Abstract
This study aims to use echocardiography to explore the prevalence of pulmonary hypertension (PH) in maintenance hemodialysis patients with different vascular accesses and analyze the risk factors for combined PH. A cross-sectional analysis was conducted on 757 end-stage renal disease patients receiving maintenance hemodialysis. Patients were categorized by the type of access used during echocardiographic examination: central vein catheter (CVC) and autogenous arteriovenous fistula (AVF)/arteriovenous graft (AVG). They were further grouped by tricuspid regurgitation velocity to determine PH prevalence. Multinomial logistic regression analysis evaluated the relevant risk factors. (1) Among maintenance hemodialysis patients, 39.23% had a moderate to high likelihood of PH; 248 patients (32.76%) had diastolic dysfunction, 184 patients (24.31%) had pericardial effusion, 381 patients (50.33%) had left ventricular hypertrophy, and 268 patients (35.40%) had aortic regurgitation. Diastolic dysfunction may indicate early heart failure and PH progression. (2) In the CVC group, 62 patients (24.22%) had moderate PH, and 9 (3.52%) had severe PH. Left atrium diameter (OR = 1.086, 95% CI 1.024–1.151, P = .006 and OR = 1.123, 95% CI 1.001–1.260, P = .048) showed statistical significance in moderate and severe PH groups, respectively. Right ventricular end-systolic diameter (RVDS) (OR = 1.519, 95% CI 1.151–2.005, P = .003) was significant in the severe PH group. (3) In the AVF/AVG group, 158 patients (31.54%) had moderate PH, and 68 (13.57%) had severe PH. RVDS (OR = 1.183, 95% CI 1.078–1.298, P < .001 and OR = 1.607, 95% CI 1.413–1.829, P < .001) showed significance in moderate and severe PH groups. Left atrium diameter (OR = 1.060, 95% CI 1.004–1.120, P = .035) showed significance in the severe PH group. The incidence of PH in maintenance hemodialysis patients is high and is closely related to volume overload, vascular access type, and right ventricular enlargement. For patients with right ventricular dilation (e.g., RVDS > 25 mm) or moderate to severe PH, careful evaluation of the benefit-risk ratio for AVF/AVG should be conducted. In selected high-risk cases, alternative access such as CVC may be appropriate. Prospective studies are needed to further compare the long-term effects of different access types on PH progression.
Keywords: AVF/AVG, PH, right heart failure, uremic cardiomyopathy
1. Introduction
In patients with end-stage renal disease (ESRD), cardiovascular disease is the primary cause of death, with pulmonary hypertension (PH) accounting for more than 60%.[1] The incidence of PH increases as the glomerular filtration rate decreases, and its pathophysiological mechanism remains unclear. Currently, PH is classified as the 5th type of PH[2] and there is no specific drug treatment available in clinical practice. Among ESRD patients on maintenance hemodialysis, the proportion with PH is as high as 17% to 70%,[3] far exceeding other diseases. Additionally, approximately 18.5% of ESRD patients may develop right heart failure,[4] which can even lead to death.[5]
In the pathophysiology of concurrent ESRD PH study shows the main factors for the overload capacity,[6] in addition, endothelial dysfunction, arteriovenous shunt caused by increased blood flow, blood contact with dialysis membrane, as well as left ventricular filling pressure.[7,8] At the same time, the study found that the rising incidence of dialysis patients with PH-related factors, including urea reduction rate is low, inadequate vitamin D receptor activator applications, as well as the left atrial diameter (LAD). Right heart catheterization is regarded as the gold standard for the diagnosis of PH,[9,10] but its clinical application is limited due to invasive procedures. A wide range of studies have been conducted to compare the hemodynamic parameters of echocardiography with those of right heart catheterization, and it has been confirmed that there is a good agreement between them.[11]
There is a lack of research is currently used in patients with PH value of the central vein catheter (CVC) prevalence data, also do not have the heart structure change in uremia in heart disease in the course of development characteristics of research, this study from a different perspective on patients with hemodialysis vascular access of PH prevalence, discuss the pathways and maintaining hemodialysis patients with PH associated risk.
2. Materials and methods
2.1. The object of study
This study was approved by the Ethics Committee of the First Affiliated Hospital of Guangxi Medical University. Single-center retrospective study: patients undergoing maintenance hemodialysis at the hospital from May 2010 to May 2022 were selected. Patients were divided into the TCC group and the autogenous arteriovenous fistula (AVF)/arteriovenous graft (AVG) group according to the type of vascular access used during echocardiographic examination. This study was approved by the hospital’s ethics committee.
Inclusion criteria
(1) Age between 18 and 80 years; (2) according to the 2012 KIDGO definition and Chinese Clinical Guidelines for Hemodialysis Adequacy,[12,13] patients who undergo hemodialysis treatment 3 times weekly, with each session lasting 4 hours, interdialytic weight gain not exceeding 5%, URR > 65%, and Kt/V between 1.2 and 1.4, meeting the criteria for maintenance hemodialysis for 3 months or longer in end-stage renal disease; (3) blood flow rate between 250 to 300 mL/min, dialysate flow rate of 500 mL/min, use of bicarbonate-buffered solution, ultrafiltration volume determined according to dry weight, defined as no signs of edema or volume overload, no hypotension, cramps, nausea, or vomiting in the latter half of the dialysis session, and regular assessment of each patient.
Exclusion criteria
(1) Patients younger than 18 years or older than 80 years; (2) pregnant women and those with a history of heart failure, congenital heart disease, pulmonary embolism, or connective tissue disease; (3) patients using 2 types of hemodialysis access simultaneously; (4) patients undergoing peritoneal dialysis in addition to hemodialysis; (5) patients in severe inflammatory states such as severe pneumonia, septic shock, or sepsis; (6) patients with a history of major central vascular surgery; (7) patients with incomplete data or whose clinical data could not be collected.
2.2. Ultrasound examination
Transthoracic echocardiography was performed in all patients using standard two-dimensional echocardiography and Doppler, and measurements[14] were performed according to the guidelines of the American Society of Echocardiography. Transthoracic echocardiography was performed in all the patients on the same day or the next day after the hemodialysis procedure and was performed by 3 dedicated physicians, with investigators unaware of any clinical information.
2.2.1. Ultrasound criteria for diagnosis of PH
In 2021 China’s diagnosis and treatment of PH guidelines and 2015 European society of cardiology guidelines and recommendations,[15,16] based on the probability of echocardiography PH classification is based on 3 additional PH and other ultrasonic indications divided the patients into 3 groups: (1) the pulmonary high pressure low possibility, 3, 2.8 m/s or less, and no other PH additional indications; (2) PH moderate possibility, 3, 2.8 m/s or less additional indications, accompanied by other PH or tricuspid regurgitation velocity 2.9 to 3.4 m/s without other additional indications PH; (3) pulmonary high pressure high possibility, tricuspid regurgitation velocity 2.9 to 3.4 m/s with other additional indications, PH or 3 > 3.4 m/s. Pulmonary artery systolic pressure (PASP) was determined from the peak tricuspid regurgitation gradient using a simplified Bernoulli equation combined with estimated right atrial pressure (RAP). PASP computation formula is as follows: PASP = 4 (V)2 + RAP, including V is tricuspid regurgitation in jet peak velocity (m/s). According to the diameter of the inferior vena cava and respiratory changes to estimate the RAP. On the basis of echocardiography PH probability of classification divided the patients into 3 groups.
According to the ultrasound doctors according to the Chinese adults echocardiography measurement guide for inspectors have left ventricular diastolic dysfunction and left ventricular hypertrophy,[17] pericardial effusion, aortic regurgitation in qualitative diagnosis.[18]
2.3. Clinical data collection
2.3.1. General information
Age, gender, height, weight, heart rate, height, and weight.
2.3.2. Clinical data
Types of underlying diseases, duration of hemodialysis treatment, smoking history, comorbidities, types of vascular access, etc.
2.3.3. Biochemical data
Platelets, hematocrit, coagulation time, blood calcium, blood phosphorus, parathyroid hormone, magnesium ions, uric acid, creatinine, albumin, β2-microglobulin, ferritin, transferrin saturation, etc.
2.4. Statistical methods
Continuous variables are expressed as median (range) or mean ± standard deviation, and categorical variables are presented as absolute numbers (percentages). All variables and outcomes were tested for normality. Except for heart rate, all continuous variables showed non-normal distributions. Descriptive statistical analyses were performed to summarize demographic and clinical characteristics. Group comparisons for categorical variables were conducted using Pearson chi-square test, while continuous variables were analyzed using nonparametric tests (e.g., Mann–Whitney U test or Kruskal–Wallis H test).
Missing data rates for key echocardiographic variables, including left ventricular ejection fraction (LVEF) and cardiac output (CO), were assessed and found to be <5%. To minimize potential bias from missing data, multiple imputation (5 iterations) was applied using the fully conditional specification method. The imputation model included all variables used in the regression analyses to ensure valid inference. Because the missingness was below 10%, no sensitivity analysis was deemed necessary, as per recommended guidelines.
Considering the large number of cardiac indicators analyzed, we addressed the risk of false-positive results due to multiple comparisons. The false discovery rate (FDR) adjustment method was applied to control for type I error in the multivariable regression analyses. Results reported as statistically significant were those that remained significant after FDR correction.
Variables identified as significant in univariate multinomial logistic regression (P < .1) were subsequently included in the multivariate models. To test model validity, the independence of irrelevant alternatives assumption in the multinomial logistic regression was evaluated using the Hausman test, with no significant violations observed. Variance inflation factors for all predictors were below 5, indicating no significant multicollinearity. A sensitivity analysis using a multilevel logistic regression model with primary disease group as a random effect was also performed, and results remained consistent. All statistical tests were two-tailed, and a P-value < .05 was considered statistically significant. Analyses were performed using SPSS software (version 29.0; SPSS Inc., Chicago, IL).
3. Results
3.1. The general characteristics of study population and the prevalence of PH
Seven hundred fifty-seven maintenance hemodialysis patients were included, observed in the median age of 54 patients (18–80 years); among them, 482 cases of patients (63.73%) for men. In 187 patients (24.70%) patients with a history of smoking; the median duration of hemodialysis was 32 months (3–133 months). Basic diseases are the leading causes of chronic glomerulonephritis (67.50%). Anemia (89.56%) and hypertension (59.97%) are the most common complications of hemodialysis patients. After a sonographic diagnosis description and prompt in 248 patients (32.76%) patients with diastolic dysfunction (restricted). In 184 patients (24.31%) by ultrasonic examination to discover the pericardial effusion; in 381 (50.33%) cases with heart examination revealed LVH; in 268 patients (35.40%) with heart found that AR. General observation in the crowd, moderate PH and high PH diseased respectively 220 cases (29.02%) and 77 cases (10.17%). In 256 patients (33.82%) using CVC as hemodialysis pathway treatment, CVC moderate possible PH group of 62 cases (24.22%), high PH may for 9 cases (3.52%); in 501 patients (66.18%) using AVF/AVG treatment for vascular access, AVF/AVG moderate possible PH group of 158 cases (31.54%), high PH may for 68 cases (13.57%) (see Table 1).
Table 1.
The overall basic clinical features of 757 cases of study population [example] (%).
| Variables | Overall (n = 757) | Moderate PH (n = 220) | High PH (n = 77) | P value |
|---|---|---|---|---|
| Male | 482 (63.67) | 135 (61.36) | 48 (62.34) | .632 |
| The median age range (,) | 54 (18–80) | 55 (19–80) | 54.5 (22–78) | .178 |
| Smoking history | 187 (24.70) | 44 (20.00) | 22 (28.70) | .145 |
| Duration of treatment (median, range) months | 32 (3–133) | 34 (3–131) | 31 (3–130) | .199 |
| Underlying illness | ||||
| Chronic nephritis | 511 (67.50) | 142 (64.55) | 50 (64.94) | .712 |
| diabetes | 82 (10.83) | 35 (15.91) | 8 (10.39) | |
| hypertension | 81 (10.70) | 19 (8.64) | 15 (19.48) | |
| Obstructive nephropathy | 40 (5.28) | 11 (5.00) | 2 (2.60) | |
| Polycystic kidney | 31 (3.96) | 8 (3.64) | 2 (2.60) | |
| Gouty nephropathy | 7 (0.92) | 1 (0.45) | 0 (0.00) | |
| Multiple myeloma | 5 (0.66) | 4 (1.82) | 0 (0.00) | |
| Comorbidities | ||||
| Anemia | 678 (89.56) | 193 (87.73) | 71 (92.21) | .482 |
| hypertension | 454 (59.97) | 124 (56.36) | 50 (64.94) | .344 |
| CHD | 47 (6.21) | 17 (7.73) | 7 (9.09) | .21 |
| Diastolic dysfunction | 248 (32.76) | 67 (30.45) | 15 (19.48) | .011* |
| Pericardial effusion | 184 (24.31) | 67 (30.45) | 14 (18.18) | .030* |
| LVH | 381 (50.33) | 124 (56.36) | 29 (37.66) | .016* |
| AR | 268 (35.40) | 110 (50.00) | 31 (40.26) | .000*,* |
| Vascular access | ||||
| AVF/AVG | 501 (66.18) | 158 (71.82) | 68 (88.31) | .000*,* |
| CVC | 256 (33.82) | 62 (28.18) | 9 (11.69) |
The P-values represent comparisons between the moderate PH and high PH groups.
AR = aortic regurgitation, CHD = coronary heart disease, LVH = left ventricular hypertrophy.
3.2. Analysis of risk factors for PH in patients with TCC access
In the use of CVC 256 patients, the overall characteristics and echocardiographic analyses were put into the nonparametric test first, and for the screening of all observed variables, the results are shown in Table 2.
Table 2.
Multi-class Nonparametric test of PH group in 256 cases of CVC [cases (%)].
| Variable | Low group (n = 185) | Moderategroup (n = 62) | High group (n = 9) | P-values |
|---|---|---|---|---|
| Age (median) | 53.000 (41.0, 62.0) | 56.000 (43.5, 64.3) | 55.000 (45.5, 59.5) | .28 |
| Duration of treatment (median, months) | 30.000 (11.0, 58.0) | 35.500 (14.3, 55.0) | 32.000 (20.0, 41.5) | .746 |
| Male | 115 (62.16) | 43 (69.35) | 8 (88.89) | .181 |
| Smoking history | 48 (25.95) | 15 (24.19) | 2 (22.22) | .94 |
| Basic diseases | ||||
| Chronic nephritis | 136 (73.51) | 37 (59.68) | 5 (55.56) | .003*,* |
| Diabetes | 15 (8.11) | 19 (30.65) | 2 (22.22) | |
| Hypertension | 15 (8.11) | 2 (3.23) | 2 (22.22) | |
| Obstructive nephropathy | 11 (5.95) | 3 (4.84) | 0 (0.00) | |
| Polycystic kidney | 5 (2.70) | 0 (0.00) | 0 (0.00) | |
| Gouty nephropathy | 3 (1.62) | 0 (0.00) | 0 (0.00) | |
| Multiple myeloma | 0 (0.00) | 1 (1.61) | 0 (0.00) | |
| Anemia | 171 (92.43) | 53 (85.48) | 9 (100.00) | .16 |
| Hypertension | 121 (65.41) | 38 (61.29) | 5 (55.56) | .728 |
| CHD | 9 (4.86) | 4 (6.45) | 1 (11.11) | .67 |
| LVH | 101 (54.59) | 41 (66.13) | 3 (33.33) | .101 |
| Diastolic dysfunction | 67 (36.22) | 22 (35.48) | 1 (11.11) | .305 |
| Pericardial effusion | 44 (23.78) | 25 (40.32) | 1 (11.11) | .022* |
| AR | 47 (25.41) | 35 (56.45) | 3 (33.33) | .000*,* |
| AOD (mm) | 29.000 (26.0, 31.0) | 30.000 (28.0, 32.0) | 32.000 (29.0, 33.5) | .037* |
| LAD (mm) | 36.000 (32.0, 41.0) | 41.000 (36.0, 45.0) | 45.000 (42.0, 51.5) | .000*,* |
| LVDD (mm) | 52.000 (48.0, 56.0) | 56.000 (51.8, 61.0) | 57.000 (54.0, 60.5) | .000*,* |
| LVDS (mm) | 32.000 (29.0, 36.0) | 36.000 (32.0, 42.0) | 37.000 (35.0, 43.0) | .000*,* |
| IVS (mm) | 12.000 (12.0, 13.0) | 13.000 (12.0, 14.0) | 13.000 (11.5, 14.0) | .255 |
| LVHM (mm) | 12.000 (11.6, 13.0) | 12.000 (12.0, 13.0) | 13.000 (10.5, 13.5) | .401 |
| RVSD (mm) | 20.000 (19.0, 22.0) | 21.000 (19.8, 22.0) | 25.000 (23.5, 25.5) | .000*,* |
| RVOT (mm) | 28.000 (26.0, 29.5) | 30.000 (27.8, 31.0) | 28.000 (26.0, 30.5) | .001*,* |
| MPAD (mm) | 25.500 (24.0, 27.0) | 27.000 (25.8, 30.0) | 27.000 (26.0, 28.0) | .000*,* |
| LVFS (%) | 37.000 (33.0, 41.0) | 35.000 (29.8, 39.0) | 35.000 (30.0, 38.0) | .025* |
| LVEF (%) | 67.000 (62.0, 71.0) | 63.500 (56.8, 69.0) | 63.000 (56.5, 67.5) | .007*,* |
| SV (mL) | 84.000 (72.0, 98.0) | 93.500 (80.0, 107.3) | 107.000 (85.0, 123.5) | .005*,* |
| CO (L/min) | 6.600 (5.8, 7.9) | 7.350 (6.5, 8.9) | 9.100 (6.0, 10.0) | .003*,* |
| LVEDV (mL) | 130.000 (109.5, 152.0) | 154.000 (130.0, 189.8) | 159.000 (137.5, 208.0) | .000*,* |
AOD = aortic inner diameter, AR = aortic regurgitation, CHD = coronary heart disease, CO = left ventricular volume, IVS = interventricular septal, LAD = left atrial diameter, LVDD = left ventricular end-diastolic diameter, LVDS = left ventricular end-systolic diameter, LVEDV = left ventricular end-diastolic volume, LVEF = left ventricular ejection fraction, LVFS = left ventricular short axis shortening rate, LVHM = left ventricular posterior wall thickness, LVM = left ventricular hypertrophy, MPAD = the main pulmonary artery diameter, RVOT = right ventricular outflow tract inside diameter, RVSD = right ventricular end-systolic diameter, SV = left ventricular stroke volume.
The statistically significant variables (P < .05) screened by sub-nonparametric test were included in the univariate regression of multi-classification Logist, and the variables with P < .1 were included in the multivariate regression of multi-classification Logist. Results show that the LAD (OR = 1.086, 95% CI 1.024–1.151, P = .006 and OR = 1.123, 95% CI 1.001–1.260, P = .048) and moderate PH and high PH group was statistically significant, RVDS (OR = 1.519, 95% CI 1.151–2.005, P = .003) and high PH group were statistically significant (Table 3).
Table 3.
256 cases of CVC associated risk factors of multiple classification of PH Logist single factor and multiple factors regression analysis [example] (%).
| Variable | Single factor regression analysis | Multiple factors regression analysis | ||||||
|---|---|---|---|---|---|---|---|---|
| Moderate PH group | High PH group | Moderate PH group | High PH group | |||||
| OR (95% CI) | P | OR (95% CI) | P | OR (95% CI) | P | OR (95% CI) | P | |
| Underlying disease | 1.002 (0.778–1.289) | .99 | 1.042 (0.594–1.826) | .886 | – | – | – | – |
| Pericardial effusion | 2.165 (1.177–3.985) | .013* | 0.401 (0.049–3.292) | .395 | – | – | – | – |
| AR | 3.806 (2.086–6.945) | 0*,* | 1.468 (0.353–6.103) | .597 | – | – | – | – |
| AOC (mm) | 1.078 (0.985–1.179) | .105 | 1.268 (1.013–1.586) | .038* | – | – | – | – |
| LAD (mm) | 1.117 (1.065–1.171) | 0*,* | 1.226 (1.111–1.352) | 0*,* | 1.086 (1.024–1.151) | .006*,* | 1.123 (1.001–1.260) | .048* |
| LVDD (mm) | 1.103 (1.052–1.156) | 0*,* | 1.153 (1.043–1.274) | .005*,* | 0.971 (0.875–1.078) | .585 | 1.011 (0.772–1.324) | .938 |
| LVSD (mm) | 1.089 (1.045–1.134) | 0*,* | 1.114 (1.031–1.204) | .006*,* | 1.063 (0.985–1.147) | .119 | 1.034 (0.842–1.271) | .75 |
| RVSD (mm) | 1.096 (0.983–1.222) | .098 | 1.517 (1.227–1.877) | 0*,* | 0.974 (0.851–1.114) | .697 | 1.519 (1.151–2.005) | .003 * * |
| RVOT (mm) | 1.212 (1.094–1.342) | 0*,* | 1.101 (0.879–1.379) | .401 | – | – | – | – |
| MPAD (mm) | 1.238 (1.112–1.378) | 0*,* | 1.169 (0.927–1.476) | .188 | – | – | – | – |
| LVFS (%) | 0.949 (0.913–0.986) | .008 | 0.951 (0.876–1.033) | .234 | – | – | – | – |
| LVEF (%) | 0.955 (0.928–0.982) | .001*,* | 0.959 (0.904–1.017) | .165 | – | – | – | – |
| SV (mL) | 1.019 (1.006–1.033) | .005*,* | 1.032 (1.002–1.063) | .037* | 1.005 (0.978–1.033) | .705 | 0.993 (0.931–1.059) | .829 |
| CO (L/min) | 1.216 (1.062–1.392) | .005*,* | 1.352 (1.024–1.785) | .033* | 1.114 (0.902–1.377) | .317 | 1.329 (0.799–2.211) | .273 |
| LVEDV (mL) | 1.019 (1.011–1.027) | 0*,* | 1.023 (1.008–1.039) | .003*,* | – | – | ||
AOD = aortic inner diameter, AR = aortic regurgitation, CHD = coronary heart disease, CO = left ventricular volume, IVS = interventricular septal, LAD = left atrial diameter, LVDD = left ventricular end-diastolic diameter, LVDS = left ventricular end-systolic diameter, LVEDV = left ventricular end-diastolic volume, LVEF = left ventricular ejection fraction, LVFS = left ventricular short axis shortening rate, LVHM = left ventricular posterior wall thickness, LVM = left ventricular hypertrophy, MPAD = the main pulmonary artery diameter, RVOT = right ventricular outflow tract inside diameter, RVSD = right ventricular end-systolic diameter, SV = left ventricular stroke volume.
3.3. The use of AVF/AVG pathways of merger of PH in patients with risk factors
Using AVF/AVG group 501 patients, the overall characteristics and echocardiographic analysis into the nonparametric test (see Table 4).
Table 4.
Five hundred one cases of AVF/AVG pathways in different PH group of variables between nonparametric test [example] (%).
| Variable | Low-PH (n = 275) | Moderate PH (n = 158) | High PH group (n = 68) | P-values |
|---|---|---|---|---|
| Age (median) | 54.000 (41.0, 63.0) | 55.000 (44.0, 65.3) | 54.000 (45.0, 63.0) | .558 |
| Duration of treatment (median, months) | 32.000 (12.0, 51.0) | 34.000 (16.5, 59.3) | 29.000 (12.0, 55.8) | .212 |
| Men | 184 (66.91) | 92 (58.23) | 40 (58.82) | .145 |
| Smoking history | 73 (26.55) | 29 (18.35) | 20 (29.41) | .093 |
| Basic diseases | ||||
| Chronic nephritis | 183 (66.55) | 105 (66.46) | 45 (66.18) | .667 |
| Diabetes | 24 (8.73) | 16 (10.13) | 6 (8.82) | |
| Hypertension | 32 (11.64) | 17 (10.76) | 13 (19.12) | |
| Obstructive nephropathy | 16 (5.82) | 8 (5.06) | 2 (2.94) | |
| Polycystic kidney | 16 (5.82) | 8 (5.06) | 2 (2.94) | |
| Gouty nephropathy | 3 (1.09) | 1 (0.63) | 0 (0.00) | |
| Multiple myeloma | 1 (0.36) | 3 (1.90) | 0 (0.00) | |
| Anemia | 243 (88.36) | 140 (88.61) | 62 (91.18) | .8 |
| Hypertension | 159 (57.82) | 86 (54.43) | 45 (66.18) | .26 |
| CHD | 14 (5.09) | 13 (8.23) | 6 (8.82) | .326 |
| LVH | 127 (46.18) | 83 (52.53) | 26 (38.24) | .128 |
| Diastolic dysfunction | 99 (36.00) | 45 (28.48) | 14 (20.59) | .030* |
| Pericardial effusion | 59 (21.45) | 42 (26.58) | 13 (19.12) | .351 |
| AR | 80 (29.09) | 75 (47.47) | 28 (41.18) | .000*,* |
| AOD (mm) | 29.000 (27.0, 31.0) | 29.500 (27.0, 32.0) | 29.000 (28.0, 31.0) | .385 |
| LAD (mm) | 37.000 (32.0, 42.0) | 39.000 (34.0, 44.0) | 43.500 (36.0, 48.0) | .000*,* |
| LVDD (mm) | 53.000 (49.0, 57.0) | 55.000 (50.8, 60.0) | 57.000 (51.3, 62.0) | .000*,* |
| LVSD (mm) | 33.000 (29.0, 37.0) | 36.000 (31.0, 41.3) | 39.000 (33.0, 45.0) | .000*,* |
| ISV (mm) | 12.000 (12.0, 13.0) | 13.000 (12.0, 14.0) | 13.000 (12.0, 13.9) | .017 * |
| LVHM (mm) | 12.000 (12.0, 13.0) | 12.000 (12.0, 13.0) | 12.000 (12.0, 13.0) | .171 |
| RVSD (mm) | 21.000 (19.0, 22.0) | 22.000 (20.0, 24.0) | 25.000 (23.0, 26.0) | .000*,* |
| RVOT (mm) | 28.000 (26.0, 30.0) | 28.000 (26.0, 31.0) | 29.000 (27.0, 32.8) | .021 * |
| MPAD (mm) | 26.000 (24.0, 28.0) | 27.000 (24.0, 30.0) | 28.000 (25.3, 30.0) | .000*,* |
| LVFS (%) | 37.000 (33.0, 41.0) | 34.000 (30.0, 39.0) | 32.000 (25.3, 35.8) | .000*,* |
| LVEF (%) | 67.000 (61.0, 72.0) | 63.000 (56.8, 68.3) | 59.000 (49.3, 64.0) | .000*,* |
| SV (mL) | 87.000 (75.0, 102.0) | 88.500 (76.8, 107.3) | 89.000 (73.0, 105.0) | .478 |
| CO (L/min) | 6.900 (5.7, 8.3) | 7.250 (5.7, 8.6) | 7.350 (5.7, 9.0) | .252 |
| LVEDV (mL) | 134.000 (112.0, 159.0) | 146.500 (124.8, 183.3) | 160.500 (130.8, 192.8) | .000*,* |
AOD = aortic inner diameter, AR = aortic regurgitation, CHD = coronary heart disease, CO = left ventricular volume, IVS = interventricular septal, LAD = left atrial diameter, LVDD = left ventricular end-diastolic diameter, LVDS = left ventricular end-systolic diameter, LVEDV = left ventricular end-diastolic volume, LVEF = left ventricular ejection fraction, LVFS = left ventricular short axis shortening rate, LVHM = left ventricular posterior wall thickness, LVM = left ventricular hypertrophy, MPAD = the main pulmonary artery diameter, RVOT = right ventricular outflow tract inside diameter, RVSD = right ventricular end-systolic diameter, SV = left ventricular stroke volume.
P < .05 variables into class Logist after single factor regression into multiple regression. Results show RVDS (OR = 1.183, 95% CI 1.078–1.298, P < .001 and OR = 1.607, 95% CI 1.413–1.829, P < .001) was associated with a significant moderate PH and high PH group, LAD (OR = 1.060, 95% CI 1.004–1.120, P = .035) and high PH group significantly correlated (see Table 5).
Table 5.
Multivariable univariate and multivariate regression analysis of PH-related risk factors in 501 patients with AVF/AVG [cases (%)].
| Variable | Single factor regression analysis | Multiple factors regression analysis | ||||||
|---|---|---|---|---|---|---|---|---|
| Moderate PH group | High PH group | Moderate PH group | High PH group | |||||
| OR (95% CI) | P | OR (95% CI) | P | OR (95% CI) | P | OR (95% CI) | P | |
| Diastolic dysfunction | 0.708 (0.463–1.082) | .111 | 0.461 (0.244–0.872) | .017* | – | – | – | – |
| AR | 2.203 (1.467–3.307) | 0*,* | 1.706 (0.986–2.953) | .056 | – | – | – | – |
| LAD (mm) | 1.059 (1.027–1.091) | 0*,* | 1.117 (1.073–1.162) | 0*,* | 1.023 (0.984–1.063) | .252 | 1.06 (1.004–1.120) | .035 * |
| LVDD (mm) | 1.053 (1.024–1.083) | 0*,* | 1.07 (1.030–1.111) | 0*,* | 1.023 (0.965–1.085) | .444 | 1.006 (0.934–1.083) | .885 |
| LVSD (mm) | 1.058 (1.031–1.087) | 0*,* | 1.088 (1.053–1.125) | 0*,* | 0.977 (0.921–1.036) | .441 | 0.971 (0.903–1.045) | .431 |
| VSI (mm) | 1.147 (1.018–1.293) | .025* | 1.132 (0.979–1.307) | .094 | – | – | – | – |
| RVSD (mm) | 1.24 (1.137–1.353) | 0*,* | 1.7 (1.505–1.920) | 0*,* | 1.183 (1.078–1.298) | 0*,* | 1.607 (1.413–1.829) | 0*,* |
| RVOT (mm) | 1.045 (0.987–1.107) | .132 | 1.144 (1.063–1.230) | 0*,* | – | – | – | – |
| MPAD (mm) | 1.131 (1.067–1.199) | 0*,* | 1.168 (1.086–1.256) | 0*,* | 1.058 (0.986–1.136) | .119 | 1.002 (0.910–1.104) | .962 |
| LVFS (%) | 0.954 (0.930–0.978) | 0*,* | 0.925 (0.898–0.954) | 0*,* | 1.016 (0.956–1.080) | .603 | 0.998 (0.917–1.085) | .96 |
| LVEF (%) | 0.957 (0.938–0.976) | 0*,* | 0.93 (0.908–0.954) | 0*,* | 0.95 (0.897–1.006) | .077 | 0.945 (0.878–1.017) | .133 |
| LVEVD (mL) | 1.009 (1.004–1.014) | 0*,* | 1.012 (1.006–1.019) | 0*,* | 1 (0.991–1.008) | .923 | 1 (0.989–1.012) | .976 |
AOD = aortic inner diameter, AR = aortic regurgitation, CHD = coronary heart disease, CO = left ventricular volume, IVS = interventricular septal, LAD = left atrial diameter, LVDD = left ventricular end-diastolic diameter, LVDS = left ventricular end-systolic diameter, LVEDV = left ventricular end-diastolic volume, LVEF = left ventricular ejection fraction, LVFS = left ventricular short axis shortening rate, LVHM = left ventricular posterior wall thickness, LVM = left ventricular hypertrophy, MPAD = the main pulmonary artery diameter, RVOT = right ventricular outflow tract inside diameter, RVSD = right ventricular end-systolic diameter, SV = left ventricular stroke volume.
4. Discussion
Previous research has revealed that patients with renal insufficiency with common PH, its associated factors including GFR lower, age, anemia, etc, at the same time associated with deterioration of chronic kidney disease. Study also found that compared with patients with hemodialysis, peritoneal dialysis in patients with a lower incidence of PH, but about different pathway in patients with PH and the incidence of actual comparison is unclear.
At the same time, maintaining hemodialysis patients exists generally consistent with other literature reports of LVH[19,20] diastolic dysfunction,[21] and the characteristics of pericardial effusion.[22] Chronic volume overload, high blood pressure, high output internal fistula, anemia, and uremic toxin accumulation are the cause of maintenance hemodialysis patients LVH.[23] PH moderate possibility, and reached the highest proportion of patients with LVH and possibility to high PH, the proportion of patients with LVH declined obviously. LVH is characterized by cardiac structural changes, such as collagen accumulation, fibrosis, and calcification, cause the systolic and diastolic dysfunction.[24] It is important to note that the ratio of diastolic dysfunction in patients with continues to decline, and as early as before the left ventricular systolic function decline, although did not reach statistical significance, but in the transformation of LVH to contraction dysfunction is still hard to distinguish between process. However, we speculate that in the formation of the PH and driven by ERSD diastolic function decline may represent heart failure by the centrality to gradually dilated phenotypic change early in the development of heart failure.
At present, there are few studies on the maintenance of pericardial effusion in hemodialysis centers. The research thinks, myocardial cell edema is one of the important mechanisms of pericardial effusion and PH,[25] pericardial effusion may be associated with venous return pressure,[26] also may be associated with uremia caused by pericarditis.[27,28] Anemia is a critical complication of dialysis patients with ESRD, can lead to various diseases and systemic hypoxia. Lower hemoglobin or red blood cells can be induced by hypoxia, pulmonary vascular smooth muscle proliferation.[29] Kidney epo to reduce and iron deficiency is associated with elevated levels of the element iron, restrain bowel transportation and intake of iron.[30] Iron deficiency may affect pulmonary vascular function through hypoxia-inducible factors. Hemoglobin < 10 g/dL, the risk of chronic kidney disease/and anemia in patients with ESRD PH significantly.[31] Although this review did not clarify the causal relationship between PH and anemia or ferritin, previous studies have shown that patients with PH have lower levels of iron and hemoglobin.[32]
Currently, the standard of care for patients initiating hemodialysis follows the “fistula first” principle, which considers arteriovenous fistulas as the preferred dialysis route, followed by arteriovenous AVG. Compared with CVC, AVF/AVG has a lower rate of infection, hospitalization and mortality. Compared with the AVG, AVF needs less intervention measures to maintain patency, and may have a longer servicelife of the function.[33]
According to KIDOGO guidelines, in patients with fistula is regarded as the preferred path, CVC should not be used for long-term hemodialysis treatment. This proposal is based on the previous research found that CVC use could lead to infection and hospitalization rates increase, such as inadequate dialysis poor prognosis. In practice, however, some patients based on personal willingness and vascular conditions, retained the CVC as long-term vascular access. For PH patients with CVC, their disease status and characteristics were reflected without the use of AVG/AVF. Despite a drop in PH prevalence, but still relatively normal crowd of PH is elevatory, why still need to further clarify.
Through the analysis, the results showed that with the increase of PH, CVC pathway in patients with AO, LAD, LVDD, LDDS, RVDS, SV, CO, EDV index gradually rise. Increase phenomenon in a at the same time, the left ventricle, left ventricular function indicators LVFS, LVEF have fallen, but showed no significant difference. Continues to decline, the proportion of left ventricular diastolic dysfunction presents the LAD continues to increase and the characteristics of SV continuous increase of left ventricular remodeling. In the later stage, RV was significantly enlarged. These cardiac characteristic changes indicate that the development of PH in CVC hemodialysis patients is closely related to left heart related factors, and the volume load aggravates the development of PH.
PH associated with left heart disease is the most common form of PH,[34] which is also divided into postcapillary or the second category of PH,[35] that is, heart failure with preserved ejection fraction occurs in the later stage, and obvious RV expansion and decompensation of the right ventricle occur, which is common after the increase of volume load. Left heart failure is one of the most common causes of PH.[36] PH is one of the important reasons lead to right heart failure.[37] We know that PH–HFpEF is the main mechanism of diastolic stiffness,[38] atrial myopathy is more likely to turn into atrial fibrillation[39] and left atrial functional mitral insufficiency,[40] and PH–HFrEF hemodynamic driver is LV expansion, secondary mitral insufficiency and left atrial.[41]Central venous catheter pathway, therefore, the patients of PH overload capacity and its long-term average. Although hemodialysis may alleviate short-term volume overload, more attention should be paid to volume management during non-dialysis hours. In addition, the toxin of uremic patients and dialysis process itself, as a result of hemodynamic changes are will increase the damage of cardiac cells in ischemia and oxidative stress. After the long-term course of uremic cardiomyopathy is still difficult to avoid.[42]
In patients with PH, the use of AVF/AVG pathways of patients with the increase of pulmonary artery pressure, the diastolic function of normal proportion gradually reduce, AOD, LAD, LVDD, LVDS, RVDS, RVOTD, main pulmonary artery diameter (MPAD), SV, CO, LVEDV increased, but the LVFS and LVEF is on the decline. Compared with patients with CVC, AVF/AVG in patients with LVH is low, the proportion of the AOD, LVDD, LVEDV, RVDS, RVOTD, and CO increased more obviously, and left entricular function LVFS and reduced LVEF are significant, although only RVDS statistically significant, But late LAD and PH levels may exist independently. This study reveals the AVF/AVG in patients with PH is closely related to the expansion of the RV, major effect the RV and internal fistula, and the influence of left atrial is gradually appeared in the late. It has also been found in other studies that the progression of PH leads to RV enlargement and right ventricular systolic dysfunction.[43] Related research has been focused on that, after the establishment in the AVF/AVG form directly link between systemic and pulmonary circulation, impact on left and right ventricle. In terms of systemic circulation, it is manifested as a decrease in diastolic blood pressure; in terms of pulmonary circulation, is characterized by pulmonary pressure. Cardiac structural changes can reflect the cause of PH. Studies have found that PH after AVF/AVG is closely related to right ventricular structural changes, but further investigation is needed.
Artery–vein connection may lead to “short circuit” of blood flow, because blood flow from the fistula does not promote tissue perfusion. When arterial resistance decreases, CO and ventricular work increase, and venous return increases, aggravating the volume load.[44] Three-dimensional echocardiography can measure RVEF, but it is load-dependent and cannot solely evaluate myocardial contractility. Three-dimensional echocardiography can measure RVEF, but it is load-dependent and cannot solely evaluate myocardial contractility.[43] Morphological changes in the RV are an important aspect of RV remodeling. Pulmonary hypertension causes interventricular septal curvature abnormalities, and when RV pressure exceeds LV pressure by 5 mm Hg, the septum significantly shifts.[45] Right heart function including the RV and RA function.[46] Loss of right ventricular function is closely related to poor prognosis, which may not be linked to increased afterload but independently associated with poor outcomes.[47] Loss of right ventricular function is closely related to poor prognosis, which may not be linked to increased afterload but independently associated with poor outcomesd.[48]
In this study, we found that patients treated with central venous catheter is exist in PH cases, but the overall prevalence of PH lower than patients treated using AVF. At present, the research on maintenance hemodialysis lead to PH prevalence, there is no literature for different pathways. After adjusting for patient data, we found that the incidence of PH in patients treated with AVF was significantly higher than that in patients treated with central venous catheter. Central venous catheter to treat patients with PH may be associated with basic diseases lead to overload capacity, through the control volume, perhaps can relieve or reverse cardiac structure deterioration, but also must recognize that some patients with PH is the likely cause of the sustained progress in other unknown factors, especially the study found that patients with central venous catheter PH is associated with the RV to expand. Along with the increase of PH, the RV enlargement, mean PH may lead to the right ventricle structural abnormalities, including tricuspid regurgitation and RVDS increases. Given the number of patients with central venous catheter treatment to reduce gradually, can provide information and materials co., Ltd., the specific mechanism remains to be further discussed in animal model studies.
4.1. Limitations
This study has several limitations. It is a single-center, cross-sectional analysis based on retrospective data, which may introduce selection bias and limit generalizability. Causality between vascular access type and PH cannot be established. Echocardiography, though practical, is not the gold standard for PH diagnosis, and right heart catheterization was not available. Additionally, some potentially relevant indicators, such as BNP levels and longitudinal follow-up data, were not included. Despite applying multiple imputation and FDR correction, residual confounding may still exist. Prospective, multicenter studies are needed to validate these findings and clarify the impact of vascular access on PH progression.
5. Conclusion
This study retrospectively analyzed 10 years of single-center data to compare the prevalence of PH in patients with different types of hemodialysis access, and to explore the associated cardiac structural differences induced by each access pathway. The findings suggest that PH is highly prevalent among maintenance hemodialysis patients, and is closely related to volume overload, the type of vascular access, and right ventricular enlargement. AVF/AVG may lead to direct right ventricular dilation, increasing both pressure and volume load, thereby elevating the risk of PH. Although the “Fistula First” principle remains the standard recommendation in renal replacement therapy, in specific high-risk populations (such as patients with right ventricular dilation (RVDS > 25 mm), moderate to severe PH, severe illness, or limited life expectancy) careful evaluation of the benefit-risk ratio of AVF/AVG is warranted. In such cases, the use of tunneled CVC may be a reasonable alternative. Future prospective, multicenter studies are needed to confirm these findings and to further compare the long-term cardiovascular outcomes associated with different vascular access strategies in patients at risk of PH.
Acknowledgments
We appreciate the guidance and strong support of our mentors and departmental colleagues during the research and collaboration on this paper.
Author contributions
Conceptualization: Jingwen Zhou.
Data curation: Jingwen Zhou.
Formal analysis: Jingwen Zhou.
Writing – original draft: Jingwen Zhou.
Writing – review & editing: Jingwen Zhou.
Abbreviations:
- AVF
- autogenous arteriovenous fistula
- AVG
- arteriovenous graft
- CVC
- central vein catheter
- ESRD
- end-stage renal disease
- FDR
- false discovery rate
- LAD
- left atrial diameter
- LVEF
- left ventricular ejection fraction
- PH
- pulmonary hypertension
- PASP
- pulmonary artery systolic pressure
- RAP
- right atrial pressure
The author has no funding and conflicts of interest to disclose.
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
How to cite this article: Zhou J. Prevalence and risk factors of pulmonary hypertension in maintenance hemodialysis patients based on echocardiography. Medicine 2026;105:7(e43845).
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