Gomerulonephritis Flashcards
What does glomerulonephritis mean?
- Disease of the glomerulus
- Most are immunologically mediated
- Present with proteinuria, haematuria, or both
- Diagnosed by renal biopsy
- Can progress to kidney failure (except minimal change disease)
Nephrotic or nephritic?
- Spectrum from:
- Nephrosis
- Proteinuria due to podocyte pathology
- to
- Proteinuria due to podocyte pathology
- Nephritis
- Haematuria due to inflammatory damage
- Nephrosis
Describe the investigations into a suspected glomerulonephritis?
- Bloods:
- FBC, U&E, LFT, CTP, immunoglobulins, electrophoresis, complement
- Autoantiboidies: ANA, ANCA, anti-dsDNA
- Culture
- Urine
- MC&S, Bence jones protein, A:CR/P:CR
- Imaging
- CXR (pulmonary haemorrhage), Renal US (size/anatomy for biopsy
- Renal biopsy
- Required for diagnosis
Describe the process of renal biopsy?
- Pre-procedure
- BP <160/95, FBC, G&S, written consent required
- Stop anticoagulation (aspirin 1 week, warfarin PT <1.2, LMWH 24h)
- Post-procedure
- Bed rest for 4 hours
- Monitor BP, pulse, urine
- Aspirin, warfarin can be restarted next day if no complications
General management of glomerulonephritis conditions?
- Treat as CKD
- BP control
- Inhibition of RAS
- Specific treatment depending on histology, severity and comorbidity
Types of Nephritic glomerulonephritis?
- IgA nephropathy
- Henoch-schonlein purpura (HSP)
- Post-streptococcal GN
- Rapidly progressive GN
- Anti-glomerular basement membrane (anti-GBM) disease
Describe IgA nephropathy?
When is their a worse prognosis?
- Common in rich countries
- Mesangial IgA and C3
- Haematuria, proteinuria <1g, HTN
- Idiopathic, flares triggered by upper RT infections, coeliac, liver disease
- Worse prognosis in men, hypertension, raised creatinine, proteinuria
Describe the diagnosis and treatment of IgA nephropathy?
- Diagnosis
- Renal biopsy: IgA deposition in mesangium
- Treatment
- Acei/ARB: reduce proteinuria and protect renal function
- Corticosteroids + fish oil: if persistent proteinuria and GFR >50
Describe Henoch-schonlein purpura (HSP)?
- Small vessel vasculitis
- Variant of IgA nephropathy in children:
- IgA deposition in kidney + skin/joints/gut
- Presentation:
- Purpuric rash on extensor surfaces, polyarthritis, abdominal pain, nephritis
Describe the diagnosis and treatment of HSP?
- Diagnosis
- Clinical
- Immunofluorescence for IgA and C3 in skin
- Renal biopsy identical to IgA nephropathy
- Treatment
- Acei/ARB: reduce proteinuria and protect renal function
- Corticosteroids + fish oil: if persistent proteinuria and GFR >50
- Corticosteroids for gut involvement
Describe post-streptococcal GN?
- Following thoat or skin infection
- Streptococcal antigen deposits in glomerulus
- Presentation:
- Varies from haematuria => acute nephritis
What are the symptoms of acute nephritis?
- Oliguria
- Oedema
- Haematuria
- Hypertension
Describe the diagnosis and treatment of post-streptococcal GN?
- Diagnosis
- Evidence of strep infection
- Raised ASOT, anti-DNAse B, reduced C3
- Treatment
- Supportive
- Antibiotics to clear bacteria
Describe anti-GBM disease?
Anti-glomerular basement membrane disease
- (Goodpastures)
- HLA-DR15
- Usually crescenteric nephritis
- Auto-antibodies to type IV collagen in GBM
- Renal + lung disease
Diagnosis and treatment of anti-GBM disease?
- Diagnosis
- Anti-GBM in circulation/kidney
- Crescenteric nephritis on biopsy
- Treatment:
- Plasma exchange, corticosteroids, cyclophosphamide
Describe Rapidly progressive GN?
- Any aggressive GN, progressing to renal failure
- Causes:
- Small vessel/ANCA vasculitis
- Lupus nephritis
- Anti-GBM disease
Describe the diagnosis of rapidly progressive GN?
- Breaks in the GBM allow influx of inflammatory cells
- Crescents seen on renal biopsy
Describe the treatment of Rapidly progressive GN?
- Corticosteroids and cyclophosphamide
- Treat cause:
- Anti-GBM/ANCA vasculitis: plasma exchange
- Lupus nephritis: monoclonal antibodies
What is pictured here?
- Immunofluorescence for IgA
- Linear stain characteristics of anti-GBM disease
What is pictured here?
- Crescentic GN
- Proliferation of epithelial cells
- Macrophages with rupture of Bownman’s capsule
What is the definition of nephrotic syndrome?
- Triad:
- Oedema
- Proteinuria >3g/24hr
- Hypoalbuminaemia (30g/L)
What are the types of cause of nephrotic syndrome?
- Primary renal disease
- Secondary to a systemic disorder
Primary renal causes of Nephrotic syndrome?
- Minimal change
- Membranous nephropathy
- Membranoproliferative GN
- Focal segmental glomerulosclerosis (FSGS)
Secondary causes Nephrotic syndrome?
- DM
- Lupus nephritis
- Myeloma
- Amyloid
- Pre-eclampsia
What makes up the filtrations barrier of the kidney?
- Podocytes
- Glomerular BM
- Endothelial cells
Describe the pathophysiology of nephrotic syndrome?
Podocyte pathology => proteinuria
Presentation of nephrotic syndromes?
Generalized, pitting oedema
Describe the general management of nephrotic syndromes?
- Reduce oedema
- 1L fluid/day + salt restriction
- Loop diuretics eg furosemide (+thiazide diuretic if resistant)
- Aim for 0.5-1kg weight loss per day
- Treat underlying cause
- Renal biopsy to diagnose
- Reduce proteinuria
- ACE-i/ARB
Describe the complications that can occur with nephrotic syndromes?
- Thromboembolism
- Tx with LMWH + warfarin
- Infection
- Ensure pneumococcal vaccination
- Hyperlipidaemia
Describe Minimal change disease?
- Normal histology, no immune deposits
- Idiopathic, NSAIDs, lithium or haematological malignancies
- Does not cause renal failure
Describe the diagnosis of Minimal change disease?
- Light microscopy is normal
- Electron microscopy shows effacement of podocyte foot processes
Describe the treatment of Minimal change disease?
- Glucocorticoids
- Frequenct relapses:
- Increase dose or
- Cyclophosphamide
Describe Focal segmental glomerulosclerosis (FSGS)?
- Most common glomerulonephritis seen on renal biopsy
- Categories:
- Primary (idiopathic)
- Secondary (HIV, heroin, lithium, HTN, obesity)
- Risk of progressive CKD and renal failure
- Disease may recur after renal transplant
Describe the diagnosis of FSGS?
- No acute inflammation
- Scarring of glomeruli in certain segments of biopsy
- Podocyte foot fusion in primary disease
- Higher proteinurias indicate worse prognoses
Describe the treatment of FSGS?
- ACEi/ARB and BP control in all
- Primary disease:
- Corticosteroids
- Recurrence in transplants:
- Plasma exchange and rituximab
Describe Membranous nephropathy?
- Granular subepithelial IgG
- Primary (idiopathic, HLA-DQA1)
- Secondary to:
- Malignancy
- HBV
- Lupus
- Heavy metals, penicillamine
Describe the diagnosis of Membranous nephropathy?
- Anti-phospholipid A2 receptor antibody
- Diffuse thickened GBM
- Spikes on silver staining
Describe the treatment for Membranous nephropathy?
- ACEi/ARB and BP control in all
- High progression risk:
- Corticosteroids + cyclophosphamide
- 1/3 progress, 1/3 remit, 1/3 remain stable
Describe Membranoproliferative glomerulonephritis?
Aka mesangiocapillary glomerulonephritis
- Higher in low-middle income countries due to infection
- Divided into:
- Immune complex associated
- C3 glomerulopathy
Describe Immune-complex associated Membranoproliferative glomerulonephritis?
- Deposits of immune complexes
- Activate complement in the kidney
- Underlying cause in most causes:
- Infection, monoclonal gamopathy, autoimmunity
Describe C3 glomerulopathy Membranoproliferative glomerulonephritis?
Defect in the alternative complement pathway (C3 nephritic factor)
Describe the diagnosis of Membranoproliferative glomerulonephritis?
- Proliferative glomerulonephritis with electron dense deposits
- Immunoglobulin deposition in immune-complex associated version
Describe the treatment for Membranoproliferative glomerulonephritis?
- ACEi/ARB and BP control in all
- Immune-complex disease
- Treat the cause
- C3 glomerulopathy
- Treatments to block C3 activation
When performing light microscopy, what does the term focal mean when describing glomerular disease?
Affecting some but not all glomeruli
When performing light microscopy, what does the term diffuse mean when describing glomerular disease?
Affecting >50% of glomeruli
When performing light microscopy, what does the term segmental mean when describing glomerular disease?
Affecting a portion of the glomerulus
When performing light microscopy, what does the term global mean when describing glomerular disease?
Affecting all of the glomerulus
When performing light microscopy, what does the term necrotising mean when describing glomerular disease?
- Severe injury leading to an area of necrosis
- Usually associated with vasculitis
When performing light microscopy, what does the term crescenteric mean when describing glomerular disease?
A crescent-shaped area of inflammatory cells responding to severe glomerular injury
When performing electron microscopy, what do subendothelial immune deposits indicate?
- Deposits found between the endothelial cells and the GBM
- Often with nephritic presentations
When performing electron microscopy, what do intramembranous immune deposits indicate?
- Deposits found within the GBM
- Found in the dense deposit variant of Mesangiocapillary glomerulonephritis
When performing electron microscopy, what do subepithelial immune deposits indicate?
- Found between the epithelial cells and GBM
- Often with nephrotic syndromes
- eg Membranous presentation of lupus
What are . the features often present in someone with Henoch-schonlein purpura?
- Arthralgia
- Haematuria +/- proteinuria
- Petechial rash of buttocks and lower legs
- Abdominal pain from vasculitis of the GIT
