Nephrotic syndrome

Question 1

Clinical nephrosis syndrome definition

presentation

Answer 1

Increased the permeability of the glomerulus to proteins, causing frank/massive proteinuria, above 3g/day albumin, 4.5g/day protein. Loss of albumin, immunoglobulins, AT3, and lipids.

Presentaion:
Proteinuria
Lipiduria
Hypoalbuminuria
Hyopgammaglobulinemia - infections

Hypercoagulability - thrombi
Hyperlipidemia, 
Hypercholesterolemia
Generalized pitting edema
Edema and causes functional hypovolemia and decreased GFR. RAAS activation and exacerbated edema, may or may not present with hypertension. 

Edema may cause decompensated heart failure, and acute pre-renal AKI, progressing to renal failure.

Note that there is NOT azotemia or hematuria,, as seen in nephritis. At least initially.

Question 2

Frequent complications of nephrosis syn

Answer 2

Thrombi

Infections

Pre-renal AKI

Accelerated atherosclerosis and cardiovascular events.

Question 3

Treatment of minimal change nephropathy

Answer 3

Methylprednisolone, 1mg/kg, Tapered off over 2-3 months.

Diuretics and Anticoagulants if needed for symptoms

Question 4

Treatment of Focal Segmental Glomerulosclerosis

Answer 4

Prednisolon for 8-16 weeks, tapering off (not usually very responsive to the steroids)

For relapsing FSGS:

Cyclophosphamide

Cyclosporine + Prednisolone

Mycophenolate mofetil.

Plasmapheresis in resistant FSGS

Question 5

Membranous nephropathy, microscopic description

Answer 5

Most common adult nephropathy

An in-situ reaction of either antibodies against podocyte foot process antigens, or against planted antigens in the sub-epithelial region, granular staining (even though its called membranous, it is GRANULAR STAINING) of IC deposits in the subepithelium.

Spike and dome pattern on EM. Some of the deposits get degraded and leave cavities in the BM.

The podocytes lay down new basement membrane because they don’t like being on the IC deposits, causing a diffuse thickening of the capillary walls,

Question 6

Membranous nephropathy

prognosis and treatment

Answer 6

Spontaneous remission in 20%
Spontaneous partial remission in 25-40%
The rest will progress to end stage kidney by about 15 years, 15% by about 5 years.

Treatment: based on degree of proteinuria
< 3.5g/day, symptomatic treatment
- diuretics, ACEIs or ARBs, anticoagulation as needed

> 3.5g/day with symptoms: immunosuppression as well as symptomatic treatment
Alternating monthly treatments of prednisolone and cyclophosphamaide.

May also give Rituximab - Binds B-cell CD20 receptor, promotes B-cell apoptosis and inhibits activation.

Question 7

Membranoproliferative glomerulonephritis

microscopic description

Answer 7

Mesangial and endothelial cell proliferation
Thickened basement membrane.
Tram Track splitting of the GBM in both types 1 and 2,
more so in type 1.

IC or planted antigens are located in the subENDOthelial layer.

Question 8

Membranoproliferative GN types and associated diseases

Answer 8

Type 1: SLE, HBV and HCV
Circulating IC or planted antigens in the subendothelial layer

Type 2: idiopathic, anti-C3 convertase autoantibodies and excessive complement activation.
circulating ICs are deposited inside the lamina densa of the GBM, the middle layer of the basement membrane.

Question 9

Membranoproliferative GN prognosis and treatment

Answer 9

Spontaneous remission 10-20%
End stage kidney in 60% in 15 years.

treatment:

Aspirin ad dipyridamol for 3 years

Prednisolone 2-3 years

Prednisolone and Azathioprine/mycophenolate motefil.

Dense deposit disease eculizumab - monoclonal complement C5 inhibitor

Question 10

Treatment of SLE:

Answer 10

Renal disease in SLE can cause RPGN and usually need aggressive immunosuppresion.

• Steroids
• Cyclophosphamide
• Mycophenolate mofetil
• Rituximab