Acute Glomerular Diseases

Question 1

How does the GFR differ for acute glomerulonephritis and RPGN?

Answer 1

Acute- the GFR remains relatively stable

RPGN- the GFR decreases quickly

Question 2

What are the 2 main types of PRIMARY acute glomerulonephritis?

Answer 2

1. idiopathic MPGN

2. IgA nephropathy (10%)

Question 3

What are the infectious causes of acute glomerulonephritis?

Answer 3

1. PSGN (post-strep)

2. bacterial endocarditis

Question 4

What are the secondary NON-infectious causes of acute glomerulonephritis?

Answer 4

1. microangiopathic thrombosis - HUS (hemolytic uremic syndrome), TTP (thrombotic thrombocytopenic purpura)
2. SLE, cryoglobinemia, systemic vasculitis

Question 5

A patient presents with sudden onset edema, hematuria, and loss of renal function 2-3 weeks after a sore throat (or skin rash,,whichever). They have hypertension and acute kidney injury.

What is the cause, usual outcome, and distinguishing features in the lab workup? What will be in the urine?

Answer 5

Cause: Post-strep acute glomerulonephritis

Outcome: most completely resolve after initial episode

Lab for pharyngitis strain:
Increased ASO antibodies and anti-DNAse B antibodies, impetigo, hypocomplementuria

Lab for cellulitis strain:
anti-DNAse B

Urine: RBC casts

Question 6

A person presents with edema, hypertension, congested circulation. The GFR is measured and is shown to have been declining over a period of weeks to months. (Cr rises by 2mg/dl over 3 months)
Renal biopsy shows cresent formation in the glomeruli

What is the likely diagnosis?
What is the outcome?

Answer 6

RPGN

There is little tendency to spontaneously recover

Question 7

There are many different IF patterns associated with RPGN.

What are the 2 types that will have linear staining?

Answer 7

1. Type 1 Anti-GBM- affects just the kidney. Ab directed against a3 of collagen IV
2. Goodpasture’s syndrome- affects the kidney and the lungs

Question 8

What are the primary causes of RPGN?

What will IF show for them?

Answer 8

1. type 1 MPGN
2. IgA nephritis

Both have granular staining because they are caused by depositing immune complexes (type 1 MPGN is subendothelial/endocapillary/lobar, IgA is mesangial)

Question 9

What are the secondary cause of RPGN that have granular staining due to circulating immune complexes?

Answer 9

1. SLE
2. HUS - with palpable purpura in lower extremities
3. post-infectious

Question 10

What are the 4 causes of RPGN with NO immune deposits?

Answer 10

1. idiopathic
2. Wegener’s (c-ANCA)
3. microscopic polyarteritis nodosa (p-ANCA)
4. Churg-Strauss (allergic angiitis- p-ANCA)

Question 11

What is the effect of RPGN on the excretion of sodium and water? What is the result of this?

Answer 11

In RPGN there is a progressively decreased GFR which means less Na and water are getting excreted. This leads to volume overload, pulmonary congestion and hypoxemia.

Question 12

Describe the urine osmolarity and the urine [Na] in the early stages of RPGN.

Answer 12

In the early stages, the tubule is still able to reabsorb Na, so the urine Na is low and the urine Osmolarity is high (because the tubules are still able to concentrate urine.

Question 13

Why does hyperkalemia develop in patients with RPGN?

Answer 13

There is a low filtration rate, so more K is reabsorbed in the proximal tubule.
Na is getting reabsorbed, so there is decreased distal delivery.
Hyperaldosteronism does NOT occur because of the volume expansion from fluid retention

Question 14

What acid base disturbance is most associated with RPGN?

Answer 14

NG and acid gap metabolic acidosis

Question 15

What SPECIFICALLY are anti-GBM antibodies being directed at in anti-GBM disease?

Answer 15

a3 chain of type 4 collagen in the basement membrane

Question 16

A patient presents with subnephrotic proteinuria, hematuria, and sediment with RBC, WBC, and RBC and granular casts.
They also have hemoptysis and anemia. What is the likely cause?

You do a biopsy. What are you likely to find on LM of the kidney?
IF?

Answer 16

Goodpasture’s disease with anti-GBM antibodies directed against the a3 chain of collagen IV in the lungs and kidneys

LM- cresentic glomerulonephritis
IF- linear deposition of IgG on the basement membrane

Question 17

A patient presents with rhinorrhea, bloody/purulent nasal discharge, oral/nasal ulcers, arthralgia, myalgia and sinus pain. They have hematuria, hypertension, and increasing Cr.
You do a renal biopsy.
LM shows segmental necrotizing glomerularnephritis
IF shows nothing

Based on history, what is your suspicion?
What is the next test you want to perform?
What are treatments?

Answer 17

Based on the URT symptoms and renal involvement you suspect Wegener’s.

The lack of IF and necrotizing glomerulonephritis agrees.

Next order a test for anti-proteinase 3 (C-ANCA.) If it is positive, you can diagnose Wegener’s.

Treat with cyclophosphamide and steroids

Question 18

A patient presents with allergic rhinitis, asthma, and peripheral blood eosinophilia. They have renal symptoms that include subnephrotic proteinuria, nephritic sediments RBC casts.

IF shows nothing.

What is suspected?
How do you confirm?

Answer 18

Churg-Strauss because of the eosinophilia and RPGN presentation.

Confirm with anti-MPO for P-ANCA

Question 19

A patient presents with hypertension, variable kidney insufficiency and bleeding caused by a renal artery microaneurysm rupture. They may have some kidney infarction.
Urinalysis shows hematuria and subnephrotic proteinuria.
Which vessel is most likely involved, and what vasculitis may be causing it?

Answer 19

The renal artery is involved and it is probably PAN

30% positive for Hep B antigen

Question 20

What are the 6 classifications of Lupus nephritis?
Which 2 stages present with a RPGN clinical picture?
What is Rx?
What is the MOST COMMON abnormality associated with SLE?

Answer 20

1. minimal mesangial SLE nephritis
2. mesangial proliferative SLE nephritis
3. Focal (like RPGN)
4. diffuse (like RPGN)
5. membranous (nephrotic)
6. advanced sclerosing (chronic GN)

Treat 3 and 4 with cyclophosphamide and steroids

Proteinuria is the most common symptoms

Question 21

Although the different classes of SLE renal involvement have distinct histology, clinical presentation and prognosis, there is substantial overlap. This means to get a good sample, you need to biopsy how many glomeruli?

Answer 21

25

Question 22

What are the 2 types of thrombotic microangiopathy?
They affect multiple organ systems, but what 2 symptoms are always present?
What is treatment?

Answer 22

1. thrombotic thrombocytopenic purpura (TTP)
2. hemolytic uremic syndrome

They both have thrombocytopenia and microangiopathic hemolytic anemia

Treat with empiric plasma exchange therapy

Question 23

Most patients with TTP have a deficiency in what enzyme? What is the result?

Answer 23

ADAMTS13 which leads to large vWF multimers because that enzyme usually cleaves the multimers.

The multimers bind platelets and cause agglutination

Question 24

What are the 2 main causes of HUS?

Answer 24

1. infection by shiga-toxin E coli

2. complement dysregulation by genetic mutation

Question 25

Patients with TTP generally have higher incidence of __________________ symptoms while patients with HUS has more __________involvement.

Answer 25

TTP- neurological symptoms | HUS- kidney involvement

Question 26

Hypocomplementemia is a common finding in what 4 nephritic disorders?

Answer 26

1. SLE type III and IV 2. post-infection 3. MPGN 4. mixed cryoglobinemia

Question 27

What is the complement level for anti-GBM, ANCA, IgA nephropathy?

Answer 27

normal

Question 28

What 5 syndromes are associated with asymptomatic hematuria and proteinuria?

Answer 28

1. IgA nephropathy 2. Thin BM disease 3. Alport's (hereditary nephritis) 4. MPGN 5. Mild glomerulonephritis

Question 29

What is seen on IF for IgA nephropathy? | What is seen on LM?

Answer 29

IF- prominent globular deposits of IgA on the mesangium (with some IgG and C3) LM- mesangial proliferation and matrix expansion

Question 30

What causes IgA nephropathy?

Answer 30

Defective mucousal immunity where IgA reacts against an unknown antigen. The IgA are glycosylated so they cannot be destroyed by RES. Once deposited, they start inflammatory response which stimulates PDGF for mesangial proliferation

Question 31

A patient presents with gross hematuria 24 hours after an URI (synpharyngitic syndrome). They have flank pain during the episode. What are you suspicious of?

Answer 31

IgA nephropathy

Question 32

What are the 3 ways IgA nephropathy can present?

Answer 32

1. gross hematuria <24hrs after URI 2. microhematuria and mild proteinuria (incidental finding in routine exam) 3. acute glomerulonephritis with hypertension, edema, renal insufficiency

Question 33

Because of the benign course of IgA nephropathy and thin basement membrane disease, when should you perform a renal biopsy?

Answer 33

Only if there are signs suggestive of a more severe or progressive disease such as: 1. protein excretion >1g/day 2. elevated Cr 3. hypertension

Question 34

What is the cause of thin basement membrane disease?

Answer 34

familial disorder with a 150-225 GBM instead of 300-400. | This results in benign familial hematuria

Question 35

A man presents with slowly progressive glomerulonephritis. He has hearing loss and lenticular abnormalities (eye probs). His grandfather has the same problem. What is the likely cause?

Answer 35

Alport's syndrome (hereditary nephritis) | X-linked disorder

Question 36

What gene is mutated in X linked Alport syndrome? AR alport syndrome? What does this lead to?

Answer 36

COL4A5 gene is mutated and it is a mutation in the a5 chain of collagen 4. This disrupts the novel collagen formation when a3, a4 and a5 combine

Question 37

What disorder is associated with a mutation in the a3 chain of col 4? a3/a4? a5?

Answer 37

``` a3 = goodpastures a3/a4 = AR alports a5 = x-linked alports ```

Question 38

What changes occur to the GBM as Alport syndrome progresses?

Answer 38

1. thinning of GBM (not pathognomonic bc TBMD) 2. longitudinal splitting of GBM 3. laminated appearance

Question 39

When does hematuria begin in Alport's disease? By what age have they progressed to ESRD?

Answer 39

5- first signs of hematuria Cr and BP rise-->hypertension, CKD, increased proteinuria 16-35 --> ESRD

Question 40

What is the treatment for the renal component of Alport's syndrome? What is a limitation?

Answer 40

Dialysis or Transplantation if they have ESRD With transplant Ab will form against GBM (Goodpastures a3) because their original kidney lacked the novel protein formed by a3a4a5. Treat with immunosuppresion