Severe hyponatremia can produce challenging diagnostic and therapeutic dilemmas. This is because significant morbidity and mortality can accompany overly rapid correction of hyponatremia, especially with the use of hypertonic solutions, e.g., osmotic demyelination, etc.

In a recent AJKD paper, Yessayan and colleagues from Henry Ford Hospital present a patient with acute kidney injury (AKI) and severe symptomatic hyponatremia. The authors discuss a novel approach to correct severe symptomatic hyponatremia with concomitant kidney failure utilizing continuous renal replacement therapy (CRRT) by altering the sodium content of the replacement fluid. Interestingly, when the 2007 Hyponatremia Guidelines were published, there was no mention of use of extracorporeal therapies (such as CRRT) in the treatment algorithms. Should this modality be incorporated in updated recommendations for hyponatremia management?  Corresponding author Lenar Yessayan (LY) discussed these topics with eAJKD Contributor Edgar Lerma (eAJKD).

eAJKD: What are the modalities available to treat patients with AKI who present with severe symptomatic acute hyponatremia?

LY: The treatment guidelines (2013 Expert Panel Recommendations, 2014 EU Hyponatraemia Guideline Development Group) do not address the unique situation where AKI and hyponatremia coexist. In reality, we often do not know the duration of hyponatremia. In the unique situation of AKI with symptomatic acute hyponatremia (<48 hours), prompt and definitive intervention is necessary. Review of the literature suggests correction of 4-6 mEq/L with hypertonic saline within the first 4 hours is adequate in the most seriously ill patients. In the meantime, preparation for CRRT/RRT should be initiated in those who need immediate renal replacement therapy. In particular, attention should be given to diluting the replacement fluid solution to the desired sodium concentration.

In patients with chronic hyponatremia and AKI, continuous venovenous hemodiafiltration (CVVH) with customized fluid bags can regulate the sodium correction rate to stay within recommended therapeutic targets and still deliver the desired solute clearance. If the rate of rise is too fast, the CVVH prescription may need to be adjusted to lower the hourly clearance rate or the replacement fluid bags may be adjusted to lower [Na+] concentration. In an emergency, 5% dextrose water may be administered intravenously to lower the serum sodium.

eAJKD: What are the pros and cons of using conventional HD in these patients?

LY: Pros: Very fast correction of serum Na (within hours) where it is indicated without the risk of worsening volume overload. For patients with acute hyponatremia and presenting serum sodium >120 mEq/L, intermittent HD for 3-4 hours targeting a single pool Kt/V of 1-1.2 with a fresh dialysate sodium level 8-10 mEq/L higher than the patient’s serum sodium level may be considered. Such therapy would cause the serum sodium to rise by about 6 mEq/L by the end of the HD session with the possibility of avoiding overall ECF volume expansion through simultaneous ultrafiltration.

Cons: Hemodialysis will always result in rapid correction of the serum sodium concentration. The rate of correction would be faster at higher blood flows and clearance rates, in smaller patients (smaller total body water volume), and with a larger difference between fresh dialysate and the serum sodium concentration. Since we often do not know the exact time of the onset of hyponatremia, the rapid rate of correction might put the patient at risk for osmotic demyelination syndrome. The rate of correction will also be too great for all patients presenting with serum Na values below 120 mEq/L since the lowest fresh dialysate sodium is 130 mEq/L on most commercial dialysis systems. The accuracy of the fresh dialysate sodium level and therefore of the systemic sodium control is also dependent on the accuracy of the composition of the acid- and bicarbonate concentrates and the reliability of proper, automated dilution with deionized water by the dialysis machine.

eAJKD: What are the pros and cons of using CVVH in these patients?

LY: Cons: Lack of commercially available hyponatremic dialysate or replacement fluids. Most hyponatremic formulations (Na 120-130 mEq/L range) are calcium-free and require the added complexity of use in combination with hypertonic citrate- and Ca-infusions, making them impractical for highly predictable and safe correction of severe hyponatremia using historical regional citrate anticoagulation protocols.

Pros: By using CVVH, the serum sodium correction rate can be controlled by making successive dilutions of the replacement fluid bags every 24 hours and yet being able to deliver the desired clearance for other solutes. Through kinetic modeling of the systemic sodium level, we can estimate the concentration of the replacement fluid required every 24 hours to achieve a specific desired serum sodium change. The purely convective sodium kinetics in CVVH allows us to predict sodium dialysance accurately, even without online clearance tools.

eAJKD: In this particular case, you used the NxStage PureFlow dialysate solution. How different is this compared to other manufacturer’s solutions?

LY: There are solutions with different concentrations of electrolytes by the same and/or different manufacturers. They exist in different volumes and in different electrolyte concentrations. For example, the NxStage PureFlow dialysate RFP solutions can vary in the sodium, potassium, bicarbonate, calcium, and chloride concentration. The bags have a volume of 5 liters, therefore most patients can be treated with a total of 5-15 modified bags per day. The clinician should reconcile the patient’s needs with the replacement fluid bag electrolyte concentration. The clinician should also recognize that the dilution incurred by addition of free water or exchanging the solution with free water would dilute all other electrolytes. In our case we chose RFP 401 and provided the estimated changes for different volumes of free water added or exchanged. However, the two formulas described in the manuscript could be applied to any solute in any original bag to estimate their final concentration in the replacement fluid bags.

eAJKD: In this paper, you described two methods by which you adjusted the replacement solution in order to achieve the desired Na concentration. Please elaborate, and is there a preferred method for any given situation?

LY: We purposely provided the clinician with two methods to adjust the replacement fluid solution. The first method is the addition of sterile free water to a certain volume of a replacement fluid bag. This is simpler, does not waste any replacement fluid, and is the preferred approach when feasible. In cases of severe hyponatremia, the sodium dilution and therefore the volume of sterile water that would need to be added may exceed 1 liter and hence the volume capacity of the original bag. To overcome this, the second method is to simply exchange a certain volume of replacement fluid with sterile free water. For example, in our case, 1250 mL of sterile water would have been needed to lower the sodium concentration of a 5-L RFP 401 bag to 112 mEq/L. Replacement fluid bags by different manufacturers may not have this much extra space and even if they do, often the maximum volume of a replacement fluid bag may not be readily available at the manufacturer’s site or written on the bag. The second more complex method would come in handy in these situations.

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