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Opinion

How Would You Prescribe the Dialysate Sodium Concentration for Your Patients?

by
Friedrich K. Port
1,2
1
Departments of Medicine (Nephrology) and Epidemiology, University of Michigan, Ann Arbor, MI 48109, USA
2
Arbor Research Collaborative for Health, Ann Arbor, MI 48104, USA
Kidney Dial. 2022, 2(1), 1-3; https://doi.org/10.3390/kidneydial2010001
Submission received: 18 November 2021 / Revised: 15 December 2021 / Accepted: 16 December 2021 / Published: 23 December 2021
(This article belongs to the Special Issue Expert Opinions on the (Hemo)dialysate Sodium Prescription)

Abstract

:
Low sodium dialysate was commonly used in the early year of hemodialysis to enhance diffusive sodium removal beyond its convective removal by ultrafiltration. However, disequilibrium syndrome was common, particularly when dialysis sessions were reduced to 4 h. The recent trend of lowering the DNa from the most common level of 140 mEq/L has been associated with intradialytic hypotension and increased risk of hospitalization and mortality. Higher DNa also has disadvantages, such as higher blood pressure and greater interdialytic weight gain, likely due to increased thirst. My assessment of the evidence leads me to choose DNa at the 140 level for most patients and to avoid DNa below 138. Patients with intradialytic symptoms may benefit from DNa 142 mEq/L, if they can avoid excessive fluid weight gains.

An opinion piece by Chief Medical Officers in the US recommended in 2014, a volume-first approach to hemodialysis and suggested a dialysate sodium concentration (DNa) of 134–138 mEq/L [1]. This stimulated a broader debate and I am happy that this forum provides an opportunity to review and discuss optimal DNa levels.
Historically, some interesting experiences with extremes of DNa have been reported. High levels of DNa were thought to impair the removal of excess sodium and water for the typically volume overloaded patient. An accidental use of very high DNa of 154 mEq/L for all patients in one dialysis unit was not discovered until one month later when the erroneous dialysate composition was corrected. The authors showed surprisingly only minor clinical changes during the month, i.e., increases in interdialytic weight gain (IDWG) and among hypertensive patients an increase in blood pressure [2]. Stewart et al. [3] reported that “patients felt much better” with intentional chronic use of dialysate sodium levels of 145 versus 132 mEq/L, however they report that higher ultrafiltration rates were required (presumably because increased thirst and weight gain). These experiences show the expected effects on blood pressure and thirst, but these effects seem to be relatively small given the very high DNa levels employed.
The clinical experience around 50 years ago was predominantly with a DNa range of 130 to 132 mEq/L. This low level provided some removal of sodium by diffusion from the higher serum sodium level to the lower DNa, while most sodium removal occurred by ultrafiltration with intradialytic reduction in body weight. At that time a major concern was the dialysis disequilibrium syndrome, which frequently complicated hemodialysis sessions, particularly for patients with high urea levels and short treatment times. This syndrome included new onset of headaches, vomiting, drowsiness or restlessness, asterixis, psychosis, and even seizures during or immediately after a dialysis session. In recent decades, this syndrome has become very rare and young nephrologists may no longer be familiar with this once common complication.
A clinical trial tested the hypothesis that the dialysis disequilibrium syndrome was driven by rapidly decreasing serum osmolality through a combination of decreasing levels of both blood urea and serum sodium. Rapidly decreasing serum osmolality during dialysis has been shown to cause increased cerebrospinal fluid pressure and intracranial pressure due to a delayed diffusion of urea. The trial used an individualized higher DNa that was based on the patient’s predialysis serum sodium level and the expected fall in urea during high efficiency hemodialysis, with the aim to raise serum sodium during dialysis to minimize the reduction in osmolality due to the fall in blood urea [4]. The tailor-made DNa averaged 149 mEq/L. The intradialytic fall in serum osmolality in the study group was only 5.8 versus 26 mOsm/kg in the control group that used a standard dialysate of 133 mEq/L. The study group documented significantly less disequilibrium syndrome based on lower symptom scores during dialysis. This was confirmed by blindly read EEG monitoring during dialysis, which showed marked worsening in the control group but very little change in the study group during the 4-hour dialysis [4]. Since the 1970s, higher DNa levels (around 138–140 mEq/L) became a common practice and manifestations of the disequilibrium syndrome were rarely observed. The choice of DNa seems to have contributed to this substantial improvement in the care of hemodialysis patients.
A large cohort from the international Dialysis Outcomes and Practice Pattern Study (DOPPS) was analyzed by Marshall et al. [5] and revealed that mean DNa ranged by country, from 138.3 in the UK to 140.8 in Italy, and showed a slight downward trend from 140.06 mEq/L in 1996 to 138.9 in 2015, with the more pronounced decrease in the United States at 0.53 mEq/L per average 4 year phase of DOPPS. Variation in DNa levels during hemodialysis (sodium modeling) is not discussed here, since its use has markedly declined to <10% [5]. Of interest is the finding that a large fraction of dialysis facilities individualized the DNa prescription ranging by country from 12% of their patients in Japan to 75% in Italy [5]. Individualization of DNa within a dialysis facility suggests that some clinical indication was used for the choice of DNa for specific patients, which could bias associations with clinical outcomes (i.e., confounding by indication). Due to this concern, Hecking et al. [6] showed results of analyses that were limited to those facilities that used a single DNa choice for 90–100% of their patients. These DOPPS analyses found that higher DNa prescription (per 2 mEq/L) was significantly associated with lower mortality risk (Hazards Ratio (HR) = 0.88) at any predialysis serum sodium category and also that cardiovascular mortality was lower (HR = 0.81). Additionally, Cox models showed for higher “uniform” DNa that the risk of hospitalization (excluding those due to vascular access) was slightly lower (HR = 0.97) and even cause-specific hospitalizations due to fluid overload were also significantly lower (HR = 0.94). Furthermore, higher predialysis serum sodium levels were associated with lower mortality. In cross-sectional analyses, the predialysis systolic blood pressures were only minimally higher for patients treated in facilities with uniformly higher DNa (0.9 mmHg per 2 mEq/L) [7], likely because a large fraction of patients was treated for hypertension. Since IDWG was greater and blood pressure was somewhat higher with higher DNa levels, the findings of fewer hospitalizations and lower mortality with higher (uniform) DNa may seem surprising. They may be interpreted as suggesting greater harm from lower DNa than any harm from higher DNa levels.
It is interesting to note that the results on outcomes by DNa were in the opposite direction for patients treated at dialysis facilities where DNa was prescribed by patient indication rather than uniformly, which may explain why reported outcomes by DNa varied markedly in other publications where facility DNa individualization was not considered [8]. Such selection might lead to a biased finding of higher mortality with higher DNa as observed by Hecking et al. [6] with individualized DNa. An illustration of individual patient selection to a higher DNa might be for patients prone to intradialytic hypotension, who may be at risk of cardiac events and mortality. To avoid this confounding by indication bias, observational studies of the effect of DNa must avoid any influence of patient selection to different DNa choices within a dialysis practice.
One may argue that patients treated at facilities with uniform DNa are virtually “randomly” assigned to their facility’s DNa. Prospective randomized clinical trials will give a clearer picture: In a 12-month trial of outpatient hemodialysis using DNa 135 vs. the standard of 140 mEq/L, Marshall et al. [9] showed less interdialytic weight gain with low DNa, but could not document improved ventricular mass. However, this study observed more intradialytic hypotension in the low DNa group, even to the degree of several patients dropping out of the study. In a study by Causland et al. [10] moderate and even mild intradialytic hypotension was strongly associated cardiac arrhythmias. This may explain the increased risk of hospitalization and mortality with “uniform” low DNa compared to higher DNa as noted above by Hecking.
On balance, based on the early and more recent experience in hemodialysis, it seems that lower DNa (133–138 mEq/L) is likely harmful in terms of intradialytic hypotension and patient-reported symptoms, while even substantially higher DNa (>140 mEq/L) is associated with increased thirst, weight gain, and higher blood pressures, but perhaps not hospitalizations and mortality.
To answer the specific question, my choice of DNa would be 140 mEq/L if used uniformly for all patient in my (hypothetical) dialysis facility. If I decided to individualize DNa prescription, I would choose a DNa of 142 mEq/L for patients who have neither excessive interdialytic weight gains nor difficult-to-control hypertension. As new randomized clinical trial results become available, we might revise this opinion, but not likely by more than 2 mEq/L.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Conflicts of Interest

The author declares no conflict of interest.

References

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MDPI and ACS Style

Port, F.K. How Would You Prescribe the Dialysate Sodium Concentration for Your Patients? Kidney Dial. 2022, 2, 1-3. https://doi.org/10.3390/kidneydial2010001

AMA Style

Port FK. How Would You Prescribe the Dialysate Sodium Concentration for Your Patients? Kidney and Dialysis. 2022; 2(1):1-3. https://doi.org/10.3390/kidneydial2010001

Chicago/Turabian Style

Port, Friedrich K. 2022. "How Would You Prescribe the Dialysate Sodium Concentration for Your Patients?" Kidney and Dialysis 2, no. 1: 1-3. https://doi.org/10.3390/kidneydial2010001

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