Nephrotic Syndrome Causes Flashcards
When can you call something IgM nephropathy?
(probably never without asking Alex)
*legit IgM at 3+ (on 4+ scale)
*legit (mesangial) IgM equal or greater than 2+ (on 3 scale)
*EM immune complex deposition in the mesangium
what do you need to rule out before calling something IgM nephropathy?
IgM nephropathy must be differentiated from IgA nephropathy, mesangial proliferative lupus nephritis, and the resolving phase of acute postinfectious glomerulonephritis. IgM nephropathy is distinguished by dominant mesangial staining for IgM (with/without C3) and the presence of severe foot process effacement in the setting of idiopathic nephrotic syndrome.
It would otherwise be minimal change disease but you see a good deal of IgM in the mesangium…
COULD be IgM nephropathy (if it exists)
*still most likely MCD with some IgM in the mesangium
*all up to the relative intensity of staining
Most common drugs associated with MCD
“Secondary minimal change”
This variant is defined as nephrotic syndrome with biopsy findings of MCD arising in the setting of drug use.
**The commonest drug association is with non-steroidal anti-inflammatory drugs (NSAIDs)
(less common): lithium, interferon, mercury-containing skin lightening cream, and pamidronate have also been implicated.
* Remission of the nephrotic syndrome within weeks of withdrawal of the offending drug supports a drug effect.
Non-drug causes of secondary MCD
Hodgkin’s disease and other hematologic malignancies (CLL, AML, AITL, intravascular lymphoma, Mycosis fungoides, (T)ALL)
**Support for a pathogenic association includes the response of the MCD to therapy directed to the Hodgkin’s disease and the timing of recurrences of nephrotic syndrome with relapses of Hodgkin’s disease.
**(rarely) thymoma, bee stings, food allergies, childhood immunizations, infectious mononucleosis, HIV infection, and SLE
*A close temporal relationship between the inciting agent or disease and the development of the nephrotic syndrome supports a pathogenic role, but coincidental occurrence may be impossible to exclude in an individual case.
Drug induced secondary FSGS causes
Heroin (“Heroin nephropathy”)
Interferon-α, β, or γ
Lithium
Pamidronate
Sirolimus
Anabolic steroids
“Adaptive” secondary FSGS causes
Oligomeganephronia
Very low birth weight
Unilateral renal agenesis
Renal dysplasia
Reflux nephropathy
Sequela to cortical necrosis
Surgical renal ablation
De novo FSGS in the renal allograft
Any advanced renal disease with reduction in functioning nephrons
What viral infections can cause secondary FSGS?
HIV-1 (“HIV-associated nephropathy”) –> collapsing especially
Parvovirus B-19
SV40
CMV
Hemophagocytic syndrome
What do you need for perihilar FSGS pattern?
more than 50% of segmentally sclerosed glomeruli show perihilar area segmental sclerosis with hyalinosis
**At least 1 glomerulus with perihilar hyalinosis, with or without sclerosis. Greater than 50% of glomeruli with segmental lesions must have perihilar sclerosis and/or hyalinosis
What IF findings push you towards primary membranous (as opposed to secondary membranous)
in primary MN, there is typically dominant staining for IgG4.
IgG1 is also commonly seen, but IgG2 and IgG3 are usually absent
(IgG4 is usually the most dominant subclass)
What IgG subclass staining pattern makes you think of MN secondary to malignancy?
IgG1,2, and 4 of about equal intensity but ABSENCE of IgG3
(or just way dimmer IgG3 compared to the other subclasses)
If you are trying to prove that your MN is really the presenting symptom of a new Lupus Nephritis you would want to see what IF staining pattern?
All subclasses of IgG stain in Lupus, but usually IgG4 is the dimmest. So you get subclasses and they do NOT show IgG4 dominance (like should be there in primary MN)
What viral infection is most notorious for causing secondary MN?
Hepatitis B virus, particularly in children
(also hep C, but less commonly)
