Dobson Renal Path #3 Flashcards
What is associated with a Linear IF pattern?
GBM issue
What has subepithelial humps?
acute proliferative GN, SpeB
What has membranous deposits?
Membranous nephropathy and Heymann nephritis
Subendothelial deposits?
Lupus nephritis and membranoperoliferative GN
Mesangial deposits?
IgA nephropathy
What is a key event for the development of protieinuria?
breakdown of slit diaphragms in glomerular membrane
Pathogenesis of membranous nephropathy? Gomerular pathology light and IF?
- in situ immune complex PLA2R antigen in cases of primary disease
- DIffuse capillary wall thickening
- granular IgG and C3
- spike and dome
Main clinical features of nephritic syndrome?
- Hematuria
- rbc and casts
- Proteinuria
- with or w/o edema
- Azotemia
- Htn
Minimal change disease pathogenesis, glomerular pathology light and EM?
- loss of glomerular polyanion with podocyte injury
- normal light microscopy with lipids in tubules
- EM shows effacement of foot processes with no deposits
Histology of acute proliferative posinfectious GN?
- diffuse proliferation fo glomerular cells associated with influx of leukocytes caused by immmune complexes
What is a common cause of post infectious acute proliferative GN?
Group A beta hemolytic streptococci
What lab test would be used to document post streptococcal infections if you suspect post infectious GN?
ASO titer
In goodpasture syndrome, what are the renal and extra renal features, what lab findings will be helpful, patient demographics, treatments?
- teens-20’s M>F, smokers
- Kidneys and lungs hemoptysis and nephritic syndrome
- hematuria, htn, BUN Creatine elevated (azotemia)
- linear GBM fluorescence
- auto antibodies against noncollagenous domain of alpha 3 chain of collagen IV
- steroids
In lupus nephritis what are the renal and extra renal features, what lab findings will be helpful, patient demographics, treatments?
Subendothelial deposits, Class 1: least common
Class 4 (diffuse) is most common and severe form of lupus. involvement of >50% of all glomeruli. lateral crescents fill bowman’s space
loop wire! loopus
In HSP, what are the renal and extra renal features, what lab findings will be helpful, patient demographics, treatments?
- purpuric skin lesions on extensor surfaces and butt
- abdominal pain
- intestinal bleeding
- arthralgia
- renal in ⅓ patients following upper respiratory infection
- nephritic &/or nephrotic syndrome
- IgA deposited in glomerular mesangium similar to IgA nephropathy
- kids 3-8 yrs typically, but if an adult they have more severe renal manifestations
In IgA nephropathy, what are the renal and extra renal features, what lab findings will be helpful, patient demographics, treatments?
(Berger disease) most common type of GN worldwide
Nephritic: RPGN type 2, mesangial immune complex deposits, normal complement, concurrent infection, associated with celiac disease, recurrent hematuria
What is RPGN?
- aka cresentic GN
- severe glomerular injury that develops rapidly with progressive loss of renal function
- divided in 3 groups
- Type I (anti GBM)
- Type II (Immune complex)
- Type III (Pauci Immune)
If RPGN is untreated what happens?
- death from renal failure in weeks to months if untreated
- associated with loss of renal function, severe oliguria, and nephritic syndrome signs
Common histologic picture associated with RPGN?
Crescentic glomerulonephritis
With RPGN Type II, what are the renal and extra renal features, what lab findings will be helpful, patient demographics?
- SLE is a cause of this type of GN, it’s insidious or chronic remitting relapsing disease
- skin, joints, kidney, serous membranes
- dsDNA and Smith Ag positive
- F>M, reproductive age, hispanics, african american, caucasian
Most common pattern of SLE? (for boards, not exam)
IV diffuse lupus nephritis
Histological features of SLE RPGN Type II
- subendothelial deposits causing circumfrenetial thickening of capillary wall looks like wire loop structure on light microscopy
- crescent’s filling bowmans capsule
- granular pattern on IF
30 yr old female with diarrhea and chronic fatigue. PE shows pale conjunctiva and tachy. Hgb is 9 and urine dipstick is positive for 1 protein and blood. Work up includes upper endoscopy and biopsy of duodenum. which renal bx would be most likely?
- Glomerulosclerosis
- Crescents with IgA
- Mesangial IgA deposits
- Subepithelial humps
- Granulomas with caseous necrosis
Celiac disease with Crescent IgA
What causes Type III pauci immune RPGN?
- GPA (WeGNers)
- triad W=V for vasculitis, G=granuloma, N=necrosis
- acute necrotizing granuloma of respiratory tract
- PR3 ANCA positive
- 80% die w/o treatment
Nephrotic syndrome?
- massive proteinuria >3.5g
- hypoalbuminemia with plasma albumin <3 g/dL
- Generalized edema
- Hyperlipidemia and lipiduria
In nephrotic syndrome what proteins make up highly selective protienuria?
Low moleculr weight proteins such as albumin
in nephrotic syndrome what type of protein does a poorly selective (non selective) proteinuria consit of?
high molecular wieght globulins in addition to albumin
What are the priamary causes of nephrotic syndrome most commonly and associated ages?
- lesion primary to the kidney such as:
- minimal change disease (most common in US kids)
- membranous nephropathy (most common in older adults)
- FSGS (occurs at all ages)
Three most common secondary causes of nephrotic syndrome?
- Diabetes
- Amyloidosis
- SLE
What is membranous nephropathy?
- form of chronic immune complex disease causes nephrotic syndrome
- mostly primary causes
- secondary causese are:
- Drugs such as penicillamine, captopril,, NSAIDs
- Tumors
- SLE
- Infections (hepatidities, syphilis,schistosomiasis, malaria)
- AI
What characterizes membranous nephropathy on histology & what is the autoantibody?
- diffuse thickening of glomerular capillary wall due to accumulation of IgG or complement
- granular IF
- antibodies to PLA2R autoantigen
Even though we don’t see immune complexes on histology with minimal change disease, why is it believed that it is still immune mediated? (5 reasons)
- respiratory ifections and prophylactic immunization
- response to corticosteroids and other immunosuppressives
- associated with other atopic disorders
- HLA haplotypes
- increased incidence with Hodgkin lymphoma
What is the principal lesion in minimal change disease?
- visceral epithelial cells show a uniform and diffuse effacement of foot processes being reduced to rim of cytoplasm with loss of recognizable intervening slit diaphrgams
What is FSGS?
- Causes 10% & 35% of nephrotic syndromes in kids and adults
- most common cause for nephrotic syndrome in adults
Secondary FSGS causes?
- HIV
- Heroin addiction
- Sickle Cell
- Morbid obesity
- Long standing IgA nephropathy
- Adaptive response to loss of renal tissue
What is on histology with FSGS?
- EM scleroitic and nonsclerotic areas show diffuse effacement of foot processes
- IF shows IgMand C3 in sclerotic areas in mesangium
Collapsing variant of FSGS is associated with ___.
Collapsing variant of FSGS is associated with HIV.
MPGN presentation?
- nephritic or nephrotic range of proteinuria
- Type I which has IgG and complement (granular pattern)
- Type II (Dense Deposit Disease)
- activation of complement is most important factor
- Belongs to group of disorders called C3 glomerulopathies
What features help differentiate type I and II MPGN?
- large and hypercellular glomeruli with a lobular appearance
- Type one shows a GBM with “tram track” “double contour” “split” appearance with deposits outside
- DDD has deposits within membrane so it is thick also described as “split”
Berger disease? What is, clincial presentation, key feature, associated disease?
- aka IgA nephropathy
- presence of prominent IgA deposits in mesangial regions and recurrent hematuria
- gross hematuria after an infection
- 30-40% have only microscopic hematuria
- may/may not have proteinuria
- some develop acute nephritc syndrome some with RPGN
- recurrent hematuria-lasts several days and ends but comes back every few months
- increased frequency with celiac disease
What is Alport syndrome? Gene mutation and inheritance pattern?
- hematuria with progressioni to chronic renal failure associated with nerve deafness and eye disorders such as lens dislocation, cataracts, and corneal dystrophy
- defects in genes related to collagen IV
- X linked
EM findings in Alport syndrome?
- GBM shows irrecular foci of thickening alternating with thinning and pronouced splitting and lamination of lamina dense producing basket weave appearance
Thin basement membrane nephropathy?
- aka benign familial hematuria
- associated with alport but only has hematuria no other eye or nerve defecits
What is leading cause of ESRD?
Diabetic nephropathy
What is the earliest manifestion of diabetic nephropathy?
low amounts of albumin in the urine (>30 but <300)
diabetic nephropathy histology changes?
- thickening of GBM
- mesangial widening and thickening of tubular basement membranes
What is Kimmelstiel-Wilson deposit?
- Diabetic nephropathy aka interacpillary glomerulosclerosis or Kimmelstiel wilson
- ovoid masses in peripheral part of glomerulus in a PAS stain
- afferent and efferent arterioles show hyalinosis
38 yo white female with hematuria and edema. Elevated urine protein, BUN creatinine with evolving renal insufficiency. Congo red negative, IF shows IgG C3 kappa and lambda light chains granular pattern. Postive for DNAJB9. What is it?
- Fibrillary GN, rare disease
- recurs in kidney transplants
