Dialysate Sodium in Hemodialysis and Arterial Stiffness

To the Editor: Response to “Dialysate Sodium, PWV, and Clinical Outcomes: The Missing Link of Sodium Stores and the Need for Rigorous Trials”. We thank Dr Sahutoglu for his interest in our manuscript and we appreciate the opportunity to reply to his concerns regarding mainly our results on pulse wave velocity (PWV).¹

The duration of intervention for each dialysate sodium level in our study was 2 weeks, which can be considered short.² In this short duration the differences in PWV are more likely to be associated with the effect of different dialysate sodium concentrations on peripheral blood pressure (pSBP) and may not reflect structural changes of the arterial wall. It was previously shown, that even during the interdialytic intervals, small changes in PWV may occur in hemodialysis patients, reflecting this phenomenon.³ It is also well-established that in hemodialysis patients PWV can be pathogenetically divided into BP-dependent and BP-independent components, with different associations with adverse outcomes.⁴ Furthermore, the adverse vascular stiffening effect of high sodium intake has been shown in experimental and clinical studies⁵ while it seems that sodium can directly act on endothelial cells promoting mechanical stiffness through multiple mechanisms such as the activation of epithelial sodium channels and the release of NO⁶ which can directly affect vascular tone. Thus, more research is necessary in order to clarify if short-term changes in dialysate sodium concentration can also influence arterial stiffness in patients receiving hemodialysis.

Moreover, the aim of our study was to emphasize the short-term effect of different dialysate sodium concentrations on BP and arterial stiffness parameters; long-term effects on these modifiable factors and long-term implications on hard outcomes such as all-cause and cardiovascular mortality were beyond the scope of our study.

Dr Sahutoglu refers to the results of a recent study published by Printer et al. This observational study involved more than 68,000 patients receiving hemodialysis over a follow-up period of almost 10 years. According to the results, dialysate sodium concentration ≤138 meq/l was associated with higher mortality compared to >138 meq/l,⁷ adding to previous similar findings in the field. However, the presence of intradialytic hypotension in the former group could lead to more adverse ischemic events and an increased mortality rate. In our opinion, despite the large population and the long follow-up period of this study, the results should be interpreted with caution, as it is not clarified if the high mortality rate is associated with low dialysate sodium concentration per se, or associated complications, such as intradialytic hypotension episodes. In our study, we were very careful to study 3 groups at 137, 139, and 141 mEq/l, i.e., by protocol, we avoided evaluating lower sodium dialysate concentrations, due to existing safety concerns. We strongly believe that it is precarious to suggest high dialysate sodium concentration in all patients receiving hemodialysis, as the association between high sodium intake—arterial hypertension and cardiovascular risk is well-established.

Finally, we agree with Dr Sahutoglu that the use of magnetic resonance imaging of tissue sodium stores (²³NaMRI) has improved our understanding of sodium pathophysiology and homeostasis. Long-term clinical trials with hard end-point outcomes that would take into account third sodium compartment measurements could further enhance our clinical guidance for individualization of sodium prescription in hemodialysis with the prospect of better clinical outcomes.

CONFLICT OF INTEREST

The authors declare no conflict of interest.

Data availability

No new data were generated or analysed in support of this research.

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