Glomerulonephritis Flashcards
hypo-complementemic GNs
- lupus GN
- PIGN
- cryoglobulinemic GN
- MPGN
GNs with normal complements
- IgA nephropathy
- ANCA-associated GN
- anti-GBM nephritis
GNs with granular pattern on IF
- lupus GN
- PIGN
- cryoglobulinemic GN
- MPGN
- membranous nephropathy
- IgA nephropathy
ONLY GN with LINEAR pattern on IF
anti-GBM nephritis
ONLY GN with pauci-immune pattern on IF
ANCA-associated GN
IgA nephropathy presentation
- variable clinical presentation
- asymptomatic hematuria with mild proteinuria
- gross hematuria (sometimes with flank pain) within a FEW days of URI
mechanism of AKI in IgA nephropathy
- crescentic IgA nephropathy
- tubular obstruction from erythrocytes
treatment of IgA nephropathy if proteinuria < 1 g/day
conservative therapy: ACEI/ARB, fish oil, vitamin d, and statin
treatment of IgA nephropathy if proteinuria > 1 g/day
- conservative therapy: ACEI/ARB, fish oil, vitamin d, and statin
IN ADDITION TO - steroids x 6 months
- if crescentic (RPGN), ADD cyclophosphamide
LN classification
- normal glomeruli on LM
- mesangial immune deposits on IF
class 1; minimal mesangial LN
LN classification
- purely mesangial hypercellularity of any degree or mesangial matrix expansion on LM
- mesangial immune deposits
class 2; mesangial proliferative LN
LN classification
- active or inactive focal, segmental or global
- endo- or extracapillary GN involving < 50% of all glomeruli
- typically with focal subendothelial immune deposits, with or without mesangial alterations
class 3; focal LN
LN classification
- active or inactive focal, segmental or global
- endo- or extracapillary GN involving > 50% of all glomeruli
- typically with diffuse subendothelial immune deposits, with or without mesangial alterations
- this class is subdivided into S (segmental) when 50% of involved glomeruli have segmental lesions, and G (global) when 50% of involved glomeruli have global lesions
class 4; diffuse LN
LN classification
- global or segmental subepithelial immune deposits or their morphologic sequelae on LM and on IF or EM, with or without mesangial alterations
class 5; membranous LN
histological prognostic features in LN
- class 4 (diffuse proliferative LN)
- high activity and chronicity on biopsy
- crescents
- interstitial fibrosis
- segmental necrotizing lesions
clinical prognostic features in LN
- HTN
- anemia
- high baseline Cr
- high baseline proteinuria
- delay in treatment
epidemiologic prognostic features in LN
- black race
- low socioeconomic status
induction therapy of class 3 or class 4 LN with or without class 5 LN
- steroids and cyclophosphamide (standard NIH protocol)
OR - steroids and MMF (noninferior to CP)
maintenance therapy of class 3 or class 4 LN with or without class 5 LN
MMF
ANCA GN clinical presentation
- kidneys
brown, tea-colored urine
ANCA GN clinical presentation
- joints
pain and swelling
ANCA GN clinical presentation
- trachea and lungs
- cough (often mistaken for PNA)
- hemoptysis
- dyspnea
ANCA GN clinical presentation
- skin
- purpura
- pruritus
- hives
- rash
ANCA GN clinical presentation
- sinus/nose
- rhinorrhea
- nose pain
- nasal congestion
- epistaxis
- crusting of nares (poor prognostic factor indicative of relapse)
ANCA GN clinical presentation
- GIT
- abdominal pain
- hematochezia/melena
ANCA GN clinical presentation
- eyes
- eye pain
- blurry vision
- headache
ANCA GN clinical presentation
- ears
- hearing loss
ANCA GN clinical presentation
- neuro
foot drop; mononeuritis multiplex
MC presenting symptom of ANCA
“I just don’t feel right”
vasculitis symptoms
flu-like symptoms including;
- fever
- body aches
- poor appetite
- weight loss
ANCA classification
- renal limited vasculitis
- microscopic polyangiitis (MPA)
- granulomatosis with polyangiitis (GPA)
- eosinophilic granulomatosis with polyangiitis (EGPA)
MCC of RPGN, especially as patients get older
ANCA-associated GN
better way to classify ANCA
- renal-limited MPO-ANCA vasculitis
- PR3-ANCA granulomatous vasculitis with lung and renal involvement
- MPO-ANCA necrotizing vasculitis with multi-organ involvement
- pauci-immune, necrotizing glomerulonephritis in setting of positive MPO-ANCA
induction therapy for ANCA GN
- pulse steroids for everyone (taper at 8 weeks)
- plasmapheresis (everyone with pulmonary hemorrhage or “severe” renal failure)
- cyclophosphamide or rituximab
maintenance therapy for ANCA GN
- azathioprine
OR - rituximab
goal to come off steroids in treatment of ANCA vasculitis by what time frame?
6 months
treatment for ANCA GN relapse
rituximab
“DOUBLE positive” ANCA serologies with very high titers for anti-MPO should raise suspicion for
drug-induced ANCA vasculitis
drugs that can cause lupus
- procainamide
- hydralazine
- minocycline
- diltiazem
- penicillamine
- isoniazid
- quinidine
- anti-TNF alpha therapy
- methyldopa
drugs that can cause ANCA
- hydralazine
- levamisole (cocaine contaminant)
- propylthiouracil (PTU)
- minocycline
MCC of chronic GN worldwide
IgA nephropathy
other common cause of acute and chronic GN
LN
crescentic GN on LM, and linear pattern on IF
anti-GBM nephritis
anti-GBM nephritis with lung involvement
Goodpasture’s disease (pulmonary-renal involvement)
epidemiology of anti-GBM nephritis
- bimodal age and gender
- young MEN in 2nd and 3rd decade
- OLDER WOMEN in 6th and 7th decade
up to 1/3 of patients with anti-GBM nephritis have concurrent
ANCA, usually MPO
prognosis of anti-GBM
- very poor
- must be diagnosed and treated early
anti-GBM treatment
- plasmapheresis daily until anti-GBM Ab cleared
- pulse steroids then taper over 6 months
- cyclophosphamide (PO is better) x 3 months
does anti-GBM relapse?
very rarely; considered to be “one and done”
should you f/u anti-GBM after treatment and how?
- yes!
- anti-GBM titers
PIGN key clinical features
- occurs after acute infection
- classic nephritic picture with microscopic or gross hematuria
- AKI
- proteinuria
- HTN
- edema
- VERY LOW C3
- low/normal C4
PIGN is more common in
children
causative agents of PIGN
- Staphylococcus becoming more common
- Streptococcus
PIGN key LM findings
- diffuse ENDOcapillary proliferative GN
- crescents in severe cases
PIGN key IF findings
“STARRY SKY” pattern; GRANULAR deposits in capillary walls and mesangium with C3 staining +/- IgG
PIGN key EM findings
SUBepithelial hump-shaped deposits
classical complement pathway consumption is triggered by
immune complexes (Ag and Ab)
if classical complement pathway is triggered what is expected on IF?
C3 and Ab staining, such as IgG
if you ONLY see C3 staining on IF then you can assume what?
alternative complement pathway was triggered
- LM; mesangial proliferation with mesangial interposition and GBM duplication
- IF; C3 with IgG and/or IgM, C1
MPGN type 1
- diverse glomerular histology w/ or w/o MPGN pattern
- C3 alone
C3 glomerulopathy (previously MPGN type 2)
types of C3 glomerulopathy
- C3 GN (MPGN type 1 pattern)
- DDD
- C3 GN (MPGN type 3 pattern)
- LM; mesangial proliferation with mesangial interposition and GBM duplication, usually with MEMBRANOUS features
- IF; C3 with IgG and/or IgM, C1
MPGN type 3
classical complement pathway triggered by what conditions?
- infection
- cancer
- autoimmune disease
- allergic reaction
alternative complement pathway HYPERACTIVITY triggered by
- mutations
- auto-Abs
- monoclonal gammopathy
possible treatment for C3 glomerulopathy that targets C5
eculizumab
name the 4 possible HCV related GNs
- type 1 MPGN a/w type 2 cryoglobulinemia
- MPGN without cryoglobulinemia (probably false negative d/t difficulty checking cryoglobulins)
- membranous nephropathy
- FSGS, TMA a/w anti-cardiolipin Ab, fibrillary GN, and immunotactoid GN
how many types of cryoglobulins are there?
3
cryoglobulinemia
- type 1
- what IGs and type?
MONOclonal IgG, IgM, or IgA
cryoglobulinemia
- type 1
- a/w what diseases?
lymphoproliferative d/o’s; MM, WM, CLL, B-cell NHL
cryoglobulinemia
- type 2
- what IGs and type?
- MONOclonal IgM, IgM, or IgA with RF activity
OR - POLYclonal IgG
cryoglobulinemia
- type 2
- a/w what diseases?
- infections, mainly HCV
- autoimmune d/o’s
- lymphoproliferative d/o’s
- rarely idiopathic
cryoglobulinemia
- type 3
- what IGs and type?
POLYclonal mixed IGs (all isotypes) with RF activity from one polyclonal component (usually IgM)
cryoglobulinemia
- type 3
- a/w what diseases?
- infections, mainly HCV
- autoimmune d/o’s
- rarely idiopathic
RF is only positive in which types of cryoglobulinemia?
types 2 and 3
hallmark LM and EM findings of cryoglobulinemia
- LM = MPGN, nodular pattern
- EM = precipitating cryoglobulins in glomerulus
hallmark laboratory features of HCV-cryoglobulinemic GN
- variable proteinuria
- hematuria
- renal insufficiency
- LOW C4, sometimes low C3
- RF positive (if type 2 or 3)
- elevated transaminases in 70%
treatment of HCV-associated cryoglobulinemic MPGN
- IF mild to moderate proteinuria
- IF slow but progressive loss of kidney function
- IF eGFR > 50
interferon + ribavirin +/- protease inhibitor
treatment of HCV-associated cryoglobulinemic MPGN
- IF mild to moderate proteinuria
- IF slow but progressive loss of kidney function
- IF eGFR < 50
interferon ONLY
treatment of HCV-associated cryoglobulinemic MPGN
- IF nephrotic range proteinuria
- IF rapidly progressive loss of kidney function
- plasmapheresis x 2-3 weeks
- rituximab x 4 weeks or CP x 2-4 months
- pulse steroids +/- taper
- after controlling acute vasculitis, treat HCV
definition of hemolytic-uremic syndrome
- microangiopathic hemolytic anemia (MAHA)
- thrombocytopenia
- AKI
expected laboratory findings of microangiopathic hemolytic anemia (MAHA)
- schistocytes on PBS
- elevated LDH
- low haptoglobin
- elevated bilirubin
90% of HUS is typical, which means what?
- caused by Shiga-like toxin
- prodromal episode of diarrhea
10% of HUS is “atypical,” which means what?
- heterogeneous d/o
- NO diarrhea
- NO Shiga toxin-producing E. coli infection
classification of atypical HUS
# familial # sporadic: - idiopathic - pregnancy-associated - HELLP syndrome - drug-induced - organ transplantation - HIV # cancer
most common protein affected by genetic abnormalities in patients with aHUS
factor H
treatment for aHUS
plasmapheresis then eculizumab
eculizumab works by targeting
C5
Alport syndrome defect in
type 4 collagen α-5 chain gene (COL4A5)
most common GN inherited by X-linked pattern
Alport syndrome
can Alport syndrome be inherited by AR or AD pattern?
yes
clinical presentation of Alport syndrome
- microscopic hematuria
- subnephrotic range proteinuria
- declining renal function
- sensorineural hearing loss
- anterior lenticonus of eye
diagnosis of Alport syndrome if NO ESTABLISHED family history
renal biopsy
renal biopsy findings of Alport syndrome
EM required***
- GBM THICKENING
- lamellation –> “BASKET-WEAVE” appearance
diagnosis of Alport syndrome if POSITIVE family history
GENETIC TESTING for α3, α4, and α5 chains of type 4 collagen
epidemiology of Alport syndrome
MALE predominance
thin basement membrane nephropathy renal biopsy findings
# EM required*** - diffuse GBM ATTENUATION (thinning)
epidemiology of thin basement membrane nephropathy
- familial (often), or sporadic
- no gender difference
thin basement membrane nephropathy presentation
- microscopic hematuria
- NORMAL renal function
thin basement membrane nephropathy AKA
benign familial hematuria
thin basement membrane nephropathy caused by
COL4A3 or COL4A4 gene mutation
GNs a/w subENDOthelial deposits
- MPGN type 1
- MPGN type 3
- cryoglobulinemia
- LN class 3
- LN class 4
GNs a/w double contours (same list as GNs a/w subENDOthelial deposits + 2 more)
- MPGN type 1
- MPGN type 3
- cryoglobulinemia
- LN class 3
- LN class 4
- TMA
- chronic transplant glomerulopathy
diffuse thinning of GBM
thin basement membrane disease
irregularity and multilayering or splitting of the GBM
Alport’s syndrome
diffuse thickening of the GBM
- diabetic nephropathy
- hypertensive nephrosclerosis
- Alport’s disease
mainly IgG LINEAR deposition in capillary walls
anti-GBM disease
nonspecific LINEAR IgG or “PSEUDOLINEAR” IgG deposition in capillary walls
diabetic nephropathy
GRANULAR parietal deposition of IGs and COMPLEMENT
- subENDOthelial
MPGN type 1
GRANULAR parietal deposition of IGs and COMPLEMENT
- subEPIthelial
PIGN
GRANULAR parietal deposition of IGs and COMPLEMENT
- subENDOthelial AND intramembranous
membranous GN
what Ab in granulomatosis with polyangiitis ANCA?
anti-PR3 ANCA
what Ab eosinophilic granulomatosis with polyangiitis ANCA?
anti-MPO ANCA
ONLY GN with granular pattern on IF AND NORMAL complements
IgA nephropathy
GRANULAR parietal deposition of IGs and COMPLEMENT
- subENDOthelial, subEPIthelial, AND intramembranous
MPGN type 3
“SAUSAGE-LIKE” (ribbon-like), osmiophilic deposits
- GBM deposits
DDD
GN a/w Drusen bodies in retina
DDD (C3 deposition in retina)
- MPGN pattern LM
- negative IF
- GBM deposits with ribbon-like pattern
DDD
treatment for DDD
eculizumab
- MPGN pattern LM
- negative IF
- subENDOthelial AND mesangial deposits
C3 GN
treatment for C3 GN
rituximab and plasmapheresis
