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Approach to Rapidly Progressive Glomerulonephritis RPGN
1. 08.05.14
Clinical Approach
to
Rapid Progressive
Glomerulonephritis
Dr Garima Aggarwal
- DM Nephrology
- Amrita Institute of Medical Sciences,
- Kochi, India
2. 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.
3. 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
6. 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*
8. 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
Chronic - WEEKS TO MONTHS ; >3months
• Glomerular filtration rate (GFR) <60 mL/min per 1.73 m2 or
• evidence of kidney damage - albuminuria or abnormal findings
on renal imaging
have been present for three months or more.
9. • The clinical diagnosis of these cases may be
called Rapidly Progressive Renal Failure
(RPRF), which may be defined as progressive
renal impairment over a period of DAYS TO FEW
WEEKS.
• ~ 2weeks to 3 months
• heterogeneous group of clinical syndromes
• ‘Renal Emergency’
• may progress to irreversible end-stage renal
disease (ESRD) needing life-long renal
replacement therapy
13. HISTORY
RPRF vs CKD vs AKI
History of hematuria, frothing of urine, HTN,
Oliguria/Anuria, progressive renal failure
SYSTEMIC FEATURES
hemoptysis, longstanding asthma or petechiae is
suggestive of vasculitis
arthralgia, oral ulcers or photosensitivity indicates
presence of lupus.
Backache, fractures or bone pains - multiple
myeloma.
Recent Drug history, fluid loss, sepsis
Long-standing history of DM/ HTN
14. PHYSICAL EXAMINATION
Pallor – s/o CKD*,
Normal/ High BP. - TMA and renal artery stenosis.
Oral ulcer or butterfly rash is indicative of lupus
Skin petechiae may indicate lupus or vasculitis
Evidence of atheroembolic disease
Upper Respiratory tract involvement – sinuses*
RS – signs of asthma/alveolar hmghe
CNS- peripheral neuropathy
19. Rapid progressive renal failure
Systemic features – Pulmonary renal/ rashes/
peripheral neuropathy/ flu like syndrome
Hematuria, sub nephrotic proteinuria, active
urinary sediment
Low complements
ANCA/ ANA/ Anti GBM/ ASLO – positive
Renal Biopsy
20. 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
• (RPGN III) Anti-GBM glomerulonephritis
with a large cellular crescent
forming a cap over the
glomerular tuft
21. IMMUNOFLUORESCENCE
RPGN I RPGN II RPGNIII
(Anti GBM) (IC mediated) (pauci immune)
Linear staining Granular mild or absent
IgG and C3 glomerular glomerular tuft
staining staining
Diff Igs +/or
complements
22. linear staining for IgG -
diffuse binding of anti-
GBM Ab
Granular staining on IF in
PSGN
Scanty Background
staining of puaci
immune
23. ELECTRON MICROSCOPY
• RPGN I and III – absence of electron dense
immune complex deposits
• RPGN II – Multiple electron dense deposits
24. Anti GBM Disease EM – Absence of electron
dense IC deposits with distinct breaks in the
GBM – triggering crescent formation
MPGN showing several electron
dense IC deposits subepithelial
and sub endothelial
25. RPGN
Clinical/serology/Bx
Linear IF, IgG
Anti GBM +ve
Granular IF,
immune complex
Anti dsDNA, ANA/
Low C3-C4/ IgA/
ASLO, etc +ve
No IF,
ANCA +ve
Lung Hmrhge
YES
Goodpasture
syndrome
NO
Anti GBM
GN
26. RPGN
Clinical/serology/Bx
Granular IF,
immune complex
Anti dsDNA, ANA/
Low C3-C4/ IgA/
ASLO, etc +ve
No IF,
ANCA +ve
IgA Acute MPGN Others
Staph/strep
infection Mesangio DD Sub others
No Systemic Cap. Epithelial
Vasc. Vasculitis
IgA HSP PSGN MPGN I MPGN II MN SLE, etc
27. RPGN
Clinical/serology/Bx
No IF,
ANCA +ve
Sytemic vasculitis No Systemic
features
ANCA GN
Vasculitis with Granulomas Eosinophilia
No asthma or No asthma Granulomas
granulomas Asthma
Microscopic Wegeners Churg-Strauss
Polyangitis Garnulomatosis Granulomatosis
28. 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.
29. RPGN Type I: Goodpasture’s Syndrome
• The anti-GBM antibodies
cross-react with pulmonary
alveolar basement
membranes to produce the
clinical picture of
pulmonary hemorrhage
associated with renal
failure.
30. •Patchy parenchymal consolidations are present, which usually are
•bilateral, symmetric perihilar, and bibasilar.
•The apices and costophrenic angles usually are spared
31. Pauci immune vasculitis
• A group of small vessel vasculitis related to
ANCA.
• Can be renal limited/systemic.
• Systemic –microscopic
polyangitis,Wegener’s
granulomatosis,Churg Strauss syndrome.
• Wegener’s-Granulomatous inflammation +
necrotizing vasculitis.
• Churg Strauss-Eosinophil-rich and
granulonatous inflammation + necrotizing
vasculitis.
• Microscopic polyangitis-necrotizing
vasculitis.
37. 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
P-ANCA on ethanol fixed slide
P-ANCA exhibits intense positive perinuclear staining of the multi-lobed
nucleus with a poorly defined cell border.
A 1+ or greater fluorescence is considered a positive result
patients with circumferential crescents, > 80%glomeruli -advanced renal failure- may not respond well to therapy crescents <50 percent of the glomeruli, noncircumferential, follow a more indolent course or in rare cases even undergo a remission.
— an immune complex (type 2) disease that does not fit into any of the identifiable categories; and a pauci-immune (type 3) disease that is ANCA-negative.
There are also a number of renal diseases that do not fit easily under these current definitions. These patients are neither Acute Kidney Injury (previously called acute renal failure) nor Chronic Kidney Disease (previously called chronic renal failure).
ANTI GBM- 2 peaks- 1st peak 2nd and 3rd decade – 2nd peak sixth and seventh; IC GN – majority of cgn IN CHILDREN;
Disease of elderly
Detailed and appropriate history taking is essential both to make the initial diagnosis of
But maybe seen in vasculitis syndromes, SLE, TMA
Hepatitis B – PAN, mpgn/ MN?IgA, Hepatitis C – Mixed Cryoglobulinemia
Diagnosis, prognosis, chronicity, guide treatment
Anti GBM – lesions are in similar temporal evolution as opposed to ANCA
