Renal - Glomerulonephritis: Nephrotic Syndrome

Question 1

What is the classic triad of signs in nephrotic syndrome?

Answer 1

• Proteinuria (>3g/24h)
• Hypoalbuminaemia (<30g/L)
• Oedema

Question 2

Name 5 causes of nephrotic syndrome

Answer 2

• Minimal change disease
• Membranous glomerulonephritis
• Focal segmental glomerulosclerosis
• Amyloidosis
• Diabetic nephropathy

Question 3

What occurs to clotting risk and thyroxine levels during nephrotic syndrome?

Answer 3

• Loss of antithrombin III, proteins C and S and associated rise in fibrinogen levels predisposes to thrombosis
• Loss of thyroxine binding globulins lowers total, but not free, thyroxine levels

Question 4

Amyloidosis: overview of MOA

Answer 4

• Amyloidosis describes extracellular deposition of insoluble fibrillation protein (amyloid)
• accumulation of amyloid fibrils in arterioles/arteries and within glomerulus (mesangial expansion) is similar to modular lesions seen in diabetic nephropathy

Question 5

Minimal change Glomerulonephritis: PC and renal biopsy appearance

Answer 5

PC

• Typically a child with nephrotic syndrome (account for 80%)
• nephrotic syndrome
• normotension
• highly selective proteinuria: albumin/transferrin leak out of glomerulus
• Renal biopsy: fusion of podocytes

Question 6

Minimal change Glomerulonephritis: causes and management

Answer 6

Causes: Hodgkin’s, NSAIDs, rifampicin, infectious mononucleosis

Management

• majority of cases are steroid responsive
• cyclophosphamide is next step for steroid resistant cases

Question 8

Membranous Glomerulonephritis: PC, pathophysiology and prognosis

Answer 8

• Presentation: second most common nephrotic syndrome in adults, proteinuria, nephrotic syndrome, chronic kidney disease
• Pathophysiology: IgG Auto antibodies made against BM form immune complexes, which form MACs and then release proteases and oxidases which damage capillary walls and make them leaky. (Low serum C3 levels) There is decreased selectivity of filtration and non selective proteinuria.
• Prognosis: 1/3 improve, 1/3 remain same, 1/3 progress to renal failure

Question 9

Focal segmental glomerulosclerosis: cause, prognosis and rx

Answer 9

• Cause: May be idiopathic or secondary to HIV/heroin
• Prognosis: poor, little response to steroids, tends to progress towards renal failure.
• Rx: dialysis/other renal support measures

Question 10

Focal segmental glomerulosclerosis: PC and Pathophysiology

Answer 10

• PC: proteinuria, nephrotic syndrome, CKD

- Pathophysiology: unclear, get segmental sclerosis of glomerulus, which leads to decreased selectivity and proteinuria

Question 11

Diabetic nephropathy: stages

Answer 11

1. Hyperfiltration: increase in GFR
2. Latent stage: peak in GFR
   - Mesangial cells secrete matrix, increasing glomerular size and causing kidney hypertrophy
3. Microalbuminaemia: GFR returns to normal levels
   - Appearance of Kimmelstiel-Wilson nodules, podocyte disruption and increase of permeability
4. Over proteinuria: fall in GFR
   - Diffuse glomerular histopathological changes, worsening systemic HTN
5. End stage renal disease

Question 12

Why is RAAS inhibition important for management of diabetic nephropathy/nephrotic syndrome?

Answer 12

Angiotensin II has following effects:

• Increases glomerular permeability to proteins
• Stimulates mesangial cell proliferation and increases secretion of mesangial matrix
• Causes efferent arteriolar constriction, increase glomerular pressure
• Use ACEi

Question 14

Outline the Mx for a pt with nephrotic syndrome

Answer 14

• Monitor U&E, Fluid balance, wt
• treat underlying cause (eg steroids/cyclophosphamide)
• Oedema: salt and fluid restriction + furosemide
• Proteinuria: ACEi/ARB
• Lipidaemia: statin
• VTE: enoxaparin/local guideline anticoagulate
• HTN: follow pathway based on age/ethnicity