This single-center, retrospective cohort study was conducted at the Hemodialysis Center of Youyang Hospital, The First Affiliated Hospital of Chongqing Medical University, from 1 January 2023 to 30 June 2025. Patients were stratified into the SV group and the ACEi/ARB group according to their prescribed medication regimen initiated at baseline. The decision to prescribe SV or ACEi/ARB was made by the treating physician based on blood pressure control needs and clinical judgment regarding organ protection. The study protocol adhered to the Declaration of Helsinki and was approved by the institutional ethics committee. The requirement for informed consent was waived due to the retrospective design.

Inclusion Criteria: (1) Age ≥18 years; (2) Regular hemodialysis for ESRD for ≥ 3 months (4 h/session, 2–3 times/week); (3) Diagnosis of hypertension with new initiation or switch to either SV or ACEi/ARB drugs for ≥6 months; and (4) Availability of complete echocardiographic and clinical laboratory data at baseline and 6-month follow-up.

Exclusion Criteria: (1) NYHA class IV heart failure or hospitalization for acute heart failure within the preceding 6 months; (2) significant structural heart disease (severe valvular disease, hypertrophic cardiomyopathy, or pericardial disease); (3) severe comorbidities, including active malignancy, severe infection, or hepatic dysfunction (Child-Pugh class C); (4) history of angioedema; and (5) incomplete clinical data.

The diagnosis of hypertensive nephropathy was established clinically based on a composite of criteria: (1) a documented history of long-standing hypertension preceding the onset of kidney dysfunction; (2) evidence of hypertension-mediated target-organ damage, such as hypertensive retinopathy and/or left ventricular hypertrophy (LVH); (3) the absence of features suggestive of an alternative primary renal disease, including active urinary sediment or nephrotic-range proteinuria, when such data were available; and (4) the exclusion of other plausible etiologies based on a comprehensive chart review (21). In this retrospective cohort, kidney biopsy was not routinely performed and was generally reserved for atypical clinical presentations.

Patients were stratified into the SV group and the ACEi/ARB group according to their prescribed medication regimen. The initial oral dose of SV was 50 mg twice daily, with titration every 2–4 weeks up to a maximum of 200 mg twice daily, according to blood pressure response and tolerability. The final dosage of SV in the study group is detailed in Supplementary Table S1. The numbers of MHD patients with hypertension who received 50 mg twice daily, 100 mg twice daily, and 200 mg twice daily were 6 (13.04%), 28 (60.87%), and 12 (26.09%), respectively. The oral dose of ACEi/ARB drugs for patients was the tolerable dose. Concomitant antihypertensive medications were generally maintained at stable doses throughout the observation period to minimize confounding variables, unless dose adjustments were clinically required due to safety concerns.

Clinical and demographic data were retrieved from the Hospital Information System (HIS) and Laboratory Information System (LIS). Baseline characteristics included age, gender, dialysis vintage, primary etiology of ESRD, comorbidities (e.g., diabetes mellitus, coronary heart disease), and concomitant medications.

Laboratory indicators were collected at baseline and at the 6-month follow-up. These included N-terminal pro-brain natriuretic peptide (NT-proBNP), serum creatinine, blood urea nitrogen, serum potassium, serum calcium, serum phosphate, intact parathyroid hormone, hemoglobin, albumin, high-sensitivity C-reactive protein (hs-CRP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), β2-microglobulin, spKt/v, and serum ferritin.

Transthoracic echocardiography was performed by experienced sonographers using a standardized protocol at baseline and at 6 months (±2 weeks) after initiation of treatment. All measurements were taken in accordance with the current recommendations of the American Society of Echocardiography (ASE) and the European Association of Cardiovascular Imaging (22). Key parameters included left ventricular end-diastolic diameter (LVEDd), left ventricular end-systolic diameter (LVESd), interventricular septum thickness in diastole (IVSTd), and posterior wall thickness at end-diastole (PWTd).

Left ventricular mass (LVM) was calculated using the Devereux-modified ASE cube formula:LVM(g)=0.8×{1.04[(LVEDd+IVSTd+PWTd)3−(LVEDd)3]}+0.6LVM was then indexed to body surface area (Du Bois formula) to obtain the left ventricular mass index (LVMI, g/m²).

Left ventricular ejection fraction (LVEF) was measured using the biplane Simpson's method. All other linear dimensions were measured in the parasternal long-axis view at end-diastole.

Pre-dialysis blood pressure was measured in the sitting position using a calibrated electronic sphygmomanometer after at least 5 min of rest. At both baseline and 6-month follow-up, blood pressure was recorded immediately before three consecutive hemodialysis sessions, and the average of these three measurements was used for analysis.

The primary efficacy endpoint was the change in LVMI from baseline to 6 months.

The secondary endpoints including the LVEDd (mm), LVESd (mm), IVSTd (mm), PWTd (mm), and LVEF (%). Other secondary objectives included the changes in NT-proBNP, systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse pressure.

Safety and tolerability were assessed by monitoring adverse events (AEs), specifically symptomatic hypotension, intradialytic hypotension, angioedema, cough, hepatic dysfunction, and hyperkalemia (serum potassium >5.5 mmol/L). Intradialytic hypotension was defined as a decrease in SBP ≥20 mmHg or mean arterial pressure ≥10 mmHg during dialysis that was accompanied by symptoms (e.g., cramping, headache, lightheadedness, vomiting, chest pain) or required intervention (e.g., reduced ultrafiltration, fluid administration, or blood flow reduction).

All statistical analyses and diagrams were conducted using GraphPad Prism, version 9.0, and SPSS version 27.0 software (IBM Corp., Armonk, NY). Categorical variables are presented as percentages (%) and counts, while normally—distributed continuous variables are reported as the means ± standard deviations (SD). Non—normally distributed continuous variables are represented by the median and interquartile range (IQR). To compare the mean values before and after treatment, a paired t-test was used if the differences followed a normal distribution. Conversely, the Wilcoxon signed—rank test for paired samples was utilized when the differences did not adhere to a normal distribution. To compare longitudinal changes between groups, we applied a two-way repeated-measures ANOVA and reported the treatment group × time interaction P value. Multiple linear regression analysis was performed to identify independent predictors of changes in LVMI. Variables were selected for the multivariate model based on clinical relevance and significant baseline differences observed between the groups. No adjustment for multiplicity was applied for secondary endpoints. To further address potential selection bias and baseline imbalances, a sensitivity analysis was performed using propensity score (PS) adjustment. A logistic regression model including age, sex, dialysis vintage, hypertensive nephropathy, baseline LVMI, SBP, and baseline use of CCBs and α-blockers was used to calculate the PS for receiving SV. This PS was then included as a covariate in the linear regression model for the change in LVMI. A two-tailed P-value < 0.05 was considered statistically significant.

The study screened 286 MHD patients from our hospital between January 1, 2023, and June 30, 2025. Among them, 204 were diagnosed with hypertension. According to the exclusion criteria, we excluded 15 patients with a dialysis duration of less than three months, 4 patient who died during follow-up, 22 patients not taking SV or ACEi/ARB class antihypertensive drugs, and 52 patients with incomplete clinical data were excluded. Finally, 111 patients were included. The cohort included 46 patients in the SV group and 65 in the ACEi/ARB group (Figure 1).

Baseline characteristics are summarized in Table 1. The mean age was 56.17 ± 13.47 years, and 68.5% were male. The average BMI was 22.20 ± 3.37 kg/m², and the median dialysis duration was 45.50 (21.0–78.25) months. The main cause of ESRD was glomerulonephritis (35.1%), followed by diabetic nephropathy (25.2%), hypertensive nephropathy (21.6%), and other causes (18.0%). Most patients (91.0%) underwent dialysis three times per week. Regarding other medications, 58.6% of patients received calcium channel blockers, 28.8% received β-blockers, and 24.3% received α-blockers. Notably, dialysis vintage was longer in the SV group compared to the ACEi/ARB group (64.50 vs. 34.00 months; P = 0.010). The proportion of patients with hypertensive nephropathy was also higher in the SV group (34.8% vs. 12.3%; P = 0.005). Additionally, the use of calcium channel blockers (80.4% vs. 43.1%) and alpha-blockers (43.5% vs. 10.8%) was significantly more frequent in the SV group. Baseline echocardiographic parameters were comparable between the two groups (Supplementary Table S2).

In the SV group, LVMI significantly decreased from 139.08 ± 36.38 g/m² at baseline to 133.56 ± 31.68 g/m² at 6 months (P = 0.006, Table 2). In contrast, the ACEi/ARB group showed no significant improvement in LVMI, which changed from 139.82 ± 39.96 to 140.93 ± 37.51 g/m² (P = 0.615, Table 2). Two-way repeated-measures ANOVA (Table 3) showed that although the main effect of time (P = 0.153) and the main effect of group (P = 0.557) on LVMI were not statistically significant, the Time × Group interaction was significant (P = 0.033). This interaction suggests that the reduction in LVMI over time was significantly different between the two treatment arms, with a notable advantage observed in the SV group. Figure 2A displays the change in LVMI between the two groups [−5.52 (−9.35 to −1.69) vs. 1.11 (−3.27 to 5.50)].

LVEF changed from 60.43 ± 9.16% to 59.45 ± 10.09% in the ACEi/ARB group (P = 0.091), and from 60.28 ± 7.26% to 62.80 ± 8.88% in the SV group (P = 0.003; Table 2). ANOVA demonstrated a significant Group × Time interaction for LVEF (P < 0.001; Table 3). Figure 2B displays the change in LVEF between the two groups [2.52 (0.88–4.16) vs. −0.99 (−2.13 to 0.16)]. Other echocardiographic indices, including LVEDd, LVESd, IVSTd, and PWTd, did not change significantly over 6 months in either group (P > 0.05; Table 2). Consistently, ANOVA showed no significant group  ×  time interaction for LVEDd, LVESd, PWTd, IVSTd or Log-transformed NT-proBNP (P > 0.05; Table 3).

The ACEi/ARB group achieved a significant reduction in SBP of 9.81 mmHg (P < 0.001), DBP of 3.19 mmHg (P = 0.035) and pulse pressure of 6.63 mmHg (P = 0.002, Table 4). Similarly, the SV group showed significant decreases in SBP (−10.46 mmHg, P < 0.001), DBP (−4.13 mmHg, P = 0.021) and pulse pressure (−6.32 mmHg, P = 0.004, Table 4).

Log-transformed NT-proBNP levels also declined significantly in both cohorts. The SV group showed a reduction from 3.55 ± 0.55 to 3.39 ± 0.45 (P = 0.030), and the ACEi/ARB group showed a reduction from 3.62 ± 0.65 to 3.45 ± 0.59 (P = 0.008, Table 2).

After adjusting for potential confounders including age, male gender, dialysis vintage, hypertensive nephropathy, concomitant CCBs, concomitant β-blockers, baseline LVMI, and baseline SBP, treatment with SV remained a significant independent predictor of LVMI improvement (P = 0.023; Table 5). Baseline LVMI was also significantly associated with changes in LVMI (P < 0.001; Table 5).

In the sensitivity analysis using propensity score adjustment, the propensity score was included in the regression model. The results confirmed that SV treatment was significantly associated with a greater reduction in LVMI (β = −8.20, 95% CI −14.69 to −1.71, P = 0.014) (Table 5).

The AEs are summarized in Table 6. The overall incidence of new-onset intradialytic hypotension was 6.3% (7 patients), with comparable rates between the ACEi/ARB (6.1%, n = 4) and SV (6.5%, n = 3) groups. Hyperkalemia occurred in 8.1% of patients (n = 9), including 5 (7.6%) in the ACEi/ARB group and 4 (8.6%) in the SV group. No cases of angioedema or cough were reported. Importantly, no patients required dose reduction or treatment discontinuation due to adverse events.