Wednesday, February 1, 2017

Hyponatremia and ESRD

Hyponatremia can be seen in patients with end-stage renal disease (ESRD), often as a consequence of a patient’s increase in free water intake in the setting of the kidneys’ diminished ability to regulate sodium and water homeostasis. I recently received a question from a resident asking for some insight into the management of such patients.
To begin, it should be noted that uremic patients with chronic hyponatremia are thought to be protected from osmotic demyelination syndrome (ODS) after hemodialysis. In this situation, urea may act as an effective osmole, whereby the decline in blood urea nitrogen (BUN) levels during dialysis could offset serum hypertonicity.  Additionally, animal studies have shown that azotemic rats were protected from ODS due to a reaccumulation of organic osmolytes  such as myoinositol and taurine within two hours of correction of hyponatremia
Though rare, case reports of ODS in uremic patients with hyponatremia do exist. One case described a uremic patient who developed ODS after being initiated on hemodialysis with an initial serum Na of 100 meq/L that corrected to 121 meq/L after three hours against a dialysate sodium concentration of 140 meq/L. It is important to note that ESRD patients in other case reports who went on to develop ODS had other risk factors for the development of the disease, such malnutrition and chronic alcoholism.
I recently helped care for an ESRD patient who was admitted with probable sepsis. His serum sodium on admission was 122 meq/L.  Because we had no outside records available at the time, we assumed his hyponatremia had been present for at least 48 hours. The patient had no uremic symptoms and had no need for urgent small solute clearance or volume removal. Nephrology was consulted for routine dialysis needs.
In choosing our dialysis prescription, we attempted to limit the increase in sodium to no more than 1 meq/L/h, or 3 meq for a 3-hour treatment.  We elected to reduce the blood flow rate to 100 ml/min, use the lowest possible sodium concentration bath allowed in the dialysate (130 meq/L), and use a dialysate flow rate of 600 mL/min.  Cocurrent flows were not used.  After a 3-hour dialysis session, the patient’s serum sodium rose to 125 meq/L, and hourly measurements of serum sodium during dialysis revealed that the patient’s sodium had indeed risen by 1 meq/L/h.
Our calculation was derived from a helpful approach described by Wendland and Kaplan, which showed that the rate in rise of serum sodium could be estimated by the product of the concentration gradient between the patient’s sodium and the dialysate sodium multiplied by the clearance. To do this, we would begins with the following formula:
Change in total body Na = Clearance (L/h) * (dialysate Na – patient Na)
By minimizing the blood flow rate to 100 mL/min and maximizing the dialysate flow rate to 600 mL/min, we assumed that there would be near-total equilibration between the patient’s serum sodium and the sodium concentration of the dialysate bath.  Thus, clearance would be approximately equal to the blood flow rate.
Thus, using our patient as an example:
Change in total body Na = Blood flow rate (L/h) * (130 meq/L – 122 meq/L)
A blood flow rate of 100 mL/min = 6 L/h
Therefore, the change in total body Na after 1 hour of dialysis would be:
6 L/h * 8 meq/L = 48 meq/h
Our patient’s total body water was 48L.  If we add 48 meq Na to our patient’s initial total body Na of 5856 meq (48L * 122 meq/L), we obtain the new total body Na after 1 hour of dialysis: 5856 meq + 48 meq = 5904 meq.
Dividing this value by the patient’s total body water would give us the new serum sodium after 1 hour of dialysis, assuming no ultrafiltration or volume changes.
5904 meq/48L = 123 meq/L
Thus, the patient’s serum sodium would rise by approximately 1 meq/L after 1 hour.
It would be interesting to discuss other options are available for managing ESRD patients with chronic hyponatremia.  Assuming there is no urgent need for small solute clearance, would continuous renal replacement therapy be a safer option?  If uremia is indeed “protective” against ODS, should we avoid low dialysate flow rates and concurrent flows?  How would the prescription change if the patient were to need more aggressive small solute clearance?
It seems that there is more than one way to manage these patients, and factors such as co-morbidities and electrolyte abnormalities need to be taken into consideration when formulating a dialysis prescription.
Posted by Devika Nair, MD
Nephrology Fellow, Vanderbilt


Dr. Helbert Rondon said...

Nice post. A common misconception is that the rate of sodium correction (e.g. 1 mEq/L/h) is important when in reality there is no evidence for this (Kidney Int. 1992 Jun;41(6):1662-7). The actual absolute magnitude of correction is what matters (e.g. < 8 or < 10 mEq/L per 24h depending on the risk of ODS). As you mentioned there are several ways you can deal with hyponatremia in ESRD. Extremely low Na should merit reduction of blood flow as you explain in your post but I am not sure that decreasing the blood flow in this particular patient with a Na of 122 was necessary unless you believe the patient was at an extremely high risk for ODS. Perhaps just using the lowest Na dialysate available (130) would have been enough. We cannot compare apples with oranges. Na concentration in the dialysate or Na "bath" is Na dissolved in water. The Na of 122 is not Na dissolved in water but in total plasma (or serum) which is only 93% water. So the actual Na concentration of the patient in water is 122/0.93 or 129. So, not that much different from Na in dialysate. Also the transfer of Na from dialysate to patient is greatly reduced due to the Donnan effect (negative charges from albumin attract cations like Na and do not allow easy transfer of Na+ into the patient).

devika said...

Thanks for the very helpful comments - agree that using low blood flows was probably not needed and that low dialysate [Na] would have been enough. His only additional risk factor for possible ODS was chronic alcoholism and lack of uremia (if we think uremia is protective as discussed above), but these were probably not significant enough to warrant conservative measures. Would be interested in hearing how patients requiring more urgent RRT needs would be managed.

Roger Rodby said...

Dr. Nair,
nice job and discussion, these are difficult cases. See

for a nice thread on this.

As for CRRT v HD for hypoNa, certainly CRRT, being as slow as you want it, is easier to control the rate and magnitude of Na change.

Dr. Rondon's point is well taken, the rate suggestions came from the fact that ODS was seen when a certain increase was seen over a certain time (change/time = rate), a rate less than that seen with ODS was suggested. But the better way to think about it is what change do you want in osmolality and why. If a patient is symptomatic, do you really want to raise their PNa by 1/2 meq/hour? Of course not you want to raise it immediately, but don't overshoot and that is why bolus 3% may be the best way to go. bolus check bolus check bolus check stop stop stop (and watch for a water diuresis in cases of non ESRD & AKI).

Your ESRD (or AKI) pt is trickier, and I think you did well. Your concern is not raising it too much, you do not want to be the "second" case of ODS from HD, as ODS is catastrophic.

He brings up a very interesting point that I never thought about (yikes), and that is the effect of the Na of dialysate being lower than we think (poorly worded but you get it). Normal Saline is 154 meq/l for that exact reason, the plasma water Na concentration is ~154, but measures at 140s because of the effect of proteins and lipids in the blood (in effect we all have pseudohyponatremia).

So, why is dialysate Na 140? and shouldn't that lower our dialysis patient's PNa to the 130s? Using his same calculation, a HD pt with a PNa of 138 has a water Na of 148, and dialysis against a water Na of 140 would only drop that patient?

Roger Rodby, MD
Rush, Chicago

PS, thanks for the Donnan explanation, I've been working on that for years, still not there since for every negative anion (albumin in this case) there is a cation too, so why would albumin selectively hold Na?

Amit Langote said...

Excellent post Devika. You may find interesting, couple of other posts on this topic from @ajkdblog and @errantnephron here :

Roger Rodby said...

"So, why is dialysate Na 140? and shouldn't that lower our dialysis patient's PNa to the 130s? Using his same calculation, a HD pt with a PNa of 138 has a water Na of 148, and dialysis against a water Na of 140 would only drop that patient? "

I believe I have found the answer. When in doubt go back to your mentors.
Answer and Full disclosure to follow! (gotta finish a manuscript first).


devika said...

thanks so much - these responses are why i've always loved this blog :)

Dr. Helbert Rondon said...

I believe the answer to Dr. Rodby's question is in the Donnan Effect (as I mentioned before) which occurs at the level of the dialysis filter membrane where protein form a barrier which complexes with sodium and precludes passage of free sodium ions. This enough to compensate for any difference in Na between plasma and dialysate. You can find a comprehensive review about this phenomenon in: Flanigan MJ. Sodium flux and dialysate sodium in hemodialysis. Semin Dial. 1998;11:298-304.

Oded said...

I posted a comment on Feb 3...not sure where it went so I'll repeat.

If PNa = 138, then:

"Active" PNa = plasma water Na x Gibbs-Donnan factor for monovalent cation = 138/0.93 x 0.96 = 142, i.e. minimally different from dialysate Na of 140.