Nephrotic Syndrome II - Nichols Flashcards
What are the two main categories of nephrotic syndromes?
Podocytopathies and Membranous Nephropathy
What are the two major podocytopathies?
Minimal Change Disease
Focal Segmental Glomerulosclerosis
Where is the primary affected site in Membranous Nephropathy?
Subepithelial layer of the basement membrane
What is a similar disorder to membranous nephropathy but is considered a nephritic syndrome?
Post-strep glomerulonephritis, which also has subepithelial deposits.
Who is primarily affected by minimal change disease?
the very young and the very old typically white and male
What percentage of nephrotic syndromes are caused by minimal change in children? in adults?
75% in children butonly 25% in adults
What can minimal change disease be secondary to?
Hodgkins disease, thymoma,t-cell leukemia, use of non-steroidal anti-inflammatory drugs of interferone-alpha use
Describe the proteinuria in minimal change disease?
highly selective, largely allowing only passage of albumin
What is the damage seen in minimal change disease?
effacement (shown by electron microscopy) and detachment of podocyte foot processes
How is steroid use for tx with minimal change disease?
great (90%) in children
adults have slow response
If not responsive to steroids, think FSGS
What is the general definition of a nephrotic syndrome?
Results from an increased permeability of the GBM, with effacement of podocytes and detachment of foot processes, allowing proteinuria
What are several key findings in nephrotic syndrome?
massive proteinuria edema hypoalbunemia hyperlipidemia and lipiduria hypercoagulability (due to Anti-Thrombin III loss)
What is focal segment glomerulosclerosis characterized by?
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
Who typically is seen with FSGS?
adults males and blacks
FSGS causes 64% of nephrotic syndromes in blacks
What can fsgs be secondary to?
hiv, parvovirus b19 infxn, injecting drug use (heroin), lithium, pamidronate, obesity, reflux nephropathy or sickle cell nephropathy
What are various mutations that can lead to fsgs?
podocin, alpha-actinin-4 and transient receptor potential cation channel 6
what mutation to african-americans have that lead to increased fsgs and arterionephrosclerosis?
a mutation in the apoL1 gene
Explain that mechanism of suPAR?
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.
Explain the pathology of fsgs
increased mesangial matrix, occluded capillary lumens, and depos of proteinaceous material (hyalinosis) ((which goes on to become sclerotic))
Initially, what glomeruli are affected by fsgs? what glomeruli become affected in later fsgs?
initially only juxtamedullary, later cortical
What are the two primary spots that fsgs localizes in the glomerulus?
the vascular pole of the glom
the urinary pole of the glom
When localization of fsgs is in the vascular pole, what is commonly seen in pts?
htn
when localization of fsgs is to the urinary pole of the glom, what is commonly seen in pts?
heavier proteinuria, more common in whites
Explain the significance of collapsing type of fsgs?
the glomerular tufts collapse, leading to heavier proteinuria and worst renal survival.
more common in black children
associated with drug toxicity or hiv infection
what do people with fsgs usually present wiht?
proteinuria (nonselective compared to minimal change disease)
microscopic hematuria
renal insufficiency
hypertension
how do you treat fsgs?
corticosteroids (with poor response) calcinuerin inh (cyclosporine and tacrolimus)
What is the prognosis of fsgs?
half develop end-stage renal disease within 10 yrs of dx
How can you differentiate between fsgs and minimal change disease?
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
What is the most common cause of nephrotic syndrome in adults?
membranous nephropathy (aka membranous glomerulopathy)
What is membranous nephropathy?
chronic, slowly-progressive disease characterized by gGBM thickening, subepithelial immune complex deposits and effacement of foot processes
when does one typically seen membranous nephropathy?
40s and up white males
What are secondary causes of membranous nephropathy?
AI diseases ie sle sickle cell carcinoma complement deficiencys hep b syphilis malaria
Describe the general (next question is specifics) mechanism of membranous nephropathy?
autoimmune complexes formed from binding of filtered autoantibody to incrinsic, locally generated antigen
What is NEP?
neutral endopeptidase is a target antigen in congenitla membranous nephropathy
What do the majority of membranous nephropathy pts have antibodies against?
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
When looking at membranous nephropathy through light microscopy, what is the only you cans ee?
increased thickening of the gbm
What does electron microscopy show in membranous nephropathy?
thickening due in part to abundant subepithelial deposits, forming a “spike and dome” appearance. also effacement of overlying foot processes.
What does immunofluorescence show in membranous nephropathy?
granular subepithelial deposits of IgG and C3 along gbm, no inflammation because complement is activated where there are not circulating inflammatory cells.
What are signs and symptoms of membranous nephropathy
variable proteinuria, microscopic hematuria and non-selective proteinuria,
how do you treat membranous nephropathy?
ACEi or Angiotensin receptor blockade to lower bp
steroids for progressive cases
what are risk factors for progression of membranous nephropathy?
male, severe proteinura (>10g/day), htn, azotemia, tubulointerstitial fibrosis and glomerulosclerosis.
What is the prognosis for membranous nephropathy?
spontaneous resolution in 40% progressive failure in 30% and renal dysfunction in 30%
Is post-infectious glomerulonephritis related to nephrotic syndrome
nope
What is post-infxs glomerulonephritis?
acute immune comlex glom.nephrit. with proliferation of glomerular cells and infiltration by neutrophils.
What is the typical presentation of post-infxs glomerulonephritis?
proteinuria, edema azotemia, htn, gross hematuria (smoky or tea colored), oliguria, low c3 but normal c4 (alternative activation).
What does immunofluorescence reveal in post-infxs glomerulonephritis?
diffuse granular deposits of IgG and C3 in capillary walls and masngium. Dome-shaped subepithelial electron-dense deposits referred to as humps
How do you treat post-infxs glomerulonephritis?
aggressive mgmt of htn, careful loop diuretics
have good prognosis
