Diuretics vs. Ultrafiltration: Isn’t the debate settled yet?

We have all been called in to see patients who have developed AKI after receiving mechanical ultrafiltration (UF) for acute decompensated heart failure (ADHF). In almost all situations I have experienced, UF was started early, perhaps without optimization of diuretic therapy. The UF program at our institution is run by the Cardiology service. In spite of the weight of the current evidence, I have seen a distinct specialty specific bias towards UF (Cardiology), and against UF (Nephrology).

After I received the nth consult for AKI in the above setting, I decided to review some evidence for a cardiologist friend. I thought it’ll make for a review of a pertinent situation that we all will continue to face.

In brief, three major randomized trials have compared UF against diuretics in ADHF, over the last eight years. The first one was the RAPID-CHF trial.  The primary end point was weight loss at 24 hours. A larger trial was published in 2007, the UNLOAD trial. Both these trials showed a greater rate of fluid loss with UF than diuretic use. The UNLOAD trial also showed fewer rehospitalizations at 90 days, for the UF group. From a renal perspective, there was no significant increase in creatinine with UF reported in either trial.

The results from the above two trials really made UF almost a “first line” treatment for ADHF. On top of it all, I saw data from a study in Italy increasingly (and perhaps, erroneously) getting extrapolated to UF use for treatment of ADHF. Essentially, the Italian study had shown that intermittent hemodiafiltration could increase diuretic responsiveness and reduce the level of inflammatory cytokines.  Equating hemodiafiltration to ultrafiltration would make me cringe as I struggled to explain the difference to my cardiology colleagues!

Finally, we had the CARRESS-HF trial late last year which tried to answer the same question in a slightly different way (stepped algorithm for dosing diuretics vs UF). At 96 hours, there was no significant difference in weight loss between the two groups. The primary end point of increase in serum creatinine was significantly worse in the UF group.  The UF group also showed a significantly higher rate of other serious adverse events (eg, bleeding, anemia, thrombocytopenia, dyselectrolytemia, sepsis, heart failure). There also was a trend towards higher mortality for patients who received UF.

Given the relatively recent nature of the evidence against UF, it might be some time before we see a universal change in clinical practice. So I guess we nephrologists will continue to see patients of refractory ADHF with AKI, where perhaps diuretics weren’t used in a stepped fashion, or UF was used early. At this time, the American College of Cardiology recommends that UF be used only as a second line treatment for patients who do not respond to diuretic optimization.   

I am curious to know what your experience has been in this setting? Have you experienced a difference of opinion between nephrologists and cardiologists?  

Posted by Veeraish Chauhan

Thromboembolic Prophylaxis in Patients with AFib and CKD: Caught between the Devil and the Deep Blue Sea

I often get curb-sided by cardiologists and internists for my opinion on using warfarin or other anticoagulants for thromboembolic risk prophylaxis in CKD +/- Afib patients. A similar conundrum of using anticoagulation for stroke prophylaxis in dialysis patients was discussed about three years ago on this blog by Conall. Like many other issues in patients with CKD, things are not always black-and-white, and a lot could depend on patient and physician preference.  This often makes the “right answer” a confusing exercise, since CKD patients are also at a higher bleeding risk. Most randomized trials addressing this issue have excluded patients with a GFR below 30. Furthermore, newer direct thrombininhibitors (dabigatran), or Factor Xa inhibitors(apixaban, rivaroxaban) are available, which might be better than warfarin, at least in the early-CKD patient (although the lack of a reversing antidote is a potential pitfall). Finally, warfarin has a well-established link with vascular calcification (a mortality risk) in dialysis patients. As nephrologists, it is imperative that we are knowledgeable about the best-available data that can help us make an evidence-based recommendation, and so I put together a concise decision-table with links to primary literature sources.

In addition to the “traditional” risk factors for stroke in patients with AFib (as exemplified by the acronym CHADS), it is known that CKD itself is an independent risk factor for stroke. Thus CKD patients, both with, and without AFib, are at an increased risk of stroke. This has been demonstrated in CKD as well as dialysis patients, and the risk worsens with decline in GFR. 

Thus, with the above background in mind, the two main variables that determine what, if any, anticoagulation is to be used in this setting, are (1) the stage of CKD, and (2) the CHADS2 score:

CHADS2 Score	CKD STAGE
	Stage 3, eGFR 30-59	Stage 4, eGFR 15-29	Stage 5, eGFR less than 15, or dialysis
0	Either ASA or AC (weak recommendation)	ASA vs. AC (warfarin) vs. no antithrombotic treatment given bleeding risk??	ASA vs. AC (warfarin) vs. no antithrombotic treatment given bleeding risk??
>1	AC (Direct thrombin inhibitors (dabigatran), and Factor Xa inhibitors (rivaroxaban, apixaban) potentially superior to warfarin	AC (warfarin preferred since no data on direct thrombin or factor Xa inhibitors)	AC (warfarin preferred since no data on direct thrombin or factor Xa inhibitors)

 

ASA = Aspirin

AC = Anticoagulation

?? = Expert opinion only, no strong evidence available - weight risks vs. benefits

Remember that no antithrombotic therapy is warranted if bleeding is a concern

Posted by Veeraish Chuahan

(Apologies for any formatting issues)

Hypothermia Protocol and Dialysis

I recently received an inpatient consultation to see a CKD 5D patient. The reason for consult, as is mostly the case with dialysis patients was that he “needs hemodialysis”.

This dialysis patient wasn’t the average bear though. He had had a witnessed cardiac arrest, was treated by EMS, and defibrillated. He had a return of spontaneous circulation after being pulseless for 20 minutes. As soon as he got to the ER, he was initiated on our standard institutional therapeutic hypothermia protocol.  I was called in to dialyze him because (it wasn’t his usual day) the cardiologist wanted to perform a left heart cath on him the following day, and they “did not want dialysis to interfere with that schedule”. My clinical assessment did not reveal a severe degree of volume overload. He wasn’t hyperkalemic, and had only a mild degree of lactic acidosis that was nicely compensated by him being appropriately ventilated. Due to the concerns that I talk about below, I did not see an emergent reason to dialyze him.

I would like to focus on a few teaching points from a nephrologist’s perspective that I took away from this scenario:

1. Therapeutic hypothermia entails cooling post cardiac arrest patients to 32-34 degrees Celsius, ideally within 6 hours of a cardiac arrest.  Both intravascular and surface cooling methods are used. At my institution, the protocol involves administering up to 3 liters of 0.9% saline (which has been cooled to a temperature of 4 degrees Celsius), over an hour. This is complemented by cooling vests. Once target temperature is reached, the cooling phase is continued for 12-24 hours, after which the patient is rewarmed gradually at the rate of 0.5 degrees Celsius/hour.
2. Sub-physiological body temperatures expectedly have adverse effects. Hypothermia can hamper leukocyte function, increasing infection risk later. Cardiac effects include bradycardia and prolonged QT interval (both were present in this patient). Finally, for us nephrologists, here are some adverse effects and pertinent points that we need to keep in mind for such patients:
3. Hypothermia can cause hypokalemia via two different mechanisms. Low temperature causes a transcellular shift of potassium in to the intracellular compartment. This effect is possibly mediated by increased beta adrenergic and sympathetic activity. In fact, hypokalemia in the setting of hypothermia must be repleted extremely cautiously, if at all, given the risk of rebound hyperkalemia as potassium moves back out of the cells when the patient is rewarmed. This rebound hyperkalemia can be frequently fatal due to arrhythmias.
4. The second mechanism by which hypothermia causes hypokalemia is by the induction of polyuria, also known as “cold diuresis”. This hypokalemia is mediated by increased urinary flow, and is seen in conjunction with hypovolemia, hypophosphatemia, and hypomagnesemia. I didn’t observe any of these in my patient, maybe because of his oligo-anuric status at baseline. Nevertheless, close monitoring of volume status and electrolytes is required.
5. Hypothermia interferes with platelet function and with the clotting cascade. In fact, as per this review, 22% of patients had bleeding post-hypothermia induction. That might be a concern when making the decision to dialyze post-hypothermia patients with heparin.
6. The other issue that I ran in to, that was specific to dialysis patients, was the concern about the patient’s temperature. As we know, most HD machines warm blood before returning in to the patient. With most machines, the warmer cannot actually be turned off and only goes as low as 35 degrees Celsius. In other words, dialysis can inadvertently warm the patient up to this temperature (from the target temp of 32 degrees, per the hypothermia protocol)! CRRT machines do have adjustable temp settings that goes down to 32 degrees, so that might be a safer alternative. Given the risk of inadvertently warming the patient, and because I did not see any emergent indication for dialysis, I did not dialyze the patient. I believed that in that situation, his hypothermia protocol took precedence over dialysis.

In my experience, I have observed that referring non-renal physicians often consider inpatient hemodialysis an ancillary service, akin to placing an order for an x-ray or a lab draw. Seasoned fellows have heard this phrase all too often, “I want you to come down and dialyze this patient”. You are then left with the unenviable task of explaining to the non-renal physician that the decision to dialyze would be made by the nephrologist after proper assessment of the patient (isn’t why they consulted you in the first place?). Let’s not allow our familiarity and comfort with dialysis technology lull us in to putting our guard down. Dialysis is an inherently intense and complicated procedure where multiple clinical parameters need to be closely watched. It’s a fact that is often lost in translation.

Posted by Veeraish Chauhan