Welcome to this episode of KD Go Conversations and Nephrology.
This episode, titled CKD Evaluation and Measurement, is
provided by KD Go and is supported by an independent
educational grant from AstraZeneca.
Here's your host, Doctor Peter Lynn.
Hello and welcome to KD Go Conversations and Nephrology.
I'm Doctor Peter Lynn, director of the K Heart Research Center.
And family physician in Toronto, Canada and joining me today to
discuss the importance of CKD evaluation and measurement is
Doctor Madelina Madeiro. Dr. Madeiro is the Head of
Nephrology Division at the National Heart Institute in
Mexico City and her clinical and research interests include CKD
Progression, chronic chemodialysis and CKD of unknown
origin. Welcome Doctor Madeiro to the
program. Thank you, Doctor Lane, and
thank you, Katie. Go.
It's an honor for me to be here today with you.
It's really good to have you here and I think the CKD of
unknown origin makes you sound like a UFO hunter.
So it's kind of interesting to hear that term.
But today I guess we're going to focus in on trying to detect
kidney disease. I must admit our kidneys work
very hard for us and they never complain and by the time they
complain, they are quite damaged.
So therefore we have to go looking for this damage.
So can you just go over what are the tools that we can use to
look for chronic kidney disease? Thank you, Doctor Lynn, that's a
great question and you are absolutely right.
Kidneys do not hurt until very late stage.
So we have some tools to assess kidney function in the earlier
stages and these tools are EGFR. So this is estimated glomerular
filtration rate and albuminuria and these both are critical to
detect and to risk stratify chronic kidney disease.
We know that lower estimated GFR and higher albuminuria are both
strongly associated with risk of cardiovascular events, kidney
failure and mortality. So their measurement is crucial
for effective risk stratification of persons with
chronic kidney disease. The presence and severity of
algumineuria also guides the use and dosage of treatments that we
know delay chronic kidney cyst progression, so such as ACE
inhibitors, ARB and SGLT 2 inhibitors.
So the ideal screening and diagnosis approach would consist
of a triple marker panel with serum creatinine serum cystatin
C. And urine albumin to creatinine
ratio. We usually prefer albumin uria
over proteinuria. However, we know that in
resource limited settings we can also use proteinuria for
detection of a protein or albumin in the urine.
There are now equations such as CKD EPI that are used to
estimate GFR from markers such as creatinine and sistatin C and
the combination of both creatinine and sistatin C.
And the latest equation is without inclusion of a
coefficient for black rays. So we have these very useful
equations that can either use the statin C creating or both.
And you know the fact that rays was removed.
It's a very important. Event in the nephrology
practice. This was all done due to the
concerns about continuing use of race in GFR and led to the
removal of the race coefficient. So a big rationale for CKD
screening is the availability of many effective interventions to
delay CKD progression and that reduce cardiovascular risk.
Yeah, that's actually very interesting, The fact that
you're talking about renal risk as well as cardiovascular risks.
Really having these measurements would be helpful for us to
manage our patients. And as you were saying, you
know, serum creatinine, we can get and with the equations, then
we can estimate the glomerical for attrition rate.
And so that tells us about how to use other medications, how
well the kidneys are functioning.
And often times I, you know, for simplicity sake, I tell my
patients that's the speed of your kidneys that it's working
at. And I usually tell them we want
at least 60 miles an hour or higher.
And you're only at 30 miles an hour and they seem to understand
that concept of speed. And as you were putting it, the
urine, albumin, creatinine ratio is very important as well
because I tell patients it's a quality of your kidneys.
In other words, we want to keep the good stuff in which in our
case, we've had that as albumin as being good things to keep in
your body. And creatinine, which is waste
product as you were mentioning, we want to get rid of that.
And so therefore we want to make sure that the kidney is getting
rid of garbage and keeping in the good stuff.
So that measures the quality. Of the kidney.
So I think that part maybe we haven't explained that so well
to patients. Do you find that people may be
doing serum creatinines and and maybe not the albumin creatinine
ratio? Yeah, that's that's a very good
analogy, Doctor Lynn. And you're right.
I mean, people do measure creatinine for the most part,
and many labs have automated each GFRS, but I find that a lot
of people and are not having their urine albumines checked.
And you know this is very important because it is a big
risk factor for outcomes such as kidney disease progression and
cardiovascular events. And we know that our patients
with kidney disease have an even higher risk of dying from
cardiovascular causes and reaching to kidney failure.
So both markers are very important in the evaluation of
chronic kidney disease. And that makes a lot of sense,
so I must admit. In the beginning we only focused
on creatinine and then we had the lesions, so we only focused
on that. But the album and creatinine
ratio together gives extra information, so we need both
pieces. So let's say we now have an
abnormal test. You've identified a patient.
How do we go about finding out the cause of the CKD?
Cuz I think a lot of us just assume it's diabetes or
hypertension, but how do you go about thinking about the
different causes that would put a patient in a CKD position?
Thank you, Doctor Lynn. That's a very important
question. It's not everything diabetes or
hypertension. So when we evaluate a patient
with known or suspected chronic kidney disease, clinicians
should inquire about additional symptoms that might suggest a
systemic cause. For instance, if a patient has
hemoptysis or a rash or lymphadenopathy or hearing loss
or neuropathy, this may Orient us towards something either
genetic or towards Glumerlar disease.
If a patient has for instance, urinary hesitancy, urgency or
frequency or incomplete bladder emptying, then this may guide us
towards urinary obstruction. Moreover, patients should be
assessed for risk factors of kidney disease and this include
potential nephrotoxins such as non steroidal and inflammatory
medications, phosphate based bowel preparations, herbal
remedies such as those containing aristologic acid.
Antibiotic therapies such as gentamizing and chemotherapies.
Also a history of kidney stones or recurrent urinary tract
infections may guide us towards the cause.
Of course, as we mentioned earlier, presence of
comorbidities such as hypertension, diabetes or
autoimmune diseases may lead us towards the cause of the kidney
disease. And family history of kidney
disease is important. There are times where we need to
do genetic testing, for instance in younger people with
polycystic kidney disease where they still do not have cysts, or
with inherited forms of focal segmental glomerular sclerosis
as this may allow an earlier treatment or make us take
decisions such as a big decision on a family member that may be a
kidney donor, for instance. Finally, imaging.
Studies such as an ultrasound give us an idea of the
chronicity of the disease and helps us to rule out
obstruction. And then when we have done all
these, a lot of the times we still do not know the cause and
we need to perform a kidney biopsy, for instance, in a
patient that has albuminuria or hematuria and we are not 100%
sure of the cause, then it is important.
To have a kidney biopsy as with the histologic diagnosis, we're
going to have a more precise diagnosis and a better
management. A fundamental justification for
the early detection of CKD is that we now have a lot of
available evidence based interventions to slow chronic
kidney disease progression as I mentioned earlier and this would
help us reduce its complication accurate diagnosis and staging
of CKD impact the choice of the treatments.
And this is one of the most important causes to establish
what's really generating or causing the kidney disease in
our patients. For those just tuning in, you're
listening to KD Co Conversations in Nephrology.
I'm Doctor Peter Lynn. And speaking with me today is
Doctor Magdalena Madero. We're discussing the importance
of CKD evaluation and measurement.
Yeah, you make a very good point.
So now that we've identified a patient with CKD, finding the
cause will then direct our therapies and also risk stratify
the patient. So finding the cause is actually
as important as detecting the disease in the 1st place of
course. And and yet many of us may just
say, oh, the EGFR is a little bit low and then we stop there.
So all of these lists of diseases that you just mentioned
reminds us that there are many causes that can bring a patient
to that state of chronic kidney disease.
So let's say we have these tests now.
And let's say we've got a cause as well.
So we know which cause is causing the CKD.
Then when do we consider it as CKD progression?
Because a lot of times a nephrologist and the referral
centers would say if the CKD progresses, then please refer to
us. So what does that mean in terms
of CKD progression? Yeah.
So that's a very good question, Dr. Lean.
And this is something we have debated as nephrologist over
years. Progression can be defined in
many ways. It can be defined as a sustained
drop in e.g. Fr for longer than three months
and a 25% or greater decrease in e.g.
Fr from baseline. Rapid progression, for instance,
is usually defined as more than 5ML minute loss.
In 12 months, there are also slopes of EGFR decline that have
been accepted as a definition, such as 30 or 40% decline in
EGFR, let's say at two years. Because, you know, I have to
admit that in the past we used to define progression as
doubling of the creatinine or kidney failure, but these events
are very. Drastic and you don't want to
wait until this happens to define progression, and that's
why we have been establishing other definitions of CKD
progression. There's also regression and
regression can be defined as a sustained higher e.g.
Fr category for longer than three months and a 25% or
greater increase in the e.g. Fr from baseline.
So this means that not everything is progression.
Patients can actually get better from the disease.
And this would be considered as a regression.
Progression is important because it can help us guide the
frequency of monitoring or assess a treatment progress, and
This is why we need to establish a progression.
Yeah, that's actually a very good point.
In other words, the direction, the speed at which it's
dropping, those are all very useful information.
And to your point is that it changes how quickly we refer,
how often we assess them and review their testing.
So these are all important things for us to do.
Now you had mentioned something about systatin C and that caught
my attention because I'm not sure if everybody is aware of
systatin C So when would systatin C be appropriate
testing? So in other words, when would
our traditional creatinine egfr estimates sort of not be as
accurate and what kind of scenarios would we say that a
systatin C would probably do better in assessing real
function? Thank you.
That's a great question. Ideally, cystatin C should be
used for the initial diagnosis. The use of cystatin C alone or
in combination with creatinine strengthens the association
between the EGFR and the risk of death and kidney failure across.
Diverse population. So number one, it better
categorizes risk #2. It should be used when the
diagnosis of CKD is uncertain. For instance, patient that has
G3AA1, so patient with mild CKD and no albuminuria #3 when
muscle mass is low, such as in the case of amputations, or the
opposite when there's a large muscle mass, such as observing
football players or bodybuilders.
Where creatinine may be under or over express and this would over
or underestimate estimated GFR. And finally, a more accurate
estimation of e.g. Fr is required a lot of the
times for dosing on certain antibiotics such as chemotherapy
assessment of kidney function in kidney donors for instance.
So therefore there would be certain situations where
systatin C is better and I guess as you were pointing out that
creatinine is muscle breakdown. So therefore if there's changes
in muscle mass, that might affect it as well.
And so there are situations where our creatinine friend may
not be as accurate. And that's why systatin C which
is sort of reduced at a regular rate in the cells and it's
mainly filtered out and there's no secretion of it in the renal
area that basically that might give a better measurement and
you listed some very important times.
Where we need a more accurate measurement and that's where the
systatin C would be useful. And I think that's very useful
for us to know because many of us may not have heard of
systatin C as the new way of staying for real function.
So I think that brings us to a close for this particular
session. I want to thank you very much,
Dr. Maduro, for your insights into the importance of CKD
evaluation and measurement. You nicely told us about the
EGFR and how that sort of measures the speed of kidney
function. That's one component of it.
Albumin creatinine ratio is another important component.
Of assessing renal function. And so therefore both of them
together would tell us about the speed of the kidney as well as
the quality as I sort of Simply put it for my patients.
And then you talked a little bit about cyst and C and it's
important role in certain circumstances or maybe the
creatinine may not be estimating the glomeris filtration rate as
well. And also to identify the causes
of CKD because you listed all these causes that would have
very different treatments and different trajectories.
And they would need different strategies to make sure that we
can prevent the kidney progression.
And then you nicely told us about kidney progression and
what we should be looking for deterioration, the e.g.
Fr changing classes of CKD and also this rapid drop of five
mils per minute over a 12 month period.
So we have things that we can look out for.
So that way we can make sure that the patient gets the care
in a timely fashion. And I think all of this, I'm
hoping with your knowledge and insight will help us all make
sure that we can detect CKD. And make sure that we manage
these patients as well as we can so that we can avoid those
complications that you were saying used to be the only thing
we measure which was doubling of creatinine and end stage disease
dialysis. Hopefully we will avoid those
horrible things for our patients by diagnosing them earlier and
making sure that they do well. So thank you very much Doctor
Madeira for your insights and all your hard work in terms of
treating patients and sort of getting the benefits of all this
knowledge make sure that the patients will benefit from this
new. Treatment strategy and
detection. Thank you, Dr. Lin, for all
these very important and interesting questions.
You just gave a very nice summary of what we have
discussed and it has been an honor to share this forum with
you. Great pleasure with you.
And it's so easy to summarize when you put things beautifully.
So thanks very much again. Thank you.
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Thanks for listening.