Edited by: Janusz Witowski, Poznan University of Medical Sciences, Poland
Reviewed by: Kevin Woollard, Imperial College London, United Kingdom; Bruno Vogt, University of Bern, Switzerland
†These authors have contributed equally to this work
This article was submitted to Integrative Physiology, a section of the journal Frontiers in Physiology
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Carotid intima media thickness (cIMT) displays prognostic value as a marker of cardiovascular risk in dialysis patients. However, few data are available regarding the impact of dialysis modality on cIMT. The aim of this study is to determine whether the modality of dialysis influences cIMT values. We compared 237 peritoneal dialysis (PD) and 451 hemodialysis (HD) patients without previous cardiovascular disease included in NEFRONA, a prospective, observational and multicenter study. This cross sectional study included the determination of cIMT in 6 carotid territories by arterial ultrasound. cIMT was determined in territories without atheroma plaque and averaged. A second analysis was performed using all territories, giving a truncated cIMT value of 1,5 mm to territories presenting with atheroma plaque. Age and plaque presence at baseline were the clinical variables more closely associated to cIMT in dialysis patients. The evaluation of the impact of the modality of dialysis on cIMT showed that PD patients had lower cIMT than HD patients, both in territories with no plaques and when using truncated cIMT values. No differences were found between right and left sides, neither in cIMT or truncated cIMT values. Lineal multivariate analysis adjusted by several clinical variables showed a statistically significant association of PD with a lower cIMT (slope -0.036; SD 0.010). These results were also confirmed when truncated cIMT values were used. We conclude that the modality of dialysis has an impact on cITM. HD patients have greater global cIMT than PD patients, and PD is and independent factor associated with a lower cIMT.
In the last 35 years, the incidence of end-stage renal disease (ESRD) has raised dramatically. ESRD patients have a 5-year survival probability of 50% (
Traditional risk factors are not useful to predict CVE on dialysis patients. The use of the traditional algorithms in risk stratification in CKD consistently underestimate the risk of the CKD patients of having a CVE (
There are significant differences between both modalities of dialysis. PD patients have a potentially higher atherogenic profile than their counterparts on HD, due to the recurrent peritoneal loading with glucose-based dialysis solutions, and to the continuous peritoneal leak of proteins. On the contrary, HD patients show a worse preservation of residual kidney function, which may contribute to inflammation, endothelial dysfunction and vascular calcification. Moreover, PD is associated with a stable fluid status and blood pressure pattern compared to periodic fluctuations found in HD. Therefore, the modality of dialysis itself could have a differential effect on cIMT determining factors.
With the aim of shedding some light on this clinical concern, we evaluated cIMT in a selected sub-cohort of the NEFRONA study, in order to determine whether the modality of dialysis influences cIMT.
The ethics committee of University Hospital Arnau de Vilanova from Lleida, Spain, approved the study. All included patients signed informed consent and the study complied with the principles of the Declaration of Helsinki.
The NEFRONA project is a prospective, multicentre, observational cohorts study from Spain aimed to assess the atherosclerotic burden in CKD patients, including patients with ESRD. The rationale and baseline description of NEFRONA cohort have been reported in detail elsewhere. (
At recruitment, patients were asked to complete a questionnaire including family history regarding premature CVD, clinical history (diabetes, hypertension and dyslipidaemia), cardiovascular risk factors (such as smoking habit), and medication use. Anthropometric data and medical history were also obtained from all patients at the time of recruitment. Biochemical data were obtained from a routine blood test 3 months either before or after the vascular ultrasound. For HD patients, blood samples were retrieved just before the second session of the week. High-sensitivity C reactive protein (hsCRP), 25-hydroxy-vitamin D and 1,25-hydroxy-vitamin D were quantified in a centralized laboratory. ABI measurements were performed with a protocol previously described (
Patients underwent B-mode ultrasound in both carotid arteries with the Vivid BT09 device (General Electric Instruments, Freiburg, Germany) and a 6–13 MHz broadband linear array probe. For imaging, patients were in supine position with the head turned 45° contralateral to the side of the probe. cIMT was measured in the last centimeter of the far wall of the common carotid artery, the bulb section and in the first centimeter of the internal carotid artery. Measurements were made in plaque-free arterial segments. Atheromatous plaque, following the recommendations of the ASE Consensus Statement (
Ultrasound explorations were carried out by the same itinerant team of five trained technicians. Images were analyzed by a single reader in a blinded fashion using the EchoPAC Dimension software (General Electric Healthcare, Harten, Norway) in the UDETMA (Unit for the Detection and Treatment of Atherothrombotic Diseases, Hospital Universitari Arnau de Vilanova, Lleida, Spain). To assess the quality of the measurements a sample of 20 individuals was measured 3–5 times on different days, obtaining an intraclass correlation coefficient of 0.93.
Quantitative variables are shown as means and standard deviations, and its differences between groups were compared with the Student’s
A total of 451 HD and 237 PD patients were included. Table
Demographic data.
HD ( |
PD ( |
||
---|---|---|---|
Age (years) | 54 (14) | 51 (14) | 0,004 |
Sex (man) | 272 (60,3) | 137 (57,8) | 0,567 |
Smoker | 250 (55,4) | 135 (57,0) | 0,381 |
Diabetes | 107 (23,7) | 47 (19,8) | 0,143 |
Hypertension | 406 (90,0) | 229 (96,6) | 0,001 |
Dyslipidemia | 214 (47,5) | 153 (64,6) | 0,000 |
Plaque presence at baseline | 325 (72,1) | 156 (65,8) | 0,054 |
BMI (kg/m2) | 26,3 (5,0) | 26,7 (4,8) | 0,341 |
SBP (mmHg) | 136 (23) | 144 (24) | 0,000 |
Time on dialysis (months) | 33 (43) | 20 (19) | 0,000 |
Total cholesterol (mg/dL) | 156 (39) | 180 (43) | 0,000 |
HDL cholesterol (mg/dL) | 46 (16) | 49 (15) | 0,016 |
LDL cholesterol (mg/dL) | 84 (32) | 104 (34) | 0,000 |
Triglycerides (mg/dL) | 141 (81) | 137 (66) | 0,498 |
Glucose (mg/dL) | 103 (40) | 101 (37) | 0,526 |
Hematocrite (%) | 35,7 (4,3) | 36,6 (4,4) | 0,013 |
Calcium (mg/dL) | 9,0 (0,7) | 9,2 (0,7) | 0,005 |
Phosphate (mg/dL) | 4,8 (1,4) | 5,1 (1,2) | 0,008 |
Uric acid (mg/dL) | 6,1 (1,4) | 6,0 (1,2) | 0,22 |
iPTH (pg/mL) | 309 (281) | 277 (255) | 0,164 |
Sodium (mEq/L) | 139 (3) | 139 (3) | 0,036 |
Potassium (mEq/L) | 5,1 (0,8) | 4,5 (0,6) | 0,000 |
usCRP (mg/L) | 5,6 (10,7) | 6,1 (13,9) | 0,624 |
25OH vitamin D (ng/mL) | 16,4 (8,3) | 12,8 (5,5) | 0,000 |
1,25(OH)2 vitamin D (pg/mL) | 8,6 (5,1) | 7,7 (4,8) | 0,039 |
Treatment with Calcium-containing P binders | 186 (41,2) | 119 (50,2) | 0.015 |
Total Kt/V | 1,56 (0,39) | 2,52 (0,63)∗ | NC |
Calcium content in dialysis fluid | 0.001 | ||
2.5 mEq/L | 182 (41,9) | 72 (35.8) | |
3 mEq/L | 221 (50,9) | NA | |
3,5 mEq/L | 31 (7,1) | 129 (64.2) |
Variables influencing cIMT on dialysis patients.
Figure
Averaged intima media thickness in carotid arterial territories depending on the dialysis modality.
Among all clinical and biochemical variables considered, the ones more closely related to cIMT were age and plaque presence at baseline, both positively correlated (Table
Statistically significant correlations between different parameters and cIMT values.
IMT |
IMT truncated |
|||
---|---|---|---|---|
Sex (women) | −0.138 | 0.000 | −0.137 | 0.000 |
Age | 0.545 | 0.000 | 0.613 | 0.000 |
BMI | 0.232 | 0.000 | 0.233 | 0.000 |
Diabetes | 0.213 | 0.000 | 0.271 | 0.000 |
Dyslipidemia | 0.077 | 0.049 | 0.129 | 0.001 |
ABI | 0.082 | 0.037 | 0.137 | 0.000 |
Phosphate | −0.086 | 0.027 | ||
Potassium | 0.112 | 0.004 | 0.130 | 0.001 |
Glucose | 0.122 | 0.002 | 0.158 | 0.000 |
Plaque presence at baseline | 0.421 | 0.000 | 0.663 | 0.000 |
Type of dialysis (PD) | −0.165 | 0.000 | −0.130 | 0.001 |
When patients were stratified according to sex and age, the relationship of these variables to cIMT was clearly visible, with cIMT values increasing with age (showing a statistically significant
Averaged intima media thickness in carotid arterial territories stratified by age and sex. Dark bars: Males; White bars: Females.
Averaged intima media thickness in carotid arterial territories stratified by side. Dark bars: HD patients; White bars: PD patients.
To better assess the influence of dialysis type on cIMT, we generated different models by means of lineal multivariate analysis. Univariate regression assessing the effect of dialysis type on cIMT showed a statistically significant association of PD with a lower cIMT value. (Table
Lineal multivariate analysis.
Model 1 |
Model 2 |
Model 3 |
|||||||
---|---|---|---|---|---|---|---|---|---|
Slope | Slope | Slope | |||||||
Type of dialysis (DP vs. HD) | −0.051 | 0.012 | 0.000 | −0.034 | 0.010 | 0.001 | −0.033 | 0.010 | 0.001 |
Sex (women vs. men) | −0.041 | 0.010 | 0.000 | −0.036 | 0.010 | 0.000 | |||
Age (year) | 0.013 | 0.001 | 0.000 | 0.004 | 0.000 | 0.000 | |||
Hypertension | 0.041 | 0.017 | 0.016 | ||||||
Plaque presence at baseline | 0.036 | 0.012 | 0.002 | ||||||
Diabetes | 0.033 | 0.012 | 0.006 | ||||||
Type of dialysis (DP vs. HD) | −0.084 | 0.025 | 0.001 | −0.041 | 0.019 | 0.033 | −0.044 | 0.017 | 0.008 |
Sex (women vs. men) | −0.076 | 0.019 | 0.000 | −0.038 | 0.017 | 0.023 | |||
Age (year) | 0.005 | 0.000 | 0.000 | 0.008 | 0.001 | 0.000 | |||
BMI | 0.004 | 0.002 | 0.019 | ||||||
SBP (mmHg) | 0.001 | 0.000 | 0.005 | ||||||
Plaque presence at baseline | 0.269 | 0.021 | 0.000 | ||||||
Diabetes | 0.063 | 0.020 | 0.002 |
Our results show that on dialysis patients, cIMT values correlate to gender, age, plaque presence at baseline, BMI and diabetes. In non-dialysis population, previous studies also found association of cIMT with age and sex (
Currently, studies about dialysis impact on ultrasound measured cIMT have shown contradictory results. Despite all studies have found higher cIMT on dialysis patients than in non-dialysis population,(
Recently, the same NEFRONA cohort with a matched case-control design revealed that the modality of dialysis did not influence atheromatous vascular disease progression (assessed as an increase in the number of atheromatous plaques) neither did cardiovascular outcomes (
The possible causes of higher cIMT in HD patients than in PD patients are unknown. However, it is well stablished that hypertension, and particularly blood pressure variability (BPV), plays a major role in cIMT increase (
There is growing evidence that calcium supplements can increase atherosclerotic CVE (
Another risk factor for atherosclerosis development is hypertension (
Our results also show that there are no differences between left and right sides in cIMT neither, in PD nor HD patients. Several reports have shown a significantly higher proportion of cerebral ischemic events diagnosed in the left hemisphere than in the right (
Strengths of our study are the relatively high number of patients being, as far as we know, the biggest cohort used to determine the effects of dialysis on cIMT. Therefore, we have been able to adjust the models for many potential confounders. Furthermore, and although the study is multicentric, the execution and the analysis of the ultrasounds have been made by a single team, avoiding the high variability associated to the cIMT measurements. On the other hand, we have to mention some limitations. First, the exclusion of patients that presented CVE on the recruitment phase avoid extrapolating our results to the entire ESRD population. Second, we only have a single BP measurement and no fluid status data that could support the hypothesis that higher BPV in HD patients may be related to thicker cIMT. Third, the lack of determinations of cardiovascular biomarkers that could affect cIMT like pro-BNP or troponins, preclude us to determine whether the effect of dialysis modality is related to these biomarkers or to some other factor.
In summary, we have shown that cIMT is higher in HD than in PD and that being in PD is an independent risk factor associated with lower cIMT in dialysis patients.
MeB, EF, ÀB, and JV designed the study. SC, MP-F, and JV analyzed the data. MC-M, MiB, and MB-L performed the experiments. JV wrote the manuscript.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
The authors would like to thank the NEFRONA team (Eva Castro, Virtudes María, Teresa Molí, Teresa Vidal, Meritxell Soria) and the Biobank of RedInRen for their invaluable support. The NEFRONA study investigator group is composed by the following: Aladrén Regidor, Ma José. Hospital Comarcal Ernest Lluch (Calatayud); Almirall, Jaume; Ponz, Esther. Corporació Parc Taulí (Barcelona); Arteaga Coloma, Jesús. Hospital de Navarra (Pamplona); Bajo Rubio, Ma Auxiliadora; Díaz, Raquel Hospital La Paz (Madrid); Belart Rodríguez, Montserrat. Sistemes Renals (Lleida); Gascón, Antonio, Hospital Obispo Polanco (Teruel); Bover Sanjuan, Jordi. Fundació Puigvert. IIB Sant Pau (Barcelona); Bronsoms Artero, Josep. Clínica Girona (Girona); Cabezuelo Romero, Juan B; Muray Cases, Salomé. Hospital Reina Sofía (Murcia); Calviño Varela, Jesús. Hospital Universitario Lugus Augusti (Lugo); Caro Acevedo, Pilar. Clínica Ruber (Madrid); Carreras Bassa, Jordi. Diaverum Baix Llobregat (Barcelona); Cases Amenós, Aleix; Massó Jiménez, Elisabet. Hospital Clínic (Barcelona); Moreno López, Rosario. Hospital de la Defensa (Zaragoza); Cigarrán Guldris, Secundino; López Prieto, Saray. Hospital Da Costa (Lugo); Comas Mongay, Lourdes. Hospital General de Vic (Barcelona); Comerma, Isabel. Hospital General de Manresa (Barcelona); Compte Jové, Ma Teresa, Hospital Santa Creu Jesús (Tarragona); Cuberes Izquierdo, Marta. Hospital Reina Sofía (Navarra); de Álvaro, Fernando; Hevia Ojanguren, Covadonga. Hospital Infanta Sofía (Madrid); de Arriba de la Fuente, Gabriel. Hospital Universitario Guadalajara (Guadalajara); del Pino y Pino, Ma Dolores. Complejo Hospitalario Universitario Torrecardenas (Almería); Diaz-Tejeiro Izquierdo, Rafael; Ahijado Hormigos, Francisco Hospital Virgen de la Salud (Toledo); Dotori, Marta. USP Marbella (Málaga); Duarte, Verónica. Hospital de Terrassa (Barcelona); Estupiñan Torres, Sara. Hospital Universitario Canarias (Santa Cruz de Tenerife); Fernández Reyes, Ma José. Hospital de Segovia (Segovia); Fernández Rodríguez, Ma Loreto. Hospital Príncipe de Asturias (Madrid); Fernández, Guillermina. Clínica Santa Isabel (Sevilla); Galán Serrano, Antonio. Hospital General Universitario de Valencia (Valencia); García Cantón, Cesar. Hospital Universitario Insular de Gran Canaria (Las Palmas); García Herrera, Antonio L. Hospital Universitario Puerto Real (Cádiz); García Mena, Mercedes. Hospital San Juan de Dios (Zaragoza); Gil Sacaluga, Luis; Aguilar, Maria. Hospital Virgen del Rocío (Sevilla); Górriz, José Luis. Hospital Universitario Doctor Peset (Valencia); Huarte Loza, Emma. Hospital San Pedro (Logroño); Lerma, José Luis. Hospital Universitario Salamanca (Salamanca); Liebana Cañada, Antonio. Hospital de Jaén (Jaén); Marín Álvarez, Jesús Pedro. Hospital San Pedro de Alcántara (Cáceres); Martín Alemany, Nàdia. Hospital Josep Trueta (Girona); Martín García, Jesús. Hospital Nuestra Señora de Sonsoles (Ávila); Martínez Castelao, Alberto. Hospital Universitari de Bellvitge (Barcelona); Martínez Villaescusa, María. Complejo Hospitalario Universitario de Albacete (Albacete); Martínez, Isabel. Hospital Galdakao (Bilbao); Moina Eguren, Iñigo. Hospital Basurto (Bilbao); Moreno Los Huertos, Silvia. Hospital Santa Bárbara (Soria); Mouzo Mirco, Ricardo. Hospital El Bierzo, Ponferrada (León); Munar Vila, Antonia. Hospital Universitari Son Espases (Palma de Mallorca); Muñoz Díaz, Ana Beatriz. Hospital Virgen del Consuelo (Valencia); Navarro González, Juan F. Hospital Universitario Nuestra Señora de Candelaria (Santa Cruz de Tenerife); Nieto, Javier; Carreño, Agustín. Hospital General Universitario de Ciudad Real (Ciudad Real); Novoa Fernández, Enrique. Complexo Hospitalario de Ourense (Ourense); Ortiz, Alberto; Fernandez, Beatriz. IIS-Fundación Jiménez Díaz (Madrid); Paraíso, Vicente. Hospital Universitario del Henares (Madrid); Pérez Fontán, Miguel. Complejo Hospitalario Universitario A Coruña (A Coruña); Peris Domingo, Ana. Hospital Francesc de Borja (Valencia); Piñera Haces, Celestino. Hospital Universitario Marqués de Valdecilla (Santander); Prados Garrido, Ma Dolores. Hospital Universitario San Cecilio (Granada); Prieto Velasco, Mario. Hospital de León (León); Puig Marí, Carmina. Hospital d’Igualada (Barcelona); Rivera Gorrín, Maite. Hospital Universitario Ramón y Cajal (Madrid); Rubio, Esther. Hospital Puerta del Hierro (Madrid); Ruiz, Pilar. Hospital Sant Joan Despí Moisès Broggi (Barcelona); Salgueira Lazo, Mercedes; Martínez Puerto, Ana Isabel. Hospital Virgen Macarena (Sevilla); Sánchez Tomero, José Antonio. Hospital Universitario de la Princesa (Madrid); Sánchez, José Emilio. Hospital Universitario Central de Asturias (Oviedo); Sans Lorman, Ramon. Hospital de Figueres (Girona); Saracho, Ramon. Hospital de Santiago (Vitoria); Sarrias, Maria; Serón, Daniel. Hospital Universitari Vall d’Hebron (Barcelona); Soler, María José; Barrios, Clara. Hospital del Mar (Barcelona); Sousa, Fernando. Hospital Rio Carrión (Palencia); Toran, Daniel. Hospital General de Jerez (Cadiz); Tornero Molina, Fernando. Hospital de Sureste (Arganda del Rey); Usón Carrasco, José Javier. Hospital Virgen de la Luz (Cuenca); Valera Cortes, Ildefonso. Hospital Virgen de la Victoria (Málaga); Vilaprinyo del Perugia, Ma Merce. Institut Catala d’Urologia i Nefrologia (Barcelona); Virto Ruiz, Rafael C. Hospital San Jorge (Huesca); Vicente Pallarés Carratalá Clinica MEDEFIS (Vila-real. Castellón), Carlos Santos Altozano CS Azuqueca de Henares (Guadalajara); Miguel Artigao Ródenas CS Zona III (Albacete); Inés Gil Gil Área Básica Sanitaria de Arán. CAP Viella (Lleida); Francisco Adan Gil CS Alfaro (La Rioja); Emilio García Criado Centro de Salud del Carpio (Córdoba.); Rafael Durá Belinchón CS Godella (Valencia); Jose Ma Fernández Toro CS Zona Centro (Cáceres); Juan Antonio Divisón Garrote Centro de Salud de Casas Ibáñez. Consultorio de Fuentealbilla (Albacete).