Nephrotic syndrome

Question 1

What is nephrotic syndrome?

Answer 1

Nephrotic syndrome is a process by which damage occurs to the podocytes such that they no longer function. As a result, they are unable to prevent protein entering the ultrafiltrate and therefore proteinuria is present (3.5g/day). This will cause the urine to be frothy (proteinuria causes froth). A reduction of proteins in the intravascular space reduces the oncotic pressure and therefore fluid is not retained in the intravascular space. This causes a leakage of fluid and presents with oedematous (peri-orbital, peripheral etc.). Furthermore, the main loss of protein is a decrease in albumin. The liver will compensate for this decrease in albumin and consequently there will be an increase in lipids. Another protein lost is anti-thrombin III, this reduction results in a hypercoagulable state. This reduction in anti-thrombin III can results in thrombosis of the renal vein as the anti-thrombin III level in the renal vein is especially low. Thrombosis of the renal vein can embolise and cause DVT’s or PE’s.

Overall:
 Loss of podocyte function = Proteinuria (frothy urine) and excess fluid loss
 Oedematous state
 ↓ albumin is compensated for by ↑lipids
 ↓ Anti-thrombin III results in a hypercoagulable state and ↑ likelihood of DVT/PE

Question 2

What are the causes/types of nephrotic syndrome?

Answer 2

• Membranous nephropathy
• Minimal change disease
• Focal segmental glomerulosclerosis (FSGS)
• Mesangiocapillary GN (MCGN)
• Diabetic nephropathy
• SLE
• Amyloidosis,
• Hepatitis B/C

Question 3

What is ‘minimal change nephropathy’, how is it detected and how is it treated?

Answer 3

Minimal change nephropathy is the commonest cause of nephrotic syndrome in children. In adults it can be idiopathy or in associated with drugs (NSAIDs) or paraneoplastic (usually Hodgkin’s lymphoma).

Biopsy will appear normal under light microscopy (hence the name). Electron microscopy shows effacement of the podocyte for processes.

Treatment: 90% of children and 70% of adults undergo remission with steroids.

Spontaneous remission can occur, and this suggests the benefits of steroids is to hold disease until the poorly understood underlying process abates. Approximately 1% of patient will develop ESRF.

Question 4

What is membranous nephropathy, how does the biopsy appear, how is it treated and what is the prognosis like?

Answer 4

Immune deposits on basement membrane and a second membrane forms over these deposits with irregular spikes where several immune complexes deposited
Membranous nephropathy accounts for 20-30% pf nephrotic syndrome in adults and 2-5% in children. Mostly idiopathic, but can be associated with malignancy, hepatitis c, drugs and autoimmunity (thyroid, SLE).

Biopsy: diffusely thickened GBM with IgG and C3 deposits on immunofluorescence.

Treatment:

• Secondary treatment involves treating the underlying cause, proteinuria often remits.
• In idiopathic membranous nephropathy, treatment involves general measure such as ACE/ARB and diuretics.

Prognosis: Spontaneous complete remission occurs in up to 30% and partial remission in 24-40% by 5 years.

Question 5

what is focal segmental glomerulosclerosis (FSCS), how does the biopsy appear, how is it treated and what is the prognosis like?

Answer 5

FSGS may be primary (idiopathic) or secondary (vesico-ureteric reflux, IgA nephropathy, vasculitis). FSGS presents with nephrotic syndrome or isolated proteinuria.

Biopsy: some glomeruli have scarring of certain segments i.e. focal sclerosis, with IgM and C3 deposits in affected areas.

Treatment: responds to corticosteroids in approx. 30%

Prognosis: if untreated most will progress to ESRF. Spontaneous remission occurs in <10%. Those presenting with abnormal renal function have a much poorer prognosis- 30-50% will progress to ESRF.

Question 6

What is mesangiocapillary glomerulonephritis, how does the biopsy appear, how is it treated and what is the prognosis like?

Answer 6

Previously divided into type I, II and IIII, now divided into immune complex mediated and complement mediated.
Immune complex mediated is driven by circulating immune complexes, which deposit in the kidney and activate complement via the classical pathway. An underlying cause can be found in most cases e.g. hepatitis C, SLE
Complement mediated is less common and involves persistent activation of the alternative complement pathway.

Biopsy: mesangial and endocapillary proliferation of the capillary walls.

Treatment:
o Treat underlying cause as priority.
o ACEi/ ARB for all patients
o Immunosuppression if rapid progression of disease with steroids +/_ cyclophosphamide if rapid deterioration in renal function]

Prognosis; poor when no underlying cause can be found. In patients who reach ESRF it can recur in transplants and lead to graft loss