Latest / Cardio Pod: Heart of the Matter / The Intersection of Heart Failure and the Kidney

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The Intersection of Heart Failure and the Kidney · Cardio Pod: Heart of the Matter

0:00
I'm Chris O'Connor, and this is Heart of the Matter podcast of the Heart Failure Collaboratory.
0:11
As principal investigator, we're really excited to have a team of my colleagues here to talk
0:15
about acute decompensated heart failure and acute kidney injury.
0:21
And I'd like to just have my colleagues go around the room and introduce themselves.
0:24
Dr. Januzi?
0:25
Yeah.
0:26
Hi, Chris.
0:27
Thanks for having me today.
0:28
I'm Januzi from the Massachusetts General Hospital Heart Center.
0:32
Maria Rosa-Constanza?
0:34
I'm from the Midwest Cardiovascular Institute, and I'm obsessed with cardiorenal medicine.
0:40
Dr. Sotka?
0:43
Mitch Sotka from the Inova Heart and Vascular Institute in Falls Church, Virginia.
0:47
Dr. Abraham?
0:48
Hi, Bill Abraham, a heart failure specialist at the Ohio State University.
0:54
John Tierling?
0:56
John Tierling from San Francisco VA Medical Center and University of California, San Francisco.
1:03
And I share Maria Rosa's enthusiasm for cardiorenal, maybe not quite as obsessed.
1:08
We'll have to see.
1:10
Marv Constan?
1:11
Hi there, it's Marv.
1:12
I'm a heart failure cardiologist, as other people are.
1:16
And I'm at the Cardiovascular Center at Tufts Medical Center in Boston.
1:20
Last but not least, in fact, most important that we have our nephrologist, Dr. Stephen
1:26
Koca.
1:27
Thanks, Chris.
1:28
Steve Koca, I'm a nephrologist at the Icahn School of Medicine at Mount Sinai in New York
1:33
City.
1:34
Thanks for having me on.
1:35
Steve, we're going to get you to start us off because we've all been struggling for
1:40
decades on what to do with a rise in creatinine when our patients are admitted with acute
1:46
decompensated heart failure.
1:48
Is it acute kidney injury you've introduced with your colleagues, a term called permissive
1:53
hypercratinemia, which we think sounds really interesting.
1:57
Tell us what AKI is and what is permissive hypercratinemia.
2:03
Acute kidney injury is what the nephrology community renamed the old acute renal failure,
2:10
starting with the ADCIE consortium back in 2004.
2:14
And the renaming has more to do with when you can't do something to treat a condition,
2:20
you'd like to show activity so you reclassify things.
2:24
And it did lead to a lot of angst because, as you know, a lot of old school acute renal
2:29
failure is hemodynamic in nature and does not necessarily involve kidney tubule injury,
2:36
which would be the acute renal failure classically associated with acute tubular necrosis.
2:43
In heart failure especially, this is one area where the cardiology literature at least has
2:48
been, I think, more correct for years because the term often used in the paper to describe
2:54
this acute rise in creatinine has been worsening renal function, WRF.
3:02
As we have explored various non-invasive urinary biomarkers to try to ascertain whether patients
3:10
are having tubular injury, the so-called troponin of the kidneys, and there's been various that
3:16
have been investigated now for many years, Engal, Kim Won, Iolatine, to name a few.
3:22
What we've seen in several studies is that even when the creatinine rises in heart failure,
3:29
there's quite low expression of a lot of these kidney tubule injury biomarkers.
3:34
Again, as you would expect with the pathophysiology, that's about how to classify things.
3:40
More importantly than all that though is that what does it mean for the patient and for
3:46
outcomes?
3:47
I think we've seen numerous papers over the last decade showing that unlike AKI that occurs
3:54
in sepsis or with nephrotoxins or with paddle renal syndrome or other things, the WRF that
4:02
can be seen in heart failure, so long as it is accompanied by appropriate therapy in that
4:08
being decongestion, actually does not portend any bad prognostic signal.
4:13
In some cases, portends better outcomes after discharge than if one were not to have this
4:20
rise in creatinine.
4:22
Steve, that really is well stated and I'm going to ask my cardiology colleagues to jump
4:28
in here.
4:29
Dr. Rosa, what does that mean to the clinician though?
4:33
We can't really tease out a rise in creatinine that could be worrisome and injurious.
4:39
There's a lot of drugs there.
4:40
There could be concomitant nephrotoxicity.
4:42
How do we distinguish what Steve just said?
4:45
I think one of the distinctive features is the duration.
4:50
And I'd like to hear what Steven thinks about that.
4:53
If it's a transient increase in serum creatinine during decongestive therapy, as you said,
5:01
this is a hemodynamic event and is not a toxic event to the kidney.
5:08
But as Steven already pointed out, what really predicts poor outcomes is ineffective decongestion.
5:19
So our efforts should be aimed at effective decongestion.
5:24
I realize that there are cases in which it's not easy to determine the hemodynamic status
5:32
of the patient.
5:34
And in those cases, I personally have a low threshold to do a right heart cath to see
5:42
what the intracardic pressures are.
5:45
Of course, I look at the pressures if a patient has a cardiomem's device in place.
5:53
And more recently, we have increased the adoption of measurement of blood volume and plasma
6:03
volume because that may help you also determine the fluid status.
6:08
Terrific.
6:09
I'm going to ask Jim Januzi, who knows something about biomarkers, are there urinary biomarkers
6:17
that can help us distinguish this?
6:19
Jim, give us your thoughts.
6:21
Yeah, thanks, Chris.
6:22
So the first biomarker that I recommend people to measure is a physical exam biomarker in
6:28
these patients to really try to get to the bottom of mechanisms for why kidney function
6:36
may be worsening.
6:37
And coming into the past decade, there was the misconception that the mechanism of worsening
6:44
kidney function in our patients was related to cardiac output, inadequate cardiac output,
6:49
which is almost never the case.
6:51
And that is when it is the case, you can see it from across the room, the patients under
6:55
perfused and in shock.
6:57
Whereas overwhelmingly, more often than not, as Dr. Costanzo has said and Dr. Coca, this
7:05
is related to inadequate decongestion and severe right heart plethora.
7:09
So physical examination is quite useful in this setting.
7:12
But regardless of that, to address the question you've asked, yeah, we've looked at different
7:17
ways to noninvasively try to understand whether worsening kidney function is related to congestion
7:24
versus some other mechanism.
7:26
And so the strategy that Dr. Coca mentioned of measuring different individual markers
7:31
has always been a little bit challenging because if you have a marker that tells you that something
7:35
is happening to the kidneys, but there are so many different ways that those markers
7:39
can be abnormal, it's important to have a modifier of some kind.
7:43
So we published many years ago now, probably almost 20, that if you took NT-proBMP and paired
7:51
it up with a kidney injury marker or a marker of kidney dysfunction, it's the individuals
7:58
with very elevated values for NT-proBMP that have a congestive mechanism.
8:03
We subsequently followed that up looking at more newer markers, including N-gal, including
8:08
Kim-1, and again showed that it's the double whammy of a marked elevation of natriuretic
8:14
peptide and an elevated N-gal, for example, that identifies patients who particularly
8:20
respond more favorably to aggressive diuresis.
8:23
And interestingly, often with improvement in kidney function in that setting, a high-risk
8:29
population at risk for future events, so it's reassuring to see them get better, but it
8:34
identifies somebody who's at a higher risk for worse outcomes.
8:38
Fantastic.
8:39
But so we're faced with a patient that comes in and this rising creatinine, I'm going to
8:45
ask John Tierlink and Marv, what do you do with the medicines?
8:51
What do you do if they're on an ACE inhibitor or an ARB or an ARNI?
8:55
What do you do with the MRA?
8:57
If they're come in with ADHD and a rising creatinine?
9:01
So I guess I'll start with this one.
9:03
First of all, the first thing to target is your diuretic dosing to make sure that you're
9:07
going to be giving effective diuretic dosing.
9:10
And I think one of the things we see most frequently on the wards and patients who are
9:14
being quote refractory to diuretics is that they're getting 10 or 20 or maybe only 40
9:21
of intravenous Lasix and they're being considered refractory to Lasix and to the furosemide
9:28
dosing.
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So first thing is to make sure that when you're giving your doses, you need to give adequate
9:33
diuretic dosing.
9:35
And I think dose, the dose trial, not to get confused with the nomenclature, the dose trial
9:40
actually provided some guidance to that where you go twofold from your dose of your oral
9:44
outpatient diuretic and start there.
9:47
And that's a good starting point.
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And you move from that point.
9:50
In terms of ACE inhibitors and so RAS blockade, I tend to actually try to continue it depending
9:57
on how bad the creatinine is.
10:00
It depends on the individual and I will actually go more by EGFR here.
10:05
Granted, the EGFRs have their limitations in terms of measurements within the acute
10:09
renal failure setting or the worsening renal failure setting, but I still use it as a guide.
10:15
And there I will be more cautious and probably withdraw the ACE inhibitors, RAS inhibition
10:21
around an EGFR of 30 or below.
10:24
But before that, I still try to keep them on board.
10:27
Other people clearly have different practice patterns.
10:30
I think it's absolutely essential that you continue the beta blockers.
10:32
We've learned that from all of our acute heart failure trials.
10:35
You should not withdraw beta blockers unless it's the setting of cardiogenic shock.
10:41
And the SGLT2 inhibitors, we also tend to continue even though some of the studies have
10:46
suggested it's not been approved for lower EGFRs, though we've been pushing that envelope
10:51
as well as current studies.
10:54
So that's my overall approach.
10:55
Marv, I'm interested in hearing kind of what you'd have to say to that.
10:58
Yeah, thanks.
10:59
Thanks, John.
11:00
And Chris, thanks for having me.
11:02
I really agree with everything John said and I would just sort of add to it.
11:07
You know, if a patient comes in to the hospital on a good regimen of guideline-directed medical
11:13
therapy, one thing you would like to do at the end of the game is to still have them
11:19
on good guideline-directed medical therapy.
11:22
And as you watch the patient and if the creatinine worsens while the patient's here and the patients
11:29
come in on an RNA or an ACE inhibitor, you can be pretty sure that those drugs are not
11:37
what's responsible for this new rise in creatinine.
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And so it's a question of how much fortitude do you have to a certain extent.
11:46
But I would have in my mind that if I'm going to cut back or I'm going to stop it because
11:52
I think it's rising so far and so fast, I got to figure out a way to get the patient
11:57
back on it because I don't think really this was the cause of the creatinine elevation.
12:02
And the other thing, you know, about it, I'd go even a step further, is if you think about
12:07
the fact, and this is well over a decade old or more, the fact that rising creatinine has
12:13
an adverse effect on outcome.
12:16
And we know now and some of the things that Steve said, that's far too oversimplified
12:22
and not the case at all.
12:25
And one of the things I think, one of the reasons the elevation in creatinine has an
12:30
association with that outcome is because the docs stop the drug.
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And so you're not treating them with drugs that, you know, will benefit them in the long
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run, recognizing that if it's rising to a great extent and prolonged, you know, you
12:48
may have no choice than to consider stopping it.
12:51
But I really try not to and continue to decongest.
12:54
That's what we do with drugs.
12:56
But Bill, you've been working on it and Marie Rosa, you've been working on devices that
13:01
might actually improve renal function in the setting of ADHD.
13:05
Could you comment on that?
13:06
Yeah, no, I'm happy to jump in first.
13:09
First of all, you know, I want to say that I think the mechanisms for a rising or a worsening
13:14
creatinine, worsening renal function in the setting of heart failure are complex.
13:19
And I think while we have focused most recently on post renal mechanisms, renal venous congestion,
13:26
that there are pre renal, intra renal and post renal components to this in many patients,
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much of it mediated by neuro hormonal activation.
13:35
It's a good reason to try to maintain those neuro hormonal inhibitors and antagonists
13:40
during treatment.
13:42
But I think the mechanisms are quite complex.
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Secondly, you know, I would say that decongestion does supersede worsening renal failure or
13:52
function in this setting.
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We want to push the diuretics to more completely decongest the patient to improve their clinical
14:00
outcomes.
14:01
On the other hand, I'm not quite sure that a rising creatinine or a falling EGFR occurs
14:07
with no cost to the patient in this setting.
14:11
And at the very least, I think it does result in some worsening of diuretic resistance,
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which makes the treatment of these patients a little bit more difficult.
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Not an argument not to persist.
14:22
We certainly need to persist.
14:24
And I think Marv comes up with a very interesting comment about how there are a lot of behavioral
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challenges that we have to overcome here, literally retraining most nephrologists and
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cardiologists out there to persist, push the diuretics despite the rising creatinine.
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So there's a lot of challenges here for sure.
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But another approach is simply to develop approaches that can result in more complete
14:48
decongestion of the patient without worsening renal function and maintaining diuretic responsiveness.
14:55
And certainly in the device development arena, there are a number of approaches that are
14:58
being actively pursued.
15:00
For example, the implantation of many pumps that can improve renal perfusion, essentially
15:08
a temporary mechanical circulatory systems that target the kidney.
15:14
Other approaches to enhance interstitial decongestion, perhaps by moving more fluid from the interstitial
15:21
end of the circulation and then out through the kidney, we can improve diuretic resistance
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and avoid worsening renal function in some patients.
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And remember, the kidney is an encapsulated organ.
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So if you can promote interstitial decongestion within the kidney or reduce renal afterload,
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perhaps you can have it all.
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That is diuretic responsiveness, complete decongestion and no worsening of renal function.
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So I think that there are a lot of exciting developments currently under investigation.
15:54
And Maria Rosa, we may have harmed one of those devices, ultrafiltration in our studies
16:00
because we stated perhaps this permissive hypercratinemia.
16:07
Tell us what's happening from your angle in the device world.
16:10
If I can start with telling you about my talk at the American Heart, it was one of the talks
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was pearls of wisdom for cardio renal trialists.
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And I chose six.
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Number one is that we as cardiologists need to know renal physiology perfectly, just like
16:35
our colleagues.
16:37
The second one was to collaborate always with a trusted nephrologist like Steven.
16:44
The third one was you have to really not mix up acute situations with chronic situations
16:52
because chronic kidney disease definitely is associated with poor outcomes.
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The fourth was to be thoughtful about the composite cardio renal outcomes that you select.
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The fifth one was embracing of novel statistical methods.
17:15
And the sixth one, which is what I try to apply every day is never surrender.
17:22
To answer your question, and this is why I listed those pearls, is because when we conducted
17:30
the avoid trial, the trial was stopped by the sponsor for reasons other than safety
17:38
or futility.
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And so we simply presented at the HFSA the reanalysis of avoid using the win ratio.
17:50
And using the win ratio, UF wins across the board, including cardiovascular mortality
17:58
at 90 days.
18:00
So we have launched a new trial called the reverse HF, which is a new and improved avoid
18:10
trial.
18:12
And we're going to analyze the data using the win ratio, but we have also introduced
18:18
other monitoring methods and specifically an improved hematocrit sensor to provide some
18:27
guidance to the investigator as to when the patient is sufficiently decongested.
18:34
And I believe that Dr. Koca is on the steering committee, so he can give you additional comments
18:41
in this regard.
18:43
That's going to be an exciting trial to hear about.
18:45
Before we get Steve's comments, Mitch, you think a lot about renal function as an endpoint
18:52
for development.
18:55
Is it an adequate standalone endpoint for regulatory approval?
19:00
I think that the crucial aspect of any endpoint is that you need to be able to measure it.
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And in this case, we don't have a measurement that is independent of the other issues going
19:13
on, such as congestion.
19:15
So when you see an elevated creatinine or a GFR that is calculated based on that creatinine,
19:21
I find it hard to understand exactly what the measurement is telling you.
19:26
And so that I think if we, in an ideal world, I care what is happening to kidney during
19:32
a decompensated heart failure event.
19:35
I care what is happening to the kidney after a decompensated heart failure event.
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And I think perhaps the best measurement is going to be the follow-up longitudinal outcomes
19:44
for kidney function following an acute decompensation.
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But perhaps in the setting of congestion and decongestion, it will be hard to know what
19:56
is exactly happening with the kidney.
19:58
And perhaps it is unlikely to beneficially affect management or be a useful endpoint.
20:06
Let's see what Steve has to say.
20:07
We tried to develop a drug called Rolophelin and we had a phase two look promising phase
20:13
three, nothing there, but we did put durability of renal function as part of the composite
20:21
and we thought that was a step forward.
20:24
I don't even know what durability is.
20:26
Is it 14 days, 30 days, 60 days, 90 days?
20:29
Steve help us out.
20:30
For the purposes of regulatory agencies, you're going to have to show 90-day improvements
20:36
in outcomes.
20:38
And certainly when I talk about this, I bring up the Rolophelin story, the ultrafiltration
20:44
story, naceratide, et cetera, the billions of dollars that have been spent in trying
20:48
to target the kidney primarily to try to fix this cardio renal syndrome and so far has
20:56
not succeeded.
20:57
And there are some innovative therapies ongoing at a Bayesian level.
21:02
I want to be proven wrong and let's see if something there helps.
21:06
But I'll give you an example from a cardiac surgery study, the Pravaki, Pravaki acronym
21:12
was randomized patients with high injury biomarkers under post-op immediately after cardiac surgery
21:19
to the K-Degal bundle, which I call apple pie and ice cream.
21:23
It was improve hemodynamics, avoid nephrotoxins, no contrast procedures next 72 hours.
21:30
And it reduced all AKI and moderate and severe AKI by about 25%, an absolute risk reduction
21:40
about 25%.
21:42
Sounded great, but the make outcomes, major adverse kidney endpoints at 30, 60 and 90
21:48
days were relatively similar and in some cases numerically higher in the apple pie and ice
21:56
cream K-Degal bundle for the patient.
21:59
So you really need to prove that durability was my point there.
22:02
Steve, clinically, this is something that we in the heart failure world have been sort
22:07
of seeing more and more over the years, whether in clinical trials or in our own clinical
22:11
practice, which is, you know, there was a time when we'd get that frenzied phone call
22:16
that the creatinine had gone from one to 1.3 and the house officer called it AKI.
22:23
I call that effective decongestion now.
22:27
So what we've learned is in fact, rather than fearing what we used to call worsening
22:33
renal function, provided that as Dr. Constan pointed out, we keep on going with medical
22:39
therapy that rise in serum creatinine may actually be, I don't want to say a target
22:44
for therapy because that overstates the potential role and could potentially be risky to say
22:51
you should routinely aim for it.
22:53
But on the other hand, it's not what we sort of one dimensionally looked at it as, which
22:59
was a marker of risk.
23:01
And what are your thoughts and Maria Rosa and others about the data from say the heart
23:07
failure network studies that suggested that the larger benefits were seen in people with
23:11
these rises in creatinine?
23:13
I think the problem was that a rise in serum creatinine of equal to or greater than 0.3
23:23
milligrams per deciliter was made an endpoint and is a meaningless endpoint because it did
23:29
not alter outcomes whatsoever.
23:33
And one of the things I showed in the talk I mentioned earlier was that all of the studies
23:39
in acute heart failure that included that measurement in their outcomes were either
23:47
neutral or negative because it's not a meaningful renal outcomes.
23:53
Hence the four pearl be considerate about the cardiorenal outcomes you choose because
24:00
that's not a wise one.
24:03
In terms of biomarkers, and this is a question for both Stephen and Jim, one thing that is
24:12
lacking, I think, on the day to day care of the patient is measurement of urinary sodium.
24:20
I find it quite useful in telling me the degree of diuretic resistance.
24:26
I know it's a poor man measurement of diuretic resistance, but it really helps because I
24:34
have patients that have received IV diuretics, I say in the emergency room.
24:40
And when I measure the urinary sodium is 34.
24:44
Obviously, that patient is not having an effective natural resource and you need to do something
24:50
about it.
24:51
Yeah, it's interesting.
24:53
In the biomarker world, there's a joke that if it costs less than $10, it's a blood test,
24:58
and if it's more than 10, it's a biomarker.
25:01
Urinary sodium is inexpensive, it's easily measured.
25:04
And I frankly wonder why we have not been measuring it more frequently, particularly
25:09
to the extent that it really is a companion diagnostic for the very drug that we're giving,
25:15
a loop diuretic.
25:17
There were great data just presented at the American Heart Association meeting looking
25:21
at the impact of acetazolamide therapy on urinary sodium, showing that in parallel with
25:27
greater decongestion in the ADVOR study, there was heightened naturesis.
25:33
Similar data with sodium glucose co-transporter 2 inhibitors now also from mPulse.
25:38
It really is important to start thinking about, particularly in those patients where we get
25:43
that phone call, the diuretic isn't working, what do I do?
25:47
Probably the next step would be a urinary sodium measurement to understand if in fact
25:52
you're getting effective diuresis or not.
25:54
And if you are not, then it's a question of why.
25:57
Let's come back to that.
25:58
That's a really good point.
26:00
I was going to just reinforce what Jim said, and I think we should be moving this conversation
26:04
to measurements of diuretic resistance or responsiveness rather than worsening renal
26:10
function.
26:12
That being said, it would be nice to develop some consensus in regard to what rise in creatinine
26:18
really is too much, because I think if we leave this open-ended, practitioners are going
26:23
to become very uncomfortable with what we're trying to say here.
26:28
The 1 to 1.3 is a no-brainer, but what about 1 to 2 or 1 to 2 and a half?
26:34
Is there some level at which one acknowledged that maybe something else should happen?
26:38
The patient needs a right heart catheterization.
26:41
We should be measuring urinary sodium or something else in that setting.
26:46
But I think to leave this open-ended, we're going to have an awful lot of uncomfortable
26:50
practitioners out there in the community.
26:52
I just throw an idea out.
26:55
I'd love Steve's reaction.
26:56
I don't know if we have time.
26:58
I'm thinking of two things.
26:59
One is I'm thinking about congestion to the extent, and Bill alluded to this, the
27:03
extent that it increases renal vein pressure is probably the principle hemodynamic force
27:11
behind renal impairment and heart failure.
27:14
Now when we decongest, there's a paradox because we should be reducing renal vein pressure.
27:22
But at the same time, if we're having intravascular decongestion, then we're hemoconcentrating.
27:30
And hemoconcentration seems to be associated with a rise in creatinine.
27:35
And I just want to propose that in the setting of intravascular decongestion, there's a disconnect
27:42
that happens between the serum creatinine and the actual GFR.
27:47
That hemoconcentration itself is driving the creatinine up and doesn't necessarily mean
27:54
kidney impairment.
27:56
And the comment that Maria Rosa said earlier in the trial that she was talking about monitoring
28:02
the degree of hemoconcentration that's occurring as you're diureseing, I think that's the direction
28:09
that we might want to think of going.
28:11
Marv, I have a slide on that.
28:13
The intensivists have a correction factor for dilution of serum creatinine when IV fluids
28:18
are administered.
28:19
We call this the pseudo-AKI of diureseing and hemoconcentrating, where you're going
28:25
to get that rise in creatinine as you shrink plasma volume.
28:28
So it's a beautiful point.
28:30
And as the hemoconcentration, when it's quantified in these studies, is the clinical phenotype
28:38
that is associated with the best long-term survival.
28:41
And all the points everyone has made today were all brilliant.
28:45
And it also just still shows how much complexity there is out there around the syndrome.
28:49
And we're going to be talking about it a long time because our colleagues do need help.
28:54
And it's really that art of medicine.
28:56
When is the rise too much?
28:58
I remember once a colleague wrote to me, oh, Dr. Coco, I'm practicing permissive hypercreatinemia,
29:05
permissive AKI.
29:06
The BUN was like 140 and creatinine was eight.
29:08
And I just cringed because that was clearly excessive.
29:13
And it's clearly we're in a range much lower than that.
29:17
And if you have a rapid trajectory of rising creatinine or declining kidney function and
29:24
they're still overtly wet, I always tell the fellows, we've got to look for other things
29:29
going on.
29:30
Are they getting septic?
29:31
Are they getting slip some nephrotoxins?
29:33
Let's spin the urine, look for cast, let's check urinary sodium.
29:36
And you do all the detective work that are the reasons I went into a non-invasive specialty
29:41
like nephrology, where you take all these clues and try to figure out what's going on.
29:47
Because every patient is different and things can go awry, but we could go on for an hour.
29:52
We could go on for it.
29:53
We're going to have to wrap up.
29:54
But I mean, this crew would go on for several hours, Steve, and just love dialoguing with
30:00
you.
30:01
But I'm going to ask each panelist to give us a short soundbite about where do we take
30:06
this field going forward?
30:09
Acute decompensated heart failure, rising creatinine, what's a take home message you
30:14
would like to give to the audience or where would you like the field to go from investigation?
30:18
John Dearly.
30:19
I think I'd start out with changing the paradigm in terms of pathophysiology and recognize
30:23
the importance of the afterload on the kidney in acute heart failure and having that be
30:28
an important aspect that you build into your therapeutic approach.
30:33
I think first thing we have to do and I think Bill alluded to it, I think we have disconnect
30:38
we have to make.
30:39
So we have to disconnect house officers brains from the creatinine stop diuresis reflex.
30:48
Think that thinking about creatinine as an arise as an adverse event.
30:55
Sometimes it represents an adverse event.
30:57
But I think we have to back away from that and really think about hemoconcentration and
31:02
how it's impacting creatinine and look for other biomarkers if we're really interested
31:07
in kidney function.
31:09
Mitch decongestion supersedes changes in creatinine period and your keep it simple.
31:18
I love it.
31:19
Maria Rosa.
31:20
Can you top that hard too?
31:22
Because I was going to say the same thing, but my next, the message I would like to leave
31:27
this podcast with is that we need to enhance our collaboration with our nephrology colleagues
31:37
and we need to work together because I doubt that unilateral decisions are going to advance
31:44
the field.
31:46
Jim Januzzi.
31:47
Yeah.
31:48
Thanks very much for the opportunity to join today, Chris.
31:51
I'm going to agree with what everyone has said with three points.
31:55
The first is almost always you need more diuresis.
31:58
So whenever in doubt, you know, turn it up.
32:01
I think that's number one, right?
32:03
Number two, mechanistically, there's still much we need to learn about understanding
32:09
hemo concentration effects that Dr. Kahnstam has talked about in order to better understand
32:15
when to stop.
32:16
We haven't really thought about enough and developing mechanistic tools for developing
32:23
means to know when a person non-invasively has reached a diuretic limit is really important.
32:28
And then lastly, it would be very nice to be able to see further proliferation of therapies
32:34
that do not activate the renal angiotensin aldosterone system.
32:38
The SGLT2 inhibitors are a great example of that sort of timid step forwards towards a
32:43
therapy that can enhance diuresis without worsening kidney function due to AKI.
32:48
They worsen kidney function for other reasons.
32:51
This is, I think, going to be an important future for the diuretic space.
32:55
And we give the nephrologist the near last word.
32:59
We have to break the tinnismus with rise in serum creatinine, just like we've done now
33:05
in the outpatient setting with SGLT2 inhibitors.
33:08
And we embrace the dip in GFR, the rise in creatinine due to that reduction in intraclomerular
33:14
pressure.
33:15
We have to come up with some easy to remember, love the rise or whatever, or something with
33:23
moderation because, again, not too high.
33:25
But that classic dip we all see now with every SGLT2 inhibitor trial where it's this modest
33:31
change, we know that it's going to be better outcomes.
33:34
And it really just comes down to decongestion and hold the fort with the kidney function
33:40
unless it's really going awry.
33:42
Wow.
33:43
What a conversation.
33:45
And maybe what I heard is if we could move the field, I like the concept of the urine
33:49
sodium, maybe Mitch, an EHR trial where we randomize knowledge of a urine sodium versus
33:55
not to see what we could do in a large sample size.
33:58
But what a terrific conversation today.
34:01
Thank you very much for being here on Heart of the Matter podcast.
34:04
The collaboratory realizes that we need more collaboration with nephrologists, that's for
34:09
sure to tackle this field.
34:12
But thank you everyone.
34:13
And we look forward to conversations going further.
34:15
Have a great day.