So if we see a child who has
proteinuria, what are we going to do?
Let’s say this girl comes in
and she has trace protein.
Well, we’ll probably do the
first void urine dipstick.
So we send the child home with a cup,
have them pee in the cup first thing
in the morning and bring it in
and then if there is no protein
in that urine, we’re done.
But if it is positive, we’re
going to work the child up.
However, if the child has +1 or more protein
or if we decide to work the child up,
we’re going to obtain
her first morning void
and then we’re going
to check urinalysis
and we’re going to do the check of the
urine protein to creatinine ratio.
So let’s imagine we have a child
with a protein to creatinine ratio.
If it’s more than 0.2,
let’s do a complete H&P.
Let’s check the urinalysis.
We’ll get C3 and C4 levels to try and drill
down on what is causing the problem.
We may get other testing as needed.
If we suspect lupus,
we would check an ANA.
If we have reason to suspect
HIV, we would do that test.
If we suspected post-strep glomerulonephritis
because there was also blood
and the child had a history of sore
throat, we might get ASO titers.
Likewise, we might get renal ultrasounds
or VCUG if we’re worried about reflux.
And we might do a renal biopsy if we
can’t figure out what’s going on.
If it’s less than 0.2, we’re not
going to do anything right now.
Let’s check it again next year or if
the patient comes in symptomatic,
say with generalized edema.
But what if our little girl is symptomatic?
What if she has what we suspect
as nephrotic syndrome?
She has protein in her
urine and she has edema.
Well, here’s an electron micrograph
of a child with nephrotic syndrome
and what you can see
is the podocytes.
The areas around that glomerular
filtration area are widened.
They’re damaged and as a result,
fluid is able to get through
and protein is able
to get through.
It’s no longer an effective filter.
So these children will
They may have hypoalbuminemia from
their loss of albumin into the urine.
They will develop edema
and interestingly, they can
also get a hyperlipidemia.
The reason for the hyperlipidemia is
complex and we don’t need to go into it.
But what’s key is that we’re measuring
for hyperlipidemia, high LDL for example,
because we want to
make the diagnosis.
In children, a high LDL is not particularly
concerning for cardiovascular events.
We are not worried they’re going
to have a heart attack as a child.
We are using the hyperlipidemia value
primarily as a diagnostic measure.
Patients can be quite edematous
with nephrotic syndrome.
The most likely place
is in this first child
where you have swelling
around the eyes.
It can be gravitationally
and so, you should look
around the genitalia as well
or it could be diffuse as in our child
with his whole face is really swollen.
So when we look at
we think about causes as
either primary or secondary.
Around 90% of cases of nephrotic
syndrome in children are primary.
It can be idiopathic
or it just happens.
It may be FSGS.
We showed examples of one
FSGS earlier on this talk.
It could be minimal change disease.
We’ll talk about
that in a minute.
Or it could be mesangial proliferation.
There are several diseases that can cause
nephrotic syndrome level urine proteinuria.
Examples include lupus,
NSAID administration or other drugs,
post-strep glomerulonephritis which is more
common the blood but can also be protein,
Henoch-Schonlein purpura which is more
commonly blood but can also be protein
or simply just renal scarring.
There are also some gene mutations
which can predispose patients
to nephrotic syndrome.
The NPHS2 mutation
encodes for podocin.
This is the protein in the
podocytes of the glomerulus
and confers a bad outcome
in nephrotic syndrome.
These patients frequently progress
to end-stage renal disease.
The WT-1 mutation is in the
Wilms tumor suppressor gene.
It’s associated with certain
types of nephrotic syndrome
and especially the
NPHS1 mutation is a Finnish-type
congenital nephrotic syndrome
which presents within
the three months of life.
It’s unlikely, I would guess,
that an exam would ask you about
certain specific mutations
but you should keep in mind that
there are genetic influences
that can worsen
So if we suspect
we are going to do some testing
specifically the urinalysis,
the protein to creatinine ratio
which as we said is more than 2.
We will check serum albumin
especially in edematous child,
they are usually quite low.
And like I said before,
we’re going to check for hyperlipidemia
especially at high total cholesterol.
Electrolytes maybe abnormal
especially patients may develop a low
sodium as they’re holding on to fluid.
Patients may have an elevated BUN/creatinine
if they have renal insufficiency.
And in patients who have
lupus, an ANA is valuable,
but remember ANA false
positive rates are very high,
about a third of people have
a falsely positive ANA.
Rarely, hepatitis can cause
a nephrotic syndrome.
So in patients where we have hepatitis,
we would screen for hepatitis B or C.
C3 and C4 are abnormal in lupus
and C3 is abnormal in
So let’s switch gears and talk a little
bit about the minimal change disease.
I’m mentioning this because the name
itself is often confusing to people.
Minimal change disease is
called minimal change disease
because the biopsy looks normal when
you look at it in the microscope.
You have to do electron microscopy
to see what the problem is.
An electron microscopy takes a while
before you get your results back.
This is not a benign disease.
Minimal change disease does not mean that
the changes are minimally causing problems.
It means that you can’t see the
changes under the microscope.
So these patients may not do well,
most do do well, but many do not.
So how do we manage
We’ve talked about all
these different diseases.
We need to drill down on
what we typically do.
90% of patients will
respond well to steroids.
Most of these have
minimal change disease.
It’s a common cause of nephrotic syndrome.
So when you see a patient with nephrotic
syndrome, you’re going to start steroids.
If the patient does not respond well to
steroids, that’s when you need a biopsy.
We don’t biopsy them immediately
because the fact to the matter is
many will respond to steroids
and that’s our treatment.
So knowing exactly which kind
for sure may not be necessary
and the renal biopsy is not a
totally benign phenomenon.
We do use ACE inhibitors or if
they’re not tolerating that,
an Angiotensin II receptor inhibitor
for patients with hypertension
associated with their
So how do we manage
We’re going to start them off on prednisone
and we’re going to leave them on
prednisone for a long time, six weeks.
Then, we will do a gradual taper
off the prednisone for six weeks.
Not only is this preventing a
rebound steroid deficient state,
but also it’s allowing for a gradual
taper of the effect against the kidney.
And then, we’re simply going
to watch them for a relapse.
These children will need to be screened
routinely for protein in their urine.
Around 5% of children with
minimal change disease
develop end-stage renal disease
or die from their illness.
The majority get better.
Long term complications from
steroids are difficult to manage
and this can be an ongoing
problem in these patients.
In patients with poorly
responsive nephrotic syndrome,
they may end up with the
sequelae of chronic steroid use
like moon facies or striae or
decreased bone mineral density.
Overall for patients
with nephrotic syndrome,
the prognosis is divided into thirds.
One-third of patients
will never relapse again,
are going to live long happy lives
without any kidney problems.
One-third of patients will suffer
a few relapses here and there,
will end up on recurrent steroids but
will generally be able to control things.
But one-third of patients end
up with frequent relapses,
end up on steroids for
long periods of time
and will suffer the
consequences of that care.
That’s my summary of nephrotic
syndrome and proteinuria in children.
Thanks for your attention.