approach to rapidly progressive glomerulonephritis rpgn
DESCRIPTION
Clinical approach to Rapidly Progressive Renal failure and Rapidly Progressive Glomerulonephritis. Diagnosing crescentic Glomerulonephritis and Pauci immune vasculitis syndromes - churg strauss, wegeners and good pasture syndromesTRANSCRIPT
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Clinical Approach to Rapid Progressive Glomerulonephritis
Dr Garima Aggarwal- DM Nephrology
- Amrita Institute of Medical Sciences,- Kochi, India
08.05.14
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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.
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• 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
CRESCENTIC GN
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Normal Kidney
Crescent
Normal glomerulus
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TYPES OF RPGN — Type 1: Anti-GBM antibody disease Type 2: Immune complex —
• IgA nephropathy• postinfectious glomerulonephritis• lupus nephritis• cryoglobulinemia.
Type 3: Pauci-immuneANCA-positive- Wegener’s, microscopic polyangiitis or
Churg StrausANCA-negative, pauci-immune RPGN
Type 4: Double-antibody positive disease — Type 4 has features of both types 1 and 3. Idiopathic*
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Rapid Progressive Renal Failure?
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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.
Types of Renal Failure (DURATION)
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• 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
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RPRF
TUBULO INTERSTITIAL
GLOMERULAR
VASCULAR
ATINATNMYELOMA
KIDNEY
RPGN Atheroembolic renovascular dis.
B/L Renal Vein thrombosis
TMA – HUS/TTP Mal. HTN Sys. Sclerosis
APLA
RARELY – Occult viscera sepsis, Sarcoidosis, Obstructive Nephropathy
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Clinical Approach?
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HISTORYRPRF vs CKD vs AKIHistory of hematuria, frothing of urine, HTN,
Oliguria/Anuria, progressive renal failure SYSTEMIC FEATUREShemoptysis, longstanding asthma or petechiae is
suggestive of vasculitisarthralgia, 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
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PHYSICAL EXAMINATIONPallor – s/o CKD*, Normal/ High BP. - TMA and renal artery stenosis. Oral ulcer or butterfly rash is indicative of lupusSkin petechiae may indicate lupus or vasculitisEvidence of atheroembolic disease Upper Respiratory tract involvement – sinuses*RS – signs of asthma/alveolar hmgheCNS- peripheral neuropathy
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ROUTINE INVESTIGATIONS
CBCLeucocytosis – Sepsis, vasculitis, TE disEosinophilia – Churg StraussTCP – HUS/TTP, TMAPeripheral smear – fragmented RBCs - TMA
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URINE ANALYSISDysmorphic RBCS, active sediments, Rbc casts,
Sub Nephrotic Proteinuria – Vasculitis, Lupus – RPGN
Isomorphic RBCs , Eosinophiluria – AIN, TE disNephrotic Range proteinuria – causes other
than RPGN
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Hypercalcemia – Sarcoidosis, MyelomaRaised LDH – TMALow complements – Lupus Nephritis,
Cryoglobulinemia, PSGN(C4 normal)Raised ESR, CRP – Vasculitis, SLEHBsAg – MPGN , Vasculitis Hepatitis C – MPGN, VasculitisChest X ray – cavities/nodules – ANCA ass
systemic vasculitis
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SEROLOGICAL TESTSANA, APLA – Lupus Nephritis, APLAANCA – Pauci Immune GNAnti GBM – Goodpasture’s Syndrome/Anti GBM disASLO, Anti DNAse- PSGNCryoglobulins- CryoglobulinemiaAnti Scl70 – Systemic sclerosis
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Rapid progressive renal failureSystemic features – Pulmonary renal/ rashes/
peripheral neuropathy/ flu like syndromeHematuria, sub nephrotic proteinuria, active
urinary sedimentLow complementsANCA/ ANA/ Anti GBM/ ASLO – positive
Renal Biopsy
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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
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IMMUNOFLUORESCENCERPGN I RPGN II RPGNIII(Anti GBM) (IC mediated) (pauci immune)
Linear staining Granular mild or absentIgG and C3 glomerular glomerular tuft staining staining
Diff Igs +/orcomplements
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linear staining for IgG - diffuse binding of anti-GBM Ab
Granular staining on IF in PSGN
Scanty Background staining of puaci immune
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ELECTRON MICROSCOPY
• RPGN I and III – absence of electron dense immune complex deposits
• RPGN II – Multiple electron dense deposits
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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
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RPGNClinical/serology/Bx
Linear IF, IgGAnti GBM +ve
Granular IF, immune complexAnti dsDNA, ANA/ Low C3-C4/ IgA/ ASLO, etc +ve
No IF,ANCA +ve
Lung Hmrhge
YES
Goodpasturesyndrome
Anti GBM GN
NO
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RPGNClinical/serology/Bx
Granular IF, immune complexAnti dsDNA, ANA/ Low C3-C4/ IgA/ ASLO, etc +ve
No IF,ANCA +ve
IgA Acute MPGN OthersStaph/strepinfection Mesangio DD Sub others
No Systemic Cap. EpithelialVasc. VasculitisIgA HSP PSGN MPGN I MPGN II MN SLE, etc
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RPGNClinical/serology/Bx
No IF,ANCA +ve
Sytemic vasculitis No Systemic features
ANCA GNVasculitis with Granulomas EosinophiliaNo asthma or No asthma Granulomasgranulomas AsthmaMicroscopic Wegeners Churg-StraussPolyangitis Garnulomatosis Granulomatosis
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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.
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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.
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•Patchy parenchymal consolidations are present, which usually are •bilateral, symmetric perihilar, and bibasilar. •The apices and costophrenic angles usually are spared
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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.
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Wegener’s Granulomatosis
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Microscopic Polyangitis
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Churg- strauss Syndrome
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Microscopic polyangitis
Wegener’sGranulom-atosis
Churg Strauss
Kidney +++ ++ +
Skin ++ ++ +++
Lungs ++ +++ ++
Neurological + ++ +++
URT + +++ +
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cANCA pANCA Negative
W.G 70 % 25 % 5%
Mic.polyangitis
40% 50 % 10 %
Churg Str. 10 % 60 % 30 %
Pauci immune GN
20 % 70 % 10 %
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C-ANCA on ethanol fixed slide
P-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 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
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