TOPIC 8 : nephrotic syndrome

Question 1

basic principles of nephrotic syndrome

Answer 1

glomerular disorders characterised by proteinuria >3.5g/day resulting in:

1) hypoalbuminemia( <25g/L)-pitting edema
2) hypogammaglobulinemia-increased risk for infection
3) hypercoagulable state-due to loss of antithrombin III
4) hyperlipidemia (>10mmol/L) and hypercholesterolemia- may result in fatty casts in urine.

-if a patient presents with edema, it is advised to check for proteinuria(dipstick) to avoid missing renal disease

Question 2

pathophysiology of nephrotic syndrome

Answer 2

injury to podocytes–> proteinuria
-podocytes wrap around the glomerular capillaries and maintain the filtration barrie, preventing large molecular weight proteins from entering the urine. effacement of the foot processes or loss of podocytes can cause heavy protein loss.

Question 3

causes of nephrotic syndrome (6)

Answer 3

1) minimal change disease
2) focal segmental glomerulosclerosis(FSGS)
3) membranous nephropathy
4) membrenoproliferative glomerulonephritis
5) diabetes mellitus
6) amyloidosis

Question 4

assessment of nephrotic syndrome

( signs&differential diagnosis)

Answer 4

signs:

1) pitting edema (severe, rapid onset) occuring in areas of low tissue resistance e.g periorbital area
2) massive proteinuria
3) hypoalbuminemia
4) BP normal
5) GFR normal

differential:

1) CHF (JVP, pulmonary edema, mild proteinuria)
2) liver disease (albumin production defect)

All adults should undergo BIOPSY but avoided in children unless no response to steroids(response=MCD)
Biopsy is difficult in pts with nephrotic sy because of the hypercoagulable state and the edema.

Question 5

Complications of nephrotic syndrome (3)

Answer 5

1) susceptibility to infections: 20% (loss of IgG in urine and immunosuppressive treatments)
2) thromboembolism: 40% DVT, PE,RVT, hypercoagulable state due to clotting factors adn platelet abnormalities
3) hyperlipidemias: hepatic lipoprotein synthesis in response to low oncotic pressure

Question 6

treatment of nephrotic syndrome

Answer 6

1) reduce edema: loop diuretics eg furosemide used often in high doses. Gut edema may prevent oral absorption so IV route is useful
2) reduce proteinuria: ACEi or ARB
3) reduce risk for complications: anticoagulation & statins
4) treat underlying cause: infection, malignancy or systemic disease

Question 7

Minimal change disease(8)

Answer 7

1) most common cause of nephrotic syndrome in children
2) usually idiopathic, may be associated with HODGKIN LYMPHOMA (increased production of cytokines–> these cytokines damage the podocyte foot processes)
3) normal glomeruli on H&E stain
4) lipid may be seen in proximal tubule cells
5) effacement of foot processes on electron microscopy (EM)
6) No immune complex deposits, so negative immunofluorescence.
7) SELECTIVE PROTEINURIA (loss of albumin but not immunoglobulins)
8) excellent response to steroids

Question 8

Focal segmental glomerulosclerosis (FSGS) (6)

Answer 8

1) most common cause of nephrotic syndrome in HISPANICS &AFRICAN AMERICANS
2) usually idiopathic, may be associated with HIV, heroin, sickle cell disease orcan be secondary due to vesicoureteral reflux, IgA nephropaathy, Alport’s sy, vasculitis
3) focal=some glomeruli, segmental=only part of the glomerulus involved
4) effacement of foot processes on EM
5) no immune complex deposits, negative IF
6) poor response to steroids, progresses to CRF
- responds to corticosteroids in 30%, cyclophosphamide or cyclosporine considered if steroid resistant

Question 9

membranous nephropathy (5)

Answer 9

1)most common cause in CAUCASIAN ADULTS
2)usually idiopathic, may be associated with Hep B,C , solid tumors(paraneoplastic sy), SLE or drugs (NSAIDS, penicillineamine), syphilis, malaria
3)thick glomerular basement membrane on H&E
due to immune complex deposition(granular IF), Subepithelial deposits with ‘spike and dome’ appearance on EM
4)Poor response to steroids, progresses to CRF
5)treatment of the idiopathic form involves ACEi/ARB &diuretics

Question 10

Membranoploriferative glomerulonephritis (4)

Answer 10

1)thick glomerular basement membrane on H&E , ‘tramtrack appearance’
due to immune complex deposition (granular IF)
2)divided into two types based on the location of the deposits:
i)Type I- subendothelial associated with HBV, HCV, SLE
ii) Type II- intramembranous, associated with C3 nephritic factors (autoantibody stabilises C3 convertase, leading to overactivation of complement, inflammation and low levels of circulating c3)
3)poor response to antibiotics, progresses to CRF
treatment should focus on the underlying cause, ACEi and ARB used for all. steroids can be used in case of rapid progression of the disease and in combination with cyclophosphamide if rapid deterioration in renal function
4)also can be divided in another way:into immune complex mediated (type1) and complement mediated (type 2)(C3 nephritic factor- less common)

Question 11

Diabetes Mellitus &Kidneys

Answer 11

• high serum glucose leads to non enzymatic glycosylation of the vascular basement membrane resulting in hyaline arteriolosclerosis (because the BM becomes leaky and protein leaks in)
• mostly in the efferent arteriole, thus its diameter decreases, pressure increases and thus there in hyperfiltration–> microalbuminuria–> eventually leading to nephrotic syndrome
• the mesangium becomes sclerosed–> KIMMELSTIEL WILSON NODULES
• ACEi slow the progression of hyperfiltration induced damage

Question 12

amyloidosis &Kidneys

Answer 12

• kidney is the most commonly involved organ in systemic amyloidosis
• amyloid deposits in the mesangium resulting in nephrotic syndrome
• characterised by apple green birefringence under polarized light after staining with congo red.