1Department of Nephrology-Dialysis and 2Department of Cardiology, Silvestrini Hospital, Perugia, Italy
Correspondence and offprint requests to: Riccardo Maria Fagugli, MD, S. C. Nefrologia e Dialisi, Ospedale Silvestrini, Azienda Ospedaliera di Perugia, S. Andrea delle Fratte, 06100 Perugia, Italy. Email: rmfag{at}tin.it
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Abstract |
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Methods. Hypertension was determined according to the WHO criteria (office BP 140/90 and/or the use of antihypertensive therapy). Twenty-four hour BP monitoring and echocardiography were performed on midweek inter-HD days. Blood chemistries, dialysis dose (spKt/V) and bioimpedance were analysed on midweek HD days.
Results. Hypertension was present in 74.5% of patients. There were no differences for age, spKt/V, haemoglobin, serum creatinine and residual renal function between normotensive and hypertensive patients. Twenty-four hour systolic BP (SBP), 24 h diastolic BP and 24 h pulse pressure were higher in hypertensive patients, in spite of antihypertensive therapy. LVH was present in 61.8% of patients. BIA revealed that ECW% was increased in LVH+ patients (LVH+ = 47.5 ± 7.9%, LVH = 42.4 ± 6.2%, P = 0.01) and in hypertensive patients compared with normotensives (46.5 ± 7.7% vs 43 ± 7.2%, P = 0.02). Dry body weights and inter-HD body weight increases did not differ between hypertensive and normotensive patients nor between patients with or without LVH. ECW was correlated with SBP (r = 0.35, P < 0.01) and with left ventricular mass index (LVMig/sqm) (r = 0.49, P < 0.001). A stepwise multiple linear regression model revealed that LVMig/sqm was significantly correlated with ECW%, SBP and male gender (r = 0.65, P < 0.001).
Conclusions. LVH and hypertension are present in a majority of HD patients and they are closely correlated with one another. We found associations between fluid load, measured by BIA and expressed as ECW, and BP and LVM.
Keywords: extracellular water; haemodialysis; hypertension; left ventricular hypertrophy
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Introduction |
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Patients and methods |
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Hypertension was determined according to the WHO criteria (office BP140/90 and/or the use of antihypertensive therapy). Blood chemistries were determined at the beginning of midweek HD sessions. On the same day, body composition was studied by BIA at 20 min after the end of dialysis. On the following midweek inter-HD day, 24 h ambulatory BP monitoring and echocardiography were performed. These examinations were performed using the following methods.
Blood chemistries
Haemoglobin, uric acid, serum urea and serum creatinine were determined using standard procedures.
Office pre-HD blood pressure (OBP)
During the month before ambulatory monitoring, OBP values were recorded at the beginning of each HD session by expert dialysis technicians. Each value was derived from the mean of three consecutive measurements. The mean of 12 such values, monitoring a period of 1 month, was designated as OBP.
Ambulatory blood pressure measurement (ABPM)
ABPM was recorded on inter-HD days using an A&D Takeda TM2421 (A&D, Tokyo, Japan) [7]. BP readings were taken at 15 min intervals from 7 a.m. to 10 p.m. for awake BP and at 30 min intervals from 10 p.m. to 7 a.m. for asleep BP. ABPM recordings having >10% of values missing were excluded from the study. Dipper patients were classified as having night-time systolic BP (SBP) decreases of at least 10% compared to the daytime values. The SBP night/day (N/D) ratio was also calculated.
Echocardiography
Standard two-dimensional and two-dimensional-guided M-mode echocardiography was performed with a Sonolayer SSA-270 (Toshiba, Nasu, Japan) using a 3.75 MHz transducer. Echocardiograms were taken according to the American Society of Echocardiography guidelines on inter-HD midweek days. We measured left ventricle internal diastolic diameter (LViDD), diastolic posterior wall thickness (PWT) and interventricular septum thickness (IVS).
LVM was calculated using the Devereux formula [8]: LVM (g) = 0.8 x 1.04 x [(LviDD + IVS + PWT)3 LviDD3] + 0.6. LVMi was calculated by dividing LVM by body surface area. Sex-specific criteria were used to determine the presence of LVH (males, LVMi 131 g/m2; females, LVMi
100 g/m2) [9].
Relative wall thickness (RWT) was calculated using the following formula: RWT = (2 x PWT)/LViDD; values of >0.45 in the presence of LVH suggested left ventricular concentric hypertrophy. Fractional shortening (FS%), a measure of left ventricle function, was calculated as follows: FS% = [LViDD LViSD (left ventricle internal systolic diameter)] x 100/LViDD. Systolic dysfunction was defined as FS < 25%.
Bioimpedance measurements
Impedance measurements were performed at the bedside according to standard, tetrapolar, whole-body (handfoot) techniques using a single-frequency (50 kHz) analyser (BIA-101; AkernRJL Systems, Florence, Italy). Although there may be differences between multi-frequency and single-frequency BIA determinations of total body water (TBW) and related parameters [10], previous studies failed to detect significant improvements from single to multiple frequency (5, 50, 100, 500 and 1000 kHz) analysers in the measurement of total body resistance (R) and reactance (Xc) [11,12]. Therefore, we performed single-frequency measurements with the same operator at 20 min after midweek HD. R and Xc values were collected and used in specific formulas supplied by the manufacturer [1315] to determine TBW, body cell mass (BCM) and ECW, which was reported as a percentage of TBW. In order reveal any potential flaws associated with the equations, we also reported R, Xc and PA (the arc tangent of the Xc/R ratio). When using a 50 kHz fixed-frequency BIA device, R is related to TBW, and Xc is related to ECW [16]; a decrease in PA, which captures the relative contribution of Xc and R, is the consequence of cell membrane reduction [17].
Statistical analysis
Results are expressed as means ± SD. Unpaired Students t-tests and MannWhitney tests were used when applicable to investigate differences between hypertensive and normotensive patients and between patients with and without LVH. The 2 test was used to analyse non-parametric data. Pearsons correlation coefficients and multiple linear regression analysis were used to identify the possible determinants of hypertension and LVMi. Multiple stepwise linear regression was performed using LVMi as the dependent variable and gender, age, HD age, Kt/V, haemoglobin, 24 h SBP and ECW% as independent variables. The variables entered in multiple linear regression to predict LVMi were tested after studying simple regression analysis. Two-tailed P-values of <0.05 were considered to be significant.
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Results |
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Of the hypertensive patients, 20.7% were kept off pharmacological treatment, 24.5% were treated with only one drug, and the remaining patients were given a combination of antihypertensive drugs. Angiotensin-converting enzyme inhibitors were prescribed to 22% of patients, calcium channel blockers to 52.4%, ß-adrenergic-receptor blockers to 15.9%, -ß-adrenergic blockers to 18.8%, central
-agonists to 34.1% and direct vasodilators to 3.7%. There were no differences in epoeitin treatment between hypertensive and normotensive patients (84.5 ± 79 vs 83.1 ± 72.6 IU/kg/week). BIA revealed that Xc was lower in hypertensive patients than in normotensives (49.5 ± 12 vs 57 ± 16.3
, P = 0.01), whereas ECW% was higher in hypertensives (46.5 ± 7.7 vs 43 ± 7.2, P = 0.02). We found no differences for TBW% (hypertensives, 55.9 ± 6.4; normotensives, 55.6 ± 6.1) or BCM% (hypertensives, 33.8 ± 7.8; normotensives, 35.5 ± 6.9). dBw and inter-HD body weight increases (
Bw) did not differ between hypertensive and normotensive patients (dBw, 65.5 ± 11.7 vs 61.1 ± 13.4 kg;
Bw, 2.63 ± 1.02 vs 2.64 ± 1.26 kg). ECW was correlated with the age of patients (r = 0.29, P < 0.01), SBP (r = 0.35, P < 0.01) and PP (r = 0.34, P < 0.001).
LVH was present in 61.8% of patients, 37 male and 31 female (Table 1). The pattern of LVH was eccentric in 73.5% of cases. The length of HD treatment, in months, did not differ between patients with (+) or without () LVH (29.3 ± 43.8 vs 31.6 ± 34.5 months). There were no differences between LVH+ and LVH patients for residual renal function (LVH+, 0.87 ± 1.77 ml/min; LVH, 1.18 ± 1.51 ml/min), spKt/V, haemoglobin, or uric acid (Table 2). SBP, DBP, PP and the SBP N/D ratio were significantly higher in LVH+ patients (Table 3). BIA revealed decreases in Xc and PA and an increase in ECW% in LVH+ patients (Table 4). The two groups were not different for dBw (LVH+, 63.1 ± 11.9 kg; LVH, 66.4 ± 12.5 kg) or Bw (LVH+, 2.57 ±1.14 kg; LVH, 2.73 ± 0.97 kg).
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Discussion |
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Several studies with renal patients have investigated the relationship between hypertension and fluid or salt overload. Blumberg et al. [18], >30 years ago, realized that there was a strong association between fluid overload and hypertension. Since then, a large number of studies have examined this topic. Özkahya et al. [19] demonstrated that narrow control of sodium intake combined with strict ultrafiltration produced reductions in dBw, in BP and, consequently, in the need for antihypertensive drugs. Rahman et al. [20] reported that high interdialytic weight gains were correlated with high BP. Chen et al. [21], while measuring ECW%, observed that hypertensive HD patients had higher levels of ECW compared with their normotensive counterparts and that a reduction of ECW performed in a restricted group of over-hydrated hypertensive patients was accompanied by a decrease in BP. Other studies seem to confirm the observation that a reduction in ECW causes normalization of BP in HD patients, or at least a better control of BP. The long HD sessions used by Charra et al. [22] appeared, at least in part, to produce optimal BP control as a consequence of fluid overload reduction. Katzarski et al. [23] studied hypertensive and normotensive patients on standard (4 h thrice-weekly) and long-term (8 h thrice-weekly) HD while using BIA and measuring inferior vena cava diameters. Hypertensive patients on standard HD showed increases in ECW compared with their normotensive counterparts and with patients on long-term HD; the same pattern of results was demonstrated for inferior vena cava diameters. In another study, short daily HD sessions normalized BP in >90% of patients, and the reductions in BP and LVMi were closely correlated with reductions in fluid overload measured by BIA as ECW [24]. Therefore, since reductions in fluid overload appear to be crucial for the control of cardiovascular complications in HD patients, instruments are needed that could allow assessment of true dBw. Clinical approaches for estimating dry weight are often unsatisfatory, because many factors can induce measurement errors such as lean body mass reduction, intra-HD hypotension due to cardiac dysfunction, or altered increases in total peripheral resistance and venous capacity [25]. Spiegel et al. [26], using BIA in patients that achieved clinically determined ideal dBw, observed that 50% of these showed increased volumes. This observation indicates that HD patients frequently do not reach a physiologic dBw and that methods other than clinical determination are needed to assess fluid overload. Although biochemical markers, such as atrial natriuretic peptide or cyclic guanidine monophosphate, represent a sensible method for assessing overload, there are specific limitations, such as congestive heart failure, tricuspid and mitral valve disease and altered left atrial haemodynamics. In addition, these markers require a sophisticated and expensive technology available to only a few centres, making their determination unsuitable for routine clinical use. The measurement of inferior vena cava, although widely available, is affected by inter-operator error and shows large variability [27].
BIA of body composition may provide an easy, cheap and a widely distributed tool for the study of fluid overload in HD patients. This technology is based on the assumption that the conduction of current through the human body is characterized by two components: R due to water and ions and Xc due to the capacitor property of cellular membranes. BIA seems to be useful in the assessment of dBw in HD patients. ECW reduction during HD sessions correlates significantly with ultrafiltrate removal and changes in body weight [21]. A recent study by Cooper et al. [6] demonstrated that TBW estimated by BIA did not differ significantly from estimations using D2O dilution, which is the gold standard for water measurements.
Our study, by using BIA determinations of ECW, confirmed previous reports of an association between fluid load and hypertension, supporting the hypothesis that hypertension is strongly associated with ECW increases in HD patients. The prevalence of hypertension in our patients was not different from that generally observed in HD populations, and our patients had high BP values even though they were treated with antihypertensive drugs. With the increase in HD age, we observed a tendency for better BP control, which may be explained by progressive reductions in fluid overload or decreases in left ventricular function.
We found that volume overload was linked not only with hypertension but also with LVH. This link with ventricular hypertrophy is a novel finding and is consistent with the observation that LVMi was correlated not only with BP but also with ECW. The finding that LVH was eccentric in the majority of patients confirms that the increase in LVMi was related to volume overload, which itself is the cause of both hypertension and LVH. This observation is in line with the findings of Hart et al. [28], who assessed the role of volume overload in the aetiopathogenesis of early LVH in the general population. In contrast to what was observed for BP values, we do not report a correlation between LVMi and dialysis history, which is in line with the observations of Foley et al. [29], who observed a progressive cardiac enlargement and LVH after dialysis onset, particularly during the first year of HD therapy.
We also analysed haemoglobin to assess the role of this risk factor in the development of LVH. We found that anaemia was not a relevant risk factor for LVH, which may be due to haemoglobin levels that were corrected to a target range resulting in no difference between the normotensive and hypertensive groups. However, there is controversy over the role of anaemia in LVH. For example, Foley et al. [30] failed to find a regression with LVH after correction of anaemia with epoietin .
In conclusion, our study confirmed the association between ECW, a derived parameter of BIA measurements, and BP. More importantly, we also found that fluid load was associated with left ventricular mass in HD patients. BIA may thus be considered a useful tool that is inexpensive and simple to use for the clinical diagnosis of fluid overload in HD patients.
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Acknowledgments |
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Conflict of interest statement. None declared.
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References |
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