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Randomized Controlled Trial
. 2024 Jun 1;19(6):712-722.
doi: 10.2215/CJN.0000000000000431. Epub 2024 Feb 13.

Dialysate Sodium Lowering in Maintenance Hemodialysis: A Randomized Clinical Trial

Dana C Miskulin  1 , Hocine Tighiouart  2   3 , Caroline M Hsu  1 , Daniel E Weiner  1
Affiliations
Randomized Controlled Trial

Dialysate Sodium Lowering in Maintenance Hemodialysis: A Randomized Clinical Trial

Dana C Miskulin et al. Clin J Am Soc Nephrol. .

Abstract

Key Points:

  1. Treatment to dialysate sodium 135 versus 138 mEq/L led to no difference in the rate of change in intradialytic hypotension, but symptoms were greater in the low arm.

  2. Use of a dialysate sodium concentration of 135 versus 138 mEq/L led to a small reduction in interdialytic weight gain, but had no effect on predialysis BP.

  3. Raising dialysate sodium concentration from 135 to 140 mEq/L reduced intradialytic hypotension and was associated with a marked increase in BP.

Background: Lowering dialysate sodium concentration may improve volume and BP control in patients on maintenance hemodialysis.

Methods: We randomized 42 participants 2:1 to dialysate sodium 135 versus 138 mEq/L for 6 months. This was followed by a 12-week extension phase in which sodium was increased to 140 mEq/L in low-arm participants. The primary outcome was intradialytic hypotension (IDH). Secondary outcomes included dialysis disequilibrium symptoms, emergency room visits/hospitalizations, interdialytic weight gain, and BP. Longitudinal changes across arms were analyzed using linear mixed regression.

Results: Treatment to dialysate sodium 135 versus 138 mEq/L was not associated with a difference in a change in the rate of IDH (mean change [95% confidence interval], 2.8 [0.8 to 9.5] versus 2.7 [1.1 to 6.2] events per 100 treatments per month); ratio of slopes 0.96 (0.26 to 3.61) or emergency room visits/hospitalizations (7.3 [2.3 to 12.4] versus 6.7 [2.9 to 10.6] events per 100 patient-months); difference 0.6 (−6.9 to 5.8). Symptom score was unchanged in the 135 mEq/L arm (0.7 [−1.4 to 2.7]) and decreased in the 138 mEq/L arm ([5.0 to 8.5 to 2.0]; difference 6.0 [2.1 to 9.8]). Interdialytic weight gain declined in the 135 mEq/L arm and was unchanged in the 138 mEq/L arm (−0.3 [−0.5 to 0.0] versus 0.3 [0.0 to 0.6] kg over 6 months; difference [−0.6 (−0.1 to −1.0)] kg). In the extension phase, raising dialysate sodium concentration from 135 to 140 mEq/L was associated with an increase in interdialytic weight gain (0.2 [0.1 to 0.3] kg) and predialysis BP (7.0 [4.8 to 9.2]/3.9 [2.6 to 5.1] mm Hg) and a reduction in IDH (odds ratio, 0.66 [0.45 to 0.97]).

Conclusions: Use of a dialysate sodium concentration of 135 as compared with 138 mEq/L was associated with a small reduction in interdialytic weight gain without affecting IDH or predialysis BP, but with an increase in symptoms. Raising dialysate sodium concentration from 135 to 140 mEq/L was associated with a reduction in IDH, small increase in interdialytic weight gain, and marked increase in predialysis BP.

Clinical Trial registration number: NCT03144817.

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Conflict of interest statement

C.M. Hsu is supported by NIH/NCATS grant KL2TR002545 and 1K12TR004384. C.M. Hsu’s funder had no role in study design, data collection, reporting, or the decision to submit. Caroline M. Hsu also reports Ownership Interest: Amazon, Google, and Microsoft; Research Funding: the Paul Teschan Research Fund grant from DCI, and salary support to my institution from DCI. D.C. Miskulin and D.E. Weiner receive salary support from DCI. D.C. Miskulin also reports Research Funding: Reata Inc. and Regulus Inc. H. Tighiouart reports Ownership Interest: Ford, Citi, Merck, Oracle, Bank of America, Exxon Mobile, TJ Maxx, Cheniere Energy, Organon. D.E. Weiner reports Research Funding: All compensation paid to Tufts MC: Bayer (site PI), Cara (site PI), and Vertex (site PI); Advisory or Leadership Role: Co Editor-in-Chief, NKF Primer on Kidney Diseases, 8th Edition; Editor-in-Chief, Kidney Medicine; Medical Director of Clinical Research, DCI.; Member, ASN Quality and Policy Committees and ASN Representative to KCP; and Member, Scientific Advisory Board, National Kidney Foundation; and Other Interests or Relationships: Member, Adjudications Committee, ProKidney REACT Trial (George Institute CRO) and Member, Safety and Clinical Events Committee for “A Prospective, Multi-Center, Open-Label Assessment of Efficacy and Safety of Quanta SC+ for Home Hemodialysis” Trial (Avania CRO).

Figures

None
Graphical abstract
Figure 1
Figure 1
Pre- and postdialysis plasma sodium concentration over the randomized study by treatment arm. (A) Predialysis plasma sodiumconcentration. (B) Postdialysis plasma sodium concentration. Figures show side by side box plots with “Standard” as dialysate sodium 138 mEq/L (black) and “Low” as 135 mEq/L (gray). Solid dots represent the mean values, and the open dots are outliers. Numbers along the y axis show the number of participants at each time period.
Figure 2
Figure 2
Interdialytic weight gain over the randomized study by treatment arm. The figure shows side by side box plots with “Standard” as dialysate sodium 138 mEq/L (black) and “Low” as 135 mEq/L (gray). Solid dots represent the mean values, and the open dots are outliers. Numbers along the x axis show the number of participants at each time period.
Figure 3
Figure 3
Change in predialysis systolic BP and interdialytic weight gain associated with raising the dialysate sodium concentration from 135 to 140 mEq/L in the nonrandomized extension phase. (A) Predialysis systolic BP. (B) Interdialytic weight gain. Figures show box plots with “Before Study Extension Date” representing the treatment period at dialysate sodium 135 (gray) and “After Study Extension Date” at dialysate sodium 140 mEq/L (black). Numbers along the x axis represent the number of participants with measures at each time period. Percent interdialytic weight gain is the difference between the predialysis weight of the current treatment and the postdialysis weight of the previous treatment divided by the estimated dry weight.
See this image and copyright information in PMC

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