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 Table of Contents  
ORIGINAL ARTICLE
Year : 2022  |  Volume : 20  |  Issue : 1  |  Page : 127-133

Role of dialysate sodium and serum sodium gradient in intradialytic hypertension of regular hemodialysis patients


Internal Medicine Department, Al-Azhar University of Cairo, Egypt

Date of Submission29-Jul-2021
Date of Decision28-Nov-2021
Date of Acceptance06-Dec-2021
Date of Web Publication4-Mar-2022

Correspondence Address:
MBBS Mohamed M Fayed
Internal Medicine Department, Al-Azhar University of Cairo, Postal Code: 22762
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/azmj.azmj_84_21

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  Abstract 


Background and aim Sodium (Na+) balance largely depends on interdialytic dietary salt intake and intradialytic Na+ removal during hemodialysis (HD) for chronic renal failure cases. To preserve a normal Na+ equilibrium, interdialytic Na+ increase should be filtered during HD. Sodium gradient (Na+ G) is obtained by subtraction of the dialysate Na+ concentration and the patient’s own pre-HD plasma sodium concentration. The aim was to evaluate the role of dialysate and serum Na+ G in patients with intradialytic hypertension (IDH).
Patients and methods A cross-sectional observational study was done to evaluate the role of Na+ G in IDH in a cohort of HD patients followed in the dialysis center of Damanhur Fever Hospital. Among 119 prevalent patients on MHD in our center during period from March 2021 to July 2021, we found 26 patients with IDH, so we selected a control group of 26 patients with intradialytic normotension (age and sex matched). So, the study included 52 patients (age and sex matched) who were divided into two groups: group A included 26 patients who were intradialytic normotensive, and group B included 26 patients with IDH.
Results A total of 52 patients were included in our final analysis. The sample included patients who are diagnosed with ESRD and under regular HD schedule, with a mean±SD age of 54.4±12.3 years. Comparison of different sodium concentrations revealed that there was no significant difference between pre-dialytic, and postdialytic Na serum levels, along with no difference in sodium gradients, with P values greater than 0.05.
Conclusion IDH was not significantly associated with sodium gradient, age, sex, hemoglobin level, and predialytic and postdialytic serum sodium concentrations.

Keywords: dialysate sodium, hemodialysis, intradialytic hypertension, sodium gradient


How to cite this article:
Fayed MM, Mohamed EA, Zidan HA, Assem AA, El-Sayed MA. Role of dialysate sodium and serum sodium gradient in intradialytic hypertension of regular hemodialysis patients. Al-Azhar Assiut Med J 2022;20:127-33

How to cite this URL:
Fayed MM, Mohamed EA, Zidan HA, Assem AA, El-Sayed MA. Role of dialysate sodium and serum sodium gradient in intradialytic hypertension of regular hemodialysis patients. Al-Azhar Assiut Med J [serial online] 2022 [cited 2022 Jun 29];20:127-33. Available from: http://www.azmj.eg.net/text.asp?2022/20/1/127/339081




  Introduction Top


Hemodialysis (HD) remains the most widely used modality of renal replacement therapy for patients with end‑stage renal disease worldwide and is usually performed for 3–5 h, 3 days per week [1]. Cardiovascular disease is recognized as the commonest cause of mortality in patients with maintenance HD; moreover, hypertension is known to be a complicating factor, especially during HD session [2]. However, a notable group of patients demonstrate increase in BP during the HD, which is termed intradialytic hypertension (IDH) [3], but, to date, there is no standard definition, and the most popular definition is an increase in systolic blood pressure (SBP) greater than 10 mmHg from before to after dialysis [4]. This phenomenon, which is termed IDH, is a neglected and poorly understood complication of HD. So, early identification and management of this complication will decrease the cardiovascular risks [5].

Its prevalence may differ from one study to another. Observation studies in the 1990s demonstrated that hypertension during dialysis occurs in 5–15% of patients; recently, this condition has been reported to reach an incidence of 28.4% [6]. Among 100,000 HD patients who were under follow-up for 5 years, a mean SBP decline of 14 mmHg was reported in the group with better survival, whereas the mortality rate was higher among patients with either any rise in SBP (IH) or a 30-mmHg reduction in SBP (intradialytic hypotension) [7].

The pathogenesis of IDH is a complex process, which is not well known; however, multiple factors are involved in the pathogenesis of IH. It includes overload of extracellular fluid and increased interdialytic weight gain, high cardiac output, initiation of the renin-angiotensin system, stimulation of the sympathetic nervous system, endothelial dysfunction, peripheral vessels constriction, and poor compliance to antihypertensive drugs by dialysis as well as the use of erythropoiesis-stimulating agents [8].

In patients with CKD, sodium (Na+) equilibrium is largely affected by interdialytic dietary salt intake, besides intradialytic Na+ removal. To maintain sodium balance, interdialytic Na+ increase should be decreased during HD. A higher dialysate sodium concentration (DNa) decreases the level of dialysis discomfort and the incidence of intradialytic hypotension. However, there is a concern that a DNa higher than the serum sodium concentration (SNa) usually results in a diffusive Na+ flux from dialysate to the patient’s circulation, which leads to a positive Na+ balance during HD, and consequently, fluid overload and IDH [9]. Na+ gradient is equal to the DNa+ (dialysate Na concentration) minus the patient’s own pre-HD PNa+ (plasma Na+ concentration) [8]. However, the potential correlation between the intradialytic sodium gradient (Na+ G) and IH behavior during HD is much less defined. The literature reveals conflicting evidence regarding association between sodium gradient and incidence of IDH. We aimed in the current study to evaluate the role of dialysate and serum sodium Na+ gradient in patients with IDH.


  Patients and methods Top


This is a cross-sectional observational study to evaluate the role of Na+ G in intradialytic BP variation in a cohort of prevalent HD patients followed in the dialysis center of the division of nephrology, Damanhur Fever Hospital, El-Beheira Governorate, Egypt. Among 119 prevalent patients on MHD in our center during the period from March 2021 to July 2021, 26 patients had IDH, so we selected a control group of 26 patients with intradialytic normotensive (age and sex matched). So, the study included 52 patients (age and sex matched) who divided into 2 groups: group A included 26 patients who were intradialytic normotensives, and group B included 26 patients with IDH. All patients were diagnosed with end-stage renal disease and were on regular HD. The study was conducted in the nephrology unit of Bab El-Sharia, Al-Azhar University Hospital.

We included all of the prevalent patients in March 2021, with the following inclusion criteria: adults greater than 18 years old, two to three sessions of HD weekly, HD treatment for at least 6 months, and urinary output less than 150 ml/24 h. Exclusion criteria were established heart failure, severe hyperglycemia (pre-HD plasma >250 mg/dl), decompensated liver cirrhosis, inflammatory diseases [rheumatoid arthritis (RA), sarcoidosis, etc.], active malignancy, and hospital admission for any cause in the 4 weeks before the study.

IDH was defined as an elevation in SBP greater than 10 mmHg from before to after dialysis to determine patients with intradialytic hypertensive from those without. All included patients were evaluated by detailed medical history, thorough clinical examinations, and full laboratory tests, including complete blood count, kidney function tests, liver function tests, and predialytic plasma sodium (pNa), and dialytic sodium (dNa) concentrations, which were determined using the online conductivity measurements on HD machines. Blood pressure was measured in pre, intra, and postdialytic periods to assess the difference throughout the dialysis session.

Sample size: we used a convenient period sample. We included all patients who were diagnosed with ESRD on regular HD for at least 6 months and with a urinary output of less than 150 ml/24 h in the period between March 2021 and July 2021.

Ethical considerations: the study protocol was approved by the ethical committee of Al-Azhar University. An oral consent was taken from patients after illustration of study procedures.

Statistical analysis

Statistical analysis of data was performed using SPSS, IBM, (NY, USA). Continuous data were presented in mean±SD and compared using Student’s t-test or Mann–Whitney U-test based on normality testing. Categorical variables were presented in frequencies and percentages, and correlations were made using χ2-test. P value less than 0.05 was considered significant.


  Results Top


A sample of 52 patients were included in our final analysis from 119 prevalent patients in our center on MHD from period March 2021 to July 2021. These included 52 patients who were divided into two groups (age and sex matched): group A included 26 patients who are intradialytic normotensives, and group B included 26 patients with IDH. This sample included patients diagnosed with ESRD and who were under regular HD schedule, with a mean±SD age of 54.4±12.3 years and mean±SD BMI of 27.8±5.4. Males represented the majority of our sample (76.9%). The commonest cause of HD was ESRD owing to hypertension (90.4%), whereas 7.7% were owing to diabetic nephropathy and 1.9% lupus nephritis.

Overall, 75% received three sessions of HD a week and 25% of patients twice weekly ([Table 1]). Only 3 patients had lower limb edema (5.8%). Most of the included patients were treated with antihypertensives; 67.3% used only one drug, 17.3% had two drugs, 13.5% had three drug, and only one patient took four antihypertensive drugs. The most commonly used antihypertensive drug was BB, followed by CCB, ACE, and AB (44.2, 42.3, 19.2, and 15.4%, respectively) ([Table 2]). Comparison between groups showed no significant differences in antihypertensive drug use, with P values greater than 0.05 ([Table 2]).
Table 1 Baseline characteristics of the included patients

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Table 2 Comparison of antihypertensive drugs used in study groups

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Comparison between baseline clinical characteristics and demographics based on the development of IDH showed that there was no significant difference between both groups in terms of sex, diagnosis, number of sessions, antihypertensive drugs, and positive hepatitis viral infections, with P values greater than 0.05. However, erythropoietin injections were significantly correlated with development of IDH, with P value 0.02, as patients who received three injections weekly showed significant association with development of IDH ([Table 3]).
Table 3 Comparison of erythropoietin supplementation between study groups

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There was no significant difference between groups in terms of age, BMI, predialytic weight, postdialytic weight, and interdialytic weight, with P values greater than 0.05 ([Table 4]).
Table 4 Comparison of patterns of weight changes during dialysis between groups

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Regarding laboratory findings of pre, post, and intradialytic periods, there was no statistically significant difference between normointradialytic blood pressure and IDH patients in terms of laboratory findings, including pre and postdialytic sodium, sodium gradient, and hemoglobin, with P values greater than 0.05 ([Figure 1]). Comparison of different sodium concentrations revealed that there was no significant difference between pre, dialytic, and postdialytic Na serum levels; thus, there was no significant difference in mean sodium gradients between groups, with P values greater than 0.05 ([Table 5]). Receiver operating characteristic analysis showed that there was no significant prediction of IDH using sodium gradient, with a P value of 0.83, using a cutoff point greater than 1.5 with a sensitivity of 92.6% and a specificity of 83.3%. Receiver operating characteristic analysis showed no significant prediction of IDH using pre and dialytic plasma Na levels, with P values of 0.55 and 0.12, respectively. Sodium gradient was not significantly correlated with interdialytic weight gain, with P value of 0.19 and correlation coefficient of 0.2 ([Figure 2]).
Figure 1 Box plot showing a sodium gradient difference between groups.

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Table 5 Comparison of laboratory findings between groups

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Figure 2 Receiver operating characteristic curve showing the predictability of sodium gradient for intradialytic hypertension.

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Sodium gradient was not significantly correlated with interdialytic weight gain, with a P value of 0.19 and correlation coefficient of 0.2 ([Figure 3]).
Figure 3 Scatter plot correlating interdialytic weight gain and sodium gradient.

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  Discussion Top


IDH has been described variedly, and there is currently no uniformly recognized definition. Many studies have proposed that each dialysis patient has his unique osmolar set point for plasma sodium, so dialysate sodium (DNa) should be individualized [9].

In the current study, we investigated the role of sodium gradient in the incidence of IDH (IDH). Among 119 prevalent patients on MHD in our center during the period from March 2021 to July 2021, we found 26 patients with IDH, so we selected a control group of 26 patients of intradialytic normotensives (age and sex matched). So, the study included 52 patients (age and sex matched) who were divided into two groups: group A included 26 patients who are intradialytic normotensives, and group B included 26 patients with IDH. The sample included patients who are diagnosed with ESRD who are under regular HD schedule, with a mean±SD age of 54.4±12.3 years and mean±SD BMI of 27.85.4.

There was no statistically significant difference in the baseline characteristics of the included participants in terms of age, sex, and BMI. This came in agreement with Iring et al. [4] and Shamir et al. [10], who compared the incidence of IDH among patients with ESRD, proving that the baseline characteristics were not significantly different between study groups.

However, this was different from results yielded from a study conducted by Yang et al. [11], when they concluded that patients with IDH tend to be older than other patients who did not develop IDH.

In the present study, hemoglobin level was not significantly associated with development of IDH, with a P value of 0.21. This agrees with another Egyptian study, which revealed that hemoglobin level did not significantly affect the incidence of IDH, with P value of 0.13 [12]. Moreover, two prospective studies were conducted to correlate the hemoglobin level with IDH [4],[11], although we demonstrated that the incidence of IDH was significantly associated with weekly erythropoietin injection, with a P value of 0.02.

Widespread usage of recombinant erythropoietin injection has been confirmed to increase the incidence of IDH in late nineties, when Levin stated that 20–30% rise in IDH in the era of erythropoietin; several mechanisms are being proposed [13]. Neff et al. [14] explained that the increase of ID blood pressure associated with the rise of hematocrit after using erythropoietin led to increased blood viscosity and increased peripheral resistance, finally leading to elevation of BP. Other studies found that erythropoietin receptors present on endothelial cells stimulate ET-1, which similarly results from erythropoietin treatment [15],[16]. The results of the present study proved there was no significant correlation between incidence of IDH and increased sodium gradient, with a P value of 0.83. In addition, interdialytic weight gain was not significantly correlated with development of IDH, with a P value of 0.60.

Sensitivity analysis showed that sodium gradient was not a significant predictor of IDH, with a P value of 0.83, using a cutoff point >1.5 with a sensitivity of 92.6% and a specificity of 83.3%. Moreover, pre- and dialytic plasma Na levels were not significant predictors of IDH, with P values of 0.55 and 0.12, respectively.

These findings agree with the ones published by Kora and colleagues, who investigated the role of sodium gradient and interdialytic weight gain in the occurrence of blood pressure changes intradialytically (hypotension or hypertension) among patients with ESRD and under regular HD. They conducted a cross-sectional study on 102 HD patients and divided them into 3 groups: no BP variability, intradialytic hypotension, and IDH. The results revealed that there was no significant difference in interdialytic weight gain and sodium gradient among the three groups, with P values of 0.77 and 0.46, respectively. On the contrary, they concluded that there was a positive correlation between sodium gradient and interdialytic weight gain and consequently ultrafiltration volume and rate [12].

Moreover, these findings are consistent with the studies conducted by Trinh and Weber, who conducted a cross-section study on 110 conventional HD patients who were diagnosed with ESRD at a single center. Moreover, they concluded that there was no association between intradialytic hypotension, IDH, or arterial blood pressure and sodium gradient. Moreover, there was no significant difference in 6-month hospitalization or mortality risk in relation to sodium gradient [17]. Moreover, Shamir and colleagues recruited 80 HD patients in a cross-sectional study aiming for defining an association between intradialytic change in blood pressure and cardiac structure and function in hypertensive HD patients who were enrolled in a multicenter blood pressure in dialysis (BID) clinical trial. The results of this study found no correlation between sodium gradient and IDH, with a P value of 0.77, when compared among groups [10].

Our results disagree with Shah and Davenport, who detected an association between elevated SBP and progressive prescription of antihypertensive medications in HD patients with low dNa concentrations [18]. However, Zhou et al. [19] correlated BP and interdialytic weight gain decline with lower dNa in patients at the same volume status. In contrast, Suckling et al. [20] highlighted that a decrease in BP when using dNa of 135 rather than 145 mEq/l but did not report on symptoms.

Recently, there has been considerable evidence that minimizing sodium gradient in HD patients as there is a positive correlation with changes in BP during HD and IDWG [21],[22]

Limitations of this study included limited number of patients, as the inclusion criteria only applied for 52 patients among the frequent individuals who were undergoing HD at our center. Moreover, the limited recourse, as IDH could be missed except if the patients is connected to a monitor, which more frequently measures blood pressure, allowing detection of even asymptomatic BP rise. We concluded that IDH was not significantly associated with sodium gradient, age, sex, hemoglobin level, and predialytic and postdialytic serum sodium concentrations.

Recommendations

Large prospective trials should be conducted to assess the correlation between sodium gradient and development of IDH. Besides, prospective cohort studies should be designed to assess the risk factors associated with IDH. Moreover, the patients should be connected to monitors during the HD sessions to report asymptomatic rise of BP.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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