Glomerulonephritis Flashcards
What is Glomerulonephritis?
Glomerulonephritis includes a range of immune-mediated disorders that cause inflammation within the glomerulus and other compartments of the kidney
What is the pathological basis underlying Glomerulonephritis?
Immunological attack by antibody/T-cell upon antigens in glomerulus
-antigens can be primary or secondary (acquired/deposited)
What are the secondary factors causing deposition of antigens?
NSAID HSP
- neoplasm
- SLE
- amyloid
- infection
- diabetes
- Henoch Schonlein Purpura
What is the pathological response to the primary immunological attack in the glomerular capillaries?
Endothelial cell proliferation
Capillary wall necrosis
Glomerulosclerosis
What is the pathological response to the primary immunological attack in the basement membrane?
Thickened membrane –> structural distortion –> increased permeability
What is the pathological response to the primary immunological attack in the tubules?
Deposition of cells in Bowman’s space
What are the three layers of the glomerulus?
Fenestrated capillary epithelium
Basement membrane
Visceral layer (interdigitating podocytes)
What words are used to describe glomerular pathology histologically?
Global = whole glomerulus diseased Segmental = small patches of one glomerulus damaged Diffuse = affects >50% glomeruli Focal = affects <50% glomeruli
How can glomerular damage/glomerulonephritis present?
AKI (if initially severe enough) CKD Asymptomatic haematuria Nephrotic syndrome Nephritic syndrome Rapidly progressive glomerulonephritis
What are the stages of progression of glomerulonephritis?
Asymptomatic dipstick abnormalities
Nephrotic syndrome
Nephritic syndrome
ESRD
What investigations are appropriate in suspected glomerulonephritis?
Bloods (FBC, U&Es, CRP, culture) Urine dip (?infec) MCS (red cells/casts) Urine protein:creatinine ratio Nephritic screen Renal USS + biopsy
Why is urine protein:creatinine ratio used?
More convenient than 24hr urinary protein & equally accurate
What random protein:creatinine ratio would be suggestive of disease?
50-100mg/mmol = significant proteinuria >300mg/mmol = nephrotic range
What are the main pathological processes affecting the glomerulus?
IgA nephropathy (Beurger's disease) Minimal change nephropathy Membranous nephropathy Focal segmental glomerulosclerosis Membranoproliferative GN Post-streptococcal GN HSP Goodpasture's syndrome Systemic vasculitis Rapidly progressive GN
What is IgA nephropathy (Beurger’s disease)?
Lower end of a spectrum ending in HSP
Most common cause of GN in adults
How does IgA nephropathy present?
Mostly affects young males, often after an URTI
Haematuria (macroscopic)
Nephritic syndrome
How should suspected IgA nephropathy be investigated?
Renal biopsy (IgA/C3 deposits)
How should IgA nephropathy be managed?
Supportive
Steroids may slow decline in renal function
-20% progress to ESRD over 20yrs
What is minimal change nephropathy?
Most common cause of GN in children (75%)
Common cause of nephrotic syndrome in adults (20%)
What are the causes of minimal change nephropathy?
NSAID
Allergy
Hodgkin’s lymphoma
How should suspected minimal change nephropathy be investigated?
Light microscopy (normal) Immunofluorescence (negative) Electro-microscopy (fusion of podocyte foot processes)
How should minimal change nephropathy be managed?
Oral steroids
-99% of cases resolve in 4-6wks
-1% of cases progress to ESRD
Cyclosporin
What is membranous nephropathy?
Rare cause of nephrotic syndrome
-80-90% idiopathic
How should membranous nephropathy be investigated?
Renal biopsy (global diffuse GN w/ IgG & C3 deposits)
How should membraneous nephropathy be managed?
Alternating steroids & cyclophosphamide
-25% progress to ESRD in 10yrs
What is focal segemental glomerulosclerosis?
Idiopathic areas of segmental sclerosis
How should focal segmental glomerulosclerosis be investigated?
Renal biopsy (IgM & C3 deposits)
How should focal segmental glomerulosclerosis be managed?
Poor response to treatment
What is membranoproliferative glomerulonephritis?
Cause of nephrotic OR mixed nephrotic/nephritic syndrome
How should membranoproliferative glomerulonephritis?
Renal biopsy (large glomeruli w/ double BM)
How should membranoproliferative glomerulonephritis be managed?
No proven treatment
50% develop ESRD in 10yrs
High recurrence rate in transplants
How does post-streptococcal glomerulonephritis present?
Nephritic syndrome 1-2wks post sore throat/skin infection
How should suspected post-streptococcal glomerulonephritis be investigated?
Renal biopsy (diffuse proliferative GN w/ IgG & C3 deposits) -no need to biopsy in typical cases Bloods (raised ASOT/anti-DNAse B, reduce complement)
What is HSP?
Small vessel vasculitis & nephritic syndrome post URTI
-typically affects children 3-15yrs
Severe end of a spectrum starting w/ IgA nephropathy
How does HSP present?
Purpuric rash on extensor surfarces Polyarthritis Abdo pain (GI bleeding) Scrotal/scalp swelling GN
How should suspected HSP be investigated?
Clinical diagnosis
Confirm w/ +ve immunofluorescence in skin/renal biopsy
How should HSP be managed?
Attacks typically self limiting
If relapses/evidence of progression give corticosteroids
What is Goodpasture’s Syndrome?
Type II hypersensitivity reaction to type IV collagen
-present in glomerular/alveolar BM & ear/eye
How does Goodpasture’s Syndrome present?
Haematuria
Rapidly progressive GN
Pulmonary haemorrhage (SOB, haemopytsis)
How should suspected Goodpasture’s Syndrome be investigated?
CXR (pulmonary shadowing) Renal biopsy (IgG deposition across glomerular BM)
How should Goodpasture’s Syndrome be investigated?
Plasma exchange
Corticosteroids +/- cytotoxics
-variable prognosis
Describe systemic vasculitis
Leads to focal segmental GN
ANCA +ve
What is rapidly progressive glomerulonephritis?
Glomerulonephritis leadinging to ESRD over a few days
Presents w/ signs of renal failure & systemic disease
What are the causes of rapidly progressive glomerulonephritis?
Immune complex disease (45%, SLE, IgA nephropathy)
Vasculitis (50%, HSP, Wegeners, Churg-Strauss)
Goodpasture’s (5%)
How should rapidly progressive glomerulonephritis be managed?
Aggressive immunosuppression
-high dose steroids
-cyclophosphamide
Variable prognosis
