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Flashcards in Glomerular Disease Deck (57):
1

3 Mechanisms of Glomerular Disease

• Immunocomplex deposition: – activates complement resulting in neutrophil chemotaxis

• Antibodies against GBM or glomerular antigens

• Cytokine production

2

Glomerular disease can be:

Will present at:

focal, diffuse, global, segmental

Hematuria, decrease GFR, proteinuria

3

• 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

4

• Mild proteinuria

• Hematuria– RBCs, RBC casts, dysmorphic RBCs

• Hypertension

• Edema

Nephritic syndrome

5

Minimal change disease Focal segmental glomerulosclerosis Membranous nephropathy IgA nephropathy

All NephrOtic syndromes (proteins loss over 3.5g/day)

6

Membranoproliferative GN Acute post-infectious GN Crescentic (ANCA) GN

All NephrItic syndromes (hematuria)

7

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

8

• Most common GN worldwide • Most patients between age 10-50 • Hematuria is most prominent feature

IgA nephropathy ~ if proteinuria, mild and most cases subclinical

9

In IgA nephropathy, hematuria frequently occurs in conjunction with

an upper respiratory infection (“synpharyngitic hematuria”) *flank/loin pain can accompany hematuria

10

Pts with advanced IgA nephropathy may have

HTN

11

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

12

Prognosis of IgA nephropathy is based:

on serum creatinine, BP, and degree of proteinuria – 40% of patients will slowly develop CKD

13

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

14

Systemic disorder characterized by IgA deposition in multiple organs

Henoch Schonlein Purpura

15

Kidney involvement in Henoch Schonlein Purpura

hematuria, proteinuria; rarely progressive renal fail

16

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

17

Sudden onset hypertension, azotemia, oliguria, edema and cola- or tea-colored urine

Post-infectious GN

18

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

19

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

20

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

21

Classic nephritic syndrome with rapid progression (days to weeks) to renal failure • Sometimes referred to as “crescentic GN”

Rapidly Progressive GN

22

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

23

Classic feature early and later in Rapidly progressive GN

Segmental necrosis with red glomerulis later Crescent

24

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

25

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

26

Crescenteric GN with little deposition of immune reactants

--can be idiopathic or associated with ANCA vascuitis

 

Pauci-Immune GN

27

What are the three forms of vasculitis?

1. no granulomatous inflammation, no asthma

2. Necrotizing granulomatous inflammation; no ashtma

3. Necrotixing gran inflammation, asthma, eosinophila

1. Microscopic polyangiitits
– No granulomatous inflammation and no asthma

2. Wegener’s granulomatosis
– Necrotizing granulomatous inflammation; no asthma- C disease

3. Churg-Strauss syndrome
– Necrotizing granulomatous inflammation, asthma, eosinophilia

28

• Granulomatous vasculitis of medium to small 
arterioles
• c-ANCA + in 80%

Wegeners Granulomatosis

29

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

30

– 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

31

Helpful labs when Dx secondary nephrotic syndrome

– ANA, anti-dsDNA, complement levels
– serum & urine protein electrophoreses
– HBV & HCV serologies
– cryoglobulins
– syphilis serology

 

32

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

33

• 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

34

What causes Minimal Change Disease in Adults?

Idiopathic or associated with:

NSAIDS

Hodgkins Lymphoma

other neoplasms, infections like HIV and syphillis

35

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

36

Tx for children and adults for MCD

Corticosteroids

--children respond better and fastr

37

Most common cause of nephrotic syndrome in Caucasian adults 
• Secondary causes account for ~15-20% of cases

Membranous Nephropathy

38

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)

39

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%

40

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 

 

41

Membranous nephorpathy has ______ deposits on EM

SubEPIthelial

42

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

43

Tx for patients with membranous nephropathy

1. With poor prognostics

2. 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

44

• 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)

45

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

46

Hereditary FSGS--mutations in proteins that make up the ________

glomerular slit diaphragm

47

Key causes of secondary FSGS

HIV, NSAIDS and heroin, obesity, healed prior glomerular injury, loss of renal mass

48

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)

49

• 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

50

• Proteinuria & hematuria commonly coexist
• Hypertension occurs in 1/3
• Low C3 complement is a prominent feature
• Variable clinical presentation

Membranoproliferative Glomerulo-nephritis (MPGN)

51

Secondary causes of MPGN

Hep C virus!!! and HBV

SLE

neoplasms

 

52

Pt has subENDOthelial deposis on EM with granular C3 deposition seen on IF. 

The glomeruli are lobular and there is hypercellular glomeruli

Dx

MPGN

53

• A multi-system auto-immune disorder
– abnormal autoantibody production
– immune complex deposition
– inflammatory cell infiltration

SLE

54

• 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

55

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

56

• General principles of management of any class of lupus nephritis:
 

– aggressive BP control
– control of lipid levels
– appropriate treatment of extrarenal involvement

57

• Classes III-V: usually treated with 
_________
– Class IV: renal failure rate 25% by 5-10 years

corticosteroids + cytotoxic therapy