Renal-nephrotic syndrome

Question 1

What is Nephrotic Syndrome?

Answer 1

Nephrotic Syndrome is a glomerular disorder characterized by:

Diagnostic:
1. Massive proteinuria (>3.5 g/day) AND
2. Hypoalbuminemia (<25g/L) AND
Edema (due to low oncotic pressure)
Hyperlipidemia & lipiduria (fatty casts in urine) - not required for diagnosis

Question 2

What are the major causes of Nephrotic Syndrome?

Answer 2

Primary (glomerular) causes:

Minimal Change Disease (MCD) – most common in children and in Singapore
Focal Segmental Glomerulosclerosis (FSGS) – most common in African origins
Membranous Nephropathy – associated with autoantibodies (PLA2R) most common in European origins
IgA Nephropathy (rarely presents as nephrotic)

Secondary causes:

Diabetes mellitus (diabetic nephropathy) - most common in adults
Lupus nephritis
Amyloidosis
Infections (Hepatitis B/C, HIV, syphilis)
Medications (NSAIDs, gold, penicillamine)

Question 3

What is the pathophysiology of Nephrotic Syndrome?

Answer 3

1. Glomerular injury → Increased permeability to proteins
2. Massive proteinuria → Loss of albumin
3. Hypoalbuminemia → ↓ Oncotic pressure → Edema
4. Liver compensates → ↑ Lipoprotein synthesis → Hyperlipidemia
5. Loss of antithrombotic proteins (e.g., antithrombin III) → Hypercoagulability

Question 4

What are the clinical features of Nephrotic Syndrome?

Answer 4

• Oedema– Periorbital oedema– Lower limb oedema– Oedema of the genitals– Ascites
• Low albumin– Tiredness– Leuconychia
• Breathlessness– Pleural effusion– Fluid overload (high jugular
  venous pressure)
• Breathlessness with chest pain– Thromboemboli
• Dyslipidaemia– Eruptive xanthomata– Xanthelasmata
• Other– Frothy urine

Question 5

What is the treatment approach for Nephrotic Syndrome?

Answer 5

General management:
- ACE inhibitors/ARBs (reduce proteinuria)
- Diuretics (for edema)
- Statins (for hyperlipidemia)
- Dietary protein intake 0.8-1g/kg/day replenish hypoalbuminemia
- Prophylactic anticoagulation in membranous nephropathy according to
balance of risk of bleeding and thrombosis
- Vaccinations to prevent infections
- AKI (to monitor kidney function)

Cause-specific treatment:
Steroids (for MCD
Immunosuppressants -cyclophosphamide, rituximab for relapse. For FSGS - steroids, cyclophosphamide, Ciclosporin, MMF. For MN ritux, cyclosporin/tacrolimus +- ritux, steroids+cycophosphamide, MMF+steroids)
Manage secondary causes (e.g., diabetes, lupus, infections)

Question 6

What are the complications of Nephrotic Syndrome?

Answer 6

1. Edema (can lead to anasarca, pleural effusion)
2. Hypercoagulability → Risk of DVT/PE, renal vein thrombosis
3. Infections (loss of IgG & complement)
4. Acute kidney injury (AKI) 2’excessive diuresis/renal vein thrombosis or progression to CKD
5. Hyperlipidemia 2’ low oncotic pressure which stimulates lipoprotein production by hepatocytes

Question 7

What is normal for protein and albumin excretion per day? What is nephrotic range of proteinuria?

Answer 7

Normal protein excretion
< 150 mg/day (<0.15g/day)
Normal albumin excretion
< 10-20 mg/day
Nephrotic range >3.5g/day

Question 8

What are some investigations to assess for etiology of nephrotic syndrome

Answer 8

• UFEME, urine phase contrast
• ANA, anti-dsDNA, C3, C4, ESR
• Fasting glucose/ HbA1c
• HBSAg and anti HCV IgG, VDRL, HIV serology
• Serum and urine protein electrophoresis / serum free light chains – monoclonal protein
  BUT low detection in routine screening hence generally indicated in age >40 years
• U/S kidneys +/- Doppler renal vessels – Renal vein thrombosis– Kidney size – larger kidneys in DM, amyloidosis
• Renal biopsy (Gold standard). Indicated when persistent proteinuria >0.5g/day or rapid deterioration in renal function or presence of active urinary sediment