Cardiorenal syndrome, diuretics, and Cr

[iBS1972]

I have a patient who was admitted due to HFrEF and AKI who also has pulmonary hypertension. We have been diuresing him as he has severe lower extremity edema and elevated JVP. His AKI was attributed to cardiorenal syndrome. But ever since his admission (~4d), his Cr has been increasing. HF attending recommended continued diuresis, given patient is still volume overloaded per exam. He also notes that even though diuresis should improve renal function (via decreased preload, increased cardiac function, and renal perfussion), he has seen patients who does paradoxically result in increasing Cr. The past few days, it was decided that AKI is not due to overdiuresis as patient is still volume over-loaded. Now, we are actually uncertain as to what to do. Patient still has lower extremity edema, JVP lower, and increased Cr. We have decided to hold diuretic for today, and if Cr does not improve tomorrow, we will reintroduce diuretic as Cr rise can be comfortably concluded that it is not due to diuresis.

1. Has anyone heard of this "phenomenon" of worsening AKI with diuresis of a volume overloaded patient? Would you happen to know the pathophys or theories of this? (If so, would you please so kind as to direct me to sources that mention this, because I don't even know how to google this)

2. What are your thoughts as to what is happening? And what would you recommend for plan of action?

Thanks in advance for everyone's input!

Edit: Pt actually had HFpEF! So sorry for the mix-up! On HF service and nearly all of my patients have LV dysfunction, so it was kind of instinctive. Not sure if that changes the responses. Thanks for those who have already replied.

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[iniquus]

Flow = pressure/resistance.
Renal Blood Flow = (MAP - Venous Pressure)/renal vascular resistance
Moreover, giving someone diuretics is not equivalent to diuresis, they need to actually put out. I can start a Lasix drip in an anuric ESRD patient, but I won't really be diuresing them.

The man either has suffered an intrinsic renal injury and his SCr is on the way-up and urine output is dropping. Check the urine lytes (really the urine sodium to see if tubular function is intact) and spin the urine down. If this is entirely prerenal/cardiorenal and not progressed to ATN, then optimize his renal blood flow by ensuring there are no meds on board to increase renal vascular resistance, diurese to drop venous pressure if volume overloaded (diurese intensively with a lasix gtt, possibly with a thiazide), and consider that you may need to start a pressor if this is due to poor cardiac output and low MAPs (e.g. dopamine vs dobutamine). There is such a thing as normotensive ATN so don't let BP fool you.

 

[USCguy]

Anyone have experience using ultrafiltration in a situation like this? I used UF a few times on my CCU rotation as a resident, but that was a few years ago and those folks seemed to be so far gone that they still didn't have a good outcome even after volume status was optimized

 

[lilsebastian]

Since it's July, I need to mention that you should also be holding their ace-I/arb with major fluids shifts and rising creatinine.

Regarding UF: the CARRESS-HF trial didn't show a benefit of UF over medical therapy in patients with AKI due to cardiorenal syndrome.
Bart BA, et al. "Ultrafiltration in Decompensated Heart Failure with Cardiorenal Syndrome". The New England Journal of Medicine. 2012. 367(24):2296-2304.

 

[FutureInternist]

Flow = pressure/resistance.
Renal Blood Flow = (MAP - Venous Pressure)/renal vascular resistance
Moreover, giving someone diuretics is not equivalent to diuresis, they need to actually put out. I can start a Lasix drip in an anuric ESRD patient, but I won't really be diuresing them.

The man either has suffered an intrinsic renal injury and his SCr is on the way-up and urine output is dropping. Check the urine lytes (really the urine sodium to see if tubular function is intact) and spin the urine down. If this is entirely prerenal/cardiorenal and not progressed to ATN, then optimize his renal blood flow by ensuring there are no meds on board to increase renal vascular resistance, diurese to drop venous pressure if volume overloaded (diurese intensively with a lasix gtt, possibly with a thiazide), and consider that you may need to start a pressor if this is due to poor cardiac output and low MAPs (e.g. dopamine vs dobutamine). There is such a thing as normotensive ATN so don't let BP fool you.

FeNa in pts on diuretics does not help.

Need to check FeUrea

 

[lilsebastian]

FeNa in pts on diuretics does not help.

Need to check FeUrea

Yeah but if the urine sodium is low it's still helpful. And fena/feurea are only really useful if they're oliguric anyway.

 

[iniquus]

FeNa in pts on diuretics does not help.
Need to check FeUrea

FeNa and FeUrea in general are almost completely useless. Don't reflexively send it off. People get urine lytes all the time and use it to support their initial clinical diagnosis and disregard it when it contradicts them. It's also an unreliable test in patients with CKD with different sodium concentrating capacity.

I only recommended getting above if you read my explanation, not to calculate a fractional excretion, but to check the urine sodium. If it's low, I can rule out ATN since tubular function is intact. It speaks more towards a prerenal etiology. Beyond that, it's really the clinical context, urine microscopy, and empiric diuresis which tells you the diagnosis.

 

[ANCAdoc]

Neph here. Fascinating topic with complex physiology. We've all seen cases in a volume overloaded CHF patient whereby diuresis can improve or worsen sCr. The key is understanding the physiology as all cases are not equal and there is no formula or algorithm. In the patient where sCr worsens, often it due to decreased effective arterial blood volume (due to the diuretic) which causes AKI. In essence a pre-renal injury. Effective meaning what the kidney senses. Decreased effective arterial blood volume can be caused by diuretics when the intravascular refill rate is poor. This is what makes volume status so difficult and assessing sCr response to diuretics - there is no measure for this intravascular refill rate and can be modified by multiple variables (sepsis, albumin, etc). If diuretics are pulling intravascular volume faster than the space can refill, then BOOM AKI. I see this often in our cardiovascular unit and takes a good relationship/communication between Cardiologists and Nephrologists.

These two terms are very important and understanding these help understand AKI in cirrhosis, CHF, and nephrotic syndrome.

 

[Raryn]

Also remember that serum creatinine is a useful marker, but it only allows a meaningful estimate of GFR in a steady state.

That is, if the Cr is changing, all the assumptions that go into the Cockroft-Gault or MDRD equations are thrown out the window. You can't just look at the eGFR and assume the number means anything. You need to clinically evaluate the patient and look at other markers to see what's really going on.

Usually if they're getting worse due to diuresis while still clearly fluid overloaded is that the diuresis is too fast. Slow it down some (but don't stop it).

Everything else (albumin, ultrafiltration, chicken sacrifices, prayer) is probably useless.

 

[Instatewaiter]

Unclear volume status in a patient with worsening renal function is an indication for RHC. Occasionally we are wrong about volume status (or perfusion status).

 

[Merely]

I just took step 1 and have no idea what the hell any of you are talking about...**** m3 is gonna be bad

 

[iBS1972]

Neph here. Fascinating topic with complex physiology. We've all seen cases in a volume overloaded CHF patient whereby diuresis can improve or worsen sCr. The key is understanding the physiology as all cases are not equal and there is no formula or algorithm. In the patient where sCr worsens, often it due to decreased effective arterial blood volume (due to the diuretic) which causes AKI. In essence a pre-renal injury. Effective meaning what the kidney senses. Decreased effective arterial blood volume can be caused by diuretics when the intravascular refill rate is poor. This is what makes volume status so difficult and assessing sCr response to diuretics - there is no measure for this intravascular refill rate and can be modified by multiple variables (sepsis, albumin, etc). If diuretics are pulling intravascular volume faster than the space can refill, then BOOM AKI. I see this often in our cardiovascular unit and takes a good relationship/communication between Cardiologists and Nephrologists.

These two terms are very important and understanding these help understand AKI in cirrhosis, CHF, and nephrotic syndrome.

This makes plenty of sense. Thank you for your explanation. Just out of curiousity and intellectual edification, would you be able to think of other possible causes for the rise in serum creatinine (assuming no AIN, ATN, or post-renal obstruction)?
Also, by your explanation then, I'm guessing for management you would recommend Rary's recs-- slow it down, but don't stop the diuretic?

 

[Siggy]

I just took step 1 and have no idea what the hell any of you are talking about...**** m3 is gonna be bad

Start here:

 

[WheezyBaby]

I have a patient who was admitted due to HFrEF and AKI who also has pulmonary hypertension. We have been diuresing him as he has severe lower extremity edema and elevated JVP. His AKI was attributed to cardiorenal syndrome. But ever since his admission (~4d), his Cr has been increasing. HF attending recommended continued diuresis, given patient is still volume overloaded per exam. He also notes that even though diuresis should improve renal function (via decreased preload, increased cardiac function, and renal perfussion), he has seen patients who does paradoxically result in increasing Cr. The past few days, it was decided that AKI is not due to overdiuresis as patient is still volume over-loaded. Now, we are actually uncertain as to what to do. Patient still has lower extremity edema, JVP lower, and increased Cr. We have decided to hold diuretic for today, and if Cr does not improve tomorrow, we will reintroduce diuretic as Cr rise can be comfortably concluded that it is not due to diuresis.

1. Has anyone heard of this "phenomenon" of worsening AKI with diuresis of a volume overloaded patient? Would you happen to know the pathophys or theories of this? (If so, would you please so kind as to direct me to sources that mention this, because I don't even know how to google this)

2. What are your thoughts as to what is happening? And what would you recommend for plan of action?

Thanks in advance for everyone's input!

Edit: Pt actually had HFpEF! So sorry for the mix-up! On HF service and nearly all of my patients have LV dysfunction, so it was kind of instinctive. Not sure if that changes the responses. Thanks for those who have already replied.

In addition to what's already been discussed, a couple additional thoughts that come to mind, kind of free form

(1) with pulmonary hypertension, if there's an aspect of RV dysfunction, the patient may have a more dominant element of right sided preload dependence, and you're compromising cardiac output with overly aggressive diuresis

(2) on the flip side, you're not merely attempting to improve renal perfusion by optimization of left ventricular function. GFR is going to be a function of renal perfusion pressure, or the pressure gradient between renal arteries and veins. If you're central venous pressure is elevated, you're at risk of renal dysfunction for that reason alone, so optimization of that (in addition to lv function) is a target of your diuresis

(3) I believe you can have a direct decrease in your gfr with diuretics related to tubuloglomerular feedback.

 

[ANCAdoc]

This makes plenty of sense. Thank you for your explanation. Just out of curiousity and intellectual edification, would you be able to think of other possible causes for the rise in serum creatinine (assuming no AIN, ATN, or post-renal obstruction)?
Also, by your explanation then, I'm guessing for management you would recommend Rary's recs-- slow it down, but don't stop the diuretic?

Poor ejection fraction in those patients with end stage cardiomyopathy (or severe acute) is another cause. The edematous patient with EF 15% and worsening sCr with diuretics. Oftentimes adding an inotrope improves perfusion and you can watch the sCr improve daily. This is used in HF units as a bridge to more advanced therapy (LVAD, transplant, etc). If advanced therapy is not an option then hospice is best.

Back on the poor interstitial refill rate causing decreased effective circulating arterial blood volume and then AKI, once the blood volume is compromised (as sensed by the kidney), then all of those neurohormonal mechanisms you studied in medical school kick in and become mal-adaptive. The renin-angiotensin-aldosterone system which causes further vasoconstriction and retention of salt and water, along with activation of the sympathetic nervous system. It's a downward spiral. And diuretics in general do lower eGFR via tubuloglomerular feedback. In cases where the patient is volume overloaded but it's not emergent (no impending respiratory compromise) then scaling back the diuretic to allow for improved renal function is one option. This is a day to day decision on when to resume and at what dose. In the emergent patient (on BiPAP heading towards a vent) then high dose diuretics and ultimately if the kidneys fail then RRT.

 

[obiwan]

I just took step 1 and have no idea what the hell any of you are talking about...**** m3 is gonna be bad

don't worry, i'm an attending physician and i have no idea what they are talking about..... creatinine up, call nephrology LOL

 

[Merely]

don't worry, i'm an attending physician and i have no idea what they are talking about..... creatinine up, call nephrology LOL

LOL I love you

 

[iBS1972]

Also remember that serum creatinine is a useful marker, but it only allows a meaningful estimate of GFR in a steady state.

That is, if the Cr is changing, all the assumptions that go into the Cockroft-Gault or MDRD equations are thrown out the window. You can't just look at the eGFR and assume the number means anything. You need to clinically evaluate the patient and look at other markers to see what's really going on.

Usually if they're getting worse due to diuresis while still clearly fluid overloaded is that the diuresis is too fast. Slow it down some (but don't stop it).

Everything else (albumin, ultrafiltration, chicken sacrifices, prayer) is probably useless.

Thanks for the clarification. You say that creatinine stops being an accurate estimation of GFR when it is in flux. But, would you assert that it can still serve a vague picture of the kidney function? In other words, if creatinine rises, you would still conclude that the kidney's function is less than it was (for the time being)? And if Cr slowly increases say from 2.0 (baseline) by 0.1 each day and then all of a sudden it increases say from 2.5 to 4, the kidney's function dramatically decreased and it is significantly injured from whatever the cause?

 

[Raryn]

Thanks for the clarification. You say that creatinine stops being an accurate estimation of GFR when it is in flux. But, would you assert that it can still serve a vague picture of the kidney function? In other words, if creatinine rises, you would still conclude that the kidney's function is less than it was (for the time being)? And if Cr slowly increases say from 2.0 (baseline) by 0.1 each day and then all of a sudden it increases say from 2.5 to 4, the kidney's function dramatically decreased and it is significantly injured from whatever the cause?

Maybe.

Let's think about an extreme.

You have a creatinine of 1.2. You go into complete renal failure for whatever reason. Your new "steady state" might be a creatinine of infinity (reflecting your new egfr of zero). But your muscles don't make that much creatinine in a day. So I check it after your injury, it's 2.5. With no intervention, it might be 4 tomorrow, 5.5 the day after that, etc.

I figure out whats wrong (perhaps obstructive uropathy) and I fix it. Your kidneys recover. But it takes time. So rather than raising to a cr of 4 tomorrow, it might go to 3.5 before coming down the day after that. Does that transient rise mean you're getting worse? No. Clinically, you need to follow the output, electrolytes, etc.