00:01
So our second disease
that we talked about
which was a systemic disease
where podocytes are
playing a prominent role
but it's consequent to disease
is going to be
diabetic nephropathy.
00:11
This is the most
common systemic illness to
cause nephrotic syndrome
and the most common cause
of end-stage renal disease
in the United States.
00:20
Nephrotic syndrome here
can occur in both type 1
and type 2 diabetes mellitus.
00:25
In type 1 diabetics though
they tend to have retinopathy
and other forms of
microvascular disease
that precedes the
overt nephropathy.
00:33
That same rule does not apply
for our type 2 diabetics.
00:36
They can often present
with nephropathy
without having retinopathy
and it's not uncommon
for patients to come to
me actually in my office
with a recent
diagnosis of diabetes
and already manifest
with nephrotic syndrome.
00:49
So when we think about the
pathogenesis of diabetic nephropathy,
it's really multifactorial.
00:53
There are metabolic factors
that go into this things
like hyperglycemia
and pro inflammatory mediators
that lead to an increase in
synthesis of matrix proteins
as well as pro fibrotic
growth factors.
01:04
We also have
hemodynamic factors.
01:06
Our patients are
hyper filtering very
at the very early onset
of their disease process.
01:11
They have an increase in glomerular
capillary pressure and hypertension
and glomerular hypertrophy.
01:16
And finally, our patients
have a genetic susceptibility.
01:21
When we think about the
pathology of diabetes mellitus
we can see again or normal
glomerulus over here
to the left,
on light microscopy.
01:29
Again, I want you to notice how delicate
and beautiful those capillary loops are.
01:33
Are what happens in
diabetic nephropathy.
01:35
This is somebody who has
advanced diabetic kidney disease
and what my arrow is pointing
to our diabetic nodules.
01:41
This is really a diabetic
glomerulosclerosis
seen on light microscopy,
which is essentially
the mesangial area
filling up with matrix.
01:51
On EM,
what I want you to notice is
again, on our normally EM,
we have these beautiful podocytes
that are preserved in an intact,
but in diabetic kidney disease,
we have thickening of
that basement membrane
and we also have those
overlying podocytes
which oftentimes have
foot process effacement
and actually denuded
areas of basement membrane
because those podocytes are
apoptosis in the crossing
and getting picked off from the
underlying basement membrane.
02:19
So how do our patients do when
they have diabetic nephropathy?
Early disease typically manifests
with moderately increased albuminuria,
what we also call
microalbuminuria.
02:28
That means our patients have
greater than 30 milligrams
a protein in their urine.
02:33
And it may take several
years to develop
nephrotic range proteinuria
or nephrotic syndrome.
02:36
But remember there
are those cases
where you can see it
relatively quickly.
02:41
So when we think about
treatment for our patients
who have diabetes nephropathy,
critical,
critical for them to
receive an ACE inhibitor
or an ARB to reduce that
glomerular capillary pressure
and suppress their proteinuria.
02:53
SGLT2 inhibitors are also recommended due to their renal protective effects,
including reducing intraglomerular pressure and hyperfiltration,
which can help reduce proteinuria and renal function decline.
03:06
A nonsteroidal selective mineralocorticoid receptor antagonist may also be added
for patients with proteinuria despite other therapies.
03:16
When they have nephrotic
syndrome again,
we're going to want
that loop diuretic
in order to mobilize that
volume off their body
and a low sodium diet.
03:23
We want strict blood pressure
control less than 130/80.
03:27
We want to treat their
hyperlipidemia and dyslipidemia.
03:29
We learned in our chronic
kidney disease lecture
that these patients are
exquisitely sensitive
and vulnerable to developing
cardiovascular events.
03:37
And we want strict
glycemic control.
03:39
We want those patients
to have a hemoglobin A1C
of less than 7%.
03:46
So remember if your
patient is a diabetic
even before they ever
manifest with any changes,
if they're hypertensive,
the very first choice that
we should be having for them
for an antihypertensives
are ACE's and ARB's.
03:59
And finally, in our patients
who are type 1 diabetics,
we can actually treat
we can actually transplant them
not only with a
kidney but a pancreas
so these patients can
ultimately undergo
a simultaneous kidney
pancreas transplant
and that actually
is quite gratifying
because we actually
can cure their disease
we can cure their diabetes.
04:20
So it's one of the
better treatments
that we have available
for our patients
who have type 1 diabetes.
04:26
And with that,
that concludes our
nephrotic syndrome lecture.