Nephrotic syndrome

Question 1

Define

Answer 1

• Nephrotic syndrome is characterised by a triad of:
o Proteinuria (> 3.5 g/24 hr)
o Hypoalbuminaemia (< 30 g/L)
o Oedema
o Hyperclipidaemia and thrombotic disease are also common features

Question 2

What are the risk factors/causes?

Answer 2

• Most commonly caused by: minimal change glomerulonephritis in children
• However, ALL forms of glomerulonephritis can cause nephrotic syndrome
• Other causes:
o Diabetes mellitus
o Sickle cell disease
o Amyloidosis
o Malignancies (lung and GI adenocarcinomas, multiple myeloma)
o Drugs (e.g. NSAIDs)
o Alport’s syndrome
o HIV

The most common cause in younger adults is FSGS, followed by minimal change nephropathy. Membranous nephropathy is the most common cause in older people, [2] [3] and diabetic nephropathy in adults with a history of long-standing diabetes.

Question 3

What’s the pathophysiology?

Answer 3

Hypercoagulability results from the loss of inhibitors of coagulation in the urine and increased synthesis of procoagulatory factors by the liver. [8] The oedema is due to a combination of a decrease in oncotic pressure from the hypoalbuminaemia, as well as a primary renal sodium retention in the collecting tubules. [9] [10] Patients with nephrotic syndrome are also at increased risk of infection due to loss of immunoglobulins and complement and other compounds being lost in the urine.

Question 4

Epidemiology

Answer 4

• 90% of nephrotic syndrome in CHILDREN is due to minimal change glomerulonephritis
• Most common cause of nephrotic syndrome in ADULTS:
o Diabetes mellitus
o Membranous glomerulonephritis

Question 5

What’s the presenting symptoms?

Answer 5

• Family history of atopy (in those with minimal change glomerulonephritis)
• Family history of renal disease
• Swelling of face, abdomen, limbs, genitalia (due to hypoalbuminaemia)
• Symptoms of the underlying cause (e.g. SLE)
• Symptoms of complications

Question 6

What are the signs?

Answer 6

• Oedema: periorbital, peripheral, genital
• Ascites: fluid thrill, shifting dullness
• Hypercholesterolaemia: xanthelasmata

Question 7

What are the appropriate investigations?

Answer 7

•	Bloods
o	FBC 
o	U&E
o	LFTs (low albumin)
o	ESR/CRP
o	Glucose
o	Lipid profile (check for secondary hyperlipidaemia) 
o	Immunoglobulins 
o	Complement

• Tests to identify the cause
o SLE - ANA, anti-dsDNA antibodies
o Infections:
• Group A -haemolytic streptococcal infection (ASO titre)
• HBV and HCV infection (serology)
• Plasmodium malariae (blood film)
o Goodpasture’s Syndrome - anti-glomerular basement antibodies
o Vasculitides - polyangiitis with granulomatosis, microscopic polyarteritis (check ANCA)

• Urine
o Urinalysis (check protein and blood)
o MC&S
o 24 hr collection (calculate creatinine clearance and 24 hr protein excretion)

• Renal Ultrasound
o Exclude other causes (e.g. reflux nephropathy)

• Renal Biopsy
In all adults and children who have unusual features and don’t respond to steroids

• Other imaging: Doppler ultrasound, renal angiogram, CT or MRI (if renal vein thrombosis suspected)