Nephrotic Syndrome II - Nichols

Question 1

What are the two main categories of nephrotic syndromes?

Answer 1

Podocytopathies and Membranous Nephropathy

Question 2

What are the two major podocytopathies?

Answer 2

Minimal Change Disease

Focal Segmental Glomerulosclerosis

Question 3

Where is the primary affected site in Membranous Nephropathy?

Answer 3

Subepithelial layer of the basement membrane

Question 4

What is a similar disorder to membranous nephropathy but is considered a nephritic syndrome?

Answer 4

Post-strep glomerulonephritis, which also has subepithelial deposits.

Question 5

Who is primarily affected by minimal change disease?

Answer 5

the very young and the very old typically white and male

Question 6

What percentage of nephrotic syndromes are caused by minimal change in children? in adults?

Answer 6

75% in children butonly 25% in adults

Question 7

What can minimal change disease be secondary to?

Answer 7

Hodgkins disease, thymoma,t-cell leukemia, use of non-steroidal anti-inflammatory drugs of interferone-alpha use

Question 8

Describe the proteinuria in minimal change disease?

Answer 8

highly selective, largely allowing only passage of albumin

Question 9

What is the damage seen in minimal change disease?

Answer 9

effacement (shown by electron microscopy) and detachment of podocyte foot processes

Question 10

How is steroid use for tx with minimal change disease?

Answer 10

great (90%) in children
adults have slow response

If not responsive to steroids, think FSGS

Question 11

What is the general definition of a nephrotic syndrome?

Answer 11

Results from an increased permeability of the GBM, with effacement of podocytes and detachment of foot processes, allowing proteinuria

Question 12

What are several key findings in nephrotic syndrome?

Answer 12

massive proteinuria
edema
hypoalbunemia
hyperlipidemia and lipiduria
hypercoagulability (due to Anti-Thrombin III loss)

Question 13

What is focal segment glomerulosclerosis characterized by?

Answer 13

deposition of basement membrane-like material associated with podocyte injury, not affecting all glomeruli and only segments of each affected glomerulus, but progressing to sclerosis

Question 14

Who typically is seen with FSGS?

Answer 14

adults males and blacks

FSGS causes 64% of nephrotic syndromes in blacks

Question 15

What can fsgs be secondary to?

Answer 15

hiv, parvovirus b19 infxn, injecting drug use (heroin), lithium, pamidronate, obesity, reflux nephropathy or sickle cell nephropathy

Question 16

What are various mutations that can lead to fsgs?

Answer 16

podocin, alpha-actinin-4 and transient receptor potential cation channel 6

Question 17

what mutation to african-americans have that lead to increased fsgs and arterionephrosclerosis?

Answer 17

a mutation in the apoL1 gene

Question 18

Explain that mechanism of suPAR?

Answer 18

soluble urokinase-type pasminogen activator receptor is a circulating factor that binds to B3-integrin on podocytes. High levels of suPAR are predictive of recurence in transplanted kidneys and a reduction in suPAR levels in blood by plasmapheresis induces disease remission.

Question 19

Explain the pathology of fsgs

Answer 19

increased mesangial matrix, occluded capillary lumens, and depos of proteinaceous material (hyalinosis) ((which goes on to become sclerotic))

Question 20

Initially, what glomeruli are affected by fsgs? what glomeruli become affected in later fsgs?

Answer 20

initially only juxtamedullary, later cortical

Question 21

What are the two primary spots that fsgs localizes in the glomerulus?

Answer 21

the vascular pole of the glom

the urinary pole of the glom

Question 22

When localization of fsgs is in the vascular pole, what is commonly seen in pts?

Answer 22

htn

Question 23

when localization of fsgs is to the urinary pole of the glom, what is commonly seen in pts?

Answer 23

heavier proteinuria, more common in whites

Question 24

Explain the significance of collapsing type of fsgs?

Answer 24

the glomerular tufts collapse, leading to heavier proteinuria and worst renal survival.
more common in black children

associated with drug toxicity or hiv infection

Question 25

what do people with fsgs usually present wiht?

Answer 25

proteinuria (nonselective compared to minimal change disease) microscopic hematuria renal insufficiency hypertension

Question 26

how do you treat fsgs?

Answer 26

``` corticosteroids (with poor response) calcinuerin inh (cyclosporine and tacrolimus) ```

Question 27

What is the prognosis of fsgs?

Answer 27

half develop end-stage renal disease within 10 yrs of dx

Question 28

How can you differentiate between fsgs and minimal change disease?

Answer 28

FSGS suggestive features: - older age - hematuria - htn - non-selective proteinuria - poor response to steroids Immunofluorescence will be neg. with minim. change. disease but can be positive in fsgs for igm

Question 29

What is the most common cause of nephrotic syndrome in adults?

Answer 29

membranous nephropathy (aka membranous glomerulopathy)

Question 30

What is membranous nephropathy?

Answer 30

chronic, slowly-progressive disease characterized by gGBM thickening, subepithelial immune complex deposits and effacement of foot processes

Question 31

when does one typically seen membranous nephropathy?

Answer 31

40s and up white males

Question 32

What are secondary causes of membranous nephropathy?

Answer 32

``` AI diseases ie sle sickle cell carcinoma complement deficiencys hep b syphilis malaria ```

Question 33

Describe the general (next question is specifics) mechanism of membranous nephropathy?

Answer 33

autoimmune complexes formed from binding of filtered autoantibody to incrinsic, locally generated antigen

Question 34

What is NEP?

Answer 34

neutral endopeptidase is a target antigen in congenitla membranous nephropathy

Question 35

What do the majority of membranous nephropathy pts have antibodies against?

Answer 35

an epitode in phopholipase a2 receptor (PLA2R) which is co-localized with IgG4 in glomeruli. There is increased deposition of C3 along the GBM, leading to complement activation and podocyte injury

Question 36

When looking at membranous nephropathy through light microscopy, what is the only you cans ee?

Answer 36

increased thickening of the gbm

Question 37

What does electron microscopy show in membranous nephropathy?

Answer 37

thickening due in part to abundant subepithelial deposits, forming a "spike and dome" appearance. also effacement of overlying foot processes.

Question 38

What does immunofluorescence show in membranous nephropathy?

Answer 38

granular subepithelial deposits of IgG and C3 along gbm, no inflammation because complement is activated where there are not circulating inflammatory cells.

Question 39

What are signs and symptoms of membranous nephropathy

Answer 39

variable proteinuria, microscopic hematuria and non-selective proteinuria,

Question 40

how do you treat membranous nephropathy?

Answer 40

ACEi or Angiotensin receptor blockade to lower bp | steroids for progressive cases

Question 41

what are risk factors for progression of membranous nephropathy?

Answer 41

male, severe proteinura (>10g/day), htn, azotemia, tubulointerstitial fibrosis and glomerulosclerosis.

Question 42

What is the prognosis for membranous nephropathy?

Answer 42

spontaneous resolution in 40% progressive failure in 30% and renal dysfunction in 30%

Question 43

Is post-infectious glomerulonephritis related to nephrotic syndrome

Answer 43

nope

Question 44

What is post-infxs glomerulonephritis?

Answer 44

acute immune comlex glom.nephrit. with proliferation of glomerular cells and infiltration by neutrophils.

Question 45

What is the typical presentation of post-infxs glomerulonephritis?

Answer 45

proteinuria, edema azotemia, htn, gross hematuria (smoky or tea colored), oliguria, low c3 but normal c4 (alternative activation).

Question 46

What does immunofluorescence reveal in post-infxs glomerulonephritis?

Answer 46

diffuse granular deposits of IgG and C3 in capillary walls and masngium. Dome-shaped subepithelial electron-dense deposits referred to as humps

Question 47

How do you treat post-infxs glomerulonephritis?

Answer 47

aggressive mgmt of htn, careful loop diuretics have good prognosis