nEPHROTIC-Membranous Nephropathy

Question 1

What is membranous nephropathy?

Answer 1

A chronic slowly progressive disease characterized by glomerular basement membrane thickening, subepithelial immune complex deposits, and effacement of foot processes.

Question 2

At what age group do we see the peak incidence of membranous nephropathy?

Answer 2

Between ages 30-50

Question 3

Are the majority of membranous nephropathy cases primary or secondary?

Answer 3

Primary (85%)

Question 4

What are some of the causes of secondary membranous Nephropathy?

Answer 4

1. SLE
2. Sickle cell disease
3. Occult carcinoma (Lung cancer, colon cancer, melanoma)
4. complement deficiency (Particularly C2)
5. Hepatitis B
6. Syphilis
7. Malaria
8. Drugs
   * -Penicillamine
   - Captopril
   - Gold
   - NSAIDs
9. Possible link with Diabetes mellitus and thyroiditis

Question 5

What is the pathogenesis in autoimmunity secondary membranous nephropathy?

Answer 5

Autoantibodies bind to NEP (main target) and M-Type phospholipase A2 which is exressed on normal podocytes.

Question 6

What is responsible for the damage to podocytes?

Answer 6

IgG4 and complement (the MAC)

Question 7

What happens to C3a andC5a in membranous nephropathy after formation of the complex?

Answer 7

Washed away in urinary space

Question 8

What are the changes detected by light microscope in Membranous nephropathy?

Answer 8

1.Only detectable change is a thickening of the GBM

Question 9

What changes are visible on electron microscopy?

Answer 9

Shows that thickening is due in part to abundant subepithelial deposits. This tracts of new glomerular basement membrane separate the deposits forming minute spikes. The babsement membrane can cover some of the deposits creating an appearance called the spike and dome pattern.

Question 10

What would immunofluresece reveal in Membranous nephropathy?

Answer 10

Granular subepithelial deposits of immunoglobulins (igG) and complement especially C3 along the GBM

Question 11

Is there any inflammation in Membranous nephropathy?

Answer 11

No. Complement is activated at a that is not in contact with circulating inflammatory cells

Question 12

What are the associations with advanced Membranous nephropathy?

Answer 12

Tubular Atrophy and interstitial fibrosis.

Question 13

What are the signs and symptoms of Membranous nephropathy?

Answer 13

1. Nephrotic syndrome
2. Asymptomatic proteinuria (non slective)
3. Microscopic hematuria may be present
4. Some may have thromboembolic complications
5. Hypertension in 30% of cases with normal GFR

Question 14

How is the diagnosis of Membranous nephropathy made?

Answer 14

Renal Biopsy (No serologic abnormalities)

Question 15

What is the treatment for Membranous nephropathy?

Answer 15

1. ACE inhibitor or ARB given as tolerated to lower BP to 125/75 mm Hg and reduce proteinuria.
2. Lipid lowering agent usually given
3. Cytotoxic agent and Prednisone indicated for progressive cases and those with nephrotic syndrome at risk for progression.

Question 16

What are the risk factors for progression?

Answer 16

1. Male Gender
2. Severe proteinuria (10grams/24 hours /more)
3. Hypertension
4. Azotemia
5. Tubulointerstitial fibrosis
6. Glomerulosclerosis

Question 17

Is Membranous nephropathy responsive to corticosteroids?

Answer 17

Often disappointing. not usually.