Nephritic Syndrome Flashcards
Traits of nephrOTIC syndrome
- 3+ proteinuria
- high cholesterol
- hypercoaguable
- low albumin
What are the classic NEPHROTIC syndromes?
- Minimal change disease (podocyte damage)
- Focal segmental glomerulosclerosis (podocyte damage)
- Membranous nephropathy (subepithelial immune complex)
What are some immune complex mediated NephrITIC syndromes?
- Post-infectious glomerulonephritis (sub- epithelial)
- Membranoproliferative glomerulonephritis (MPGN) (subendothelial)
- IgA nephropathy (mesangial)
What are the classic signs and symptoms of nephritic syndrome?
acute onset of hematuria, HTN, oliguria, MILD edema, and azotemia
THERE CAN BE EDEMA WITH NEPHRITIC
T or F. The hematuria associated with nephritic syndrome can be macroscopic or microscopic
T.
What other diseases show immune deposits in the sub endothelial and mesangial spaces?
- Lupus nephritis
- Post infectious GN (can be)
What things can cause glomerular endothelial cell injury?
- immune complexes
- TTP/HUS
- entrapment of paraproteins (common in MM)
What does damage of endothelial cells result in?
Cytokine and autacoid release which (along with activated complement) up regulate adhesion molecules on endothelial and circulating immune cells resulting in inflammation and thus HEMATURIA
Case 1. A 14-year-old Caucasian teenager presents with nephrotic syndrome and microhematuria. The patient has no history of fever, rash, arthralgias, or gross hematuria. Past medical history is unremarkable.
Physical examination reveals a BP of 138/80 mmHg and 2+ lower extremity edema.
Laboratory studies include serum creatinine level of 1.3 mg/dl, BUN of 43 mg/dl, 24-hour urine protein of 5.12 g, serum albumin of 2.7 g/dl, hemoglobin 10 g/dl, white blood cell count of 7.2k, platelets of 340k, and normal serum electrolytes.
Urinalysis shows 3+ protein and microhematuria without red blood cell casts.
Serologies were negative (included negative anti-nuclear antibody, ANCAs, hepatitis B surface antigen, hepatitis C virus antibody, and HIV).
Serum complement 3 (C3) was low
Kidney size by ultrasound was 10.4 and 10.3 cm.
creatinine is a little high for a 14 yo
albumin is low; hemoglobin is low
This patient has Membranoproliferazive glomerulonephritis (idiopathic in this age group)
Why is fever, rash, and arthralgias an important part of the history of someone with glomerular disease?
these would be indicative of vasculiitis
What are the types of MPGN? Most common?
I: most common form
II: also referred to as Dense Deposit Disease, likely a separate disease
III: VERY rare
What is MPGN type I?
hypercellularity of the glomerular turf and expanded mesangium and capillary wall changes
What do the capillary wall changes result in?
a double contour (replication) of the glomerular basement appearance referred to as a “tram track appearance” caused by displacement of immune deposits and infiltrating mesangium cells. Mesangial cells actually act like macrophages and try to remove the deposits and do this in the process
How can MPGN type I present?
- microscopic hematuria
- non-nephrotic range proteinuria (or nephrotic syndrome)
- RPGN (loss of kidney function rapidly)
Cause of MPGN type I?
may be idiopathic (in teenagers), but often associated with hep C infection in adults (sometimes hep B)
How is MPGN type I treated?
Don’t know but steroids used. Spontaneous remission can occur rarely but usually progresses to end stage renal disease
How does Dense deposit disease present?
similar to MPGN type I (also have low C3) but may have macular deposits and/or acquired partial lipodystrophy
What do 80% of DDD patients have?
C3 nephritic factor which is an antibody that stabilizes an enzyme that leads to continued destruction of C3
What is acquired partial lipodystrophy?
loss of subcutaneous fat in the upper half of the body
What imaging technique can differentiate MPGN from DDD?
not light microscopy (look the same), but will be different on EM
Also, DDD is negative for tram track appearance on silver stain
T or F. MPGN type I is involved with immune-complex mediated complement activation via the classical pathway
T. While DDD is complement activated the alternative pathway
Case 2. A 14-year-old Caucasian teenager presents with nephrotic syndrome and microhematuria. The patient has no history of fever, rash, arthralgias, or gross hematuria.
Past medical history is unremarkable. Physical examination reveals a BP of 138/80 mmHg and 2+ lower extremity edema. Laboratory studies include serum creatinine level of 1.3 mg/dl, blood urea nitrogen of 43 mg/dl, 24-hour urine protein of 5.12 g, serum albumin of 2.7 g/dl, hemoglobin 10 g/dl, white blood cell count of 7200, platelets of 340k, and normal serum electrolytes.
Urinalysis shows 3+ protein and microhematuria without red blood cell casts.
Serologies were negative (included negative anti-nuclear antibody, anti-neutrophil cytoplasmic antibody, hepatitis B surface antigen, hepatitis C virus antibody, and HIV).
*C3 and C4 levels are normal.
Kidney size by ultrasound was 10.4 and 10.3 cm.
This is IgA nephropathy (aka Berger’s Disease)
What is the most common PRIMARY glomerulonephritis worldwide?
IgA nephropathy (IgAN)- although may be secondary
What is IgAN characterized by?
deposition of IgA-containign immune complexes predominantly in the mesangium resulting in meangioproliferative patterns of injury
very variable presentation (asymptomatic all the way to RPGN)
What are some secondary causes of IgAN?
- Henoch-Schoenlein purpura
- Ankylosing spondylitis
- Dermatitis herpetiformis
- Celiac disease
- Inflammatory bowel disease
- Cirrhosis
- Psoriasis
What triggers IgAN?
infection of the upper respiratory or GI tract that presents with ‘synpharyngitic’ nephritic sediment (tea colored urine) within 1-2 days of infection
What triggers the immune complex formation in IgAN?
Galactose deficient IgA1 is produced and the body forms IgG or IgA1 antibodies against it and deposit in the mesangium where inflammation follows
What disease has gross hematuria but presents 1-2 WEEKS after infection?
Acute post-strept GN
Can you use elevated serum IgA as a test for IgAN?
No, only 50% have increased
Associations of IgAN?
-HTN
What are the risk factors for loss of renal function in IgAN?
- heavy proteinuria
- decreased GFR at onset
- older age at onset
- uncontrolled HTN
- crescent formation
What causes Anti-GBM disease (Goodpasture’s)?
Results from the formation of autoantibodies against a noncollagenous portion of the α-3 subunit of type IV collagen
What does IF look like with Anti-GBM disease?
Anti-GBM antibodies (usually of the IgG class) bind in a relatively uniform manner leading to a LINEAR (not granular) appearance on immunofluorescence
Is there a relationship between anti-GBM titers and the disease progression?
No.
How quick for Anti-GBM progress?
Rapid development of kidney failure due to focal glomerular necrosis and crescent formation
This is an example of RPGN
How does GP disease present?
Cough, dyspnea, crackles, hemoptysis may precede or coincide with renal dysfunction
Pulmonary hemorrhage exacerbated by exposures to tobacco smoke, influenza, volatile hydrocarbons
Rapidly progressive renal failure with azotemia at presentation in 50 to 70% of cases
Anemia out of proportion to renal insufficiency
Arthritis/arthralgias common
Usually normotensive
How is GP disease treated?
Treated with corticosteroids, plasmapheresis, and cytotoxic agents
GP disease is associated with ___-ANCA.
MPO (and crescent formation)
Where are the immune complexes deposited in Gp disease?
There are none, only auto-antibodies against GBM
What are crescents?
Accumulation and proliferation of cells outside the glomerular tuft which can result in compression of the tuft with rapid progression to renal failure
When does crescent formation become Referred to as diffuse crescentic glomerulonephritis?
if >50% glomeruli involved under light microscopy and called focal is less than 50% involved
Initially characterized by segmental proliferative and necrotizing lesions leading to cellular crescents leading to fibrocellular crescents leading to fibrous crescents
What is Alport syndrome?
AKA “hereditary nephritis”
Heterozygous females may have hematuria and thin basement membranes (more mild)
Affected males (present more) have persistent hematuria, progressive proteinuria, and ultimately end stage renal disease
What causes Alport syndrome?
X-linked inheritance (defects in α-5 collagen type IV; COL4A5) in 80% of cases; may be AR
What is Alport associated with?
Sensorineural hearing loss, lens abnormalities, and platelet defects; rarely esophageal leiomyomas
What will biopsy of Alport show?
Biopsy shows abnormally thin basement membranes with splintering of the lamina densa causing a “basket weave appearance”
What is Thin Basement disease?
Usually benign as long as heterozygous (NOT homozygous or compound)
Associated with defects in α-3 or α-4 collagen type IV
GBM thickness is uniformly reduced and about ½ normal
