Glomerulonephritis Flashcards
What is glomerulonephritis?
Immune-mediated disease of the kidneys affecting the glomeruli
How can glomerulonephritis be classified?
- Aetiology (Primary vs secondary)
- Histopathology
- Clinical syndromes
What are some primary syndromes of glomerulonephritis?
- Minimal change disease
- Focal segmental glomerulosclerosis
- Membranous nephropathy
- Membrano-proliferative glomerulonephritis
- IgA nephropathy
What are some secondary causes of glomerulonephritis?
Goodpasture’s disease
Circulating immune complexes
Vasculitis
What are some causes of circulating immune complexes causing glomerulonephritis?
Infection
Drugs
Cancer - Lymphomas
SLE
What are some forms of infective causes of glomerulonephritis?
Hepatitis
Bacteria - Post-streptococcal GN
HIV
How does post-streptococcal GN present?
GN symptoms occurring around 2 weeks after streptococcal infection
What are some drugs that can cause glomerulonephritis?
Gold
Penicillamine
What are some histological classes of glomerulonephritis?
Proliferative vs non-proliferative
Focal vs diffuse
Global vs segmental
Cresentic?
What is meant by proliferative GN?
GN with presence of proliferation of mesangial cells
What is meant by non-proliferative GN?
GN without presence of proliferation of mesangial cells
What is meant by focal GN?
GN in which < 50% of glomeruli are affected
What is meant by diffuse GN?
GN in which > 50% of glomeruli are affected
What is meant by global GN?
GN in which all of the glomerulus is affected
What is meant by segmental GN?
GN in which only part of the glomerulus is affected
What is meant by crescentic GN?
GN in which there are crescents:
- Epithelial cell extra-capillary proliferation
What are some clinical syndromes of GN?
Nephritic syndrome
Nephrotic syndrome
Rapidly progressive glomerulonephritis
Asymptomatic haematuria or proteinuria
What are some ways in which the humeral immune system can lead to glomerulonephritis
Ig’s against normal glomerular constituents
Ig’s against non-self antigens
Deposition of immune complexes
Complement activation and inflammatory mediators
What conditions can cause Ig’s against normal glomerular constituents?
Goodpasture’s disease
Membranous nephropathy
What conditions can cause Ig’s against non-self antigens in GN?
ANCA
IgA nephropathy
What conditions can cause deposition of circulating immune complexes in GN?
Post-infectious GN
What conditions cause complement activation and inflammatory mediator release in GN?
- C3 glomerulopathy
- Post-infectious glomerulonephritis
What are some conditions that cause cell-mediated immune response in GN, resulting in cytokine and GF release from T-cells and macrophages?
- Focal segmental glomerulosclerosis
- Crescentic glomerulonephritis
What results from mesangial damage in GN?
Inflammation within the mesangium results in proliferation and Ang2 and chemokine release
This causes proliferative lesion formation and attraction of inflammatory cells
This causes endothelial damage and therefore RBC leakage
What results from podocyte damage in GN?
Podocyte damage causes podocyte atrophy, casing loss of size/charge specific barrier
This leads to a non-proliferative lesion and protein leakage (Proteinuria)
What is rapidly progressive glomerulonephritis?
This is the immune mediated rapid loss of renal function over days, weeks or a few months, presenting with severe nephritic syndrome
What investigations are required in RPGN?
Kidney biopsy
Serological testing
Early!
Describe the histology of RPGN
Crescent formation on renal biopsy
What are some ANCA +ve causes of RPGN?
- Granulomatosis with polyangiitis (GPA)
- Microscopic polyangiitis (MPA)
What are some ANCA -ve causes of RPGN?
- Goodpasture’s disease
- Henoch-Schonlein purpura
- Systemic lupus erythematosus
What are some important history points in GN history taking?
- Foamy or frothy urine?
- Rashes/Eye symptoms/Respiratory symptoms
- Recent infections
- Family history
- Medication or drug use
What are some possible examinations findings in GN?
- Oedema - Periorbital oedema in the morning
- Huekrcke lines in nails
- Xanthelasma
- Rashes - Petechial or purpuric
- Synovitis
- Hypertension
What tests are required in GN?
Bloods
Urine investigations
Kidney USS
Renal biopsy
What bloods are required in GN?
U+E (AKI or CKD)
Immunological testing (E.g. ANCA, Anti-GBM)
What urine investigations are required in GN?
Urinalysis (Haematuria, proteinuria)
Urine microscopy
Urine Protein:Creatinine (PCR) on 24-hour urine
What are the 4 main stages of proteinuria?
Microalbuminuria (30-300mg/day)
Asymptomatic proteinuria (<1g/day)
Heavy proteinuria (1-3g/day)
Nephrotic syndrome (>3g/day)
What may be seen on urine microscopy in GN?
Dysmorphic RBCs
RBC casts
Granular casts
Lipiduria
What may be seen on kidney USS in GN?
Small kidneys
Severe cortical thinning
What are the 3 main tests which may be performed on a renal biopsy sample?
Light microscopy
Electron microscopy
Immunofluorescence
What may be seen on light microscopy in GN?
Hypercellularity - Inflammatory and reactive proliferations
Sclerosis
Crescents (In RPGN)
Granulomas (In GPA and Sarcoid)
What may be seen on electron microscopy in GN?
Immune complex depositions in the basement membran e
What may be shown on immunofluorescence in GN?
Antibody type and distribution
What will be seen on immunofluorescence in Goodpasture’s GN?
Linear IgG in basement membrane
What are the aims of treatment in GN?
Reduce proteinuria, induce remission of nephrotic syndrome and preserve long-term renal function
What is meant by complete remission of nephrotic syndrome?
Proteinuria < 300mg/day
What is meant by partial remission of nephrotic syndrome?
Proteinuria < 3-3.5g/day
What are some non-immunosuppressive management options for GN?
- Anti-hypertensives (ACEi/ARB)
- Diuretics
- Statins
- Anticoagulation (Nephrotic syndrome with hypoalbuminaemia)
- Salt and fluid restriction (Nephrotic syndrome)
What are some immunosuppressive drugs used to manage GN?
Corticosteroids
Alkylating agents
Calcineurin inhibitors
Anti-proliferative
What are some examples of alkylating agents?
Cyclophosphamide
Chlorambucil
What are some examples of calcineurin inhibitors?
Cyclosporin
Tacrolimus
What are some examples of anti-proliferative drugs?
Azathioprine
Mycophenolate Mofentil
What are some forms of immunosuppressive treatments of GN?
Drugs
Pasmapharesis
Antibodies (IV Ig)
Management of RPGN
Strong immunosuppressives
Dialysis
What is the most common form of GN in children?
Minimal change disease
What is the possible pathology of minimal change disease?
Unknown cause, however, there is thought to be some involvement of B-cells and anti-nephron antibodies
Histology of minimal change disease
Characteristic diffuse effacement of the podocyte foot processes on electron microscopy
Normal on LM and IF
Treatment of minimal change disease
- 1st line - Oral corticosteroids
- 2nd line - Cyclophosphamide/Rituximab
What is focal segmental glomerulosclerosis?
This is a histological lesion rather than a disease and is the 2nd most common cause for nephrotic syndrome in adults
Primary cause of focal segmental glomerulosclerosis
General podocyte dysfunction
Secondary causes of focal segmental glomerulosclerosis
- HIV
- Drugs - pamidronate, interferon, heroin and obesity
Histology of focal segmental glomerulosclerosis
Sclerosis in parts of some glomeruli on LM
No immune deposits or foot process effacement
Treatment of focal segmental glomerulosclerosis
- 1st line - High dose glucocorticosteroids
- 2nd line - CNIs - Calcineurin inhibitors (E.g. tacrolimus)
Prognosis of focal segmental glomerulosclerosis
50% will progress to ESRF after 10 years
What is membranous nephropathy
This is another pattern of injury found on histology, instead of a disease and is the commonest cause of nephrotic syndrome in adults
Primary cause of membranous nephropathy
Anti-PLA2R antibodies
Secondary causes of membranous nephropathy
- Infection - HepB, Parasites
- Connective tissue disease - Lupus
- Malignancy - Carcinomas, Lymphomas
- Drugs - Gold, Penicillamine
Histology of membranous nephropathy
- Thickening of GBM on LM
- Spike and dome pattern with silver staining on LM
- Subepithelial immune complex deposition in the GBM on EM
Treatment of membranous nephropathy
immunosuppression - Cyclophosphamide
What is membranoproliferative GN
MPGN is a histologic lesion and not a specific disease entity
It’s pattern of injury once identified will require further evaluation to find underlying causes.
What are the 2 primary mechanisms of MPGN?
- Immune complex deposition and activation of complement
- Complement dysregulation leading to persistent activation of alternative pathway
Histology of MPGN
- Thick capillary wall
- Glomerular membrane proliferation
- Immunofluorescent microscopy shows immune complex deposition in capillary walls
Treatment of MPGN
- Treating underlying infections etc (Hep C)
- Immunosuppression with steroids/ MMF for idiopathic cases
- Complement inhibitors such as eculizumab for disregulation
What is the most common form of GN in adults in the world?
IgA nephropathy (Berger’s disease)
How will IgA nephropathy usually present?
- 10-20 years old
- Asymptomatic microhaematuria ± Non-nephrotic range proteinuria
- Macroscopic haematuria post-infection
- AKI/CKD
What causes IgA nephropathy?
This can be caused by respiratory or GI infection and there is an association with Henoch-Schönlein purpura
Histology of IgA nephropathy
- Mesangial cell proliferation and expansion on light microscopy
- IgA deposits in mesangium on immunofluorescence
Treatment of IgA nephropathy
- SGLT2 inhibitors
- Budesonide
- Dual endothelin-angiotensin receptor antagonist (Sparsentan)
