Nephritic Syndromes Flashcards
Neprhitic
Nephrotic
Hemauturia, aotemia, variable proteinurea, oliguria, edema, and HTN
Over 3.5 g/proteinuria, hypoalbulinemia, hyperlipidemia, lipidurisa
RPGN
AKI
CKD
Acute neprhtisi, protienuria, and acute renal failure
Renal dysfunction with unexpected elevation of creatinninae and BUN…may be reversible or irreversible
CKD - renal scarring, irreversible, uremia
3 studies
Light microscopy…good view of the overall architecture
IF…complement and Igs, fibrinogen
Electron microscopy
H and E
PAS
Trichrome
Jones
Overall
Tubular basement membranes
Collagen - chornic change
Best for glomerular basement membrane
Granular vs linear IF
Grnaular - immune complex
Linear - type 2 HS
Focal
Diffuse
Segmental
Global
Focal - some but not all glomeruli
Diffuse - all or almost all glomeruli
Segmental - part but not all of glomerulus
Global - entire glomerulus
IgAN
Most common worldwide
Macroscopic heamture 1-2 days after URI in young adults and children
Older adults - microscopic with proteinuria (subnephrotic) or HTN alone or in combo
Limited to renal - IgA neprhopathy…systeimc - HSP
IgAN pathogenesis
Galatose def IgA1
Anti-glycan IgG or IgA1
More dimeric ABs in circulation
Immune complexes in mesangial area and result in loss of RBCs and other downstream pathology
Segmental glomeruloscleoriss, mesangial proliferation, endothelial cell proliferation
Sometimes seoncdary to liver dz
IgA nephropathy light microscopy/IF/electron
Light - Mesangial hypercellularity
Look for more than 3 nuclei clustered together***
IF - granular mesangial IgA and C3 deposits
Electron - mesangial immune complexes
IgA Prognosis
Poor - impair GFR…Sustained HTN, substantial proteinuria
Mesangial hypercellularity, endocapillary hypercellularity, segmental glomerulosceloriss, tubular atrophy and IS fibrosis
MEST
IgAN tx
No proven tx
General managment of glomerular dz - BP control and angiotensin 2 blockade
Fish oil?
L-T CSs
Renal transplantation for ESRD…may recur
HSP
IgA induced small vessel leukocytoclastic vasculitis
Systemic - purpura, arthralgia, ab pain and bloody diarrhea, nephritic syndrome in kdiney
Mostly in children (3-15)
1/2 of cases preceded by a URI
Self-limited process in majority of cases
Infection associated glomeruloneprhitis
IMmunological response ot microorgansim
Strep (28%) and Staph (24%)
Upper resp tract, skin, lung and HV
Comorbodities like diabetes, alcoholism, drug abuse
Decreased inicdnece due ot early detectio nand tx
APSGN
Acute post-strep glomeruloneprhitis
Children 2-14…more in males
Acute neprhtiic syndrome - gross hematuira, proteinura (subneprhotic), edema, HTN, oliguria
Onset 1-2 weeks after recovery from sore throat or longer with skin impetigo
POsitive step culture and/or increased antistreptolysin ), anti-DNAse B or antihyaluronidase tities
Mostly do NOT need biospy
APSGN pathogenesis
Nephritogenic strains of GAS, Beta hemolytic
Strep pyogenic exotoxin - antigenic determinant
In situ immune complex foromation in glomeruli…subepithalil humps…subendothelial and mesangial
Activation of alt complement (low C3 and normal C4)
Glomerulate infiltration by PMNs and monocytes
APSCGN light microscopy/IF/electron
Acute porliferative GN
Exudative GN
Can see PMNs in the glomeruli
Can see entire glumerulus is involved
Granular staining for IgG and C3
Subepithelial humps
Prognosis of APSCGN
Children - self-limited and excellent
Adults - increased incidence of decreased (mild) renal function with persistent HTN and mild proteinuria/hematuria
Tx of APSGN
Early penicillin
CSs in refractory
Tx of nephritic syndrome - BP control, Na restriction, loop diuretics
Endocariditis associated
S. aureus/epidermidis…strep viridans/pyogenes…enterococcus faecalis
Most common in rheumatic HD or IVDU
Fever, arthralgias, anemia and purpura, septic embolization New heart murmur or change Neprhitic Pos blood culture Low C3 AND C4 (classical)
Patholgoy and tx of endocarditis associated
LM - diffuse proli GN…sometime iwht cap thrombi…SBE tends to be more focal prolif GN
IF - IgG and C3
EM - mesangium, subendothelial and sbuepithelial immune complexes
IV ABs for 4-6 weeks
Membranoproliferative pattern with Ddx
AKA mesangiocapillary
Neprhitic—-nephrotic
Light micrscopie - hypercellular glomeruli with lobulation…GMB thickened with double contours (tram tracks)
Immune complex GN Decreased C3 and C4 Thrombotic microangiopathies Monoclonal depostion dz Chronic transplant glomerulopathy
Membranoproliferative pattern IF
If IgG and C3 staining…think infections (Hep C), AI or rehum, or monoclonal gammopathy
If only granular C3 and NO IgG, then raise concern for complement dysregulation
Dense deposit dz…type of MPGN
C3 convertase is depleted and causes the abnormality and leads to MPGN
Type 1 vs. type 2
Type 1 - subendothelial immune complexes
2 - Dense deposit disease…very long intramembranous immune complexes
MPGN Type 1 and 2 on IF
1 - IgG and C3…can see along the capillary loops
2 - C3 only…see very long segments
Cryoglobulinemic glomeruloneprhitis
Hyalien thrombi (cryglobulins) at arrows
Associated with HepC
Tx of MPGN
1 - treat infeciton…general managment…may use CSs..trnaslpant may help
DDD - replacing factor H with plasam infusion or eculizumab (AB to C5)…recurrence more often after trnasplant
Type 3 - no tx
SLE
15-45 y/o…more in females and non-white
Sun exposure, exacerbation during or after pregnancy
B cell hyperactivtion and defective T cell autoregulation
Wide range of autoantibodies - many against nucleic acids
Type 2 HS - hemolytic anemia (direct cell damage)
Type 3 HS - (immune complexes) - glomeruloneprhitis and arthritis
Classical pathway activation - low C3 and C4
SLE main renal and extrarenal manifestations
Protienuria - may be nephrotic Hematuria - dysmorphic with casts RPGN in 10-20 HTN Tubular abnormalities - RTA or hyperkalemia (out of proporion to decreased GFR)
Labs - anemia, thrombocytopenia, positive ANA, dsDNA, low C3 and C4
IF og lupus
POsitive for IgG, A, M, C3 and C1q
“full house”
6 stages
Minimal mesangial Mesangial prolif Focal DIfufse Membranous Advanced scleorising
Active proliferative LN tx
Induction - high dose CSs and cyclophosphamide…high dose CS and mycophenolate mofetil
Maintencne - low dose CSs with quarterly IV cyclophosphamide X 2 years OR oral azathiprine or MMF
Membranous lesion with neophrotic syndrome - in addition to genrral managment, CSs and cyclosporine or MMF
RPGN
Clinical dx…nephiritic with rapidly declinign kidney function…increased creatinine and decreased GFR >50% in 3 mos
Necrotizing GN with glomerular crescents in over 50% of glomeruli…aka crescentic glomerulonephritis
type of RPGN
1 - anti-GBM/Goodpasture
2 - immune complex…infection, SLE, HSP
Type 3 - pauci-immune - ANCA assoicated (GPA/MPA)
4 - double-antibody positive dz (1 and 3 combined)
Anti-GBM
Renal limited
Nephritic syndrome with dark urine and oliguria
Anti-GBM ABs
Goodpasture
Pulm-renal syndrome
Neprhitic syndrome with dark urine and oliguria
Hemoptysis
Ant-GBM
Teens and 20s , male predominance…could be triggered
Pathog of anti-GBM and Goodpasture
ABs at peptide within non-collagnous portion of the alpha 3 chain of type 3 collagen
LInear staining of GBM IgG and C 3
Anti-GBM prognosis and tx
If creatinine over 5, unlikely recovery
Prgression msot rapid
Plasmapheresis
Cycophosphamide
High dose CSs
Renal transplant after “burned out”
Type 2 pathology
Histology of underlying glomeruloneprhitis plus crescent formation
Granular IF
PLN, IgA, endocarditis associated, Hep C-associated, post strep GN
MPA vs PGA
MIcroscopic polyangitis - P-ANCA (MPO) positive with leukocytoclastic vasculitis
POlyangitis with granulomatosis…C-ANCA (PR3) pos with necrotizing vasculitis and ncrotizing granulomas
No linear/granular IF staining
No immune complexes on electron micros
GPA
Necrotizing granulomas in boht URT and LRT
Necrotizing or granulomatious vasculitis (lungs and upper airways)
Glomeruloneprhtisi - focal necrotizing or crescentic
Type 3 tx
2 phases…induction - CS and cyclophos
Maintencne - azathiprine or methotrexate
PLsma exchane considered in pts iwth pulm hemorrhage or require dialysis at presentation
