Using a crossover design, this clinical trial was conducted on the HD patients referred to the Hemodialysis Center of 9-Day Hospital, Torbat-e Heydarieh, Iran, between December 2022 and June 2023 (Fig. 1).

CONSORT Flow Chart of participants

The inclusion criteria were being at the age range of 18–75, suffering from end-stage renal disease (ESRD), experiencing hypotension during HD in more than 20% of the sessions within one month before the study commencement, undergoing HD for over six months, having no shortness of breath and pulmonary edema, and receiving dialysis solution with sodium bicarbonate three times a week. If the patients had taken antihypertensive medications on the day of HD, the results of those sessions were excluded from the data analysis process. Likewise, BP following blood transfusion and the use of other blood volume expanders were not included.

Hypotension during HD was accordingly defined in this study as a condition wherein the systolic BP (SBP) in the patients dropped by more than 30% below 100 mmHg, compared with that before this procedure, or the diastolic BP (DBP) was below 60 mmHg.

Intervention.

Two HD protocols were implemented via a crossover design for both study groups. In this respect, 16 HD sessions were considered for each patient in each protocol. The protocols were (a) an intervention protocol in which the liquid sodium in the dialysis solution was linear and the UF profiling was A/D, and (b) a routine protocol or HD, wherein both liquid sodium and UF in the dialysis solution remained constant. Besides, four wash-out HD sessions were utilized between these two protocols.

The HD duration in the A/D-UF profiling was about four hours. In this HD protocol, UF was divided into three phases, viz., ascending, intermediate, and venular. At the ascending phase, 25.5% of the patient’s total weight was taken with a low UF rate. There was then an aggressive phase taking 51.2% of the patient’s weight at the intermediate phase, which was the maximum UF rate. At the descending phase, 23.6% of the total weight of the patient was further taken, and the UF rate was low. The UF rate refers to the rate at which a fluid or solution is filtered through a membrane using ultrafiltration. These phases were performed during ten steps using the B BRAUN Dialog plus Dialysis Machine, in profile one (Fig. 2) (Table 1).

Ultrafiltration ascending-descending profile

For the linear sodium profiling, the sodium concentration of the dialysis solution was 150 mmol/L at the onset of HD, which diminished linearly and reached 138 mmol/L at the end of the session. This HD protocol was further divided into three phases, within ten steps, each one lasting 24 min (Fig. 3) (Table 2).

During the routine HD protocol, UF remained constant. The same volume of the dialysis was further removed in every hour of this procedure. In this protocol, sodium in the dialysis fluid was constant (140 mmol/L) all through a four-hour session.

Patients’ BP was then checked and recorded at six intervals, namely, before HD, one, two, three, and four hours after it, and following this procedure, within each session.

A two-part questionnaire was also administered to collect the data, that is, the first part was associated with the demographic characteristics, viz., age, gender, education, income, place of residence, first HD date, and vascular access, and the second part was the BP measurement checklist.

To ensure the accuracy of the study, the B BRAUN Dialog plus Dialysis Machine (Germany) was used for all samples. The dialysis solution was sodium bicarbonate buffer and its temperature was set at 37oC for all patients, the blood flow rate was between 200 and 350 ml/min, and the dialysis fluid flow rate was set at 500 ml/min.

To validate the credibility of the study findings, the patients’ BP was initially measured by the researcher and other colleagues, recruiting 10 samples, and the correlation coefficient of the measured BP levels was then determined. This value was equal to 0.93 and 0.89 as reported by the researcher and the first and second collaborators, respectively. To measure BP, the same standard mercury sphygmomanometer was used for all samples.

Our intention is to enroll 20 patients in the study. The statistical calculations used to determine the required sample size were specifically tailored for cross-over studies, with a significance level (α) of 0.05 and a power (β) of 0.80 [21].

After extracting the baseline characteristics of the HD patients with reference to their records, those with hypotension in at least more than 20% of the sessions (that is, greater than three sessions) during the last one month, meeting the inclusion criteria in this study, were selected. The patients were then randomized into two groups of 10, benefiting the web-based randomization service (http://randomozation.com) to generate the random allocation sequence.

The data were then analyzed using the IBM SPSS Statistics 20. To describe and categorize the data, descriptive statistics, viz., frequency distribution, mean, and standard deviation (SD) were exploited. Additionally, the repeated measures analysis of variance (RM-ANOVA), paired t-test, and independent samples t-test were employed to test the research hypothesis. The normality of the quantitative variables was further established via the Kolmogorov-Smirnov (K-S) test. Of note, the 95% confidence interval (CI) and the 0.05 significance level were applied in all tests.