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14
Clinical Approach
to
Rapid Progressive
Glomerulonephritis
Dr Garima Aggarwal
- DM Nephrology
- Amrita Institute of Medical Sciences,
- Kochi, India
Rapidly Progressive
Glomerulonephritis (RPGN)
Refers to a clinical syndrome characterized
by a
Rapid loss of renal function,
Oliguria or anuria,
Features of glomerulonephritis
dysmorphic erythrocyturia,
erythrocyte cylindruria,
glomerular proteinuria.
CRESCENTIC GN
• RPGN – morphologically - extensive crescent
formation.
• The severity of the disease -degree of crescent
formation.
• nonspecific response to severe injury to the
glomerular capillary wall .
• Rents are induced in the glomerular capillary
wall- movement of plasma products, including
fibrinogen, into Bowman's space with
subsequent
• fibrin formation,
• the influx of macrophages and T cells,
• release of proinflammatory cytokines-IL-1 and TNF a
Normal Kidney
Crescent
Normal
glomerulus
TYPES OF RPGN —
Type 1: Anti-GBM antibody disease
Type 2: Immune complex —
• IgA nephropathy
• postinfectious glomerulonephritis
• lupus nephritis
• cryoglobulinemia.
Type 3: Pauci-immune
ANCA-positive- Wegener’s, microscopic polyangiitis or
Churg Straus
ANCA-negative, pauci-immune RPGN
Type 4: Double-antibody positive disease — Type 4 has
features of both types 1 and 3.
Idiopathic*
Rapid Progressive
Renal Failure?
Types of Renal Failure
(DURATION)
Acute – HOURS TO DAYS ; <2 weeks
●An increase in serum creatinine of ≥0.3 mg/dL (≥26.5
micromol/L) within 48 hours;
●An increase in serum creatinine of ≥1.5 times baseline, which
is known or presumed to have occurred within the prior seven
days; or
●Urine volume <0.5 mL/kg per hour for more than six hours
Renal Biopsy
Renal Biopsy findings
LIGHT MICROSCOPY
• Hallmark lesions – Crescents
• Cellular, fibro cellular, fibrous
• Lesions usually in various
stages of activity/ resolution
• Necrotising inflammation-10%
• Fibrinoid necrosis, peri
glomerular granulomas
Anti-GBM glomerulonephritis
• (RPGN III) with a large cellular crescent
forming a cap over the
glomerular tuft
IMMUNOFLUORESCENCE
RPGN I RPGN II RPGNIII
(Anti GBM) (IC mediated) (pauci immune)
YES NO
Goodpasture Anti GBM
syndrome GN
RPGN
Clinical/serology/Bx
No IF,
ANCA +ve
ANCA GN
Vasculitis with Granulomas Eosinophilia
No asthma or No asthma Granulomas
granulomas Asthma
Microscopic Wegeners Churg-Strauss
Polyangitis Garnulomatosis Granulomatosis
RPGN Type I:
Anti GBM Disease
• Cells accumulate in
Bowman’s space, form
crescents.
• Peptides within the
noncollagenous portion of the
α3-chain of collagen type IV.
• What triggers the formation of
these antibodies is unclear in
most patients.
• There is linear deposition of
antibodies and complement
components along the GBM.
RPGN Type I: Goodpasture’s Syndrome
Skin ++ ++ +++
Lungs ++ +++ ++
Neurological + ++ +++
URT + +++ +
cANCA pANCA Negative
W.G 70 % 25 % 5%
Mic.polyan 40% 50 % 10 %
gitis
Churg Str. 10 % 60 % 30 %
Pauci 20 % 70 % 10 %
immune
GN
C-ANCA on ethanol fixed slide
C-ANCA is identified as a positive result when there is intense positive
granular staining of the cytoplasm that extends to the border of the human
granulocyte substrate displaying a 1+ or greater fluorescence
and there is absence of nuclear staining