Intradialytic Hypertension and the Impact of Reduced Dialysate Sodium: A Prospective Observational Study

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Junaid Gulzar Wani¹ , Ibtisam Nazir Khan¹ , Pankaj Kaul²

¹Department of Dialysis Therapy Technology, University School of Allied Health Sciences, RayatBahra University, Mohali, Punjab, India

²University School of Allied Health Sciences, RayatBahra University, Mohali, Punjab, India

Corresponding Author Email: junaidgulzar32@gmail.com

DOI : https://doi.org/10.51470/AMSR.2025.04.02.29

Abstract

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Introduction

End-Stage Kidney Disease (ESRD) represents the terminal stage of chronic kidney disease (CKD) and is characterized by the irreversible loss of renal function. For most patients with ESRD, renal replacement therapy becomes essential for survival, with hemodialysis (HD) remaining the most widely employed modality worldwide. Over the last several decades, HD has significantly improved life expectancy for ESRD patients; however, it is also associated with an array of complications, among which blood pressure (BP) fluctuations are among the most clinically important. Blood pressure variability during dialysis not only contributes to symptoms of intolerance during sessions but also imposes a considerable burden on the cardiovascular system, which is already severely compromised in individuals with ESRD.One of the most paradoxical and concerning phenomena observed during HD is Intradialytic Hypertension (IH), defined as a paradoxical rise in blood pressure during or immediately after a dialysis session. Whereas intradialytic hypotension has traditionally attracted more attention owing to its immediate symptomatic consequences, IH is increasingly recognized as a serious complication with long-term implications [1]. Large epidemiological studies consistently demonstrate that patients with ESRD face a cardiovascular mortality risk several-fold higher than that of age- and sex-matched individuals without kidney disease. Within this high-risk group, recurrent IH has emerged as an additional marker of adverse outcomes, including increased hospitalizations, accelerated progression of cardiovascular disease, and higher mortality.

The mechanisms underlying IH are multifactorial and remain incompletely understood. Proposed contributors include activation of the sympathetic nervous system, endothelial dysfunction, increased arterial stiffness, and volume overload. Among these, the role of dialysate composition—particularly sodium concentration—has received considerable attention. Sodium is the principal extracellular cation and plays a central role in determining serum osmolality, vascular tone, and extracellular fluid balance. The balance between sodium removal and sodium gain during dialysis sessions directly affects intravascular volume status and BP regulation. Clinical and experimental studies have long suggested that the sodium concentration of the dialysate is a determinant of intradialytic hemodynamic responses. A higher dialysate sodium concentration, while potentially beneficial for preventing intradialytic hypotension and related symptoms, is associated with increased thirst, interdialytic weight gain, and hypertension. Conversely, lowering the dialysate sodium concentration may reduce fluid accumulation and help achieve better BP control [2]. This trade-off between hemodynamic stability during dialysis and cardiovascular protection between sessions is at the center of the ongoing debate regarding optimal dialysate sodium prescription.

Evidence linking dialysate sodium to IH specifically has been accumulating. In a prospective crossover study, patients with recurrent IH were randomly exposed to periods of high versus low dialysate sodium concentrations. The findings demonstrated that BP rose during high-sodium dialysis and decreased during low-sodium dialysis, underscoring the importance of sodium balance in IH pathophysiology. Other observational reports have further supported this association, showing that reduced dialysate sodium levels are associated with attenuation of intradialytic BP surges. Importantly, several of these investigations have also reported that lowering dialysate sodium is generally well tolerated and does not significantly increase the risk of symptomatic hypotension in most patients. While the impact of dialysate sodium reduction on intradialytic BP changes is increasingly recognized, fewer studies have examined its effect on interdialytic hypertension—the elevated BP observed in the hours and days between dialysis sessions [3]. Since interdialytic hypertension has a direct and cumulative impact on cardiovascular morbidity and mortality, clarifying the influence of dialysate sodium manipulation on this aspect of BP control is crucial. Variations in dialysis practices, patient populations, and comorbidities across regions necessitate context-specific research to establish optimal sodium targets.

The clinical significance of addressing IH cannot be overstated. In patients already burdened by fluid overload, uremic toxins, and heightened cardiovascular risk, recurrent BP surges during dialysis may accelerate target organ damage and worsen outcomes. Recognizing modifiable contributors, such as dialysate sodium concentration, offers an opportunity to refine dialysis prescriptions and improve both intradialytic tolerance and long-term cardiovascular health. While pharmacological interventions to blunt IH have been explored, non-pharmacologic measures such as individualized dialysate sodium adjustment represent a practical and potentially more effective approach.In many dialysis units, standard dialysate sodium prescriptions continue to be applied uniformly, without individual tailoring to patient physiology or BP response. Such a one-size-fits-all approach may contribute to persistent IH in susceptible individuals [4]. Recent literature advocates for more personalized dialysis prescriptions that account for sodium balance, interdialytic weight gain, and BP trends. However, widespread implementation requires robust clinical evidence from diverse settings demonstrating the safety and efficacy of sodium reduction strategies. The present study was designed as a prospective observational investigation to evaluate the effect of reduced dialysate sodium concentration on interdialytic hypertension in patients undergoing maintenance HD at a tertiary care hospital. By systematically observing changes in BP patterns in relation to sodium prescription, this research aims to contribute to the growing body of evidence on the modifiability of IH. The findings have the potential to inform clinical practice, particularly regarding the optimization of dialysate sodium as a non-pharmacological intervention for improved BP control in ESRD patients. Dialysate sodium concentration is a key factor influencing BP dynamics during and between dialysis sessions. While reduction of sodium in dialysate has been shown to mitigate IH during dialysis, its impact on interdialytic hypertension remains inadequately studied [5]. This investigation seeks to address this gap by examining the consequences of reduced dialysate sodium in a real-world tertiary care setting, thereby advancing understanding and guiding safer, more effective dialysis prescriptions for patients with ESRD.

Methods

This prospective observational study was conducted over a period of six months among patients aged above 18 years undergoing maintenance hemodialysis (MHD) at [institution name]. Ethical committee approval was obtained prior to initiation, and informed consent was secured from all participants. Patients were screened according to the study’s inclusion and exclusion criteria, and those fulfilling the definition of intradialytic hypertension (IDH) were enrolled. Inclusion criteria comprised patients aged 18–80 years, able to provide informed consent, on MHD for more than three months, and demonstrating an increase in systolic blood pressure (SBP) of more than 10 mmHg from pre- to post-dialysis in at least four of the preceding six dialysis sessions [6]. Exclusion criteria included patients outside the eligible age range, those unwilling to consent, patients with dialysis vintage less than three months, and individuals undergoing dialysis for acute kidney injury. Additional exclusions were patients with pre-dialysis sodium levels <130 mEq/L or >142 mEq/L, frequent intradialytic hypotension requiring fluid resuscitation, and those with significant cardiac disease, such as low ejection fraction or documented valvular heart disease.The study was executed in two phases. In the first phase, patients underwent eight consecutive sessions using their routine dialysate sodium concentration. During this period, the following were assessed: (1) ambulatory blood pressure monitoring (ABPM) during the interdialytic period following the 7th and 8th sessions (24-hour monitoring), (2) pre- and post-dialysis blood pressure measurements, (3) number and dosages of antihypertensive medications, (4) occurrence of intradialytic adverse events, and (5) number of IDH episodes requiring intervention. In the second phase, the same patients were dialyzed for eight consecutive sessions using a reduced dialysate sodium concentration of 138 mEq/L. The same parameters—ABPM during the interdialytic period of the 7th and 8th sessions, pre- and post-dialysis blood pressures, antihypertensive medication use, intradialytic adverse events, and IDH episodes requiring intervention—were documented. Data from both phases were subsequently compared to evaluate the effect of reduced dialysate sodium on ambulatory blood pressure and intradialytic hemodynamics [7]. The study design was a prospective observational study with a total sample size of 47 participants selected using randomized convenience sampling. Statistical analysis was performed using repeated measures analysis of variance (RANOVA) for continuous variables and chi-square test for categorical data. A p-value of <0.05 was considered statistically significant.

Table 3 represents the frequency distribution of habitual and complications of intra-dialytic hypertension patients. Alcoholics and hypertensives were more numerous, and they were around 78.7%. Diabetes occupies the second top position, which was about 51%, followed by smoking, which is around 49%.

HD–Hemodialysis, SD-Standard Deviation.

Table 4 describes the descriptive statistics of ambulatory systolic blood pressure mean in Intradialytic Hypertension patients treated with dialysate sodium 140 mEq/L. The mean systolic blood pressure was higher 4^th hour post HD, which was around 163.36 mmHg, followed by 162.94 2^nd hour post HD. This shows that the mean systolic pressure increases gradually from pre-HD, post-HD, 2^nd hour, and 4^th hour post-HD.

p-valueiscalculatedbyusingRANOVAbetween2groups,

*p<0.05-***p<0.001-statistically significant, ns-not significant.

Comparison of ambulatory mean systolic blood pressure showed an F value of 31.96, and it was statistically significant.

Based on estimated marginal means*.

The mean difference is significant at the. 05 level, Adjustment for multiple comparisons: Bonferroni,1- Pre HD-Systolic Blood pressure Mean, 2- Post HD systolic Blood pressure mean,3- 2^nd Hour Systolic Blood Pressure mean,4- 4^th Hour Systolic Blood pressure mean

HD–Hemodialysis, SD-Standard Deviation

Table: describes the descriptive statistics of ambulatory diastolic blood pressure mean in Intra-dialytic Hypertension patients treated with dialysate sodium 140 mEq/L. The mean systolic blood pressure was higher post HD, which was around 87.83 mmHg, followed by 87.284^th hour post HD. The pre was 83.66 mmHg.

p-valueiscalculatedbyusingRANOVAbetween2groups,

*p<0.05-***p<0.001-statistically significant, ns-not significant.

Comparison of ambulatory mean diastolic blood pressure showed an F value of 9.086, and it was statistically significant.

Based on estimated marginal means*.

The mean difference is significant at the. 05 level, a. Adjustment for multiple comparisons: Bonferroni,1-PreHD Diastolic Blood pressure Mean, 2-Post HD Diastolic Blood pressure mean,3-2^nd Hour Diastolic Blood Pressure mean,4-4^th Hour Diastolic Blood pressure mean

6: illustrates the Frequency distribution of complications in Intradialytic Hypertension patients after being treated with dialysate sodium 140 mEq/L. Around 21.3% had shivering, 19% had muscular cramps, 15% had hyperglycemia, and about 9% had hypotension.

HD–Hemodialysis, SD-Standard Deviation.

The descriptive characteristics for ambulatory mean systolic blood pressure in individuals with intradialytic hypertension receiving dialysate sodium 138mEq/L are shown in Table 11. The mean systolic blood pressure was higher post 2^nd HD ,which was around 148.85 mmHg, followed by 147.94 mmHg 4th hour post HD. Post HDSBP was 142.60mmHg and pre HD was 145.87 mmHg.

p-valueiscalculatedbyusingRANOVAbetween2groups,

*p<0.05-***p<0.001-statistically significant, ns-not significant.

Comparison of ambulatory mean systolic blood pressure showed an F value of 8.343, and it was statistically significant.

Table 13: Using repeated measure ANOVA, intra-group comparisons of ambulatory systolic blood pressure mean at various times were made in patients with intradialytic hypertension receiving dialysate sodium 138 mEq/L.(RANOVA)

Based on estimated marginal means*. The mean difference is significant at the 05 level a. Adjustment for multiple comparisons: Bonferroni,1-Pre HD Systolic Blood pressure Mean,2- Post HD systolic Blood pressure mean, 3- 2nd Hour Systolic Blood Pressure mean,4- 4th Hour Systolic Blood pressure mean.

The descriptive characteristics for ambulatory mean diastolic blood pressure in individuals with intradialytic hypertension receiving dialysate sodium 138mEq/L are shown in Table 14. The mean systolic blood pressure was higher post 2nd HD, which was around 85.14 mmHg, followed by 84.92 mmHg immediately post HD, where the pre HD was 83.29 mmHg

p-valueiscalculatedbyusingRANOVAbetween2groups,
*p<0.05-***p<0.001-statistically significant, ns-not significant.
Comparison of ambulatory mean diastolic blood pressure showed an F value of 3.532, and it was statistically significant.

Based on estimated marginal means*.

The mean difference is significant at the05 level,

a. Adjustment for multiple comparisons: Bonferroni,1-PreHD Systolic Blood pressure Mean, 2- Post HD systolic Blood pressure mean,3-2^nd Hour Systolic Blood Pressure mean,4-4^th Hour Systolic Blood pressure mean.

Table 17 represents the frequency distribution of complications in Intradialytic Hypertension patients after being treated with dialysate sodium 138 mEq/L. None had experienced shivering. 3 patients had hyperglycemia (6.4%), 2 had hypotension (4.3%), and only one patient (2.1%) had muscle cramps.

Values are expressed in Mean±SD; SD-Standard Deviation,

*p<0.05-***p<0.001-statistically significant, ns-not significant

Patients with intradialytic hypertension are treated with dialysate sodium 140mEq/L or dialysate sodium 138mEq/L, and the results are compared in Table 18. The post-HD systolic BP, 2^nd hour SBP

And 4^th hour SBP were less in the subjects when they received 138mEq/L sodium,and the values were statistically significant.

Values are expressed in Mean±SD; SD-Standard Deviation,

*p<0.05-***p<0.001-statistically significant, ns-not significant

*p<0.05-***p<0.001-statistically significant, ns-not significant

Table 20 compares the complications seen by individuals with Intradialytic Hypertension who received treatment with dialysate sodium 140 mEq/L and dialysate sodium 138mEq/L. There was a drastic improvement in muscle cramps and shivering while giving 138 mEq/L sodium,and it was statistically significant. Though statistically not significant, complications like hypotension and hyperglycemia were reduced after giving 138mEq/L sodium.

Graph 13: Frequency distribution of the Number of Anti-Hypertensive drugs per day in Intradialytic Hypertension patients

Graph 13: shows the frequency distribution of the number of anti-hypertensive drugs per day in intradialytic hypertensive patients. Around 60% of patients took an anti-hypertensive drug once per day, 21% took 2 per day, 15% took 3 per day, and 4% of patients took 4 per day.

Values are expressed in Mean±SD; SD-Standard Deviation,

*p<0.05-***p<0.001-statistically significant, ns-not significant

Table 23 shows that the 24-hour average SBP and DBP were significantly lower while giving 138 mEq/L sodium, and it was statistically significant. Nighttime Dip% %, SBP, and DBP were lower when sodium was 138 mEq/L.

Graph 14: Comparison of ambulatory diastolic blood pressure mean between dialysate sodium 140mEq/L and dialysate sodium 138mEq/L treatment in Intradialytic Hypertension patients

Discussion

The present study demonstrated that low-sodium dialysate effectively reduces ambulatory systolic blood pressure (SBP), ambulatory diastolic blood pressure (DBP), nighttime SBP, nighttime DBP, and dialysis-related complications in patients with intradialytic hypertension (IH). Hypertension is highly prevalent in end-stage renal disease (ESRD), with nearly 90% of patients affected, and it substantially increases the risk of cardiovascular mortality, particularly among individuals undergoing hemodialysis. Previous studies have already reported that overall ambulatory BP is significantly higher in intradialytic hypertensive subjects compared to normotensive controls [8-9].The pathophysiology of intradialytic hypertension is multifactorial, involving volume overload, sympathetic overactivity, renin-angiotensin-aldosterone system (RAAS) activation, and endothelial cell dysfunction. Additionally, antihypertensive medications and dialysate composition play a role in influencing IH. Intradialytic BP variability refers to BP fluctuations during dialysis that are independent of other hypertensive events. Recent research indicates that such variability is strongly associated with cardiovascular risk among hemodialysis patients. Hypertension in ESRD is primarily driven by extracellular fluid volume expansion, which is closely regulated by sodium. Increased sodium intake raises extracellular fluid volume, impairs endothelial function, and contributes to hypertension, whereas sodium restriction improves endothelial activity and reduces BP [10-11].

The findings of this study confirm that sodium intake in hemodialysis patients is influenced not only by dietary consumption but also by the sodium concentration of the dialysate. In IH patients treated with a dialysate sodium concentration of 140 mEq/L, mean SBP progressively increased from pre-HD to post-HD and continued to rise at the 2nd and 4th hours, culminating at approximately 163.36 mmHg. In contrast, when patients were treated with 138 mEq/L sodium dialysate, the mean SBP peaked at the 2nd hour (~148.85 mmHg) but showed a slight decline by the 4th hour (~147.94 mmHg). The pre-HD SBP in this group was ~145.87 mmHg, while the post-HD SBP was reduced to ~142.60 mmHg. These observations suggest that lower sodium dialysate attenuates intradialytic BP rise and contributes to improved hemodynamic stability.The endothelial effects of sodium also play a central role. Inrig JK and colleagues demonstrated that high extracellular sodium concentrations reduce nitric oxide (NO) release from endothelial cells while simultaneously increasing endothelin-1 (ET-1) production [12-13]. This imbalance contributes to vasoconstriction and elevated BP during dialysis. Previous studies consistently support that lowering dialysate sodium improves BP control. For example, Akdag et al. reported that reducing dialysate sodium from 140 to 137 mEq/L was associated with significant improvements in BP parameters, in agreement with the present findings. Complication rates were also substantially lower in the 138 mEq/L group. At 140 mEq/L sodium, short-term dialysis complications included shivering (21.3%), muscle cramps (19%), hyperglycemia (15%), and hypotension (9%). However, when sodium was reduced to 138 mEq/L, the occurrence of these complications was markedly lower: shivering (0%), muscle cramps (2.1%), hyperglycemia (6.4%), and hypotension (4.3%). These results are consistent with reports by Jenson BM and others, who found that lower sodium dialysate reduces cramps, hypotension, headaches, and nausea during dialysis. In terms of quantitative outcomes, the 140 mEq/L group had significantly higher 24-hour SBP (175.0 ± 18.5 mmHg vs. 164.13 ± 18.57 mmHg, p = 0.006) and DBP (102.46 ± 8.03 mmHg vs. 92.63 ± 6.43 mmHg, p = 0.000) compared to the 138 mEq/L group. However, the nighttime SBP and DBP dipping percentages were similar between groups, with no statistically significant difference observed [14-16]. This suggests that while lower dialysate sodium effectively improves both daytime and nighttime BP parameters, its effect on circadian dipping may be limited. The present study demonstrates that lowering dialysate sodium concentration to 138 mEq/L offers significant clinical benefits [17-18]. It reduces both systolic and diastolic blood pressures, improves hemodynamic stability during dialysis, and minimizes treatment-related complications, thereby providing a safer and more effective strategy for managing intradialytic hypertension.

Conclusion

The findings of this study demonstrate that lowering dialysate sodium concentration to 138 mEq/L significantly reduces ambulatory systolic and diastolic blood pressure, nighttime blood pressure, and dialysis-related short-term complications in patients with intradialytic hypertension. Importantly, this work represents one of the earliest within-subject studies comparing two different sodium concentrations, thereby providing strong evidence that reducing dialysate sodium is an effective and safe strategy for controlling intradialytic hypertension in patients with end-stage renal disease.

References

• Movilli, E., Camerini, C., Gaggia, P., Zubani, R., Feller, P., Poiatti, P., … &Cancarini, G. (2013). Role of dialysis sodium gradient on intradialytic hypertension: an observational study. American journal of nephrology, 38(5), 413-419.
• Nair, S. V., Balasubramanian, K., Ramasamy, A., Thamizhselvam, H., Gharia, S., &Periasamy, S. (2021). Effect of low dialysate sodium in the management of intradialytic hypertension in maintenance hemodialysis patients: A single‐center Indian experience. Hemodialysis International, 25(3), 399-406.
• Bratsiakou, A., Iatridi, F., Theodorakopoulou, M., Sarafidis, P., Goumenos, D. S., Papachristou, E., &Papasotiriou, M. (2024). The effect of different dialysate sodium concentrations on ambulatory blood pressure in hemodialysis patients: a prospective interventional study. Clinical Kidney Journal, 17(8), sfae041.
• Bratsiakou, A., Iatridi, F., Theodorakopoulou, M., Sarafidis, P., Goumenos, D. S., Papachristou, E., &Papasotiriou, M. (2024). The effect of different dialysate sodium concentrations on ambulatory blood pressure in hemodialysis patients: a prospective interventional study. Clinical Kidney Journal, 17(8), sfae041.
• Iatridi, F., Malandris, K., Ekart, R., Xagas, E., Karpetas, A., Theodorakopoulou, M. P., … &Sarafidis, P. (2024). Low dialysate sodium and 48-h ambulatory blood pressure in patients with intradialytic hypertension: a randomized crossover study. Nephrology Dialysis Transplantation, 39(11), 1900-1910.
• Radhakrishnan, R. C., Varughese, S., Chandran, A., Jacob, S., David, V. G., Alexander, S., &Tamilarasi, V. (2020). Effects of individualized Dialysate Sodium prescription in hemodialysis–results from a prospective interventional trial. Indian Journal of Nephrology, 30(1), 3-7.
• Mendoza, J. M., Bayes, L. Y., Sun, S., Doss, S., & Schiller, B. (2011). Effect of lowering dialysate sodium concentration on interdialytic weight gain and blood pressure in patients undergoing thrice-weekly in-center nocturnal hemodialysis: a quality improvement study. American journal of kidney diseases, 58(6), 956-963.
• Vongchaiudomchoke, T., Aviphan, K., Sanyakeun, N., Wachiraphansakul, N., Sawangduan, V., Nochaiwong, S., … &Noppakun, K. (2023). Randomized Trial on the Effects of Dialysate Potassium Concentration on Intradialytic Hypertension. Kidney international reports, 8(7), 1323-1331.
• Geng, X., Song, Y., Hou, B., Ma, Y., & Wang, Y. (2020). The efficacy and safety of low dialysate sodium levels for patients with maintenance haemodialysis: A systematic review and meta-analysis. International Journal of Surgery, 79, 332-339.
• Pinter, J., Smyth, B., Stuard, S., Jardine, M., Wanner, C., Rossignol, P., … &Genser, B. (2024). Effect of dialysate and plasma sodium on mortality in a global historical hemodialysis cohort. Journal of the American Society of Nephrology, 35(2), 167-176.
• Ingwiller, M., Bozman, D. F., Florens, N., Cerasuolo, D., Vigneau, C., Couchoud, C., &Hannedouche, T. (2024). Diuretics and mortality reduction in incident dialysis patients: a two-year observational study. Scientific Reports, 14(1), 27447.
• Uchiyama, K., Shibagaki, K., Yanai, A., Kusahana, E., Nakayama, T., Morimoto, K.,. & Itoh, H. (2021). Seasonal variation and predictors of intradialytic blood pressure decline: a retrospective cohort study. Hypertension Research, 44(11), 1417-1427.
• Thein, H., Haloob, I., & Marshall, M. R. (2007). Associations of a facility level decrease in dialysate sodium concentration with blood pressure and interdialytic weight gain. Nephrology dialysis transplantation, 22(9), 2630-2639.
• Alostaz, M., Correa, S., Lundy, G. S., Waikar, S. S., & Mc Causland, F. R. (2023). Time of hemodialysis and risk of intradialytic hypotension and intradialytic hypertension in maintenance hemodialysis. Journal of human hypertension, 37(10), 880-890.
• Inrig, J. K., Molina, C., D’Silva, K., Kim, C., Van Buren, P., Allen, J. D., & Toto, R. (2015). Effect of low versus high dialysate sodium concentration on blood pressure and endothelial-derived vasoregulators during hemodialysis: a randomized crossover study. American Journal of Kidney Diseases, 65(3), 464-473.
• Xiong, Y., You, N., Liao, R., Wu, L., Liu, Y., Ling, Z., & Yu, Y. (2023). Association of intradialysis blood sodium level, blood pressure variability, and hydration status with hemodialysis-related headache: a prospective cohort study. The journal of headache and pain, 24(1), 166.
• Raimann, Jochen G., Linda H. Ficociello, Len A. Usvyat, Hanjie Zhang, Lisa Pacelli, Sandi Moore, Penny Sheppard et al. “Effects of dialysate to serum sodium (Na+) alignment in chronic hemodialysis (HD) patients: retrospective cohort study from a quality improvement project.” BMC nephrology 19, no. 1 (2018): 75.
• Vareesangthip, K., & Davenport, A. (2020). Reducing the risk of intradialytic hypotension by altering the composition of the dialysate. Hemodialysis International, 24(3), 276-281.