Original Report: Patient-Oriented, Translational Research American
Journal of
Nephrology
Am J Nephrol 2011;34:407–414 DOI: 10.1159/000331700
Received: July 23, 2011 Accepted: August 8, 2011 Published online: September 21, 2011
Hemodialysis Reduces Augmentation Index but Not Aortic or Brachial Pulse Wave Velocity in Dialysis-Requiring Patients Panagiotis I. Georgianos Pantelis A. Sarafidis Pavlos Malindretos Pavlos Nikolaidis Anastasios N. Lasaridis Section of Nephrology and Hypertension, First Department of Medicine, AHEPA University Hospital, Thessaloniki, Greece
Key Words Hemodialysis ⴢ Arterial stiffness ⴢ Wave reflections ⴢ Pulse wave velocity
Abstract Background/Aims: Arterial stiffening characterizes the vasculature of end-stage renal disease (ESRD) patients and is a strong predictor of their cardiovascular morbidity and mortality. Previous studies evaluating the effect of hemodialysis on large artery elasticity gave contradictory results. This study aimed to investigate the impact of hemodialysis on arterial stiffness and wave reflections on chronic hemodialysis patients. Methods: A total of 51 stable ESRD patients on maintenance hemodialysis were evaluated before and after the first and second dialysis session of the week. Arterial stiffness was assessed by measuring aortic and brachial pulse wave velocity (PWV). Central arterial pressure waveform parameters were estimated by radial artery applanation tonometry. Heart rate-adjusted augmentation index [AIx(75)] was used as measure of wave reflections. Results: During both dialysis sessions systolic blood pressure (SBP) and pulse pressure (PP) at brachial artery and central aorta were reduced. AIx(75) was decreased in first and second weekly dialysis session (27.5 8 1.2 vs. 21.0 8 1.5, p ! 0.001 and 24.7 8 1.2 vs. 20.5 8 1.5, p ! 0.001, respectively). In contrast, aortic
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and brachial PWV remained unchanged during both dialysis sessions. Changes in AIx(75) during hemodialysis were associated with changes in central aortic SBP, PP and ejection duration. Conclusions: This study shows that hemodialysis does not acutely affect arterial stiffness, but reduces wave reflections from periphery. This dissociation between effects of hemodialysis on PWV and AIx(75) may reflect differential impact on large and small branches of the arterial tree. Copyright © 2011 S. Karger AG, Basel
Introduction
Cardiovascular disease represents the major cause of morbidity and mortality in patients with end-stage renal disease (ESRD) [1, 2]. Previous animal experiments suggested increased stiffening of the aorta and the large central arteries in renal failure [3] and clinical studies have shown that ESRD patients have reduced aortic compliance as compared with age- and blood pressure (BP)matched individuals with normal renal function [4]. Arterial stiffness and intensity of wave reflections are considered the most important determinants of systolic BP (SBP) and pulse pressure (PP) and were shown to play a pivotal role in the pathogenesis of isolated systolic hypertension and left ventricular hypertrophy in these patients Pantelis A. Sarafidis, MD, MSc, PhD First Department of Medicine, AHEPA Hospital, Aristotle University of Thessaloniki St. Kiriakidi 1 GR–54636 Thessaloniki (Greece) Tel. +30 2310 994 616, E-Mail psarafidis11 @ yahoo.gr
[5]. Most importantly, several longitudinal studies have demonstrated the strong and independent predictive value of arterial stiffness for total and cardiovascular mortality in the general population as well as in patients with ESRD [6, 7]. Apart from the increased burden of traditional cardiovascular risk factors, a number of functional alterations associated with chronic kidney disease have been proposed as additional mechanisms for the accelerated arteriosclerosis in such patients [8, 9]. These mechanisms include increased vascular calcification due to elevated calcium-phosphate product, chronic volume overload, activation of the renin-angiotensin system, endothelial dysfunction, subclinical vascular inflammation and oxidant stress [8, 9]. However, the question whether renal replacement treatment per se affects large artery elasticity and reflecting properties of peripheral sites in ESRD patients on maintenance hemodialysis remains largely unanswered. Early studies that investigated the acute impact of hemodialysis on these parameters suffered from important methodological limitations, as they used older versions of the devices available for noninvasive estimation of arterial stiffness; thus, these studies evaluated only the effect of hemodialysis on central BP and augmentation index (AIx), that are rather indirect measurements of arterial stiffness, without simultaneous assessment of aortic pulse wave velocity (PWV) [10, 11]. Further, clinical studies that included aortic PWV measurements gave largely contradictory results. In some of these aortic PWV was shown to remain unchanged during the dialysis session [12, 13], whereas in others hemodialysis was associated with a significant increase or decrease [14, 15] in aortic PWV. In addition, in most of the previous studies of the field, parameters of arterial stiffness were evaluated only before and after the completion of a single mid-week dialysis session [10, 13–15], whereas the impact of first dialysis session of the week was poorly investigated. Therefore, the aim of this study was to investigate in detail the effects of the first (after a 3-day interdialytic interval) and the second (mid-week) dialysis sessions on arterial stiffness and central arterial pressure waveform parameters in ESRD patients on maintenance hemodialysis. Material and Methods Study Population All ESRD patients receiving chronic hemodialysis treatment in the Hemodialysis Unit, First Department of Medicine, AHEPA
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University Hospital were invited to participate in this study. Inclusion criteria were (a) ESRD under standard renal replacement treatment with 3 dialysis sessions per week; (b) patient at hemodialysis for at least 3 months prior to study enrollment; (c) patient to have provided informed written consent. Exclusion criteria were: (a) regular episodes of hemodynamic instability on dialysis (symptomatic dialysis hypotension requiring intravenous saline infusion in greater than 5% of dialysis session during the previous 6 months); (b) history of chronic atrial fibrillation or other chronic arrhythmia; (c) history of myocardial infarction or unstable angina in the 3 previous months; (d) history of transient ischemic attack in the 3 previous months; (e) stage III–IV congestive heart failure, according to the New York Heart Association classification; (f) evidence of peripheral vascular disease; (g) history of malignancy or any other clinical condition associated with poor prognosis; (h) presence of old artery-vein anastomoses for earlier arteriovenous fistula formation at an arm different than the one currently used for dialysis access. A total of 51 chronic hemodialysis patients fulfilled the inclusion and exclusion criteria and participated in the study. All patients were dialyzed with standard bicarbonate hemodialysis solutions and synthetic dialyzers, with blood flow rates of 300–350 ml/min and dialysate flow rates of 500–800 ml/min, aiming at a dialysis dose Kt/V 1 1.2. The study protocol was approved by the Ethics Committee of the Medical School of Aristotle University of Thessaloniki and the study was conducted between November 2009 and June 2010. All protocol procedures were conducted in accordance with the Declaration of Helsinki (2000 Amendment) and all subjects provided informed written consent prior to study enrollment. Study Protocol Screening evaluation included a full medical history, physical examination and standard laboratory tests. All eligible patients were studied on the first dialysis day of the week (Monday or Tuesday, after a 3-day interdialytic interval) as well as on the mid-week dialysis day (Wednesday or Thursday, after a 2-day interdialytic interval). At each day patients were evaluated 1 h before the initiation of the dialysis session, without having received their morning medication. Body weight and height were measured and body mass index was calculated as weight divided by height squared. Peripheral BP recordings at the brachial artery level were taken at the arm not used for dialysis access, using a conventional sphygmomanometer. Central aortic BP and parameters of arterial stiffness and wave reflections were determined by performing applanation tonometry of peripheral arteries, using a Sphygmocor device. All measurements were performed in a quiet room with controlled air temperature (approximately 22 ° C). Then, patients underwent the respective regular dialysis session, during which fluid loss was programmed according to their routine dry weight, set by standard clinical criteria. After the completion of the dialysis session all the above measurements were repeated.
Assessments Peripheral BP. Peripheral BP at the level of the brachial artery was measured with a conventional sphygmomanometer in the sitting posture after a 10-min rest. Three BP measurements with at least 1-min interval between them in the non-fistula arm were obtained. Phase V Korotkoff sound was recorded for diastolic BP (DBP).
Georgianos/Sarafidis/Malindretos/ Nikolaidis/Lasaridis
Pulse Wave Velocity. The SphygmoCor device (PWV and BP analysis system, ArtCor, Sydney, Australia) was used to obtain the arterial pulse waveforms and to assess aortic and brachial PWV. Pulse waveforms were obtained by performing applanation tonometry at the carotid, radial (non-fistula side) and femoral arteries. With this technique [16, 17], the artery is pressed gently against a hard underground (bone) with a pencil-type probe that incorporates a high-fidelity strain-gauge transducer with a small pressure-sensitive ceramic sensor area at the tip (SPT-301, Millar Instruments). To determine PWV, we recorded pressure waves at two sites sequentially: carotid-femoral for aortic PWV and carotid-radial for the brachial PWV. Wave transit time was calculated by the system software, using the R-wave of a simultaneously recorded electrocardiogram as reference frame. The distance traveled by the pulse wave was measured over the body surface as the distance between the recording sites at the femoral or radial artery to the suprasternal notch minus the distance from the recording site at the carotid artery to the suprasternal notch (D), as previously described [16, 17]. PWV was calculated as PWV = D/t, where t is the transit time of pulse wave between the recording sites. We measured PWV over 10 consecutive heartbeats to cover a complete respiratory cycle. The average of 3 valid measurements was used in our analysis. Pulse Wave Analysis. Radial artery pressure waveform was recorded by performing applanation tonometry with the penciltype probe described above (SPT-301, Millar Instruments). Central aortic pressure waveform was constructed with a validated radial-to-aortic transfer function from the radial artery pressure waveform (Sphygmocor, ArtCor, Sydney Australia), assuming a similar mean arterial pressure throughout the arterial tree, as previously described elsewhere [16, 17]. Brachial artery pressures were used for the calibration of central aortic pressures, assuming radial SBP and DBP to be equal to brachial SBP and DBP [16, 17]. The average of 3 valid recordings was used in our statistical analysis. The AIx was calculated as the difference between the second and the first systolic peaks, expressed as percentage of the central aortic PP [16, 17]. The subendocardial viability index was estimated as a measure of the balance between the cardiac oxygen supply and demand and was calculated as the ratio of diastolic pressure time index/systolic tension time index [18]. Statistical Analysis Statistical analysis was performed using the Statistical Package for Social Sciences (SPSS) version 17.0 for Windows XP (SPSS Inc., Chicago, Ill., USA). Continuous variables were expressed as mean 8 standard deviation. For comparisons between the beginning and the end of the dialysis session paired t tests or Wilcoxon’s Signed Rank tests were used, according to the normality of the distribution. For comparisons between the first and the second dialysis session of the week independent sample t tests or Mann Whitney U tests were used, according to the normality of the distribution. To identify possible relationships between the changes in the parameters under study during the dialysis session, bivariate correlation coefficients (r) were calculated using the Pearson’s product formula. A p value level !0.05 (two-tailed) was considered statistically significant.
Effect of Hemodialysis on Arterial Cushioning Function
Table 1. Demographic and predialysis biochemical characteristics of study participants
n Age, years Sex (M/F) BMI Duration on dialysis, months Hemoglobin, g/dl Serum urea, mg/dl Serum creatinine, mg/dl Total protein, g/dl Serum albumin, g/dl Total cholesterol, mg/dl LDL cholesterol, mg/dl HDL cholesterol, mg/dl Triglycerides, mg/dl
51 55.0814.5 35/16 24.883.9 48.1863.5 13.7817.6 146.7836.6 8.982.6 7.280.6 4.280.4 156.1833.1 83.3827.7 43.3816.1 156.6881.8
Data are presented as number or mean 8 SD. BMI = Body mass index; LDL = low-density lipoprotein; HDL = high-density lipoprotein.
Results
Baseline demographic and predialysis biochemical characteristics of study participants are depicted in table 1. The average age of study participants was 55.0 8 14.5 years, and time on dialysis was 48.1 8 63.5 months. With regards to the etiology of ESRD, 11 patients had diabetic nephropathy, 13 patients had hypertensive nephrosclerosis, 14 patients had chronic glomerulonephritis, 5 patients had polycystic kidney disease, 3 patients had obstructive uropathy and 5 patients had unknown cause of ESRD. As shown in table 2, body weight was significantly reduced in both dialysis sessions. As expected, however, intradialytic weight loss and ultrafiltration rate were significantly higher in the first dialysis session of the week as compared to the second (mid-week) dialysis session (–2.8 8 0.2 vs. –1.8 8 0.3 kg, p ! 0.001 and 0.99 8 0.1 vs. 0.72 8 0.1 kg/h, p ! 0.05, respectively). Between the start and the end of both the first and the second weekly dialysis session, significant reductions in SBP and PP at the level of the brachial artery were evident (table 2). However, the relevant reductions in brachial DBP were not statistically significant. In addition, a significant increase in heart rate before and after the dialysis sessions was noted. Hemodialysis exerted also a favorable impact on central hemodynamic parameters at both time-points studied. Central aortic SBP and PP levels were significantly reduced after both dialysis sessions, Am J Nephrol 2011;34:407–414
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Table 2. Effect of the first and the second dialysis session of the week on peripheral and central hemodynamic parameters
Parameter
First HD session (n = 51)
Body weight, kg Brachial SBP, mm Hg Brachial DBP, mm Hg Brachial PP, mm Hg Central aortic SBP, mm Hg Central aortic DBP, mm Hg Central aortic PP, mm Hg Heart rate, bpm Ejection duration, ms SEVI, %
before HD
after HD
73.081.4 143.582.7 77.281.7 66.282.4 131.582.5 78.181.7 53.382.2 69.081.4 38.380.5 122.582.8
70.381.2 138.783.2 76.881.9 61.982.7 12583.1 77.781.9 47.282.3 72.181.5 34.580.6 156.584.4
Second HD session (n = 51) p value
