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Glomerulonephritides
Dr. Tislér András
SE. 1.sz. Belgyógyászati Klinika
2013
…”
„
The term „glomerulonephritis” may refer to
• Etiology: poststreptococcal GN (PSGN)
• Serological abnormality: ANCA-associated GN
• Light microscopic findings: Membranoproliferative GN (MPGN),
mesangial proliferativa GN
• Immunfluorescent findings: IgA nephropathy (IgAN)
• Clinical syndrome: nephritic syndrome, rapidly progressive GN
(RPGN)
• Systemic disease: Lupus nephritis (LN)
Overview
• Classification of GN
• Diagnosis of GN
• Some examples
– IgA nephropathy
– ANCA-associated GN (pauci-immune GN)
Glomerular disease may be classified according to:
• Clinical syndromes (clinical presentation)
– Nephritic syndrome
– Nephrotic syndrome
– RPGN
– Isolated proteinuria/ hematuria
– Acute kidney injury
• Primary renal disease or renal manifestation of a systemic disease (secondary)
• Renal biopsy histology, proliferative or non-proliferative
– These are the different pathological types
Immune mechanisms in glomerular diseases
• Antibody against a local antigen
– Podocyte antigen (membranous GN: phospolipase A2
receptor)
– Glomerular basement menbrane antigen (Goodpasture’s)
– planted antigen (e.g. in membranous SLE)
• Deposition of circulating immune complexes with
inflammation
– E.g. IgA nephropathy, cryoglobuliemia, SLE
• Without immune complexes („pauci immun”), but with
immune mechanism
– ANCA associated diseases
•Non inflammatory (non-proliferative) glomerulopathies:
•Podocyte damage (e.g. minimal change disease)
Types of glomerular injury on light microscopy 1.
•Subepithelial immuncomplexes (membranosus GP)
•Mesangial-capillary sclerosis, podocyte damage (FSGS)
•Mesangial-matrix deposition (diabetic nephropathy, amyloid)
• inflammatory (proliferative) glomerulopathies
•Mesangial proliferation (e.g. IgA nephropathy)
Types of glomerular injury on light microscopy 2.
•Extracapillary proliferation (crescents) (e.g.Wegener’s)
•Endocapillary proliferation (poststreptococcal GN)
•Mesangiocapillary proliferation (cyroglobulinaemia, MPGN)
Glomerulonephritides
Non proliferative Proliferative
Minimal
change
disease
Fokal
segmental
glomeruloscler
osis FSGS
Membranosus
GP
Diabetic NP
amyloidosis
Mesangial
IgAN
Crescents
(extracapillary)
RPGN
ANCA
Anti-GBM
Mesangiocapillar
y
(MPGN)
cryoglobulin
SLE
HUS
Endocapillary
PSGN
Usual presentation :
Nephrotic syndrome Nephritic syndrome
Clinical diagnosis
Syndrome
Acute nephritis sy.
Nephrotic sy.
Isolated proteinuria,
haematuria sy.
Rapidly progressive
glomerulonephritis
Chronic renal failure sy.
Acute renal failure sy.
Morphological
diagnosis
Postinfect. GN
Minimal change
Focal segmental GS
Membranous GN
Membranoprolif. GN
Crescens GN (necrotic)
Mesangial prolif GN
Diabetic nephropath
Amyloidosis
Myeloma
Acute tubular necrosis
Etiological
diagnosis
Primary (unknown)
Hepatatis C
Hepatitis B
SLE
Neoplasm
Vasculitis
Wegener gr.
Goodpasture sy.
Diabetes
Amyloidosis
Myeloma
Ischemia
Overview
• Classification of GN
• Diagnosis of GN
• Some examples
– IgA nephropathy
– Membranosus glomerulopathy
– ANCA-associated GN (pauci-immune GN)
Diagnosis of glomerulonephritis
• Usual clinical presentation is the nephitic syndrome
(usually proliferative GN) but may present with nephrosis,
RPGN, isolated proteinuria/hematuria
Acute glomerulonephritis (nephritic) syndrome
• Hematuria
(dysmorphic RBCs, acanthocytes)
• Proteinuria
• Cylindruria
(cellular, RBCcasts)
• Hypertension
• Oedema
• Oliguria
• Decreased GFR
Dysmorphic RBCs, acanthocytes, RBC cast
Frequent pathologies behind the acute nephritic syndrome
(but may present in other syndromes as well)
• Post-streptococcal GN
•acute diffuse proliferative – endocapillary proliferative
• IgA nephropathy
•Mesangial proliferative
• Membranoproliferative GN
• SLE: focal vs. diffuse proliferative GN (types II-IV)
Nephrotic syndrome
• Proteinuria (usually>2-3 g/die)
• Hypalbuminemia
• Oedema
• Hyperlipoproteinemia
• Increased risk of thrombosis
• GFR may be norm.
Most frequent pathology behind the nephrotic syndrome in
adults
• Primary renal disease
– Minimal change glomerulopathy
– Focal segmental GN
– Membranous glomerulopathy
– Fibrillary (immunotactoid) GN
• Systemic disease
– Diabetes
– Amyolidosis
– SLE (type V)
Frequent complications of nephrotic syndrome
•
•Thrombosis (renal vein, deep venous)
• Frequent infections
• Acute prerenal renal failure
•Heavy proteinuria in itself contributes to the
progression of renal disease
• Accelerated atherosclerosis (?)
Isolated hematuria syndrome
• Glomerular causes (non glomerular
causes – stone neoplasm, papillary
necrosis etc. should be excluded)
•Thin basement membrane disease
•IgA nephropathy
• Alport syndrome
• persistent microhematuria
•dysmorphic RBCs, acanthocytes
•Variable proteinuria (from minimal to
nephrotic range)
•Variable decrease in GFR
Rapidly progressive GN syndrome (crescentic GN)
• Progressive loss of GFR (weeks, months)
• Active urinary sediment
– RBCs, cellular and granular casts
– Variable proteinuria
• Frequent systemic symptoms
– vasculitis
– upper-lower airway
– Pulmonary (bleeding)
– Arthritis
– fever
Causes of rapidly progressive GN syndrome
I. Anti-GBM antibodies (linear deposition
on immunfluorescence)
• Goodpasture syndr.,
II. Immune complex mediated GN (granular deposition on IF)
• Primary GN: IgA GN, Membranoproliferative GN
• Postinfectios: sepsis, abscess, endocarditis, HBV,
• Autoimmune: SLE
III. ANCA associated GN (no immune deposition = pauci immune)
• Wegener’s granulomatosis
• Microscopic polyangiitis
• Churg Strauss syndr
Kidney biopsy
• Indication: if the result have relevant prognostic or
therapeutic consequences
•Nephritic syndrome
•Nephrosis, proteinuria > 1-2g/day
•Glomerular hematuria + proteinuria > 0,5 g/day
•Acute kidney injury: unknown etiology
•posttransplantation
• contraindications:
•Uncooperative patient
•High risk for hemorrhage
•hypertension (> 140/90), anemia: HB < 100 g/l,
•hydronephrosis, acut pyelonephritis,
•multi/polycystic kidney, soliter kidney
•Kidney size < 9 cm (probably end stage kidney)
Overview
• Classification of GN
• Diagnosis of GN
• Some examples
– IgA nephropathy
– ANCA-associated GN (pauci-immune GN)
IgA nephropathy
• Most frequent primary GN (2/100000/year)
• Clinical picture:
– male:female 2:1
– Typical presentation micro or macroscopichematuria (+/- proteinuria)
– Sometimes nephritic syndrome
– Higher IgA level
– If accompanied by systemic signs (vasculitis) then it is Henoch-Schönlein purpura
• Renaél biopsy
– Mesangial proliferation
– Mesangial IgA deposition
IgA nephropathy
IgA nephropathy: prognosis and therapy
• Poor prognostic signs (36% dialíysis in 20years)
– >1g/day proteinuria
– Hypertension
– Severe proliferation
• therapy
– ACE orARB
– <130/80 Hgmm
– If proteinuria high:
• P.o. steroid (2-3 years 1mg/kg tapered)
• Fish oil (2-3g*3)
• Tonsillectomia?
– If progressive GFR decline and crescents on microscopy:
• i.v.p.o. steroid + p.o. cyclophosphamide (2,5mg/kg)
RPGN is usually associated with crescent formation
(extracapillary proliferative GN)
I. Anti-GBM antibodies (linear deposition
on immunfluorescence)
• Goodpasture syndr.
II. Immune complex mediated GN (granular deposition on IF)
• Primary GN: IgA GN, Membranoproliferative GN
• Postinfectios: sepsis, abscess, endocarditis, HBV,
• Autoimmune: SLE
III. ANCA associated GN (no immune deposition = pauci-immune)
• Wegener’s granulomatosis
• Microscopic polyangiitis
• Churg Strauss syndr
Goodpasture’s syndrome
• Rare disease: 1/1million/year
• Pathogenesis
– Antibody formation against the „non-collagenous” region
of alpha 3 chain of type IV collagen found in the
glomerulus and lung. This causes inflammation and
proliferation
– Pulmonary manifestation frequently after infection, or
other pulmonary damage
– In Alport syndrome after transplantation
Goodpasture’s syindrome
• Pulmonary-renal syndrome
– Pulmonary bleeding-RPGN
– anti GBM antitbodies
• Immunofluorescence, ELISA
• Rx
– Cyclophosphamide, steroid,
– Plasma exchange
ANCA positive glomerulonephritis
Wegener’s
granulomatosis
(PAG)
Microscopic
polyangiitis
(MPA)
Churg Strauss
syndrome
ANCA poz. 80-90% 70% 50%
antigen PR3>>MPO MPO>PR3 MPO>PR3
Patology vasculitis
Renal
pathology
Necrotising, crescent formation, „pauci immun” on
immunfluorescence
Upper
airways
Granuloma, necrosis Allergic rhinitis
Lungs Infiltration,
granuloma, bleeding
bleeding Asthma
other Vasculitis
RPGN
Neuropathia
RPGN
Eosinophilia
RPGN
Rx Cyclo, steroid, TMP/SMX, PE
Small vessel vasculitis
Wegener
uveitis
Wegener’s granulomatosis
SLE
Renal manifestations in SLE
• WHO type I: no renal change
• WHO type II: mesangial proliferative GN
• WHO type III: focal proliferative GN
• WHO type IV: diffuse proliferative GN
• WHO type V: membranous GN
• WHO type VI: chronic renal failure
• Types II-V may be associated with crescent formation and
necrosis indicating poor prognosis and necessitating agressive
immunosuppression
• Non-blomerular manifestation
– Vasculitis
– Intestitial nephritis
Overview
• Classification of GN
• Diagnosis of GN
• Some examples
– IgA nephropathy
– ANCA-associated GN (pauci-immune GN)
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