Nephrotic Syndrome Flashcards
What is Nephrotic syndrome?
Occurs when the GBM becomes highly permeable to protein, allowing them to leak from the blood into the urine.
How does Nephorotic syndrome present?
- Frothy urine
- Generalised oedema
- Pallor
What is the classic triad seen of Nephrotic syndrome?
- Low serum albumin
- High urine protein content (>3+ protein on urine dipstick)
- Oedema
List 3 other features that occur in patients with nephrotic syndrome
- Deranged lipid profile, ↑cholesterol, TAGs and LDLs
- ↑BP
- Hyper-coagulability, ↑ risk of thrombis
What is the structure of the glomerulus?
- Fenestrated endothelial cells
- GMB
- Podocytes
Study light micrograph of a ‘normal’ glomerulus
Only 1 or 2 cells per capillary tuft
Capillary lumens are open
Thickness of the glomerular capillary wall (long arrow) is similar to tubular basement membranes (short arrow)
Mesangial cells and mesangial matrix are located in central regions of the tuft (arrows)
Pathophysiology of Proteinuria? (3)
- Podocyte foot process effacement, slit diaphragm disruption, depletion of podocytes
- Mutations
- Nephrin and podocin → maintain slit diaphragm
- Alpha-actinin-4 → integrity of podocyte cytoskeleton
- Autoantibodies to podocyte antigens or circulating factors that affect podocyte
Pathophysiology of oedema in Nephrotic syndrome?
What is the general management of Nephrotic syndrome?
- High dose steroids (i.e. prednisolone)
- Low salt diet
- Diuretics → oedema
- Albumin infusions in severe hypoalbuminaemia
- Antibiotic prophylaxis in severe cases
List 3 primary and 3 secondary cause of Nephrotic syndrome
Primary
- Minimal change disease
- Membranous GN
- Focal segmental glomerulosclerosis (FSGS)
Secondary
- Diabetic nephropathy
- Amyloidosis
- Lupus
What is the most common cause of Nephrotic syndrome in children?
Minimal change disease
Causes of Minimal change disease?
Which is the most common
Most commonly it occurs with no clear underlying condition or pathology
May be secondary to
- Intrinsic kidney disease
- HSP
- Diabetes
- HIV, hepatitis and malaria
What changes are seen in minimal change disease for the following:
- Light microscopy
- Immunofluorescence
- Electron microscopy
- LM – Normal
- IF – Normal (no immune deposits)
- EM – Fusion of podocytes and effacement of foot processes
Pathogenesis of minimal change disease?
T-cell and cytokine-mediated damage to the glomerular basement membrane → polyanion loss
Resultant reduction of electrostatic charge → ↑ glomerular permeability to serum albumin
Management and prognosis of minimal change disease
Management:
- Corticosteroids (i.e. prednisolone)
- Cyclophosphamide and ACEi for steroid-resistant cases
Prognosis: Good, most children make a full recovery (may relapse)
What is commonest cause of nephrotic syndrome in adults (non diabetic)?
Focal Segmental Gomerulosclerosis (FSGS)
Causes of FSGS?
- Idiopathic
- Secondary to other renal pathology e.g. IgA nephropathy, reflux nephropathy
- HIV
- Heroin
- Alport’s syndrome or Sickle-cell
What changes are seen in FSGS for the following:
- Light microscopy
- Immunofluorescence
- Electron microscopy
LM: focal and segmental sclerosis and hyalinosis
IF: IgM and C3 deposition in sclerotic areas
EM: effacement of foot processes
FSGS is noted for having a high recurrence rate in ___________
Renal transplants
Management and prognosis of FSGS?
Management: steroids +/- immunosuppressants
Prognosis: rule of thirds
- 1/3: spontaneous remission
- 1/3: remain proteinuric
- 1/3: develop ESRF
What is the commonest cause of cause of nephrotic syndrome in adults?
Membranous glomerulonephritis
Causes of Membranous GN?
- Idiopathic: due to anti-phospholipase A2 antibodies
- Infections: hep B, malaria, syphilis
- Malignancy: prostate, lung, lymphoma, leukaemia
- Drugs: gold, penicillamine, NSAIDs
- Autoimmune: SLE, thyroiditis, RA
What changes are seen in Membranous GN for the following:
- Light microscopy
- Immunofluorescence
- Electron microscopy
LM: Thickened capillary BM, BM spikes on silver stain
IF: diffuse granular GBM staining
EM: thickened BM with subepithelial deposits → spikes on silver stain
Pathogenesis of Membranous GN?
Circulating antibodies permeate GBM and form immune complexes
(Phospholipase A2 receptor in 75-80% of primary MN)
List 4 complications of Nephrotic syndrome
- Hypovolaemia: fluid leaks into interstitial space → oedema and ↓BP
- Thrombosis: ↓ATIII + ↑clotting factors
- Infection: kidneys leak Ig’s, ↓ immune system + exacerbated by steroid treatments
- AKI or CKD
- Relapse
