Predicting Mortality in Hemodialysis Patients
The protocol of this study was approved by the Ethics Committee of University Hospital 'Dr C.I.Parhon' (Iasi, Romania). Between 26 May 2011 and 3 July 2012, we invited all patients undergoing chronic HD treatment for at least 3 months in a single unit to take part in this study. Exclusion criteria were age under 18 years; systemic infections and terminal neoplasia; metallic joint prostheses, cardiac pacemakers or stents; decompensated cirrhosis and limb amputations—since accurate bioimpedance evaluation cannot be performed in patients with these conditions.
There were 122 patients who fulfilled the pre-specified inclusion criteria; 12 patients were excluded because of limb amputation (N = 6), decompensated cirrhosis (N = 2) or presence of a cardiac pacemaker or stent (N = 4). Fourteen additional patients did not accept to be included in the study. Details of the final patient population (N = 96) are presented in Table 1. HD therapy was performed 4 h × three times per week, using high-flux Fresenius Polysulfone® membrane dialyzers (FX60). Biochemical parameters were determined on the first Monday (or Tuesday) of each month, pre-dialysis, after the long interval of dialysis.
Echographic examinations were performed after a short dialysis period, with patients in the near-to-supine or supine positions. Measurements were performed starting 15–20 min before dialysis, and 35 min after dialysis. Ultrasound scanning of the anterior and lateral chest was obtained on the right and left haemithorax, from the second to the fifth (on the left side to the fourth) intercostal spaces and from the parasternal to the midaxillary line for a total of 28 positions per examination, as was previously described.
The comet-tail sign was defined as an echogenic, coherent, wedge-shaped signal with a narrow origin in the near field of the image. In each intercostal space, the number of comet-tail signs was recorded at the parasternal, midclavear, anterior axillary and midaxillary sites. At every scanning site, ultrasound lung comets (ULC) could be counted from 0 to 10. Zero is defined as a complete absence of ULC in the investigated area, while the full white screen is considered, when using a cardiac probe, as corresponding to 10 lung comets. The sum of the comet-tail signs yielded a score denoting the extent of extravascular fluid in the lung.
On the basis of this score, we grouped the patients into three categories of increasingly severe pulmonary congestion (none or mild: <16 comets, moderate: 16–30 comets and severe: >30 comets).
The hydration state and the body composition were assessed using a portable whole body bioimpedance spectroscopy device (BCM—Fresenius Medical Care D GmbH). This device measures the impedance spectroscopy at 50 frequencies. Measurements were performed before the start and 30 min after the end of the HD treatment. This technique involves attaching electrodes to the patient's non-fistula forearm and ipsilateral ankle, with the patient in a supine position. All measurements were performed by two trained physicians.
The extracellular water (ECW), intracellular water (ICW) and TBW were determined as previously described. To facilitate the comparison between patients, the hydration state was normalized to the ECW (ΔHS = HS/ECW). The patient population was divided into a hyperhydrated, normohydrated and hypohydrated groups using a cut-off of 15% for the relative hydration status. The definition of hyperhydration for ΔHS >15% is based on the work described by Wabel et al. and Wizemann et al..
Echocardiographic evaluations were made in each patient after a short dialysis period, starting 40 min before dialysis. All echocardiographic measurements were carried out according to the recommendations of the American Society of Echocardiography by an observer unaware of the lung ultrasound and bioimpedance results.
Data are expressed as mean ± SD, median and inter-quartile range or as percent frequency, as appropriate. Comparisons among groups were made by P-value for linear trend (one-way analysis of variance or χ test). Among patients, comparisons were made by the paired t-test (normally distributed data) or by the Wilcoxon signed-rank test (non-normally distributed data). Correlations between the variables were investigated by the Pearson product moment correlation coefficient or by the Spearman rank correlation coefficient, as appropriate. Kaplan–Meier and Cox regression analysis were used to investigate the prognostic value of the lung comets score for predicting mortality. In this analysis, the backward stepwise (Wald) method was applied to phase out factors that did not have a significant influence on survival. We obtained the best multivariate model [Hosmer–Lemeshow tests—χ = 6.51, df = 8, P = 0.59, 95% confidence interval (95% CI)]. The contribution of covariates explaining the dependent variable was assessed by the Wald test, with a P-value of <0.05 considered as significant. To avoid the problem of overfitting due to the low number of incident outcomes, we performed bootstrapping validation, in order to determine the confidence intervals for estimating β in the Cox proportional hazard regression. After resampling, the Hosmer–Lemeshow analysis demonstrated that the model obtained using the backward stepwise (Wald) method was correctly selected (χ = 9.06, df = 8, P = 0.34, 95% CI). All calculations were made using a standard statistical package (SPSS for Windows, version 19.0.1, Chicago, IL).
Methods
Patients
The protocol of this study was approved by the Ethics Committee of University Hospital 'Dr C.I.Parhon' (Iasi, Romania). Between 26 May 2011 and 3 July 2012, we invited all patients undergoing chronic HD treatment for at least 3 months in a single unit to take part in this study. Exclusion criteria were age under 18 years; systemic infections and terminal neoplasia; metallic joint prostheses, cardiac pacemakers or stents; decompensated cirrhosis and limb amputations—since accurate bioimpedance evaluation cannot be performed in patients with these conditions.
There were 122 patients who fulfilled the pre-specified inclusion criteria; 12 patients were excluded because of limb amputation (N = 6), decompensated cirrhosis (N = 2) or presence of a cardiac pacemaker or stent (N = 4). Fourteen additional patients did not accept to be included in the study. Details of the final patient population (N = 96) are presented in Table 1. HD therapy was performed 4 h × three times per week, using high-flux Fresenius Polysulfone® membrane dialyzers (FX60). Biochemical parameters were determined on the first Monday (or Tuesday) of each month, pre-dialysis, after the long interval of dialysis.
Lung Comets
Echographic examinations were performed after a short dialysis period, with patients in the near-to-supine or supine positions. Measurements were performed starting 15–20 min before dialysis, and 35 min after dialysis. Ultrasound scanning of the anterior and lateral chest was obtained on the right and left haemithorax, from the second to the fifth (on the left side to the fourth) intercostal spaces and from the parasternal to the midaxillary line for a total of 28 positions per examination, as was previously described.
The comet-tail sign was defined as an echogenic, coherent, wedge-shaped signal with a narrow origin in the near field of the image. In each intercostal space, the number of comet-tail signs was recorded at the parasternal, midclavear, anterior axillary and midaxillary sites. At every scanning site, ultrasound lung comets (ULC) could be counted from 0 to 10. Zero is defined as a complete absence of ULC in the investigated area, while the full white screen is considered, when using a cardiac probe, as corresponding to 10 lung comets. The sum of the comet-tail signs yielded a score denoting the extent of extravascular fluid in the lung.
On the basis of this score, we grouped the patients into three categories of increasingly severe pulmonary congestion (none or mild: <16 comets, moderate: 16–30 comets and severe: >30 comets).
Bioimpedance Spectroscopy
The hydration state and the body composition were assessed using a portable whole body bioimpedance spectroscopy device (BCM—Fresenius Medical Care D GmbH). This device measures the impedance spectroscopy at 50 frequencies. Measurements were performed before the start and 30 min after the end of the HD treatment. This technique involves attaching electrodes to the patient's non-fistula forearm and ipsilateral ankle, with the patient in a supine position. All measurements were performed by two trained physicians.
The extracellular water (ECW), intracellular water (ICW) and TBW were determined as previously described. To facilitate the comparison between patients, the hydration state was normalized to the ECW (ΔHS = HS/ECW). The patient population was divided into a hyperhydrated, normohydrated and hypohydrated groups using a cut-off of 15% for the relative hydration status. The definition of hyperhydration for ΔHS >15% is based on the work described by Wabel et al. and Wizemann et al..
Echocardiography
Echocardiographic evaluations were made in each patient after a short dialysis period, starting 40 min before dialysis. All echocardiographic measurements were carried out according to the recommendations of the American Society of Echocardiography by an observer unaware of the lung ultrasound and bioimpedance results.
Statistical Analysis
Data are expressed as mean ± SD, median and inter-quartile range or as percent frequency, as appropriate. Comparisons among groups were made by P-value for linear trend (one-way analysis of variance or χ test). Among patients, comparisons were made by the paired t-test (normally distributed data) or by the Wilcoxon signed-rank test (non-normally distributed data). Correlations between the variables were investigated by the Pearson product moment correlation coefficient or by the Spearman rank correlation coefficient, as appropriate. Kaplan–Meier and Cox regression analysis were used to investigate the prognostic value of the lung comets score for predicting mortality. In this analysis, the backward stepwise (Wald) method was applied to phase out factors that did not have a significant influence on survival. We obtained the best multivariate model [Hosmer–Lemeshow tests—χ = 6.51, df = 8, P = 0.59, 95% confidence interval (95% CI)]. The contribution of covariates explaining the dependent variable was assessed by the Wald test, with a P-value of <0.05 considered as significant. To avoid the problem of overfitting due to the low number of incident outcomes, we performed bootstrapping validation, in order to determine the confidence intervals for estimating β in the Cox proportional hazard regression. After resampling, the Hosmer–Lemeshow analysis demonstrated that the model obtained using the backward stepwise (Wald) method was correctly selected (χ = 9.06, df = 8, P = 0.34, 95% CI). All calculations were made using a standard statistical package (SPSS for Windows, version 19.0.1, Chicago, IL).
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