Glomerulonephritis Flashcards
Define glomerulonephritis
Immune mediated disease of the kidneys affecting the glomeruli
What does damage to endothelial/mesengial cells causes?
Proliferative lesion and RBC in urine
What does damage to podocytes cause?
Non proliferative lesion and protein in urine as cell atrophies and loses size/charge specific barrier
Name the different parts of the glomerular apparatus
Podocyte
Mesangium
Endothelial cell
How does the mesangium response to injury?
Releases angiotensin II and chemokines which attracts inflammatory cells leading to proliferation
What is the effect of endothelial response to injury?
Vasculitis
Name seven ways in which glomerulonephritis can present
- haematuria
- proteinuria
- impaired renal function
- hypertension
- nephrotic syndrome
- nephritis syndrome
- nephrotic-nephritic syndrome
State two types of haematuria
Asymptomatic microscopic
Painless macroscopic
What is microalbuminuria?
30-300mg/day
Describe nephritic syndrome
Acute renal failure, oliguria, oedema/fluid retention, hypertension, active urinary sediment (RBC, granular casts)
What is nephritic syndrome indicative of?
Proliferative process affecting endothelial cells
Describe nephrotic syndrome
Proteinuria >3g/day, hypolabuminaemia <30, oedema, hyperchoelsterolaemia, normal renal function
What does nephrotic syndrome indicate?
Non-proliferative process affecting the podocytes
State six complications of nephrotic syndrome
- infection (loss of antibodies)
- renal vein thrombosis
- pulmonary emboli
- volume depletion
- vit D deficiency
- subclinical hypothyroidism
How is glomerulonephritis investigated?
Renal biopsy
Light microscopy, immunofluorescence, EM
What is the commonest cause of nephrotic syndrome in kids?
Minimal Change Nephropathy
What is minimal change nephropathy associated with?
Atopy
Post URTI
NSAIDs
Describe the biopsy of minimal change nephropathy
Normal on LM and IF
EM, podocyte apoptosis - gaps between podocytes
What is the immunology behind minimal change nephropathy?
Unknown antigen and antibody but possible caused by IL13
What is the 1st line treatment for minimal change nephropathy?
Oral steroids
What is the second line treatment for minimal change nephropathy?
Cyclophosphamide
Does minimal change nephropathy cause progressive renal failure?
No
What is the commonest cause of nephrotic syndrome in adults?
Focal Segmental Glomerulosclerosis
What can cause Focal Segmental Glomerulosclerosis?
Primary
Secondary to HIV, heroine use, obesity, reflux nephropathy
What will the biopsy of Focal Segmental Glomerulosclerosis show?
LM - sclerosis and mesangial collapse
EM - podocyte fusion (diffuse in primary, limited to sclerotic area in secondary)
How is Focal Segmental Glomerulosclerosis treated?
Prolonged steroids
What is the prognosis for Focal Segmental Glomerulosclerosis?
50% progress to ESRF after 10 years
How does membranous nephropathy present?
Proteinuria and often renal impairment - common cause of nephrotic syndrome in older patients
What may membranous nephropathy be secondary to?
Infections (HBV, parasites)
Connective tissue disease (SLE)
Malignancies (carcinomas/lymphomas)
Drugs (gold, penicillamine)
What will a biopsy of membranous nephropathy show?
EM Sub epithelial immune complex deposition in basement membrane
LM thickening of GBM
IF IgG/C3 granular deposits
How is membranous nephropathy treated?
Steroids, alkylating agents, B cell monoclonal antibodies
What antibody is membranous nephropathy associated with?
Anti PLA2r - deposits in blood and glomeruli
What is the commonest glomerulonephropathy?
IgA nephropathy
How does IgA nephropathy present?
- Macroscopic haematuria after resp/GI infection
- asymptomatic microhaematuria and maybe proteinuria
- AKI
- CKD
What disease is IgA nephropathy associated with?
Henoch Schonlein Purpura
How does HSP present?
Children with a purpuric rash, colitis, arthritis and may have fluid retention or hypertension
What does a biopsy of IgA nephropathy show?
LM- mesangial IgA
IF - IgA and C3
EM - Deposits in mesangium
Describe the pathophysiology of IgA nephropathy
- Increased circulating levels of Gd-IgA1
- Production of Anti-IgA1 antibodies
- Immune complexes form in circulation and in situ
- Local immune activation and injury
What disease is associated with crescents on biopsy?
Rapidly Progressive Glomerulonephritis
Name two types of vasculitis that cause RPG
- granulomatosis with polyangitis
- microscopic polyangitis
What ANCA negative diseases can cause RPG?
- goodpastures
- HPA
- SLE
What are crescents?
Collections of cells epithelium, inflammatory cell… that adhere to the glomerular tuft and bowman’s capsule
What can the crescents do?
Close the capillary lumen
Describe the pathological steps in ANCA positive RPG
- Priming of neutrophils induces PR3 and MPO to the cell surface where they interact with ANCA
- Promotes adherence of neutrophils to endothelial cells
- Further priming induces the release of proteolytic enzymes and reactive oxygen species
- ANCA activated neutrophils promote inflammation
What treatment can nephrotic patients receive?
Fluid salt restrictions Diuretics ACEi/ARB IV albumin if volume depleted Immunosuppression
What is complete remission of nephrotic syndrome?
<300mg/day
What is partial remission of nephrotic syndrome?
<3g/day
What immunosuppressive treatments are available for glomerulonephritis?
Corticosteroids Azathioprine Alkylating agents (cyclophosphamide/chlorambucil) Calcineurin inhibitors MMF
In severe glomerulonephritis what are the treatment options?
Plasmapheresis
IV immunoglobulin
Monoclonal antibodies
What is the treatment for RGP?
Strong immunosuppression - steroids or cytotoxins
Name three cytotoxins
- cyclophosphamide
- MMF
- Azathioprine
If immunosuppressants fail what is the last line treatment for glomerulonephritis?
Plasmapheresis/dialysis
