Acute Glomerular Diseases Flashcards
How does the GFR differ for acute glomerulonephritis and RPGN?
Acute- the GFR remains relatively stable
RPGN- the GFR decreases quickly
What are the 2 main types of PRIMARY acute glomerulonephritis?
- idiopathic MPGN
2. IgA nephropathy (10%)
What are the infectious causes of acute glomerulonephritis?
- PSGN (post-strep)
2. bacterial endocarditis
What are the secondary NON-infectious causes of acute glomerulonephritis?
- microangiopathic thrombosis - HUS (hemolytic uremic syndrome), TTP (thrombotic thrombocytopenic purpura)
- SLE, cryoglobinemia, systemic vasculitis
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?
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
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?
RPGN
There is little tendency to spontaneously recover
There are many different IF patterns associated with RPGN.
What are the 2 types that will have linear staining?
- Type 1 Anti-GBM- affects just the kidney. Ab directed against a3 of collagen IV
- Goodpasture’s syndrome- affects the kidney and the lungs
What are the primary causes of RPGN?
What will IF show for them?
- type 1 MPGN
- IgA nephritis
Both have granular staining because they are caused by depositing immune complexes (type 1 MPGN is subendothelial/endocapillary/lobar, IgA is mesangial)
What are the secondary cause of RPGN that have granular staining due to circulating immune complexes?
- SLE
- HUS - with palpable purpura in lower extremities
- post-infectious
What are the 4 causes of RPGN with NO immune deposits?
- idiopathic
- Wegener’s (c-ANCA)
- microscopic polyarteritis nodosa (p-ANCA)
- Churg-Strauss (allergic angiitis- p-ANCA)
What is the effect of RPGN on the excretion of sodium and water? What is the result of this?
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.
Describe the urine osmolarity and the urine [Na] in the early stages of RPGN.
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.
Why does hyperkalemia develop in patients with RPGN?
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
What acid base disturbance is most associated with RPGN?
NG and acid gap metabolic acidosis
What SPECIFICALLY are anti-GBM antibodies being directed at in anti-GBM disease?
a3 chain of type 4 collagen in the basement membrane
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?
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
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?
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
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?
Churg-Strauss because of the eosinophilia and RPGN presentation.
Confirm with anti-MPO for P-ANCA
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?
The renal artery is involved and it is probably PAN
30% positive for Hep B antigen
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?
- minimal mesangial SLE nephritis
- mesangial proliferative SLE nephritis
- Focal (like RPGN)
- diffuse (like RPGN)
- membranous (nephrotic)
- advanced sclerosing (chronic GN)
Treat 3 and 4 with cyclophosphamide and steroids
Proteinuria is the most common symptoms
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?
25
What are the 2 types of thrombotic microangiopathy?
They affect multiple organ systems, but what 2 symptoms are always present?
What is treatment?
- thrombotic thrombocytopenic purpura (TTP)
- hemolytic uremic syndrome
They both have thrombocytopenia and microangiopathic hemolytic anemia
Treat with empiric plasma exchange therapy
Most patients with TTP have a deficiency in what enzyme? What is the result?
ADAMTS13 which leads to large vWF multimers because that enzyme usually cleaves the multimers.
The multimers bind platelets and cause agglutination
What are the 2 main causes of HUS?
- infection by shiga-toxin E coli
2. complement dysregulation by genetic mutation
Patients with TTP generally have higher incidence of __________________ symptoms while patients with HUS has more __________involvement.
TTP- neurological symptoms
HUS- kidney involvement
Hypocomplementemia is a common finding in what 4 nephritic disorders?
- SLE type III and IV
- post-infection
- MPGN
- mixed cryoglobinemia
What is the complement level for anti-GBM, ANCA, IgA nephropathy?
normal
What 5 syndromes are associated with asymptomatic hematuria and proteinuria?
- IgA nephropathy
- Thin BM disease
- Alport’s (hereditary nephritis)
- MPGN
- Mild glomerulonephritis
What is seen on IF for IgA nephropathy?
What is seen on LM?
IF- prominent globular deposits of IgA on the mesangium (with some IgG and C3)
LM- mesangial proliferation and matrix expansion
What causes IgA nephropathy?
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
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?
IgA nephropathy
What are the 3 ways IgA nephropathy can present?
- gross hematuria <24hrs after URI
- microhematuria and mild proteinuria (incidental finding in routine exam)
- acute glomerulonephritis with hypertension, edema, renal insufficiency
Because of the benign course of IgA nephropathy and thin basement membrane disease, when should you perform a renal biopsy?
Only if there are signs suggestive of a more severe or progressive disease such as:
- protein excretion >1g/day
- elevated Cr
- hypertension
What is the cause of thin basement membrane disease?
familial disorder with a 150-225 GBM instead of 300-400.
This results in benign familial hematuria
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?
Alport’s syndrome (hereditary nephritis)
X-linked disorder
What gene is mutated in X linked Alport syndrome? AR alport syndrome?
What does this lead to?
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
What disorder is associated with a mutation in the a3 chain of col 4?
a3/a4?
a5?
a3 = goodpastures a3/a4 = AR alports a5 = x-linked alports
What changes occur to the GBM as Alport syndrome progresses?
- thinning of GBM (not pathognomonic bc TBMD)
- longitudinal splitting of GBM
- laminated appearance
When does hematuria begin in Alport’s disease? By what age have they progressed to ESRD?
5- first signs of hematuria
Cr and BP rise–>hypertension, CKD, increased proteinuria
16-35 –> ESRD
What is the treatment for the renal component of Alport’s syndrome? What is a limitation?
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
