00:01
So minimal change disease
really is the most common cause
of nephrotic syndrome in children.
00:08
So about 90% of children less
than the age of five years
who get diagnosed with
nephrotic syndrome
is going to be due to
minimal change disease.
00:15
Now interestingly,
as children start to grow up
about 50% of them over
the age of 10 years
have an increased in
percentage developing FSGS.
00:24
So only 50% will be minimal
change in the remainder
is really due to FSGS.
00:30
In adult it's much less low,
we only see about 10-15%
of all nephrotic
syndrome cases in adults
being due to minimal
change disease.
00:39
So when we think about
the etiology or causes
behind minimal change disease,
there's three broad categories
that we really need to think about.
00:46
Number 1, idiopathic,
and all that means is that
despite 40 Years of looking
we still don't know
the exact mechanism
as to what causes
minimal change disease.
00:56
But there are secondary form s
too, things like drugs,
and we just talked about one of
them in our patient case example.
01:00
Remember she was taking
high-dose ibuprofen.
01:03
So NSAIDs another reason
that is kind of the
enemy of the nephrologist
can certainly
precipitate or provoke
nephrotic syndrome right
with minimal change disease.
01:12
There certain
antimicrobial agents
that can do it as
well as lithium.
01:16
And then finally neoplasm,
Hodgkin's Disease and
Non-Hodgkins Lymphoma,
certain leukemias,
and thymoma have all been associated
with minimal change disease.
01:27
Okay, so when we think
about the pathogenesis
of minimal change disease,
the exact cause certainly
of idiopathic minimal
changes not clear.
01:34
What we do know,
is that there's some kind of
systemic T-Cell dysfunction
that's thought to result in a
glomerular permeability factor.
01:42
And that permeability factor
injures are podocytes leading to foot
process effacement and proteinuria.
01:47
So I want you to focus on
our schematic over here.
01:49
If you look at the top,
then what you see is a normal
glomerular capillary wall.
01:54
At the bottom portion,
you see that the capillary lumen,
It's lined by those endothelial
cells that are in pink
that yellow is the
glomerular basement membrane.
02:03
And then those green little guys
that look like a picket fence
are are put aside foot processes
and in between those
foot processes,
remember, they interdigitate
with each other like this
and they have a very
elegant slip diaphragm
and these guys really keep those
macromolecules like albumin
and other important things
inside of that capillary lumen
while they allow the ultra filtrate
to be filtered into Bowman's space.
02:23
But look what
happens when we have
minimal change disease that
permeability factor comes along
we then get foot price, we then get
actin cytoskeleton rearrangement
and foot process of effacement.
02:33
So if you look at our schematic,
you can see that foot processes
instead of standing
like a picket fence.
02:39
They're actually effaced
and then the slit diaphragm
that's between them is breached.
02:45
And so now we've got
macromolecules like albumin
and other large
molecules that can escape
into that glomerular filtrate into
Bowman's space and ultimately the urine.
02:55
All right, so what do we see
pathologically when we biopsy our patients.
02:58
On light microscopy,
I want you to focus on what our
actual pathological image looks like.
03:03
It's very reminiscent
of our normal glomerulus
that we showed in the beginning.
03:07
Why is that? because there are
minimal changes histologically
when we have minimal
change disease
that is why it's critical when
you're diagnosing these patients
and you're actually
requesting the biopsy
you want to make sure
one of those cores
is actually going in
for electron microscopy
because that's where you're
going to clench your diagnosis.
03:25
So here's my representation
of our electron micrograph
showing minimal change disease
and what's being shown
here is an actual loop
of capillary wall.
03:34
The inside you can
see that dark portion
that looks like a sea
is a red blood cell,
and then what my
arrow is pointing to
is actually the effacement of
our podocytes foot processes.
03:43
All you can see is
underlying basement membrane,
but those foot processes
instead of standing
like a nice picket line
are completely effaced.
03:50
So it diaphragms are breached
macromolecules can
now filter through.
03:56
So our patients typically
when they have minimal change
will present absolutely
with nephrotic syndrome.
04:01
It is not subtle.
04:02
They usually present
very profoundly.
04:05
They can have lipiduria.
04:07
Otherwise,
the urine sediment is bland
if I'm looking at it
underneath the microscope.
04:11
They have no serum
complement abnormalities.
04:14
So I'm not going to be
looking for compliment
on my serological tests.
04:17
And they often times
or to a certain degree
can present with renal failure
typically due to tubular injury
and I see that my
older population
oftentimes, it's because they're
getting concurrent diuretics
and they're very very vulnerable
to developing ischemic injuries.
04:34
Historically,
untreated minimal change disease
was actually associated
with a risk of mortality
and that's due to infection.
04:40
Remember we talked about
how those immunoglobulins
get lost into the urine
because of richment of that
glomerular capillary wall.
04:47
So when that happens patients
are at an increased risk
of infection and a risk
also of thromboembolism.
04:52
Why? remember these patients
have very high grade proteinuria
they're losing clotting inhibitors
through their urine as well.
04:59
So our patients,
fortunately are generally
responsive to steroid therapy
and have relatively
a good prognosis.
05:07
Of course as the rule always
goes in any glomerular disease,
children are going to respond
much better than adults.
05:13
So how do we treat our patients
when they present to us?
We are going to treat them
usually with high-dose steroids.
05:18
We give them for 12 to 16 weeks.
05:20
So something like prednisone
given at 1 milligram per kilogram.
05:24
It's a pretty long period
of time four months
and they get a progressive taper
over a six-month period of time.
05:30
Because this is
such an abrupt onset
and the disease is
relatively self-limiting,
we don't have to use ACE
or ARB's in her patients
unless they're
extremely hypertensive
and statins aren't always
needed, again,
because the duration
is much less shorter.
05:45
Now for some of our patients
who are steroid dependent
meaning that as I try to
taper them off their steroids,
they blossom again with
their nephrotic syndrome,
so I can't taper them
or a patient who's had a relapse
at least three times during a year.
05:58
Those patients are
considered steroid dependent.
06:00
So in that population,
I can actually give them
that alkylating agent
cyclophosphamide.
06:04
Give that for an
eight-week duration
and that can actually decrease
their dependence on steroids.
06:09
We can also use cyclosporine
as an alternative
if patients are
resistant to steroids.
06:14
But if I have a patient
that's completely resistant,
and their proteinuria is
not decreasing at all.
06:20
I might want to consider
re-biopsying them
as I may have missed
the diagnosis.
06:25
So a portion of those
patients might end up actually
having focal segmental
glomerulosclerosis
which we'll talk about shortly.
06:33
Finally,
there are some people,
were some patients who
become steroid dependent
that we can actually
treat with other therapies
that are a little bit less
toxic than cyclophosphamide
and that includes mycophenolate
mofetil which is an anti metabolites,
and rituximab, again,
we've seen that
before in membranous.
06:48
This isn't a monoclonal
antibody to CD20
and that also has
been successful
in case studies in case series
for people who have steroid
dependent minimal change disease.