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)