eJournal Club - Session length and weight gain

This month's eJournal club concerns a paper published by a fellow from our institution that attempts to get to the bottom of an interesting question: in patients with a high interdialytic weight gain (IDWG), is the dialysis session length (DSL) or the total volume gained more important? Both of these have been associated with increased mortality and both lead to an increased ultrafiltration rate (UFR). However, because they are interrelated, it is difficult to say which is more relevant.

For this study, the authors looked at more than 14,000 patients attending dialysis in the US. They excluded patients at extremes of session lengths and those who did not gain any weight between sessions. Patients with a URR less than 65% were also excluded to rule out any effects of underdialysis. The mean IDWG and DSL over 30 days were chosen as the exposures of interest. Interestingly there was high correlation between the 30-day IDWG and DSL and the 60 and 90-day means. The outcome was death from any cause. For the purposes of the analysis, the participants were divided into 2 groups for each exposure - less than or greater than 3kg IDWG and less than or greater than 240 minutes for DSL. A matched case-control study design was used.

Not surprisingly, the patients with higher IDWG tended to be younger, male, AA, had higher blood pressure and a higher prevalence of diabetes and CHF. Patients with lower DSL were more likely to be female, older and were less likely to have diabetes, CHF and CAD.

For the DSL analysis, lower DSL was associated with a HR of 1.32 (1.03-1.69) for mortality after full adjustment. For the IDWG analysis, increased IDWG was associated with a HR of 1.29 (1.01-1.69) for mortality. Thus both DSL and IDWG were independently associated with mortality.

What does this study mean for clinicians. It suggests that targeting both of these interventions could be useful. However it should be pointed out that this is an observational study and that they could not show that changing any of these exposures changed risk. Also, the because of the study design, the authors can only state conclusively that both are associated with mortality and not which one is more important. These conclusions may seem obvious but it is important to have good evidence to present to patients who may be frustrated with our requests to increase times and reduce fluid intake.

Head over the eJournal Club to continue the discussion of this paper.

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

Extended High Cut-Off (HCO) Hemodialysis for Myeloma Cast Nephropathy

There has been much recent interest in novel extra-corporeal treatments for removal of nephrotoxic free light chains (FLC) in myeloma cast nephropathy. HCO dialyzers employ high flux membranes with particularly large pores (up to 50kDa Vs 15kDa for conventional high flux) facilitating the removal of large plasma proteins such as FLC (kappa and lambda light chains have molecular weights of 22kD and 45kD respectively). HCO-HD may also be potentially beneficial in rhabdomyolysis with myoglobin having a molecular weight of 17kDa.

Extra-corporeal removal has primarily been achieved using plasma exchange and has long been a controversial topic in nephrology. HCO dialyzers are much more efficient at clearing FLC compared to plasma exchange. Multiple case reports have suggested a benefit to early use of HCO-HD in cases of cast nephropathy and a study by Hutchinson CA et al demonstrated an early reduction in FLC to be associated with renal recovery. Another paper from the same group reported on 67 patients with AKI due to cast nephropathy who received HCO-HD with modern chemotherapy. The majority of patients had sustained reductions in serum FLC concentrations (76%) and a high rate of independence of dialysis (63%). The HD regime used Gambro HCO 1100 dialyzers and was aggressive, with almost daily 8-hour sessions for the 12 days. After this, the schedule drops back to alternate days and finally to three 6-hour sessions per week after day 21. My limited experience with this regime in 2 patients demonstrated a need for regular phosphate and albumin repletion and careful monitoring of other electrolytes.

Obviously HCO-HD will only remove FLC and will not stop their production. Therefore, for a sustained response, patients need to be a on a chemo-sensitive regime. The above studies have demonstrated that patients who need a break in chemotherapy do worse, as do those with signs of chronicity on renal biopsy.

The following criteria are suggested before considering HCO-HD in patients with AKI due to cast nephropathy:

1.       Chemo-sensitive regime; bortezomib is frequently employed

2.       High serum FLC levels (>500mg/l; usually much higher)

3.      Low levels of interstitial fibrosis & tubular dropout on biopsy (i.e. evidence of salvageable kidneys)

A randomized controlled trial, led by Dr. Hutchinson, in the UK is currently on-going (Eulite Trial) which will compare conventional high flux HD with HCO-HD in patients receiving chemotherapy (bortezomib or thalidomide plus dexamethasone). HCO-HD certainly appears to be more efficient than plasma exchange at reducing FLC levels but at this point, its precise role in the management of cast nephropathy is unclear. We await the Eulite trial to hopefully clarify the potential benefit of HCO dialysis in this situation.