ICL 2.4: Nephrotic Glomerular Diseases Flashcards
which conditions are primary nephrotic syndrome?
- lipoid nephrosis
- focal glomerulosclerosis
- membranous glomerulonephritis
- membranoproliferative glomerulonephritis
which conditions are secondary nephrotic syndromes?
- DM
2. amyloidosis
what is the clinical presentation of nephrotic syndromes?
- edema
- proteinuira
- hypoproteinemia
- hyperlipidemia
- 3+ g protein/24 hours in urine
what causes the proteinuria, hypoproteinemia and edema seen in nephrotic syndromes?
- proteinuria due to leaky capillary basement membrane
- hypoproteinemia due to loss of proteins in urine
- edema due to decreased oncotic pressure
what causes hyperlipidemia seen in nephrotic syndromes?
we aren’t really sure…
possibly due to decreased oncotic pressure or increased lipoprotein synthesis in the liver since the liver is trying to replace all the lost proteins
this translates into lipiduria
what is an oval fat body?
tubular cell filled up with lipid droplets
when the patient has lipids in the urine, some of the lipids appear in the tubules and it’s associated with nephrotic syndrome most often
what is proteinuria? specifically what are they different grades?
1+ = 250-500 mg/24 hrs
2+ = 500-1000 mg/24 hrs
3+ = 1000-2000 mg/24 hrs
4+ = 2000+ mg/24hrs
nephrotic syndrome is 3+ g/24 hrs….so it’s always 4+
a 2 year old boy with recurrent nephrotic syndrome is found to have selective proteinuria
diagnosis?
renal biopsy findings?
prognosis?
lipoid nephrosis aka minimal change disease
it’s recurrent so it comes and goes
selective proteinuria is specific to this disease! it means it’s only spilling albumin!!
great prognosis; respond to steroids
what is incidence of lipoid nephrosis? what disease is it associated with?
it’s a primary nephrotic syndrome also known as minimal change disease
associated with Hodgkins lymphoma*
80% of cases in primary syndrome are in children and only 30% are in adults
more common males in children but equal risk in adults; peak age is from 1-5 years old
20-30% follow a URTI, 9% follow immunization while 70% have no preceding illness
what is lipoid nephrosis?
it’s a primary nephrotic syndrome
it’s caused by T cell-derived factor that cause podocyte damage and effacement = mechanism IV
clinical findings:
1. edema
- proteinuria; highly selective, mostly albumin –> good response to steroids
serologic tests for autoimmune disease are negative
responds to steroids but recurrent…
what is the course and prognosis of lipoid nephrosis?
responds to steroids
however, it’s recurrent…
what is the morphology of lipoid nephrosis?
LM shows no changes
IF is negative
EM will show podocyte fusion/effacement = no more projections; it’s just flat
what are the characteristics of focal glomerulosclerosis?
- hematuria
- nonselective proteinuria = albumin and globulin
- no response to steroids
nephrotic syndrome with associated hematuria = not good news; most progress to renal failure
what is clinical presentation of focal glomerulosclerosis?
it’s a primary nephrotic syndrome + nephritic
clinical findings:
1. 60-80% nephrotic syndrome
- 30% azotemia
- 25% HTN
- recurrence in renal allograft**
more likely to have non-selective proteinuria, hematuria, progression to chronic renal failure, and poor response to corticosteroid therapy
what is the morphology of focal segmental glomerulosclerosis?
LM shows juxtamedullary glomeruli with focal sclerosis –> you can’t take the superficial cortex biopsy you need the deep cortex to get the juxtamedullary glomeruli!
you can see an area of collagenous sclerosis that runs across the middle of the glomerulus in a trichrome stain (it’ll be blue)
you can also sometimes see fat droplets! which isn’t surprising because they have hyperlipidemia
what are the 2 types of focal segmental glomerulosclerosis?
there are several types but here are the main 2
- C1q aka seronegative lupus
it is the most aggressive! bad prognosis and recurs in renal transplants as early as 2-3 weeks
- collapsing with HIV or IV drugs
glomerulus is shrunk in one part of Bowman’s space and there’s hyperplasia of podocytes
there is collapse of the entire glomerulus with podocyte hyperplasia associated with HIV or drugs –> poor prognosis
what is the prognosis of focal glomerulosclerosis?
downhill course that leads to renal failure….
there are persistent episodes of proteinuria, hematuria and nephrotic syndrome
recurrence in allograft** (C1Q type can reoccur as early as 2-3 weeks after transplant ):
doesn’t respond to steroids….
a 15 year old with a history of malignant lymphoma present with nephrotic syndrome
serologic tests, BUN and creatinine levels are all normal
urinalysis shows 4+ protein
differential diagnosis?
biopsy findings?
prognosis?
membranous glomerulonephritis
malignant lymphoma and now he has a nephrotic syndrome
no evidence of autoimmune disease
what are the predisposing factors for developing membranous glomerulonephritis?
- HepB (also in PAN but that’s nephritic and has high BUN, creatinine, HTN)
- tumor (GI, non-Hodgkins lymphomas)
- poison ivy (type IV hypersensitivity reaction too!)
- immune complex diseases like SLE
- infectious –> syphilis and malaria specifically
- renal vein thrombosis
- idiopathic
- drugs like penacillamine or GOLD therapy for RA
what is membranous glomerulonephritis?
a primary nephrotic syndrome caused by chronic immunocomplexes
chronic is key because it means the immune complexes are old and by the time they get deposited in the capillaries of the glomerulus they don’t activate much compliment so compliment levels are normal and deposits are small along the basement membrane (unlike post-strep nephritic syndrome which has huge immune complex deposits)
what is the morphology of membranous glomerulonephritis?`
LM will show thick basement membrane and capillary loops but no increased cellularity!
IF will show fine granular peripheral IgG and C3
EM shows 4 stages:
1. epimembranous deposits; flat! thick BM
- intramembranous deposits and spikes; deposits inside the membrane and on each side are deposits
- intramembranous deposits
- radiolucent areas where deposits used to be; deposits vanish
what is the course and prognosis of membranous glomerulonephritis?`
slow course
doesn’t usually recur in renal allograft
membranous glomerulonephritis associations?`
HepB, non-Hodgkins lymphoma
what are the 3 types of membranoproliferative glomerulonephritis?
type I = mesangocapillary
type II = dense deposit disease
type III = mesangial proliferative
a 5 year old female with nephrotic syndrome, HTN, and hematuria for the last 6 months has a history of hearing problems. her uncle died at 22 with CKF.
HB is 10, BUN 20, creatinine 3, 2+ blood and 4+ protein and RBC casts in urine
diagnosis?
mesangiocapillary membranoproliferative nephritis (type I)
HTN and hematuria = nephritic and nephrotic!! bad news….
hearing problems which are often associated with hearing problems
not surprised she’s anemic because she’s losing blood in the urine! this is anemia of chronic disease!! so it’s a normocytic anemia
hearing problems and family history and CKD could be membranoproliferative or Alport syndrome! but alport if familial disease that has hearing, hematuria, HTN but no nephrotic syndrome!
what is the incidence of mesangiocapillary membranoproliferative nephritis?
type I membranoproliferative nephritis
5-20% of primary nephrotic syndrome cases
female > male
no preceding illnesses
what is the pathogenesis of mesangiocapillary membranoproliferative nephritis?
immune complexes that activate the complement pathway
so when you look at serum complement it’ll be decreased C3, C4 and C50
post-strep nephritis and SLE also have decreased complement
what is the morphology of mesangiocapillary membranoproliferative nephritis?
LM shows:
1. lobular pattern* –> looks like an orchid flower
- membrane changes and cell changes
- mesagnial matrix expansion
- thick BM
silver stain shows splitting of basement membrane
IF shows C3 deposits in a peripheral lobular distribution
EM shows mesangialization which is mesangial cells that have made their way into the basement membrane so they split the BM!
what is the course and prognosis of mesangiocapillary membranoproliferative nephritis?
slow course
recurs in renal allograft
which conditions recur in renal allografts?
- IgA nephrotpathy
- focal segmental glomerulosclerosis
- mesangiocapillary membranoproliferative nephritis
what is the incidence of dense deposit disease?
this is type II membranoproliferative nephritis
it’s only 0.5-2.5% of chronic glomerulonephritis cases so it’s rare
mean age is 16 years old but no sex predilection
infectious disease is sometimes a preceding illness; mainly strep and pneumonia
what is the pathogenesis of dense deposit disease?**
alternate complement pathway activation (3rd mechanism)
so you’ll have low C3 BUT normal C4 and you’ll see serum C3 nephritic factor**
this is type II membranoproliferative nephritis
what is the clinical presentation of dense deposit disease?
this is type II membranoproliferative nephritis
- proteinuria (100%)
- nephrotic (80%)
- HTN (60%)
- hematuria (50%) = nephrotic and nephritic
- decreased serum C3
what is the morphology of dense deposit disease?
LM shows the same as type I mesangiocapillary membranoproliferative nephritis:
1. lobular pattern*
- membrane changes and cell changes
- mesagnial matrix expansion
- thick BM
IF shows discontinuous linear deposits of C3 peripherally (Goodpasture show’s continuous linear deposits)
EM shows ribbon-like deposits in lamina densa
how is DM associated with renal disease?
the development of renal disease is associated with the duration of the DM, the severity and whether it’s controlled or not
DM is one of the most common causes of renal failure!
the lesions in DM are nodular
the two lesions associated with DM and renal failure:
- diffuse glomerular scarring, no nephrotic syndrome
- Kimmelstiel-Wilson disease; KW lesions associated with nephrotic syndrome
what is Kimmelstiel-Wilson disease?
microangiopathy everywhere in the whole body
ischemic lesions everywhere!
associated with DM aka diabetic nephropathy from uncontrolled DM
what is the morphology Kimmelstiel-Wilson disease?
LM shows:
1. nodular sclerosis (KW lesions)*
- hyalinization of both afferent and efferent arterioles*
- hyaline droplets that look like fibrin caps in the BM and capsular drops in the Bowman’s capsule
- vacuoles in tubular epithelium
- diffuse sclerosis**
- hyalinized vessels
- fibrotic interstitium
- thickening of tubular BM
IF will show variable trapping of IgG and EM will shows microangiopathy
GO LOOK IT’LL BE ON STEP
what are the types of amyloidosis? when do they present?
familial present in the 3rd decade
secondary presents in the 4th decade
primary presents in the 6th decade
they all have nephrotic syndrome!
