Intradialytic cerebral blood flow reduction occurs irrespective of vascular access type: a comparative study

Abstract

Background

Patients undergoing hemodialysis (HD) experience reductions in cerebral blood flow (CBF) during treatment. It remains unclear whether these changes are more pronounced in individuals with arteriovenous fistula (AVF). The study aimed to quantify and compare cerebral and cardiovascular hemodynamic changes during HD sessions in patients with AVF versus those with high-flow catheters (CVC).

Methods

In this cross-sectional study, 25 AVF patients were matched to 25 CVC patients by age, sex, and HD vintage. CBF was measured using transcranial doppler ultrasound at 15, 120, and 240 min during a routine HD session. Cardiac output (CO) was estimated pre- and post-dialysis.

Results

All CBF parameters declined significantly during HD: peak systolic velocity of the middle cerebral artery decreased by 18 cm/s (p < 0.001), end-diastolic velocity of the middle cerebral artery by 8 cm/s (p < 0.001), and mean flow velocity of the middle cerebral artery (MFVMCA) by 12 cm/s (p < 0.001). Conversely, pulsatility and resistance indices progressively increased (+ 0.3, and + 0.07, respectively; p < 0.001 for both). The main determinant of CBF reduction was CO decline. Both access group exhibited MFVMCA reductions, more pronounced in the AVF (-30.6% vs. -22.4%, p = 0.17). Cognitive impairment (MoCA < 26) was present in 72% of patients and inversely correlated with age (r=-0.51, p < 0.001).

Conclusions

HD patients experience significant cerebral hemodynamic deterioration during treatment, irrespective of vascular access type, potentially contributing to the high prevalence of cognitive impairment.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12882-026-04862-9.

Introduction

Cerebral vascular reactivity (CVR) is a fundamental physiological mechanism that preserves cerebral blood flow (CBF) in response to fluctuations in systemic blood pressure, arterial carbon dioxide levels, and other vasoactive stimuli. Impairment CVR reflects a diminished cerebrovascular reserve capacity and has been strongly associated with increased risk of cerebral ischemia. This dysfunction is frequently linked to cerebral small vessel disease and is characterized by elevated resistance and pulsatility indices, primarily resulting from arteriolar stiffness and reduced vascular compliance [1, 2].

Chronic kidney disease (CKD) is independently associated with progressive reduction in CBF, driven by systemic inflammation, vascular calcification, and the high prevalence of comorbidities such as diabetes mellitus, hypertension, and atherosclerosis [3]. These pathophysiological processes contribute to vascular stiffness, thereby impairing the cerebral circulation´s autoregulatory capacity to maintain stable perfusion across varying blood pressure levels. In patients undergoing hemodialysis (HD), these disturbances are further exacerbated by dialysis-induced hemodynamic stress, rapid intravascular volume shifts, and alterations in serum osmolality and acid-base balance. Together, these alterations precipitate episodes of transient cerebral hypoperfusion during HD sessions [4, 5]. Previous studies have reported CBF reductions ranging from 7% to 22% during HD, with a direct association between greater ultrafiltration volumes and accelerated cognitive decline [6–13].

Cognitive impairment (CI) is highly prevalent among patients with CKD, especially in those with end stage kidney disease (ESKD) receiving renal replacement therapy. CI in this population is not solely attributable to the severity of renal dysfunction but also to dialysis-related factors. Patients treated with HD, in particular, appear to experience more rapid cognitive deterioration compared to those managed with peritoneal dialysis. Among the proposed mechanisms, repeated exposure to intradialytic hemodynamic instability and acute shifts in uremic toxin levels are thought to play a pivotal role in accelerating neurocognitive decline [8].

Vascular access type may additionally influence cerebral hemodynamics. Arteriovenous fistulas (AVF), the preferred modality for long-term vascular access, induce significant cardiovascular adaptations, including reductions in systemic vascular resistance and increased cardiac output (CO) [14]. During HD, continuous AVF flow may further challenge systemic and cerebral perfusion -a phenomenon not typically observed in patients using central venous catheters (CVC) [15]. Despite its potential clinical relevance, the impact of vascular access type on cerebral hemodynamics during HD has not been thoroughly investigated.

The primary objective of this study was to quantify and compare cerebral and cardiovascular hemodynamic changes during HD sessions in patients with AVF versus those with high-flow CVCs. A secondary objective was to assess and compare basal cognitive function between the two groups, seeking to elucidate potential vascular access-related differences in cerebral flow and neurocognitive outcomes.

Materials and methods

This two-center, cross-sectional, comparative study was conducted between June 1 and July 30, 2023, at the Hemodialysis and Hemodiafiltration Unit of the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ) and the Hemodialysis Unit of Médica Santa Carmen.

Study participants

Eligible participants were adults (> 18 years), undergoing chronic HD, with stable dialysis prescription (no changes within the previous 3 months), at dry weight, and with Kt/V > 1.3. Exclusion criteria included a history of ischemic or hemorrhagic cerebrovascular disease within the past year, a prior diagnosis of CI, severe carotid stenosis, active infectious processes, and inadequate temporal acoustic windows for transcranial Doppler (TCD) ultrasound evaluation. Patients using CVCs were matched 1:1 to those with AVFs based on age, sex, and dialysis vintage. Clinical and demographic data, as well as laboratory parameters (hemoglobin, hematocrit, calcium, phosphorus, and parathyroid hormone levels), were collected from electronic medical records.

Dialysis treatment protocol

All participants underwent their routine prescribed HD treatment without any intervention or modification, thus reflecting a real-world clinical setting. Dialysis sessions lasted between 210 and 240 min. High-flux dialyzers were employed: FX CorDiax 180 Fresenius^® (24 patients) and Revaclear 400 Baxter^® (26 patients). Dialysis fluid composition included sodium 136–142 mmol/L, potassium 2–3 mmol/L, bicarbonate 32–34 mmol/L, calcium 2.5 mmol/L, and glucose 100 mg/dL. Blood flow (Qb) rates ranged from 300 to 420 mL/min, and dialysate flow (Qd) rates ranged from 500 to 800 mL/min. Dialysate temperature was uniformly maintained at 36.5 °C. Ultrafiltration volumes were individually adjusted based on each patient’s interdialytic weight gain and target dry weight. Antihypertensive medications were withheld prior to HD to prevent intradialytic hypotension and facilitate achievement of the target dry weight.

Procedures

Cerebral hemodynamic assessment

Following specialized training by an experienced neurosonographer, all TCD ultrasound assessments were conducted by a single operator (N.C.M). All examinations were systematically performed after the long interdialytic interval, with all patients positioned comfortably in upright seated posture. Cerebral blood flow velocity (CBFv) measurements were obtained at 15, 120, and 240 min during the HD session using a spectral TCD system (DigiOne Rimed^®) with a 2 MHz probe positioned via an adjustable headband through the transtemporal acoustic window. Measurements were obtained at a depth of 40–60 mm, corresponding to the middle cerebral artery (MCA) flow. Peak systolic velocity (PSVMCA) and end-diastolic velocity (EDVMCA) were defined as maximum and minimum values of the CBFv waveform, respectively. Mean flow velocity (MFVMCA) was calculated as the area under the velocity-time curve divided by the cardiac cycle duration. Derived parameters included the pulsatility index (PI = [PSV - EDV] / MFV) and resistance index (RI = [PSV - EDV] / PSV), both of which are reflective of small-vessel cerebrovascular function.

Cardiovascular hemodynamic assessment

All cardiac ultrasound assessments were performed by a single experienced operator certified in cardiovascular ultrasound. Baseline assessments were conducted 30 min before the HD session, with measurements repeated at the end of HD treatment. Cardiac output (CO) was calculated as stroke volume (SV) multiplied by heart rate (HR). SV was estimated using pulsed Doppler ultrasound to measure blood flow across the aortic valve, with the velocity-time integral (VTI) obtained from an apical five-chamber view. The left ventricular outflow tract (LVOT) area was measured from a parasternal long-axis view, assuming a circular geometry (area = π × r²). For AVF patients, fistula flow was measured using a 7.5 MHz linear probe to assess brachial artery diameter and mean velocity at the antecubital fossa. AVF flow was calculated using the formula: area × mean velocity × 60. Measurements were performed using a Siemens Acuson P500^® ultrasound system equipped with both a 2–5 MHz convex probe and a 7.5 MHz linear probe.

Derived hemodynamic variables

The following variables were calculated to reflect intradialytic hemodynamic changes:

• ΔMAP: Change in mean arterial pressure (baseline - final).

• ΔCO: Change in cardiac output (baseline - final).

• ΔMFV1: Change in MFV between 15 and 120 min.

• ΔMFV2: Change in MFV between 15 and 240 min.

Cognitive assessment

Cognitive function was evaluated by medical staff after trained by an experienced psychologist. The Montreal Cognitive Assessment (MoCA) was applied to screen for CI, with a score of < 26 points indicating CI.

Statistical analysis

Normality of continuous variables was assessed using the Kolmogorov-Smirnov test. Descriptive statistics are presented as numbers (percentages), mean (standard deviation), or median (interquartile range), as appropriate. Baseline comparisons between AVF and CVC groups were performed using the Mann-Whitney U test for continuous variables and the chi-square or Fisher´s exact test for categorical variables. Further stratification was conducted for AVF patients according to access flow (> 1,500 mL/min vs. < 1,500 mL/min).

Longitudinal cardiovascular (SBP, DBP, HR, CO) and cerebral hemodynamic variables (PSV, EDV, MFV, PI, RI) were analyzed using repeated measures ANOVA of Friedman´s test, as dictated by data distribution. To explore factors associated with a > 20% reduction in MFV during HD, bivariate and multivariate logistic regression analyses were conducted. Variables significant in the bivariate analysis, alongside those with biological plausibility, were included in the multivariate model. All statistical analyses were performed using SPSS version 25 (IBM, Armonk, NY). A two-tailed p-value < 0.05 was considered statistically significant.

Sample size calculation

Sample size estimation was based on previous studies reporting a 7 to 22% reduction in CBF during HD, with an average decline of approximately 14%. To detect a difference in CBF decline between AVF and CVC groups with 80% power and a 5% alpha error, 23 patients per group were required. Accounting for an estimated 10% dropout rate, the final sample size was set at 25 patients per group.

Results

Baseline characteristics

A total of 50 patients were included. Clinical, demographic, and laboratory characteristics are presented in Fig. 1 and Table 1. In brief, 60% of the cohort were male, with a median age of 56 years, and diabetes mellitus was the most common etiology of CKD. Twenty-five (50%) had an AVF as their vascular access. When comparing the AVF and CVC groups, no significant differences were observed in baseline characteristics, except for mean Qb, which was higher among AVF patients (380 vs. 350 mL/min, respectively; p = 0.042).

Fig. 1.

Flowchart of the study population

Table 1.

Baseline characteristics of patients

Parameters	AVF, N = 25	CVC, N = 25
Age, years (median, IQR*)	59 (47–72)	55 (41–66)
Male, n (%)	15 (60)	15 (60)
CKD etiology**, n (%)
Diabetes Mellitus	13 (52)	13 (52)
Glomerulopathies	4 (16)	6 (24)
Other	7 (28)	2 (8)
Unknown	1 (4)	4 (16)
Dialysis vintage, years (median, ICR)	4 (2–5)	3 (1–5)
Biochemical, median (IQR)
Hb, mg/dL	11 (9–12)	10 (9–11)
Hto, %	35 (31–39)	32 (30–36)
Calcium, mg/dL	9 (8–9)	8 (8–9)
Phosphate, mg/dL	5 (4–6)	5 (4–6)
PTH, pg/mL	595 (390–1090)	742 (469–1159)
Dialysis Schedule
Qb, mL/min (median, IQR)	380 (347–400)	350 (330–361)†
Ultrafiltration volume, L	2.4 (1.8–2.6)	2.2 (1.9–2.7)

AVF: Arteriovenous Fistula, CVC: Central Venous Catheter, IQR: Interquartile Range, CKD: Chronic Kidney Disease, Hb = Hemoglobin, Hto = Hematocrit, PTH = Parathyroid Hormone, Qb = Blood Flow Rate

The data presented includes median values (IQR) for non-normally distributed variables and the percentage for categorical variables. Significant differences between AVF and CVC groups are indicated with † (p < 0.05)

Cardiovascular and cerebral hemodynamic changes during the HD session

Hemodynamic changes during HD sessions are summarized in Table 2 and Fig. S1. Significant reductions were observed across several cardiovascular parameters: systolic blood pressure (SBP) decreased by a mean of 12 mmHg (p < 0.001), diastolic blood pressure (DBP) by 5 mmHg (p < 0.001), and cardiac output (CO) by 0.56 L/min (p < 0.001).

Table 2.

Changes in Cardiovascular and Cerebral Hemodynamics during HD Session in all HD patients

Time during HD	Pre-HD	120 min	240 min	p
Cardiovascular Hemodynamics
SBP, mmHg	142 ± 33	137 ± 27	130 ± 27	< 0.001*
DBP, mmHg	79 ± 19	78 ± 17	74 ± 16	< 0.001*
HR, beats/min	70 ± 11	-	72 ± 12	0.282
CO, L/min	4.42 ± 1.89	-	3.86 ± 1.96	< 0.0001**
Time during HD	15 min	120 min	240 min	p
Cerebral Hemodynamics
PSVACM, cm/s	68 (50–80)	55 (41–69)	50 (39–63)	< 0.001*
EDVACM, cm/s	21 (13–31)	18 (8–26)	13 (5–20)	< 0.001*
MFVMCA, cm/s	37 (25–48)	29 (21–40)	25 (19–34)	< 0.001*
PI	1.2 (0.9–1.6)	1.4 (1–2)	1.5 (1.2–2.2)	< 0.001*
RI	0.67 ± 0.16	0.71 ± 0.16	0.74 ± 0.16	< 0.001*

SBP: Systolic Blood Pressure, DBP: Diastolic Blood Pressure, HR: heart rate, CO: Cardiac Output, PSVACM: Peak Systolic velocity of the Middle Cerebral Artery, EDVACM: End-Diastolic Velocity in the Middle Cerebral Artery, MFVMCA: Mean Flow Velocity in the Middle Cerebral Artery, PI: Pulsatility Index, RI: Resistive Index

shows the behavior of hemodynamic variables at the cardiovascular and cerebral levels during hemodialysis. Data are presented as mean ± standard deviation for normally distributed variables and median (interquartile range) for non-normally distributed variables. Statistical significance is indicated as follows: *p < 0.001, **p < 0.0001.

Similarly, CBFv parameters demonstrated significant declines throughout HD: PSVMCA decreased by 18 cm/s (p < 0.001), the EDVMCA by 8 cm/s (p < 0.001), and MFVMCA by 12 cm/s (p < 0.001). In contrast, PI and the RI progressively increased during the HD session (+ 0.3, p < 0.001 and + 0.07, p < 0.001, respectively).

At baseline, median MFVMCA was 37 cm/s, already below the lower limit reported in various normative series (32). Notably, 32% of patients had a baseline MFVMCA < 30 cm/s, and 46% of these had values < 20 cm/s. Additionally, 36% of cohort exhibited a baseline PI > 1.4 -findings commonly associated with cerebral hypoperfusion and compensatory hemodynamic mechanisms. Importantly, these abnormalities were present prior to the initiation of HD session.

On average, a 32.5% reduction in MFVMCA was observed during HD. In risk factors analysis, the percentage change in CO was significantly associated with a > 20% decline in MFVMCA (OR 1.054, 95% CI 1.001–1.111, p = 0.048, Table S1, Figs. 2 and 3). No significant associations were found between cerebral hemodynamic changes and age, CKD etiology, hemoglobin levels, or ultrafiltration (UF) rate.

Fig. 2.

Cardiovascular and cerebral hemodynamic changes during the hemodialysis session, dividing the population by type of vascular access. A Change in cardiac output during HD comparing both group . B Comparing both group. C Change in MFVMCA during HD comparing both group. HD (Hemodialysis), MVF (Middle cerebal artery), AVF (Arteriovenous fistula), HFC (High flow catheter)

Fig. 3.

Linear regression analysis, the change in cardiac output (CO) correlates with the change in mean flow velocity of the middle cerebral artery (MFVMCA)

Hemodynamic changes by vascular access type

Comparisons between vascular access type (AVF vs. CVC) are shown in Table 3. Patients with AVF exhibited significantly higher pre-HD CO (4.92 vs. 3.93 L/min, p = 0.006). However, the percentage reductions in CO during HD was not statistically different between groups (12.5% vs. 7.6%, p = 0.73). Regarding MFVMCA, both groups demonstrated declines, with a greater mean percentage reduction observed in the AVF group (-30.6% vs. -22.4%) however, this difference was not statistically significant (p = 0.17); Fig. 2). In subgroup analyses, the primary determinant of MFVMCA change differed by access type: in AVF patients, the change in MAP was most strongly correlated (r = 0.51, p = 0.01), whereas in CVC patients, the change in CO was the predominant correlate (r = 0.42, p = 0.04).

Table 3.

Intradialytic changes in cardiovascular and cerebral hemodynamics by type of vascular access

Variable	AVF	CVC	p
UF Rate, ml/hr (median, IQR)	600 (450–645)	550 (475–675)	0.92
Change in MAP, % (median, IQR)	11.3 (1.8–16.5)	9.4 (3.7–15.5)	0.90
CO pre, L/min (mean, ± SD)	4.92 ± 1.41	3.93 ± 0.99	0.006
CO post, L/min (mean, ± SD)	4.24 ± 0.89	3.48 ± 0.813	0.003
Change in CO, % (median, IQR)	12.5 (3.7–18.9)	7.6 (3.1–18)	0.73
Change in MFVMCA 1, % (median, IQR)	18.3 (2.6–25.4)	4.9 (11.2–36.6)	0.59
Change in MFVMCA 2, % (median, IQR)	28.2 (20.6–41.8)	21.2 (13.7–38.6)	0.27
MOCA, (median, IQR)	23 (15–25)	24 (19–27)	0.35

UF: Ultrafiltration, MAP: Mean Arterial Pressure, CO: Cardiac Output, MFVMCA: Mean Flow Velocity in the Middle Cerebral Artery, MOCA: Montreal Cognitive Assessment. IQR: Interquartile Range

The table shows the changes during the hemodialysis session, where both vascular accesses are compared. Data are presented as median (IQR) for non-normally distributed variables and mean ± standard deviation for normally distributed variables. Statistical significance is indicated as follows: p < 0.05.

Further stratification within the AVF group compared high-flow (> 1,500 mL/min, n = 10) versus normal-flow AVF (< 1,500 mL/min, Table S2). Patients with high-flow AVF exhibited higher MFVMCA values at both 15 min (42 vs. 29 cm/s, p = 0.08) and at 120 min (38 vs. 24 cm/s, p = 0.08) during HD session. Additionally, baseline PI and RI were significantly lower in the high-flow AVF subgroup (PI 1.1 vs. 1.6, p = 0.03 and RI 0.64 vs. 0.76, p = 0.03, Table S2).

Cognitive changes

No significant differences were observed in MoCA scores between the AVF and CVC groups. However, it is noteworthy that 72% of patients had a pre-HD MoCA score below 26, indicative of CI. MoCA scores demonstrated an inverse correlation with age (r=-0.51, p < 0.001).

Discussion

This study demonstrated that all parameters of cerebral hemodynamics decline abruptly and significantly during HD, with magnitude of decline correlating with CO irrespective of vascular access type. Importantly, more than 20% of the cohort exhibited signs of cerebral hypoperfusion at the onset of HD, and the percentage decrease in middle cerebral artery mean flow velocity was more pronounced than previously reported. Furthermore, over two-thirds of the study population screened positive for CI, despite being younger than cohorts typically described in the literature.

In healthy individuals, CBF is tightly regulated by autoregulatory mechanisms that protect against both hypo- and hyperperfusion [12, 16]. Cerebral autoregulation maintains stable CBF despite systemic blood pressure variations of 5–10 mmHg. However, this protective mechanism is partially impaired in HD patients [5], particularly those with prolonged dialysis vintage, rendering them susceptible to abrupt CBF fluctuations. Early in the end stage kidney disease (ESKD), CBF may initially increase due to anemia-induced reductions in cerebral oxygen delivery. Nevertheless, progressive disease leads to chronic endothelial dysfunction, exhaustion of compensatory mechanisms, and subsequent declines in CBF [12].

Consistent with prior studies, our cohort exhibited significant intradialytic CBF reductions. Notably, the decline in MFVMCA (28–39%) exceeded previously reported ranges (7–22%) [6–12], likely attributable to the longer HD vintage among our patients. HD duration has been independently associated with CBF decline, as demonstrated by Xue et al. [17], who reported lower CBF and poorer cognitive performance among patients on HD for more than 73 months.

In contrast to prior reports [8, 10, 12, 13], we did not find an association between UF volume and CBF decline. Instead, reductions in MAP and CO were correlated with cerebral hemodynamic deterioration. These findings align with the physiological understanding that cerebral perfusion pressure is primarily governed by the difference between MAP and intracranial pressure, the latter influenced by microvascular function reflected in pulsatility and resistivity indices. During HD, reductions in MAP predominantly result from effective circulating volume depletion and CO reductions -both modulated by UF. The temporal pattern of MAP decline is nonlinear, with the steepest reductions typically occurring during the first third of the HD session [18]. Several factors, including pre-dialysis weight [19], antihypertensive therapy [18], plasma osmolality [20], and UF rate [21], may influence the magnitude of these changes.

Although the MFVMCA decline was greater in AVF patients compared to CVC patients, the difference was not statistically significance. Thus, our data do not support the hypothesis that AVF confer a higher risk of CBF reduction during HD. AVFs induce significant hemodynamic changes, including decreased systemic vascular resistance and increased CO immediately after creation. Although we initially hypothesized that these adaptations might impair organ perfusion, our findings suggest that the resulting hemodynamic changes are counterbalanced, preserving overall physiological stability. Nevertheless, in scenarios involving heart failure or excessive UF, this balance could be disrupted, potentially leading to cerebral hypoperfusion. Future studies with larger sample size are warranted to confirm these observations. Overall, despite the profound cardiovascular effects of AVFs, they do not appear to independently exacerbate cerebral hemodynamic deterioration beyond that attributable to CKD-related vascular dysfunction and other risk factors for CI.

In our cohort, 72% of the patients screened positive for CI, with no differences observed between vascular access types. The high prevalence of CI in HD population is documented [22–25]. The pathogenesis of CI in HD patients is multifactorial, with recurrent episodes of cerebral ischemia due to intradialytic hypotension that reduce CBF playing a critical role [4], as corroborated by our findings. Although we did not employ perfusion imaging to directly confirm ischemic injury, prior studies have established this association. Additional contributors to CI include myocardial dysfunction and chronic vascular inflammation [26–30]. Supporting this, Findlay et al. [8] demonstrated that patients experiencing the greatest CBF reductions exhibited the most significant cognitive decline over 12 months.

Several methodological limitations must be acknowledged. The sample size may have limited the statistical power to detect significant differences between groups. We did not assess arterial pH, pCO₂, and bicarbonate levels, all of which modulate cerebrovascular reactivity. Nonetheless, previous studies have yielded inconsistent associations between these parameters and CBF changes during HD [12, 31–32]. Recirculation rate for both type of access was not assessed, which may influence in the results. Additionally, a comprehensive neuropsychological battery was not performed to characterize CI by domain and severity.

This study primarily relied on relative values derived from ultrasound examination, rather than absolute measures of cerebral blood flow. This methodological choice may limit the precision and generalizability of the findings. Ultrasound-based measurements are inherently operator-dependent and may be influenced by technical variability. These factors represent potential sources of bias.

However, notable strengths of our study include the standardized acquisition of al CBF, CO, and AVF flow measurements by a single trained operator, enhancing measurement reliability. The evaluation of CO, an often-overlooked parameter in similar studies, provides novel insights into hemodynamic contributors to cerebral perfusion changes.

Conclusions

Patients undergoing HD experience abrupt and sigificant reductions in CBF during treatment, independent of vascular access type. These hemodynamic changes likely contribute to the high burden of CI observed in this population. Future research should prioritize strategies aimed at preserving CBF during HD to mitigate long-term neurocognitive sequelae.

Supplementary Information

Below is the link to the electronic supplementary material.

Author contributions

N. C. M., O. V. V. conceived the design and experiments. N. C. M., N. T. C., J. G. M., K. F. B., and M. J. L. R. collected the data and analyzed the results. N. C. M., E. R. A., E. A. L., I. A. G. R. and F. F. S. conducting experiments. N. T. C. O. V. V., J. M. A. I., and F. F. S critically revised the manuscript. All the authors revised the manuscript and agreed to be published.

Funding

This study was performed with local resources from the Department of Nephrology and Mineral Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán.

Data availability

All data generated or analysed during this study are included in this manuscript.

Declarations

Ethics approval and consent to participate

The study adhered to the principles of the Declaration of Helsinki, and all participants provided written informed consent prior to enrollment. The study protocol was approved by the Research and Ethics Committee of INCMNSZ (approval number NMM-4171-22-22-1).

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.