post strep GN are high risk in ?
patients with diabetes, malignancies, and alcohol dependency.
what is the etiology post strep GN ?
Occurs approximately 10–30 days following an acute infection:
most common cause :group A beta-hemolytic streptococci
inflaming the the mouth and tonsillitis, pharyngitis
Soft tissue infections : erysipelas : group A Streptococcus
non bullous impetigo : S. aureus or Group A streptococci
bullous : S. aureus
Osteomyelitis : Staphylococcus aureus
immune complex mediated acute GN occurs in ?
infective endocarditis
what is the pathophysiology of post strep GN ?
immune complexes containing the streptococcal antigen deposit within the subepithleila part of glomerular basement membrane
nephrotogenic aswell - molecular mimicry also likely
complement activation → destruction of the glomeruli → immune complex-mediated glomerulonephritis and nephritic syndrome
what are the clinical features of post strep GN ?
50% asymptomatic
Nephritic syndrome :
Hematuria
Hypertension: can lead to headaches
generalised Edema;
may be associated with dyspnea
neurologic symptoms (e.g., seizures)
Oliguria
azotemia related symptoms - fatigue , axterixis (flapping tremor) , decreased alertness and confusion
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Influenza-like symptoms - fever
Flank pain
how can we diagnose post strep GN?
Laboratory tests:
Normocytic, normochromic anemia
Possibly elevated BUN and creatinine (often transient)
↑ Antistreptolysin-O titer (ASO) (particularly following streptococcal infection of the pharynx)
↑ Anti-DNase B antibody (ADB) titer (particularly following streptococcal infection of the soft tissue)
↓ C3 complement
Urinalysis: nephritic sediment (e.g., hematuria and RBC casts, mild proteinuria)
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Ultrasound: enlarged kidneys
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Renal biopsy (not performed in most cases)
Indication: suspected rapidly progressive glomerulonephritis
Light microscopy:
Glomeruli are globally and diffusely enlarge
diffuse hypercellularity due to mesangial and endothelial cell increase
infiltration of monocytes and polymorphonuclear cells.
all of this block the capillary
Immunofluorescent for every post infection : granular
garland pattern, the starry sky pattern, and the mesangial pattern
The starry sky pattern is an irregular, finely granular pattern with small C3 deposits on glomerular basement membrane This pattern is often seen in the early phase of the
The starry sky pattern may turn into the mesangial pattern, which is characterized by granular deposition of C3 with or without immunoglobulin G. - closely related to resolving
sometimes deposits are large and densely packed and aggregate into a garlandlike pattern. These correspond to the humps on the subepithelial side of the glomerular capillary wall seen with electron microscopy
These types of deposits may persist for months and may be associated with the persistence of proteinuria and the development of glomerulosclerosis
Electron microscopy:
“humps” = subepithelial immune complexes (between epithelial cells and the glomerular basement membrane)
what is the treatment of post strep GN ?
In most cases the disease is self-limiting
treatmnet for nephritic syndrome :
low sodium diet
water restriction
if porteinirea or hypertension : acei or arb
if edema and pulmonary edema - loop diuretics
persisting streptococcal infection :penicillin G benzathine
If severe going into rapidly progressive : glucocorticoids,cyclophosphahemodialysis
what are the complications of post strep GN ?
Acute renal failure
Rapidly progressive glomerulonephritis
Nephrotic syndrome later in the course of the disease
what does microscopic polyangitis affect ?
small vessels
such as arterioles , venules and capillaries
what are the clinical features of microscopic polyangitis ?
NEPHRITIC SYNDROME symptoms
but hypertension
palpable purpura
raynaud phenomena
neuropathy - numbness and tingling
myalgia an arthralgia
epistaxis
erosin and perforation of nasal septum - saddle nose deformity
scleritis , uveitis
recurrent otitis media
what is microscopic polyangitis glomerulonephritis called ?
pauci immune glomerulonephritis = not associated with immune complex , antibodies or complements
what is the diagnosis of microscopic polyangitis ?
x ray
alveolar haemorrhages = come as opacities
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nephritic sediment
mild porteinurea
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biopsy of the organ it affects
(kidneys and organs)
= NO GRANULOMAS different to wegners granulomatosis
= but there is FIBRINOID NECROSIS of neutrophils
immunoflurecsnce
NO IMMUNOGLOBULIN OR COMPLEMENT DEPOSITION
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nromocytic normochromic anemia
azotemia
MPO / pANCA positive
= different to polyarteritis nodosa (large vessel affecting)
what is the treatment of microscopic polyangitis ?
immunosuppression with corticosteroids - prednisone with cyclophosphamide / azathioprim
or rituximab
Plasmapheresis may also be indicated in the acute setting to remove ANCA antibodies.
what type of vessels do henoch scholen affect ?
arterioles , venules and capillaries
what causes henoch purpura ?
preceding viral infection most commonly and upper respiratory tract one - group A strep
Gi infections also possible
what is the pathophysiology of henoch purpura ?
exposure to antigen
STIMULATION TO iGa
depostion of these iga in vascular walls and mesangium - activation of components - inflammation and damage
what are the clinical manifestation of hooch purpura ?
skin
symmetric distribution erythramatous macule colaescing into palpable purpura - esp in lower extremities and buttocks
jonts - arthritis and arthralgia
GI - colicky abdominal pain
bloody stools
kidneys - signs and symptoms of nephritic syndrome there is nephrtic syndrome edema hypertension possibly and its symptoms there is heamturea
what is the diagnosis for henoch purpura ?
cbc increas platelt count increase wbc normocytic normochornic bun andcreatinin transient elevation
serum antibodies and complement
IgA increase
IgA complex
decrease in complement
increase in creatinine or BUN
urinalysis - of nephritic syndrome
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biopsy
for severe renal involvement or persistent nephritic syndrome
skin - leukocytoclastic vasculitis with iga and C3 immune complex depostion is the hallmark
kidney
LM - diffuse mesangial proliferation because iga are dumped here
endocapillary proliferations
IF
mesangial IgA deposition
C3 complement and firbin
what is the treatmnet for henoch scholen purpura ?
milld
no treatment
nsaids and pain management and adequate hydration
severe
Iv methylprednisolone pulse therapy with cyclophosphamide and azathioprim
plasmapheresis of refractive
renal transplant if ESRD
dialysis for AKI
antihypertensive drugs
reduce salt intake and water intake
what is a serious complication of henoch scholen?
turns into rapid progressive glomerulonephritis with crescent formation
GI - intussusception or infraction
granulomatosisi with polyangitis or others known as wegners etiology ?
idiopathic = occurs more often after a upper respiratory tract infection
what are the clinical features for wegners granulomatosis ?
ENT
chronic rhinitis- saddle nose
chronic otitis / mastoiditis
lower respiratory tract - potentially life threatening :
cough , dyspnea , hemoptysis
renal - potentially life threatening
pauci immune glomerulonephritis which goes into rapidly progressive crescentic glomerulonephritis with possible pulmonary renal syndrome
with nephritic syndrome
skin
papules , vessies , ulcers
purpura of lower extremities
ocular
conjunctivitis , episcleritis , retinal vasculitis
corneal ulcers
cardiac - potentially life threatening
pericarditis , myocarditis
what are the diagnostics for granulomatosis with polyangitis
blood
creatinn and BUN high
PR3 - ANCA / C-anca
normocytic normochromic anemia
chest x ray - multiple bilateral cavitating nodular lesions
urinalyisis
nephritic sdiment
and typical nephritic syndrome
biopsy = NECESSARY TO CONFIM BIOPSY
necrotic granulomatous vasculitis of small and medium sized
WHAT IS THE TREATMNET FOR WEGNER disease ?
if mild
glucocrticoids plus methotrexate / cyclophosphamide / rituximab
moderate to severe
glucocorticoids with cyclophosphomide . rituximab
glucocrticoids tapered as soon as they respond
remission maintenace - azathioprine , rituximab and methotrexate = should be considered for a year due to the high relapse
what is the cause for good pasture syndrome ?
exposure to organic solvents - chloroform
- tobacco
- influenza a
what is the pathophysiology of good pasture syndrome ?
abnormal plasma cell production of anti - GBM - against collagen type 4
anti -GBM attack the alveoli and glomeruli basement membrane
attach to the epitope and activate the complement cascade
what are the clinical manifestations of good pasture syndrome
lungs antedate the kidney symptoms
hemoptysis
cough
dyspnea
nephritic syndrome symptoms
what is the diagnosis of good pasture’s disease ?
renal biopsy immunofluorescence
prescence of anti GBM antibodies specifically showing a strong linear ribbon-like appearance
also can have c-ANCA = antedates
x ray - alveolar haemorrhages
what is the treatmnet for goodpasturedisease ?
plasmapheresis
immunosuppressants = cyclophosphamide , prednisone , rituximab - prevent new anti-GBM antibodies
azathioprine for maintenance
what is the pathophysioogy of membranoproliferative disorders of type 1
type 1 - most common
circulating immune complexes - caused by hep b or hep c
over time they build in the glomerulus and activate CLASSICAL complement pathway
or
inapporpriate activation of complement pathway by the alternate complement pathway - C3 is converted to c3a and c3b by enzyme c3 converts
this can be due to =
> mutation
> autoanitbodies against protein that regulate the process
> c3 convertase only exist for a short time = inapropriate activation of IGg that bind to C3 converatse - making c3 converatse more stable
that special type of IgG is called nephritic factor
HERE NO IMMUNE COMPLEXES
the immune complexes or the complement end up in the sub endothelium of the basement membrane - recruiting inflammatory cells - damaging the capillary wall
and thickneing of the basement membrane
triggers mesangial cells - to proliferate and reach through the thick basment membrane = mesangial interposition causing the basemnet membrane to split around the basement membrane = DUPILICATION OF BASEMENT MEMBRANE OR TRAM TRACK
what is the pathophysioogy of membranoproliferative disorders type 2
in type 2 membranoproliferative GN there is no IMMUNE COMPLEXES - but complement deposits
dense deposits DISEASE or C3GN
activation of the alternate complement pathway
IgG auto - nephritic factor involved
c3GN - not intramembranous
DDD is more aggressive than C3GN
c3 levels are usually lo
what is the pathophysiology of membranoproliferative GN of type 3
VERY RARE
like type 1 involves immune complexes and and complements
deposited in the subendothelial space ANDsubepithelial sapce too
why should membranoproliferative GN not be confused with membranous gn ?
both have basement membrane thickening however mebranoproliferative Gn there is also mesangium thickening
what are the clinical features specific for membranoproliferative GN type 2
develop drusen - deposts within the bruch’s membrane and beneath the retinal epithelium = lipodystrophy =over time vision deteriorates , macular detachment
what is membranoproliferative GN associated with ?
type 1 immune complex mediated :
hep C / B associated nephropathy
hcvasociated cyroglobulinemia
monoclonal gammopathies
chronic bacterial - endocarditis
autoimmune
SLE
what is the diagnosis for membranoproliferative disorders
CAN HAVE BOTH NEPHROTIc AND NEPHRITIC SYNDROME - most common
renal biopsy
LM -
MPGN is derived from two histological changes
1_ glomerular basmenet membane thicening
2_increase mesangial and endocapillary proliferation giving lobular appearance f the glomerular tuft
type 1 -
silver staining we can see tram tracking
immunoflorescence findings
type 1 = igG and C3
type 2 = C3 alone NO immunoglobulin
type 3 = IgG and C3
EM =
type 1
subendothelila and mesangial immune deposits and tram track appearance
type 2 -
DDD dense
ribbon like appearance of the subendothelilal space of the basement membrane and mesangium
INTRAMEMBRANOUS depositions
c3GN = not dense deposition and not intamembranous
light depositions in mesangium , sub endothelium
type 3 = sub endothelia and mesangial and subepithelial
how can we know if MPGN is induced by secondary causes?
hep C
granular depositionof IgM and C3 and BOTH kappa and lambda light chains
IgG may or may not be present and C1q is typically negative
similar pattern for viruses
monoclonal gammapathies - monotype kappa or lambda light chains
autoimmune - full house pattern
EM - cyropercipitates in mesangium shows fingerprint pattern
how do we know if MPGN is triggered by autoimmune disease ?
full house patten of Ig deposotion - IgG and Igm , iGa , c1q , c3 , kappa andlambda light chains
how do we know if MPGN is triggered by monoclonogammpoathy
one monoclonal antibodies sound with C1q , C3 and light chain restricts
what is the mangement of MPGN?
immune complex mediated MPGN - should be evaluated for following disorders
such as hep b or c serology
chronic bacterial infections in blood cultures
test for fungi
test for parasitic infections
autoimmune disease screening
monoclonal gammopathy : serum protein electrophoresis , multiple myeloma , low grade b cell lymphoma
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compliment mediated MPGN
measure c3 , c4
genetic analysisi of mutation
normal C3 levels do not rule out COMPLIMENT MEDIATED MPGN
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give treatment to the underlying disease then treatment for only 3 conditions remain
idiopathic immune complex mediated MPGN
C3GN
DDD
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IICM MPGN
normal GFR and non nephrotic range proteinurea = ACEI, regular follow up
GFR LOW /NEphrotic range proteinurea / severe histological changes - CRESCENTS /
progressive even with ACEI
prednisolone and ACEI
add cyclophosphamide if no response
no response to cyclo = stop it and go rituximab
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c3GN / DDD idiopathic
autoantibodies to complement protein C3nef positive= glucocorticoids and rituximab
combination therapy with corticosteroids and cyclophosphamide.
Methylprednisolone 3 day pusle treatment 10-15 mg/kg, after which the patient received a conventional dose of prednisone
plasma exchange with albumin
genetic mutation in the complement pathway - benefit from treatment stopping mac from forming = eculizumab
factor h deficiency
= plasma exchange WITH albumin
if ESRD = renal transplant
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if nephrotic syndrome
Anti-aggregant therapy includes Dypiridamol along with Aspirin.
At severe nephrotic syndrome it is appropriate to administer Heparin
what is RPGN ?
characterized by rapid destruction of the renal glomeruli that often leads to end-stage renal disease
what is Eosinophilic granulomatosis with polyangiitis
characterized by necrotizing granulomatous vasculitis with eosinophilia, commonly involves the lungs and the skin
but can also affect the renal, cardiovascular, gastrointestinal, and peripheral nervous systems
what is the Etiology of eosinophilic granulomatosis with polyangiitis
unknownmaybe montelucast triggere
what are the clinical features ofeosinophilic granulomatosis with polyangiitis
Severe allergic asthma attacks (chief complaint)
Allergic rhinitis/sinusitis
Skin nodules, palpable purpura
nephritic syndrome
CNS: impaired mental status, mononeuritis multiplex (loss of motor and sensory function, with wrist or foot drop)
Pericarditis symptoms
Gastrointestinal involvement: bleeding , perforation
diagnosis of eosinophilic granulomatosis with polyangiitis
nephritic syndrome
Peripheral blood :
eosinophilia
↑ IgE level
Circulating MPO /pANCA
Biopsy (confirmatory test)
Tissue eosinophilia
Necrotizing vasculitis, and necrotizing granuloma
treatment for Churg-Strauss syndrome ?
immunosuppression with glucocorticoids; possible in combination with cyclophosphamide
diagnosis of RPGN ?
nephritic syndrome
biopsy : crescent moon - epithelial cell proliferation that displaces the glomerulus
always suspect RPGN and initiate testing immediatelywhen ?
serum creatinine rises rapidly due to renal damage
