Glomerular Disease Flashcards
3 Mechanisms of Glomerular Disease
- Immunocomplex deposition: – activates complement resulting in neutrophil chemotaxis
- Antibodies against GBM or glomerular antigens
- Cytokine production
Glomerular disease can be:
Will present at:
focal, diffuse, global, segmental
Hematuria, decrease GFR, proteinuria
- Proteinuria > 3.5 g/day
- Hypoalbuminemia
- Edema– Loss of plasma oncotic pressure vs Na/H20 retention
- Hyperlipidemia– increased hepatic protein production
- Lipiduria
- Hypercoagulability– loss of Proteins C & S
Nephrotic syndrome
- Mild proteinuria
- Hematuria– RBCs, RBC casts, dysmorphic RBCs
- Hypertension
- Edema
Nephritic syndrome
Minimal change disease Focal segmental glomerulosclerosis Membranous nephropathy IgA nephropathy
All NephrOtic syndromes (proteins loss over 3.5g/day)
Membranoproliferative GN Acute post-infectious GN Crescentic (ANCA) GN
All NephrItic syndromes (hematuria)
all the follwing below are causes of: -IgA nephropathy – Post-infectious GN – Anti-GBM disease/Goodpasture’s – Small vessel vasculitis – Lupus nephritis – Membranoproliferative GN
Acute GlomerlonephrItis
• Most common GN worldwide • Most patients between age 10-50 • Hematuria is most prominent feature
IgA nephropathy ~ if proteinuria, mild and most cases subclinical
In IgA nephropathy, hematuria frequently occurs in conjunction with
an upper respiratory infection (“synpharyngitic hematuria”) *flank/loin pain can accompany hematuria
Pts with advanced IgA nephropathy may have
HTN
What do we see on IF in pts with IgA nephropathy LM not as important
IF: Mesangial IgA deposition LM: variable mesangial hypercellularity – May see segmental proliferation, segmental sclerosis and necrosis with crescents
Prognosis of IgA nephropathy is based:
on serum creatinine, BP, and degree of proteinuria – 40% of patients will slowly develop CKD
Tx options for pts with IgA nephropathy
• Fish oil to slow progression of disease • ACE-inhibitors used to control BP • Corticosteroids, other immunosuppressants also may be used in progressive disease
Systemic disorder characterized by IgA deposition in multiple organs
Henoch Schonlein Purpura
Kidney involvement in Henoch Schonlein Purpura
hematuria, proteinuria; rarely progressive renal fail
Post-infectious GN • Post-streptococcal GN– classic example • Follows infection in nephritogenic strain of _______________________ • Occurs 7-14 days after_______; 14-28 days after _______
group A beta-hemolytic
streptococcus pharyngitis
skin infection
Sudden onset hypertension, azotemia, oliguria, edema and cola- or tea-colored urine
Post-infectious GN
What lab findings do we expect to see in post-infectious GN?
– low C3 complement level – Anti-streptolysin O (ASO) can be elevated – Urinalysis: red blood cell casts, mild proteinuria
On EM you see mesangial and large subEPIthelial ‘hump like’ deposits, Dx?
Post infectious GN -also see granular capillary wall and mesangial IgG and C3 -Neutrophil in mensangial and endocapillary cells
Outcome for children and adults with post-Step GN
• 95% of children will recover with conservative management ~1% progress to renal failure • 60% of adults will recover promptly
Classic nephritic syndrome with rapid progression (days to weeks) to renal failure • Sometimes referred to as “crescentic GN”
Rapidly Progressive GN
The following are all causes of: – Anti-GBM/Goodpasture’s – Immune complex GN • Lupus nephritis • Post-infectious • Cryoglobulinemia – ANCA associated GN (Pauci immune)
Rapidly Progressive GN
Classic feature early and later in Rapidly progressive GN
Segmental necrosis with red glomerulis later Crescent
Dx and Tx for Anti-GBM and Goodpastures
+anti-GBM antibody in blood (alone is just Anti-GBM disease) with Linear IgG and C3 on IF
Tx: plasmapherisis + Prednisone + Cytoxan
Male comes to clinic. He has glomerulonephritis and it coughing up blood. Suspected dx? Cause?
Goodpastures (more male then female; see lung and kidney involvment)
Due to circulating antiBs to alpha-3 chaing of type IV collagen
*just glomerulonephritis with circulating antibodies is Anti-GBM
Crescenteric GN with little deposition of immune reactants
–can be idiopathic or associated with ANCA vascuitis
Pauci-Immune GN
What are the three forms of vasculitis?
- no granulomatous inflammation, no asthma
- Necrotizing granulomatous inflammation; no ashtma
- Necrotixing gran inflammation, asthma, eosinophila
- Microscopic polyangiitits
– No granulomatous inflammation and no asthma - Wegener’s granulomatosis
– Necrotizing granulomatous inflammation; no asthma- C disease - Churg-Strauss syndrome
– Necrotizing granulomatous inflammation, asthma, eosinophilia
• Granulomatous vasculitis of medium to small
arterioles
• c-ANCA + in 80%
Wegeners Granulomatosis
Pt comes in with nephritis symptoms. He has past history of constant URIs (sinusitis, nasal lesions, hemoptysis) as well as purpura on his legs.
Dx?
What do you expect to see on biopsy?
Wegeners granulomatosis
see cresentic GN but NO NO IC deposits
– systemic diseases– Diabetes mellitus,SLE, amyloidosis
– infections– HIV, Hepatitis B, Hepatitis C, syphilis
– drugs– classical examples include NSAIDs, gold, penicillamine
These are all:
secondary causes of nephrotic syndrome
Helpful labs when Dx secondary nephrotic syndrome
– ANA, anti-dsDNA, complement levels
– serum & urine protein electrophoreses
– HBV & HCV serologies
– cryoglobulins
– syphilis serology
Treatment for all causes of nephrotic syndrome includes:
– ACE-inhibitor or angiotensin-II receptor blocker to lower intraglomerular pressure and reduce proteinuria
– lipid-lowering therapy (“statins”)
– diuretics, salt restriction to improve edema
• Most common cause of nephrotic syndrome in children
– peak incidence ages 2-6
– 5% progress to end-stage renal disease
– spontaneous remissions can occur
– treatment with steroids often induces remission although relapses occur in about 75%
Minimal Change Disease
What causes Minimal Change Disease in Adults?
Idiopathic or associated with:
NSAIDS
Hodgkins Lymphoma
other neoplasms, infections like HIV and syphillis
What do we wee on LM/IF and EM for Minimal Change Disease?
LM and IF are negative for changes
EM: Podocyte foot process effacement
Tx for children and adults for MCD
Corticosteroids
–children respond better and fastr
Most common cause of nephrotic syndrome in Caucasian adults
• Secondary causes account for ~15-20% of cases
Membranous Nephropathy
Key secondary causes of Membranous Nephropathy
• Secondary causes:
– Infections–HBV
– Connective tissue diseases–SLE
– Neoplasms–carcinoma of lung, colon, stomach, breast; non-Hodgkin’s lymphoma
• Consider age appropriate cancer screening
– Drugs–gold, penicillamine, mercury, NSAIDs, captopril
(know bolded for sure)
Membranous Nephropathy
• Onset is generally________
• Patients usually present with _______ and _______
– HTN & azotemia occur later
– Renal vein thrombosis occurs in ______
Insidious
heavy proteinuria & nephrotic syndrome
~ 20%
You are looking at LM and see diffuse thickening of the GBM with GBM ‘spikes’ on silver stain
Membranous Nephropathy
–see granular GBM deposits of IgG
Membranous nephorpathy has ______ deposits on EM
SubEPIthelial
Outcome of Membranous nephropathy
Rule of thirds
– 1/3 spontaneous remission
– 1/3 partial remissions with stable function
– 1/3 slowly progressive loss of renal function
Tx for patients with membranous nephropathy
- With poor prognostics
- normally
• Patients without poor prognostic factors might be managed conservatively with
ACE-I and/or ARB and followed closely
• Otherwise, steroids +/- other immunosuppressive drugs are used
• Most common cause of idiopathic nephrotic syndrome in African-Americans
• More aggressive than minimal change disease:
– Hypertension, hematuria more common
– renal dysfunction is commonly progressive
– ESRD occurs 5-20 years after presentation
Focal segmental glomeruloscerosis (FSGS)
Explain difference between Primary and Secondary FSGS
Primary FSGS–usually presents with acute onset of nephrotic syndrome
• Secondary FSGS–usually manifests with slowly increasing renal insufficiency and proteinuria
Hereditary FSGS–mutations in proteins that make up the ________
glomerular slit diaphragm
Key causes of secondary FSGS
HIV, NSAIDS and heroin, obesity, healed prior glomerular injury, loss of renal mass
Expected LM finding for FSGS
LM: Focal and segmental glomerular sclerosis with capillary collapse, hyaline and lipid deposition and adhesion to Bowman’s capsule
(Negative IF and some podocyte effacement)
• Prognosis correlates with degree of proteinuria–ACE inhibitors Decrease proteinuria
• Corticosteroids can induce remission in some patients
• Treatment for steroid-resistant patients and patients who relapse is problematic
– Immunosuppressives
• Progression to ESRD in 50% at 10 years
- Proteinuria & hematuria commonly coexist
- Hypertension occurs in 1/3
- Low C3 complement is a prominent feature
- Variable clinical presentation
Membranoproliferative Glomerulo-nephritis (MPGN)
Secondary causes of MPGN
Hep C virus!!! and HBV
SLE
neoplasms
Pt has subENDOthelial deposis on EM with granular C3 deposition seen on IF.
The glomeruli are lobular and there is hypercellular glomeruli
Dx
MPGN
• A multi-system auto-immune disorder
– abnormal autoantibody production
– immune complex deposition
– inflammatory cell infiltration
SLE
• Common cause of diffuse proliferative GN
• 40% of patients develop overt nephritis– follow U/A in SLE patients
– HTN suggests the presence of renal disease
Lupus Nephritis
Why is renal biopsy in SLE pt with renal diease important?
- Many of the different clinical syndromes of renal disease can be occur in the setting of SLE
- Renal biopsy is important in order to classify lesion in SLE
• General principles of management of any class of lupus nephritis:
– aggressive BP control
– control of lipid levels
– appropriate treatment of extrarenal involvement
• Classes III-V: usually treated with
_________
– Class IV: renal failure rate 25% by 5-10 years
corticosteroids + cytotoxic therapy
