Cardiac Function Transition in Patients with Chronic Kidney Disease Undergoing Maintenance Hemodialysis in a High-Altitude Multi-Ethnic Region: A Comparative Study Between Yi and Non-Yi Ethnic Groups

Maintenance hemodialysis (MHD) remains a commonly used renal replacement therapy for patients with chronic renal failure (CRF) and end-stage renal disease (ESRD). Despite therapeutic advances, cardiovascular disease (CVD) remains the leading cause of mortality in this population.¹ CRF/ESRD can result in left ventricular hypertrophy, heart failure, and tachyarrhythmias. The accumulation of uremic toxins, chronic inflammation, oxidative stress, anemia, and volume overload further aggravates cardiac and renal injury, contributing to the development of cardiorenal syndrome.^2,3 Previous studies have demonstrated that patients with chronic kidney disease (CKD) have a markedly increased risk of cardiovascular events, and the incidence of CVD in MHD patients is approximately 10–20 times higher than that of the general population.^4,5 Heart failure and sudden cardiac death are particularly prevalent among dialysis patients.

Globally, CKD has become a major public health challenge. According to the Global Burden of Disease Study 2023, CKD affects nearly 800 million people worldwide and continues to rise in prevalence and mortality.⁶ In China, a large nationwide survey reported that the prevalence of CKD among adults reached approximately 8.2–10.8%, corresponding to more than 80 million individuals, with relatively low awareness and treatment rates.⁷ These epidemiological data underscore the urgent need to better understand cardiovascular complications in CKD populations, especially in geographically and socioeconomically vulnerable areas.

Cold regions at high altitudes (≥2400 m) predispose individuals to pulmonary arterial hypertension and myocardial remodeling due to chronic hypobaric hypoxia and increased sympathetic activity.^8,9 Cold exposure further increases systemic vascular resistance and cardiac workload, thereby exacerbating cardiovascular stress in CKD patients.¹⁰ The Ninglang Yi Autonomous County, with a mean altitude above 2800 m, is a high-altitude multi-ethnic region predominantly inhabited by the Yi ethnic minority, with relatively limited medical resources. Delayed diagnosis, restricted healthcare accessibility, and differences in lifestyle and environmental adaptation may contribute to higher incidence and severity of cardiovascular complications compared with populations living in low-altitude regions.¹¹

However, the longitudinal patterns of cardiac functional transition and related risk factors in MHD patients from this high-altitude minority region remain insufficiently characterized. Clarifying the interaction between dialysis-related factors, environmental exposure, and ethnic background is essential for improving cardiovascular prevention strategies.

Therefore, this study systematically investigates the transition of cardiac function in CKD patients undergoing MHD in Ninglang. Ethnicity (Yi versus non-Yi) was prespecified as a descriptive and comparative variable. By evaluating laboratory parameters and echocardiographic indices over time, this study aims to elucidate the determinants of cardiac functional changes in a high-altitude multi-ethnic population and to provide evidence for targeted cardiovascular monitoring and early intervention strategies.

Materials and Methods

Study Design and Participants

This retrospective study was conducted at Ninglang Yi Autonomous County People’s Hospital, a high-altitude medical center located at a mean altitude of approximately 2800 meters.

A total of 161 patients with CKD stage 5 or ESRD who were receiving MHD between September 2017 and March 2024 were included. Among them, 103 patients were of Yi ethnicity and 58 belonged to other ethnic groups (non-Yi). There were 108 male and 53 female patients. Ethnicity was recorded in the hospital electronic medical records at the time of treatment.

Inclusion criteria were:

1. age ≥18 years;
2. diagnosis of CKD stage 5 or ESRD;
3. regular MHD treatment for at least 3 months.

Exclusion criteria included:

1. acute cardiovascular events within 3 months prior to enrollment;
2. acute kidney injury;
3. severe infection, malignancy, or systemic inflammatory disease;
4. incomplete clinical or echocardiographic data.

The study protocol was approved by the institutional ethics committee (approval number: 2024-01) and was conducted in accordance with the Declaration of Helsinki. The requirement for written informed consent was waived due to the retrospective nature of the study.

Hemodialysis Procedure

All patients underwent bicarbonate-based hemodialysis using a Fresenius 4008S dialysis machine (Fresenius Medical Care, Germany). Dialysis was performed two to three times per week, with each session lasting 4–5 hours. Blood flow rate was maintained at 200–250 mL/min. Dialysis prescriptions were adjusted individually according to clinical status.

Laboratory Assessments

Venous blood samples were collected prior to the midweek dialysis session at baseline, 3 months, and 12 months.

Serum biochemical parameters, including serum creatinine (CREA), blood urea nitrogen (BUN), albumin (ALB), calcium (Ca), magnesium (Mg), lipid profile, homocysteine (HCY), and ferritin (FER), were measured using a Hitachi 7180 automatic biochemical analyzer (Hitachi High-Technologies Corporation, Tokyo, Japan).

HCY was determined using an enzymatic cycling method. ALB was measured by the bromocresol green method. Lipid parameters were analyzed using standard enzymatic colorimetric assays.

Hematological parameters, including hemoglobin (HGB) and hematocrit (HCT), were measured using a Sysmex XT-1800i five-part differential hematology analyzer (Sysmex Corporation, Kobe, Japan).

All assays were performed in accordance with the manufacturers’ instructions. Routine internal quality control procedures were conducted to ensure analytical accuracy.

Echocardiographic Evaluation

Transthoracic echocardiography was performed using a MYLAB90 color Doppler ultrasound system (Esaote S.p.A., Genoa, Italy) equipped with a 2.5–3.5 MHz transducer. The following parameters were recorded: Left atrial diameter (LAd), Left ventricular end-diastolic diameter (LVd), Right ventricular diameter (RVd), Left ventricular ejection fraction (LVEF), Pulmonary artery systolic pressure (PASP), E/A ratio (early-to-late diastolic filling velocity ratio), Valvular regurgitation (mitral, tricuspid, and aortic). All examinations were performed by experienced cardiologists who were unaware of the patients’ ethnic classification.

Follow-Up and Data Availability

Clinical, laboratory, and echocardiographic data were collected at baseline, 3 months, and 12 months after enrollment. Due to the retrospective design, some patients had incomplete follow-up data. Therefore, sample sizes varied across parameters and time points. Statistical analyses were performed using available-case data for each comparison.

Statistical Analysis

Statistical analyses were performed using SPSS version 26.0 (IBM Corp., Armonk, NY, USA). Continuous variables were expressed as mean ± standard deviation (SD) for normally distributed data or as median (interquartile range) for non-normally distributed data. Normality was assessed using the Shapiro–Wilk test. For comparisons between Yi and non-Yi groups, independent-samples t tests or Mann–Whitney U-tests were applied as appropriate. Categorical variables were analyzed using the chi-square test. Comparisons across baseline, 3 months, and 12 months were conducted using one-way analysis of variance (ANOVA) or non-parametric equivalents, based on data distribution and availability. A two-sided P value <0.05 was considered statistically significant.

Results

Baseline Characteristics

A total of 161 patients with CKD stage 5/ESRD undergoing MHD were included in the analysis. Among them, 103 were Yi (64.0%) and 58 were non-Yi (36.0%). There were 108 males (67.1%) and 53 females (32.9%), with a mean age of 44.56 ± 14.95 years.

The prevalence of hypertension and diabetes was 20.4% and 16.2%, respectively, indicating a relatively high cardiovascular risk profile in this cohort (Table 1).

Table 1 Baseline Characteristics of Patients Undergoing Maintenance Hemodialysis (n=161)

Overall Changes in Laboratory Parameters

Comparisons of laboratory parameters at baseline, 3 months, and 12 months are presented in Table 2. CREA increased progressively over time (946.91 → 1041.83 → 1128.01 μmol/L, P<0.001). Mg also showed a stepwise increase (0.98 → 1.05 → 1.12 mmol/L, P<0.001). In contrast, ALB improved significantly during follow-up (39.44 → 42.65 → 43.54 g/L, P<0.001). FER levels declined significantly over time (P=0.002), whereas HGB and HCT remained relatively stable No significant longitudinal changes were observed in low density lipoprotein (LDL), apolipoprotein A (APOA), or HCY in the overall population.

Table 2 Comparison of Laboratory Parameters at Baseline, 3 Months, and 12 Months

Overall Changes in Echocardiographic Parameters

Echocardiographic findings are summarized in Table 3. PASP increased significantly over time (26.49 → 31.84 → 33.17 mmHg, P=0.049). Meanwhile, the E/A ratio gradually declined (0.96 → 0.83 → 0.79), suggesting progressive impairment of left ventricular diastolic function. No significant changes were observed in LAd, LVd, RVd, or LVEF during follow-up.

Table 3 Comparison of Echocardiographic Parameters at Baseline, 3 Months, and 12 Months

Longitudinal Changes in Yi Patients

In Yi patients (n=103), significant changes were observed in CREA, BUN/CREA, Ca, Mg, ALB, ALT, AST, and FER (Table 4). Mg increased consistently across time points (P<0.001), and ALB improved significantly (P<0.001). Echocardiographic parameters did not show significant longitudinal differences within the Yi group (Table 5).

Table 4 Longitudinal Changes in Laboratory Parameters in Yi Patients (n=103)

Table 5 Longitudinal Changes in Echocardiographic Parameters in Yi Patients

Longitudinal Changes in Non-Yi Patients

Among non-Yi patients (n=58), significant changes were observed in CREA, BUN/CREA, Ca, and ALB (Table 6). ALB improved significantly during follow-up (P=0.002).

Table 6 Longitudinal Changes in Laboratory Parameters in Non-Yi Patients (n=58)

No significant longitudinal changes in echocardiographic indices were observed in this group (Table 7).

Table 7 Longitudinal Changes in Echocardiographic Parameters in Non-Yi Patients

Ethnic Comparisons

Baseline

At baseline, the E/A ratio was significantly higher in Yi patients compared with non-Yi patients (1.25 vs 0.75, P=0.032), indicating possible compensatory diastolic adaptation (Tables 8 and 9). No other significant baseline differences were observed.

Table 8 Baseline Laboratory Parameters in Yi and Non-Yi Patients

Table 9 Baseline Echocardiographic Parameters in Yi and Non-Yi Patients

Three-Month Follow-Up

At 3 months, BUN/CREA and APOA differed significantly between groups (P=0.014 and P=0.041, respectively). The incidence of aortic regurgitation (AR) was higher in the Yi group (P=0.016) (Tables 10 and 11).

Table 10 Laboratory Parameters at 3 Months in Yi and Non-Yi Patients

Table 11 Echocardiographic Parameters at 3 Months in Yi and Non-Yi Patients

Twelve-Month Follow-Up

At 12 months, Yi patients had significantly higher HCY levels than non-Yi patients (35.60 vs 29.92 μmol/L, P=0.034). ALB and APOA levels were lower in the Yi group (P=0.010 and P=0.044, respectively).

The incidence of AR remained significantly higher in Yi patients (P=0.012). In addition, the E/A ratio was lower in non-Yi patients (P=0.021) (Tables 12 and 13).

Table 12 Laboratory Parameters at 12 Months in Yi and Non-Yi Patients

Table 13 Echocardiographic Parameters at 12 Months in Yi and Non-Yi Patients

Discussion

This study evaluated longitudinal changes in cardiac function in 161 patients with CKD stage 5/ESRD undergoing MHD in a high-altitude, multi-ethnic region. Over 12 months of follow-up, PASP increased progressively, while the E/A ratio declined, indicating worsening diastolic function. In contrast, LVEF remained relatively stable In addition, ethnic differences were observed in HCY levels, apolipoprotein A, and the incidence of AR.

Cardiovascular involvement in CKD is well established and represents a major determinant of morbidity and mortality.^1,12 Contemporary evidence supports the concept of uremic cardiomyopathy, characterized by myocardial remodeling, fibrosis, and impaired relaxation, often presenting as diastolic dysfunction with preserved systolic function.¹³ The pattern observed in our cohort—declining E/A ratio without significant reduction in ejection fraction—is consistent with this phenotype.

Dialysis-related factors may further contribute to cardiac stress. Repeated intradialytic volume shifts and hemodynamic fluctuations have been associated with cumulative myocardial injury and structural remodeling.^12,14 Although direct markers of myocardial injury were not assessed in this study, the gradual rise in PASP may reflect the combined influence of renal dysfunction and dialysis-related hemodynamic burden.

The high-altitude setting of this cohort adds another relevant dimension. Chronic hypobaric hypoxia is known to promote pulmonary vasoconstriction and vascular remodeling, potentially leading to sustained elevation of pulmonary artery pressure.¹⁵ The progressive increase in PASP observed here is compatible with such adaptive or maladaptive responses. In patients already exposed to CKD-related cardiovascular stress, chronic hypoxic exposure may further modify cardiopulmonary dynamics.

Ethnic differences warrant cautious interpretation. Yi patients exhibited higher HCY levels and a greater incidence of AR during follow-up. Recent studies continue to associate dysregulated HCY metabolism with endothelial dysfunction and vascular remodeling.¹⁶ However, this study does not establish causality. Differences in dietary patterns, micronutrient intake, genetic background, and healthcare access may contribute to these findings. Rather than suggesting inherent susceptibility, the results highlight the importance of context-specific cardiovascular evaluation in ethnically and geographically distinct populations.

Although clinical observation extended beyond 12 months in some patients, follow-up completeness declined after 12 months. To maintain consistency and minimize bias related to missing data, analyses were restricted to baseline, 3-month, and 12-month time points. This approach provides a more reliable assessment of temporal trends within the available dataset.

Globally, the cardiovascular burden associated with CKD continues to increase.⁶ However, data from minority populations residing in high-altitude regions remain limited. By focusing on a geographically and ethnically distinct dialysis cohort, this study provides region-specific evidence that may inform cardiovascular monitoring strategies in similar environmental contexts.

Several limitations should be considered. The retrospective design led to variable sample sizes across parameters due to incomplete follow-up. Echocardiographic data were available only for a subset of patients. Inflammatory and molecular biomarkers were not systematically assessed, limiting mechanistic interpretation. Prospective studies with standardized follow-up and comprehensive biomarker evaluation are needed to further clarify the interplay between altitude, dialysis, and cardiac function.

Conclusion

In this cohort of 161 MHD patients residing in a high-altitude region, progressive changes in cardiac function were observed over 12 months, characterized primarily by increasing PASP and declining diastolic function parameters, while systolic function remained relatively preserved.

Ethnic differences were identified in HCY levels, apolipoprotein A, and the incidence of AR, suggesting variation in cardiovascular risk profiles between Yi and non-Yi patients.

These findings contribute to the understanding of cardiac functional changes in dialysis populations exposed to chronic hypoxic environments and underscore the importance of individualized cardiovascular monitoring in geographically and ethnically distinct settings.