00:01
So some of the common diseases
that predispose to
chronic kidney disease,
again, diabetes mellitus
we talked about this before
that this is really
a number one disease
in terms of causing end-stage renal
disease within the United States.
00:14
It is a group of
metabolic diseases
that manifests as hyperglycemia.
00:18
So too much sugar,
and it could be caused by either
pancreatic beta cell dysfunction.
00:23
So our beta cells in our pancreas
don't produce enough insulin,
that would be more indicative
of type 1 diabetes,
which is more of an
autoimmune disease.
00:31
Or insulin resistance,
which is traditionally
more of type 2 diabetes
so cells don't
respond to insulin.
00:38
About 20 to 30 percent
of diabetics will develop
diabetic kidney disease
or diabetic nephropathy.
00:44
So it's important to
really keep note of that
and again target that population
to hopefully prevent
this from happening.
00:51
It accounts for about 55 percent
of new dialysis patients.
00:54
And again, I can say that when
I walk into my dialysis centers,
that's absolutely true.
01:00
Maybe even more than
50% of my patients
are there on dialysis because
of diabetic kidney disease,
so it's a significant burden
in terms of chronic
kidney disease.
01:12
So again, we're looking
at disease manifestations
from diabetic nephropathy.
01:17
We can see our pathological
image on the right.
01:20
So we've got these
diabetic nodules.
01:22
So patient end up
with glomerulopathy
and that is really characterized
by having this mesangial expansion
and that's what our
arrow is pointing into.
01:30
This is actually the
mesangial that's largely been
replaced by this matrix
kind of going out of control
creating these diabetic nodules.
01:39
We also get thickening of the
glomerular basement membrane,
which we see on a PAS stain as
well as on electron microscopy.
01:45
And ultimately over time we end up with
glomerular sclerosis or scarred glomeruli.
01:53
So in terms of how patients
will manifest clinically
it's interesting because the earliest
earliest clinical manifestation
of disease is probably
really not seen to most of us
and this means that patients
are actually hyper filtering.
02:06
They actually have
an increase in GFR
and glomerular
capillary hypertension.
02:12
If that sustained over time,
they start to develop what
we call microalbuminuria
or really what's more correctly
referred to as moderately
increased albuminuria.
02:22
That means that
urinary albumin level
is between 30 and 300.
02:27
Remember we talked about
how normal urinary albumin
should be less
than 30 milligrams.
02:32
Now when a patient
has this moderately
increased albuminuria,
it's very predictive
that they have a high
risk of progression
and future overt
nephropathy which means
that they'll develop greater
than 1 gram of proteinuria
and go on to really develop
worsening diabetic nephropathy.
02:48
So it's going to be critical in
order to Target that population
so that we can help prevent
that progression from happening.
02:55
So basically,
how can we do this or how can
we target that population?
We have to think about the
mechanism that's ongoing.
03:02
These paitents have glomerular
capillary hypertension.
03:04
We just talked about how
they're hyper filtering
so we can use things
like RA suppression
or ACE inhibitors
or Angiotensin receptor blockers
to reduce that
protein in the urine
and reduce the glomerular
capillary hypertension.
03:16
We'll talk a little bit more
about this later in the lecture.
03:20
We want to make
sure those patients
have good glycemic control
so that A1C should be targeted
less than seven percent
and then it's important to control
weight in our patients if they're obese.
03:30
Now despite our best efforts
our patients can still progress
from moderately increased
albuminuria to overt proteinuria
or severely increased
albuminuria.
03:39
That means that that
urinary albumin level is now
greater than 300
milligrams per day.
03:43
And when our patients
tend to reach this point,
they often times we'll have a
progressive decline in their GFR
and eventually manifest
with end-stage renal disease
if they don't have
effective therapy.
03:55
Now it's interesting.
03:56
I want to take just a moment to
talk about a subset of patients
that you might see with
diabetic kidney disease
but they don't have any or
very little albuminuria.
04:04
So we've seen these
patients kind of manifest
over time and it's
very interesting.
04:08
On biopsy they do have evidence
of diabetic kidney disease.
04:12
However,
they don't really manifest
with a lot of albuminuria.
04:16
And it's presumed that they have more
intro renal and vascular changes.
04:21
Now the rate of decline in GFR
in this particular
subset of patients
who don't manifest
with a lot of protein
is quite a bit slower compared
to albuminuric patients,
they have a more
favorable profile
as they're moving
through clinically.
04:34
Okay. So this is a schematic of
essentially what
I'm talking about
so you can follow the
course of patients
with diabetes over time.
04:41
So remember at the
onset these patients
before we can even detect things
sub clinically have
things going on
patients manifest with
an increase in GFR,
but they may not have
protein in their urine yet.
04:55
This then well if not treated
will then progress
to what we call
microalbuminuria or moderately
increased albuminuria.
05:02
Remember that's that greater
than 30 milligrams of protein
or albumin in the urine
but less than 300.
05:08
If those patients progress
with therapy or in the
absence of therapy.
05:13
They then develop
overt nephropathy
that means they have
greater than 300 milligrams
of albumin in the urine
and that puts them at
a very very high risk
of losing function.
05:22
So eventually they have
a decrease in their GFR.
05:25
And then finally,
they transition to
end-stage renal disease.
05:29
So therapy in these patients.
05:30
I cannot underscore is
absolutely critical.
05:35
So when we think
about the pathogenesis
of diabetic nephropathy,
it's really multifactorial.
05:40
So there's glomerular
hyperfiltration.
05:42
We talked about that
where that GFR is higher
than what it should be
in those patients have glomerular
capillary hypertension.
05:48
And there's hyperglycemia
and these advanced
glycation end products.
05:53
We also have elevated prorenin
and levels in our patients
and then impaired podocytes
pacific insulin signaling.
05:59
So quite a few different things
actually go into manifestations
or the clinical presentation
of abetik nephropathy.