Nephrotic Disease

Question 1

Definition of nephrotic disease

Answer 1

Proteinuria >3.5gms daily
Oedema
Hypoalbuminaemia
Hyperlipidaemia
Hypercoagulability

Question 2

Minimal change disease

Answer 2

Major cause of nephrotic disease in children

? cause:

• Allergic disease
• Drugs - NSAIDs, antibiotics, Li
• Cancer - Hodgkins lymphoma, NHL and leukaemia

Disease of podocytes - associated with high CD 80

Treatment:

• Diuresis and low Na diet
• Statins
• Steroids –> cyclophosphamide if non-response

Relapses common

Question 3

Membranous Nephropathy

Pathophysiology

Answer 3

Commonest cause of nephrotic disease in Caucasians
Caused by immune deposits underneath podocytes

1/3rd secondary:

• CTD - SLE
• Hepatitis B
• Drugs - Penicillamines, gold, NSAIDs, captopril
• Cancers - esp. >65yrs - Ca lung, prostate or GIT

2/3rd primary:
- 70% anti-PLA2R antibody positive
- PLA2R expressed on podocyte –> immune deposition
and complement activation -> GBM destruction

• 3% or 10% not anrti-PLA2R positive are THSD7A positive

Question 4

Membranous Nephropathy

Prognosis and treatment

Answer 4

Low risk = proteinuria <4gm/day and stable Cr = 8% CKD
Moderate risk = Proteinuria 4-8gm/day and stable Cr = 50% CKD
High risk = Proteinuria >8gm/day and reduced Cr = 75% CKD

Treatment=

• ACE-Is
• Statin
• Treat underlying cause if secondary MN
• Anti-coagulation if albumin <20gm
• If high risk = steroids and cyclophosphamide
• Can monitor PLA2R Abs for progress

Question 5

Focal segmental glomerulosclerosis

Causes

Answer 5

Sclerosis of parts of some glomeruli
Eventually –> all glomeruli

Primary = associated with SuPAR. >80% foot process effacement.

Secondary FSGS causes:

• Familial
• Infections - HIV, EBV, parvovirus B19
• Drugs - CNI, heroin, interferon Alfa, Li
• Adaptive - premature birth, reflux, HTN

Question 6

Focal segmental glomerulosclerosis

Classification

Answer 6

Classic = FSGS

Collapsing = collapse and sclerosis - associated with HIV. Poorest prognosis

Tip = segmental lesion at the tip of the glomerulus near the PT. Best prognosis

Cellular = Hypercellularity + FSGS

Perihilar = sclerosis of 50% of glomerulus at vascular pole - most commonly seen in secondary FSGS

Question 7

Focal segmental glomerlosclerosis

Treatment

Answer 7

Prednisone
If prednisone fails = cyclophosphamide or cyclosporine

40-60% of primary = remission with prednisone

Poor prognosis with worse proteinuria +/- HTN = ESRF in >50%

High recurrence rate in transplant

Question 8

Membranoproliferative Glomerulonephritis

Classifications

Answer 8

Increased mesangial and endocapillary cellularity with thickened GBM –> wire loop appearance

Immune complex mediated:

• HEPATITIS C!!! and other infections - malaria, HIV, HBV
• SLE, sjogrens syndrome
• Myeloma and MGUS

Complement mediated:

• C3 nef associated
• Inherited mutations of factor H
• Monoclonal gammopathies

Question 9

Immune complex MPGN pathogenesis

Answer 9

Results from chronic antigenaemia +/- circulating immune complexes
Occurs in chronic infection, autoimmune disease and myeloma

Caused by activated of the classical complement pathway

HCV = Kappa and lamba, IgM and C3 positive
Myeloma = kappa or lamba positive NOT BOTH
SLE = everything - C1q= most specific

Question 10

Complement mediated MPGN pathogenesis

Answer 10

Persistent activation of the alternative complement pathway
Due to:
- Presence of C3 convertase stabilising antibody - C3 Nef or
- Loss of functional factor H or
- monoclonal gammopathy

Results in isolated C3 deposition on IF

Question 11

MPGN Presentation

Answer 11

Haematuria with minimal proteinuria - 35%
Nephrotic syndrome with normal GFR - 34%
Chronic progressive GN - 20%
RPGN - 10%

Question 12

MPGN treatment and prognosis

Answer 12

ACE-Is and anti-HTN treatment
Aspirin

Immune complex = treat underlying disorder

Complement mediated =

• C3 nef = plasma exchange, rituximab or eculizumab
• Factor H deficiency = plasma exchange