Longitudinal bioimpedance vector plots add little value to fluid management of peritoneal dialysis patients
Authors: Boon K. Tan, Zanzhe Yu, Wei Fang, Aiwu Lin, Zhaohui Ni, Jiaqi Qian, Graham Woodrow, Sarah B. Jenkins, Martin E. Wilkie, Simon J. Davies
Journal: Kidney International (2015)

Bioimpedance (BI) has the potential to enable better management of fluid balance, which can worsen over time on peritoneal dialysis (PD) due to loss of residual kidney function and progressive muscle wasting. We undertook a prospective, randomized, open-label, blinded end-point controlled trial to determine whether availability of longitudinal BI measures as vector plots helped clinicians maintain stable fluid status over 12 months in 308 peritoneal dialysis patients from the United Kingdom and Shanghai, China. Patients were recruited into 4 groups nested within a single trial design according to country and residual kidney function. Nonanuric subjects from both countries demonstrated stable fluid volumes irrespective of randomization. Hydration worsened in control anuric patients in Shanghai with increased extracellular/total body water (ECW/TBW) ratio (0.04; 95% CI: 0.01, 0.06) and reduced TBW (−1.76 L 95% CI: −2.70, −0.82), but was stable in the BI intervention group whose dialysate glucose prescription was increased. However, multilevel analysis incorporating data from both countries showed worsening ECW/TBW in active and control anuric patients. Clinicians in the United Kingdom reduced target weight in the nonanuric BI intervention group causing a reduction in TBW without beneficial effects on ECW or blood pressure. Thus, routine use of longitudinal BI vector plots to improve clinical management of fluid status is not supported. Bioimpedance (BI) has the potential to enable better management of fluid balance, which can worsen over time on peritoneal dialysis (PD) due to loss of residual kidney function and progressive muscle wasting. We undertook a prospective, randomized, open-label, blinded end-point controlled trial to determine whether availability of longitudinal BI measures as vector plots helped clinicians maintain stable fluid status over 12 months in 308 peritoneal dialysis patients from the United Kingdom and Shanghai, China. Patients were recruited into 4 groups nested within a single trial design according to country and residual kidney function. Nonanuric subjects from both countries demonstrated stable fluid volumes irrespective of randomization. Hydration worsened in control anuric patients in Shanghai with increased extracellular/total body water (ECW/TBW) ratio (0.04; 95% CI: 0.01, 0.06) and reduced TBW (−1.76 L 95% CI: −2.70, −0.82), but was stable in the BI intervention group whose dialysate glucose prescription was increased. However, multilevel analysis incorporating data from both countries showed worsening ECW/TBW in active and control anuric patients. Clinicians in the United Kingdom reduced target weight in the nonanuric BI intervention group causing a reduction in TBW without beneficial effects on ECW or blood pressure. Thus, routine use of longitudinal BI vector plots to improve clinical management of fluid status is not supported. Optimal fluid management is one of the primary objectives of dialysis treatment, and there is significant concern that peritoneal dialysis (PD) patients can become progressively fluid-loaded with time on treatment, especially as residual kidney function declines.1Van Biesen W. Williams J.D. Covic A.C. et al.Fluid status in peritoneal dialysis patients: the European Body Composition Monitoring (EuroBCM) study cohort.PLoS One. 2011; 6: e17148Crossref PubMed Scopus (195) Google Scholar, 2Tan B.K. Chan C. Davies S.J. et al.Achieving euvolemia in peritoneal dialysis patients: a surprisingly difficult proposition.Semin Dial. 2010; 23: 456-461Crossref PubMed Scopus (17) Google Scholar There is a growing body of evidence that bioimpedance (BI) analysis has a role to play in assisting the clinician in managing fluid status;3Davies S.J. Davenport A. The role of bioimpedance and biomarkers in helping to aid clinical decision-making of volume assessments in dialysis patients.Kidney Int. 2014; 86: 489-496Abstract Full Text Full Text PDF PubMed Scopus (210) Google Scholar this is primarily based on observational studies showing that overhydration, as determined from BI, predicts worse survival4Pillon L. Piccoli A. Lowrie E.G. et al.Vector length as a proxy for the adequacy of ultrafiltration in hemodialysis.Kidney Int. 2004; 66: 1266-1271Abstract Full Text Full Text PDF PubMed Scopus (99) Google Scholar, 5Paniagua R. Ventura M.-J. Avila-Díaz M. et al.NT-proBNP, fluid volume overload and dialysis modality are independent predictors of mortality in ESRD patients.Nephrol Dial Transplant. 2010; 25: 551-557Crossref PubMed Scopus (189) Google Scholar and the demonstration that BI can detect changes following interventions designed to improve fluid status.6Davies S.J. Woodrow G. Donovan K. et al.Icodextrin improves the fluid status of peritoneal dialysis patients: results of a double-blind randomized controlled trial.J Am Soc Nephrol. 2003; 14: 2338-2344Crossref PubMed Scopus (306) Google Scholar, 7Machek P. Jirka T. Moissl U. et al.Guided optimization of fluid status in haemodialysis patients.Nephrol Dial Transplant. 2010; 25: 538-544Crossref PubMed Scopus (175) Google Scholar BI data comprise the following two components: resistance to an electrical current, typically passed through the body from the wrist to the ankle, which is inversely proportional to total body water (TBW), and reactance, which is the impedance to this alternating current, also measured in Ohms, as it passes through tissues with cell membranes and thus it is proportional to cell mass. These two components can be plotted as a two-dimensional vector and used to track changes in fluid status that could support clinical decisions (Figure 1). However, few clinical trials have been conducted that clearly demonstrate a benefit of BI over and above good-quality standard clinical management. Longitudinal studies of body composition indicate that progressive overhydration is usually associated with a decline in muscle mass and a potential failure to adjust the dialysis prescription so as to reduce the extracellular water (ECW) volume down in parallel with this.8Chertow G.M. Johansen K.L. Lew N. et al.Vintage, nutritional status, and survival in hemodialysis patients.Kidney Int. 2000; 57: 1176-1181Abstract Full Text Full Text PDF PubMed Scopus (161) Google Scholar, 9Johansen K.L. Kaysen Ga Young B.S. et al.Longitudinal study of nutritional status, body composition, and physical function in hemodialysis patients.Am J Clin Nutr. 2003; 77: 842-846Crossref PubMed Scopus (145) Google Scholar, 10Chan C. Smith D. Spanel P. et al.A non-invasive, on-line deuterium dilution technique for the measurement of total body water in haemodialysis patients.Nephrol Dial Transplant. 2008; 23: 2064-2070Crossref PubMed Scopus (21) Google Scholar, 11Davies S. Engel B. Chan C. et al.Breath analysis and the measurement of total body water using isotope dilution—applications in the dialysis clinic.Curr Anal Chem. 2013; 9: 593-599Crossref Scopus (11) Google Scholar We hypothesized that the longitudinal application of BI alongside clinical evaluation would help the clinician identify this problem and thus make appropriate adjustments to the prescription. To test this hypothesis, we undertook a randomized controlled trial to determine whether the additional information available from longitudinal BI over 12 months could assist in maintaining stable or improved fluid status. Using the same basic design, we included four independent randomization groups comprising nonanuric and anuric patients from three UK dialysis centers (Stoke-on-Trent, Leeds, and Sheffield) and one Chinese center (Shanghai), respectively. Our aim was to determine whether routine clinical management supported by the longitudinal plot of the BI vector, which shows the direction in which fluid status is changing, resulted in more stable fluid status than control subjects. The outcome, to which the clinicians were blinded, was fluid volumes, ECW, TBW, and their ratio (ECW/TBW), as determined from the BI measurements after the trial was completed. Recruitment, randomization, and dropout to and from the four study groups are summarized in the consort diagram (Figure 2). With the exception of the UK anuric group, recruitment was sufficient to test our primary outcome with 80% power to detect a 1-kg change (in ECW) in the Shanghai (nonanuric and anuric) patients and a 0.8-kg change in the UK nonanuric (UK nonanuric) patients. Failure to achieve power in the UK anuric group was because of a combination of lack of recruitment indicative of the low proportion of anuric patients in the three UK centers and a high dropout (66%). There was a nonsignificant increase in deaths in this patient group randomized to the BI intervention; careful analysis of these 4 deaths (cancer or sepsis) and adverse outcomes did not indicate any common factor or plausible relationship to the intervention, but this group was excluded from further analysis apart from the multivariate models. Dropout in the remaining groups was well balanced over the course of the study, as shown by Kaplan–Meier plots and log-rank tests (Supplementary Data, Supplementary Figure S1 online). There were no significant differences between patients randomized to the BI intervention or control arm in any of the groups in terms of their baseline demography, dialysis prescription, residual kidney function, peritoneal membrane function, blood pressure, or body composition (Table 1). Shanghai patients tended to be younger (mean age 54.0 vs. 58.6 years), have less comorbidity (20 vs. 60% with at least one other diagnosis), and weigh significantly less than UK patients (58.9 vs. 76.8 kg), which was reflected in a lower dialysis prescription volume. The average blood pressure and peritoneal solute transport rates (PSTR) were lower in the Shanghai patients. On comparing the nonanuric patients, normalized residual renal clearances were higher in UK patients, as was the absolute residual urine volume, unless this was corrected for body weight when the difference was nonsignificant (16.7 vs. 17.4 ml/kg). As expected, anuric patients had been on PD for longer periods: Shanghai-anuric versus Shanghai-nonanuric, 58 (26–90) versus 19 (7–41) months; and UK anuric versus UK nonanuric, 57 (36–72) versus 22 (7–33) months.Table 1Baseline characteristics of patient groups according to randomizationUK nonanuricUK anuricSH nonanuricSH anuricInterventionControlInterventionControlInterventionControlInterventionControlN587311742423837PD duration (months, range)18 (7–32)22(8–34)67(34–81)45(36–60)17(7–37)24(11–41)52(22–86)65(31–105)Age (year)58.3 ± 15.356.9 ± 14.764 ± 14.756.4 ± 1156.6 ± 11.252.5 ± 14.451.1 ± 13.155.5 ± 13.5D/P creatinine0.70 ± 0.120.68 ± 0.120.69 ± 0.10.79 ± 0.070.60 ± 0.090.58 ± 0.110.61 ± 0.090.65 ± 0.11Albumin (g/l)33.41 ± 4.4733.48 ± 3.8533.4 ± 1.934.3 ± 5.232.57 ± 2.9032.54 ± 3.6132.8 ± 4.333.4 ± 2.9Gender F/M20/3829/447/44/326/1631/1119/1914/23Comorbidity (low/medium/high)25/29/428/39/65/6/02/5/034/7/135/7/031/7/027/10/0ECW (L)18.3 ± 4.319.2 ± 4.016.4 ± 4.014.5 ± 3.016.7 ± 3.115.9 ± 2.616.3 ± 3.217.4 ± 3.5TBW (L)41.5 ± 8.242.3 ± 8.537.4 ± 5.636.1 ± 8.635.0 ± 5.233.9 ± 4.834.6 ± 6.635.8 ± 6.9ECW/TBW0.44 ± 0.070.46 ± 0.060.45 ± 0.10.42 ± 0.10.48 ± 0.060.47 ± 0.050.47 ± 0.060.49 ± 0.06H2/R (cm2/Ω)58.6 ± 13.659.6 ± 13.251.9 ± 947.6 ± 1249.4 ± 11.848.8 ± 8.149.5 ± 12.351.9 ± 12.4H2/X (cm2/Ω)538.9 ± 172570.1 ± 162487.7 ± 164384.2 ± 102526.3 ± 132497.5 ± 129502.6 ± 135560.9 ± 159Target weight (kg)76.2 ± 15.778.4 ± 18.572.4 ± 12.272.4 ± 20.659.9 ± 8.258.4 ± 8.958.0 ± 9.559.0 ± 11.0Systolic BP (mm Hg)136.8 ± 20.1143.4 ± 22.5131.8 ± 28136.4 ± 16.6130.2 ± 14.8130.5 ± 17.7128.3 ± 20.4127.2 ± 23.0Diastolic BP (mm Hg)79.7 ± 11.481.3 ± 12.375.0 ± 10.373.9 ± 12.382.7 ± 11.283.5 ± 9.579.9 ± 12.179.5 ± 10.2N587311742423837Diuretics (%)54.354.89.1029.328.602.6Beta-blockers (%)25.727.418.2034.126.218.926.3ACE inhibitors (%)24.321028.69.821.424.318.4ARBs (%)18.612.918.214.346.35024.348.4Calcium-channel blockers (%)22.924.26.414.363.471.459.671.1Alpha-blockers (%)14.32118.202.44.802.6ACE, angiotensin-converting enzymes; ARB, angiotensin receptor blocker; BP, blood pressure; ECW, extracellular water; F, female; H2/R, height2/resistance; H2/X, height2/reactance; M, male; PD, peritoneal dialysis; SH, Shanghai; TBW, total body water. Open table in a new tab ACE, angiotensin-converting enzymes; ARB, angiotensin receptor blocker; BP, blood pressure; ECW, extracellular water; F, female; H2/R, height2/resistance; H2/X, height2/reactance; M, male; PD, peritoneal dialysis; SH, Shanghai; TBW, total body water. In both the UK and Shanghai nonanuric controls and the Shanghai BI intervention group, there were no significant changes in body composition over the 12-month study period (see Figure 3a and b and Table 2). In the UK-nonanuric BI intervention group, there was a reduction in TBW (−0.9 kg, 95% confidence interval (CI): 0 to −1.74) that was associated with a reduced target weight set by clinicians (−1.7 kg, 95% CI: −0.39 to −2.96) and actual weight (−1.3 kg 95% CI: −0.09 to −2.69). Despite this, there was no change in the ECW (+0.3 kg, 95% CI: −0.69 to 1.24) or the ECW/TBW (0.01 95% CI: −0.04 to 0.01 Figure 3a). In the Shanghai anuric patients, a significant deterioration in body composition occurred in the control patients because of a fall in TBW (−1.76 kg, 95% CI: −2.70 to −0.82), increase in ECW (+0.59 kg, 95% CI: −0.67 to 1.86), and thus worsening of the ECW/TBW ratio (0.04, 95% CI: 0.01–0.06), whereas body composition remained stable in the BI intervention group (Figure 3c). This was associated with stability of the BI vector plot used to aid clinical decision-making in the intervention group, whereas in the controls there was a reduction in Height2/Resistance in keeping with reduced muscle mass and worsening in the phase angle (−0.58°, 95% CI: 0.08–1.07°), indicating a relative excess in tissue hydration (Figure 4). On multilevel analysis combining the data from both countries and all study visits, these differences remained significant and independent of baseline determinants of fluid volumes including gender, age, and grade of comorbidity (Table 3). By visit 5 (12 months), the ECW/TBW ratio worsened significantly in both the anuric control and intervention groups.Table 2Longitudinal changes on body compositionUK nonanuricShanghai nonanuricShanghai anuricControlBl interventionControlBl interventionControlBl interventionBaseline12 MonthsP-valueBaseline12 MonthsP-valueBaseline12 MonthsP-valueBaseline12 MonthsP-valueBaseline12 MonthsP-valueBaseline12 MonthsP-valueECW (l)19.5 ± 4.219.7 ± 4.60.7018.2 ± 4.318.4 ± 4.00.5716.0 ± 2.416.1 ± 2.60.8417.2 ± 2.516.7 ± 3.20.2517.7 ± 3.218.3 ± 4.60.34216.3 ± 3.216.2 ± 2.60.787TBW (l)42.9 ± 8.642.8 ± 8.80.9241.3 ± 8.440.4 ± 7.90.0534.3 ± 6.634.2 ± 6.90.8235.4 ± 5.234.7 ± 5.80.1037.2 ± 6.035.5 ± 5.90.00135.0 ± 6.534.0 ± 5.50.179ECW/TBW0.46 ± 0.060.46 ± 0.070.560.44 ± 0.080.46 ± 0.060.170.47 ± 0.060.47 ± 0.060.750.48 ± 0.080.48 ± 0.070.890.48 ± 0.060.51 ± 0.090.0130.47 ± 0.060.48 ± 0.080.221H2/R (cm2/Ω)59.8 ± 14.059.9 ± 14.40.9358.3 ± 14.556.9 ± 13.80.1349.5 ± 17.448.9 ± 100.6148.5 ± 10.449.3 ± 9.80.0854.7 ± 10.550.4 ± 9.80.00150.5 ± 12.348.5 ± 10.40.168H2/X (cm2/Ω)576 ± 171595 ± 2210.39539 ± 175543 ± 1760.88499 ± 127498 ± 1540.98538 ± 146529 ± 1830.72567 ± 147621 ± 2530.209505 ± 139511 ± 1450.815Phase angle (degrees)6.14 ± 1.26.13 ± 1.550.916.59 ± 2.086.25 ± 1.350.256.14 ± 1.206.13 ± 1.550.825.50 ± 0.825.66 ± 1.490.425.72 ± 1.305.15 ± 1.720.035.90 ± 1.365.75 ± 1.680.50Target weight (kg)78.7 ± 1978.3 ± 190.4475.2 ± 1573.6 ± 150.0159.2 ± 9.058.7 ± 9.10.2060.7 ± 8.660.3 ± 8.60.3061.4 ± 10.260.8 ± 10.50.09958.3 ± 9.858.1 ± 8.90.588Clinical weight (kg)79.3 ± 1879.0 ± 190.7275.8 ± 1674.5 ± 150.0759.2 ± 9.060 ±9.70.1360.7 ± 8.660.6 ± 8.80.9461.2 ± 10.460.9 ± 10.90.58658.3 ± 9.857.9 ± 8.40.622Bl, bioimpedance; ECW, extracellular water; H2/R, height2/resistance, H2/X, height2/reactance; TBW, total body water. Phase angle is calculated as the arc tangent ((H2/R)/(H2/X)) expressed in degrees. Open table in a new tab Figure 4Vector plot showing mean changes in bioimpedance and their associated vectors for the Shanghia-anuric patients (controls, ◊; active, ▪). Increasing H2/resistance reflects increasing body water, increasing H2/reactance, and widening of the vector plot (inversely related to phase angle), indicating increasing tissue hydration. The control group demonstrates worsening tissue overhydration despite a reduction in body water, whereas the BI intervention group was kept stable. BI, bioimpedance; H2, height2.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Table 3| Multilevel analysis of determinants of BI-derived fluid volumes (TBW and ECW/TBW) incorporating all visits (level 1), patients (level 2), and centers (level 3)Control (all)BI intervention (all)Controls (nonanuric)BI intervention (nonanuric)Controls (anuric)BI intervention (anuric)Number of patients1581491151004449Number of visits666637491435175202Mean TBW (l, 95% CI) Baseline constant34.7 (31.6, 37.8)34.1 (31.1–37.0)33.7 (31.0, 36.5)33.6 (30.4, 36.7)31.8 (29.3, 34.3)33.1 (29.6, 36.7) Gender (male)10.1∗P < 0.01. (8.4, 11.9)8.8∗P < 0.01. (7.2–10.4)11.7∗P < 0.01. (9.6, 13.9)9.2∗P < 0.01. (7.1, 11.3)8.6∗P < 0.01. (5.8, 11.4)8.8∗P < 0.01. (6.4, 11.3) Age (year)0.06 (0.0, 0.12)−0.01 (−0.07–0.05)0.00 (−0.07, 0.07)−0.01 (−0.09, 0.06)0.21∗P < 0.01. (0.09, 0.32)−0.03 (−0.12, 0.06) Comorbidity Grade 1aCompared with Grade 0 = no comorbid conditions, Grade 1=1–2, Grade 2 = 3 or more comorbidities.−0.84 (−2.81, 1.13)0.73 (−1.13, 2.60)0.38 (−1.91, 2.67)1.86 (−0.42, 4.14)−2.46 (−5.55, 0.63)−1.70 (−4.59, 1.18) Comorbidity Grade 2aCompared with Grade 0 = no comorbid conditions, Grade 1=1–2, Grade 2 = 3 or more comorbidities.−1.96 (−6.27, 2.4)0.95 (−3.63, 5.53)−1.53 (−5.86, 2.80)1.43 (−3.33, 6.20)None in this category Visit 2 versus baselinebChange from baseline visit.0.40 (−0.07, 0.86)−0.12 (−0.55, 0.30)0.44 (−0.08, 0.96)−0.44 (−0.91, 0.03)0.23 (−0.72, 1.19)0.57 (−0.30, 1.43) Visit 3 versus baselinebChange from baseline visit.0.11 (−0.36–0.59)−0.41 (−0.83, 0.0)0.12 (−0.41, 0.65)−0.57†P < 0.05. (−1.03, −0.10)0.06 (−0.91, 1.03)−0.08 (−0.92, 0.76) Visit 4 versus baselinebChange from baseline visit.−0.45 (−0.95–0.05)−0.51†P < 0.05. (−0.9, −0.06)−0.13 (−0.68, 0.42)−0.52†P < 0.05. (−1.01, −0.02)−1.49∗P < 0.01. (−2.58, −0.41)−0.46 (−1.35, 0.42) Visit 5 versus baselinebChange from baseline visit.−0.45 (−0.96–0.06)−0.79†P < 0.05. (−1.24, −0.4)−0.15 (−0.71, 0.41)−0.81∗P < 0.01.(−1.30, −0.31)−1.52∗P < 0.01. (−2.67, −0.37)−0.79 (−1.70, 0.12)ECW/TBW (ratio, expressed as percentage, 95% CI) Baseline constant46.3 (43.8, 48.7)46.4 (43.9, 48.8)46.9 (45.1, 48.7)46.3 (43.8, 48.9)47.6 (42.1, 53.1)46.8 (43.0, 50.5) Gender (male)−2.78∗P < 0.01. (−4.37, −1.18)−3.32∗P < 0.01. (−4.97, −1.67)−3.53∗P < 0.01. (−5.36, −1.69)−2.58∗P < 0.01. (−4.54, −0.62)−3.68†P < 0.05. (−7.00, −0.36)−4.26∗P < 0.01. (−7.37, −1.14) Age (year)0.07†P < 0.05. (0.01, 0.12)0.14∗P < 0.01. (0.08, 0.20)0.06†P < 0.05. (0.00, 0.12)0.12∗P < 0.01. (0.05, 0.19)0.05 (−0.08, 0.18)0.17∗P < 0.01. (0.05, 0.28) Comorbidity Grade 1aCompared with Grade 0 = no comorbid conditions, Grade 1=1–2, Grade 2 = 3 or more comorbidities.1.54 (−0.28, 3.36)2.30†P < 0.05. (0.43, 4.16)1.15 (−0.79, 3.08)1.31 (−0.81, 3.42)1.21 (−2.62, 5.05)3.97†P < 0.05. (0.33, 7.62) Comorbidity Grade 2aCompared with Grade 0 = no comorbid conditions, Grade 1=1–2, Grade 2 = 3 or more comorbidities.8.81∗P < 0.01. (4.83, 12.78)1.61 (−2.96, 6.18)8.72∗P < 0.01. (4.97, 12.46)1.71 (−2.69, 6.11)None in this category Visit 2 versus baselinebChange from baseline visit.0.08 (−0.89, 1.04)0.57 (−0.43, 1.57)−0.29 (−1.37, 0.79)0.32 (−0.93, 1.57)1.05 (−0.97, 3.06)1.11 (−0.51, 2.72) Visit 3 versus baselinebChange from baseline visit.0.52 (−0.46, 1.51)−0.09 (−1.07, 0.89)0.44 (−0.67, 1.55)−0.26 (−1.49, 0.97)0.74 (−1.29, 2.78)0.35 (−1.22, 1.91) Visit 4 versus baselinebChange from baseline visit.−0.49 (−1.53, 0.55)0.45 (−0.58, 1.48)−0.39 (−1.54, 0.76)0.37 (−0.94, 1.67)−0.83 (−3.10, 1.45)0.71 (−0.94, 2.36) Visit 5 versus baselinebChange from baseline visit.0.96 (−0.10, 2.03)0.85 (−0.19, 1.90)0.31 (−0.85, 1.47)0.50 (−0.81, 1.81)3.25∗P < 0.01. (0.85, 5.66)1.79†P < 0.05. (0.09, 3.48)BI, bioimpedance; CI, confidence interval; ECW, extracellular water; TBW, total body water.6 models are presented; in each case, the BI fluid volume is adjusted for baseline age, gender, and comorbidity; TBW at baseline is greater by 8.5–10 liters in men and falls over visits (spontaneously in anurics, because of target weight reduction in nonanurics), whereas the ECW/TBW at baseline is elevated by age, female gender, and comorbidity and increases over visits in anuric patients. Values significantly different from baseline constant are shown in bold.† P < 0.05.∗ P < 0.01.a Compared with Grade 0 = no comorbid conditions, Grade 1=1–2, Grade 2 = 3 or more comorbidities.b Change from baseline visit. Open table in a new tab Bl, bioimpedance; ECW, extracellular water; H2/R, height2/resistance, H2/X, height2/reactance; TBW, total body water. Phase angle is calculated as the arc tangent ((H2/R)/(H2/X)) expressed in degrees. BI, bioimpedance; CI, confidence interval; ECW, extracellular water; TBW, total body water. 6 models are presented; in each case, the BI fluid volume is adjusted for baseline age, gender, and comorbidity; TBW at baseline is greater by 8.5–10 liters in men and falls over visits (spontaneously in anurics, because of target weight reduction in nonanurics), whereas the ECW/TBW at baseline is elevated by age, female gender, and comorbidity and increases over visits in anuric patients. Values significantly different from baseline constant are shown in bold. There were no significant longitudinal changes in blood pressure in any of intervention or control groups (Table 4). In all the nonanuric patient groups over 12 months, there was a significant fall in the residual Kt/Vurea associated with reductions in urine volume, with the exception of the UK intervention group in which residual urine volume was maintained. Although relative preservation of urine volume in the context of loss in solute clearance is in keeping with increased diuretic use, it was not possible to demonstrate this (Table 5). The reduction in residual function in the nonanuric groups was associated with increases in the prescribed dialysis dose (volume) in all patient groups. There were no changes in plasma albumin, ultrafiltration capacity, or PSTR in any of the groups with the exception of a significant increase in PSTR in the Shanghai anuric cohort, seen in both study arms, slightly greater in the intervention arm.Table 4Longitudinal changes in secondary outcomes and dialysis prescriptionUK nonanuricShanghai nonanuricShanghai anuricControlBI interventionControlBI interventionControlBI interventionBaseline12 MonthsPBaseline12 MonthsP-valueBaseline12 MonthsP-valueBaseline12 MonthsP-valueBaseline12 MonthsP-valueBaseline12 MonthsP-valueSystolic BP (mm Hg)144 ± 25140 ± 200.209137 ± 20136 ± 200.845133 ± 16.2135 ± 18.40.375131 ± 15130 ± 210.637128 ± 24123 ± 270.638130 ± 22128 ± 260.776Diastolic BP (mm Hg)81.2 ± 1379.1 ± 100.23579.7 ± 1179.2 ± 110.81585.5 ± 886.1 ± 130.99183.3 ± 1181.9 ± 110.41079.7 ± 976.2 ± 16.20.24679.8 ± 13.181.6 ± 14.90.613Input volume (l)8.8 ± 2.59.4 ± 30.0328.7 ± 2.79.0 ± 30.0796.1 ± 1.86.5 ± 1.80.0256.6 ± 1.56.9 ± 1.40.0258.3 ± 1.38.6 ± 1.40.0837.8 ± 1.28.0 ± 1.20.157Total glucose (g)121.7 ± 5126.7 ± 60.395119.1 ± 51126.8 ± 570.067104.2 ± 35120.0 ± 390.001116.0 ± 31130.0 ± 360.003181.2 ± 41186.7 ± 510.398167.5 ± 39176.3 ± 460.037Average (glucose; g/l)1.36 ± 0.281.3 ± 0.40.2571.31 ± 0.371.34 ± 0.390.4171.71 ± 0.321.86 ± 0.340.0091.75 ± 0.271.87 ± 0.340.0062.16 ± 0.312.15 ± 0.390.8882.13 ± 0.332.19 ± 0.390.342Daily UF326 ± 629446 ± 4350.113339 ± 539439 ± 4180.203160 ± 437352 ± 4870.003166 ± 514316 ± 5680.012876.4 ± 296792 ± 4020.384833 ± 327831 ± 3630.819Urine volume (ml)1,298 ± 7461,007 ± 5990.0031,165 ± 6611,170 ± 8960.9571,084 ± 621746 ± 5590.0001,005 ± 571723 ± 6540.000NCNCNCNCRenal Ccr (L/week/1.73 m2)94.6 ± 6378.1 ± 570.02093.1 ± 66.172.3 ± 62.60.00140.1 ± 35.333.9 ± 38.70.01241.7 ± 33.127.2 ± 26.50.000NCNCNCNCRenal Kt/V1.3 ± 0.81.1 ± 0.70.0231.2 ± 0.81.0 ± 0.80.0060.8 ± 0.60.6 ± 0.60.0070.7 ± 0.50.5 ± 0.50.000NCNCNCNCAlbumin (g/l)33.5 ± 4.032.9 ± 3.70.30133.2 ± 4.733.2 ± 5.01.0038.0 ± 3.438.2 ± 4.60.46637.8 ± 2.838.4 ± 3.30.30738.9 ± 3.338.2 ± 4.30.54839.2 ± 3.038.0 ± 3.50.130UF capacity274 ± 216244 ± 2200.572226 ± 266279 ± 2940.357253 ± 111291 ± 1380.147221 ± 174266 ± 1300.299274 ± 139252 ± 1530.701241 ± 196267 ± 1290.247Solute transport0.66 ± 0.110.68 ± 0.100.1560.70 ± 0.140.73 ± 0.110.1750.58 ± 0.110.60 ± 0.120.2310.60 ± 0.100.62 ± 0.100.2550.64 ± 0.110.67 ± 0.110.0320.62 ± 0.110.67 ± 0.110.001BI, bioimpedance; BP, blood pressure; Ccr, creatinine clearance; Kt/V, urea clearance (weekly); NC, not collected; UF, ultrafiltration from peritoneal equilibration test. Open table in a new tab Table 5Proportion of 1394 clinical assessments associated with interventions that were not uniformly distributed by type, and thus, on many occasions more than one intervention was implemented, or by patient, as some had multiple interventions during the course of the studyInterventionUK centersShanghaiTotalReduce fluid intake14.8%29.9%22.5%Increase fluid intake6.8%1.8%4.4%Commence/increase diureticsaDenominator adjusted for the number of interventions in nonanuric patients.2.4%2.2%2.3%Reduce/stop diuretics1.0%-0.05%Increase dialysate glucose prescription14.5%7.9%11.3%Decrease dialysate glucose prescription1.0%0.07%0.085%Commence icodextrin0.04%NADecrease icodextrin0.03%NANA, not applicable as it is unavailable in China.There was no apparent difference in the pattern of interventions between active and control groups, and the proportion of assessments does not necessarily reflect the magnitude—e.g., there were more recorded episodes of increasing the glucose prescription in the UK, but the actual average increase in prescription in Shanghai was greater.a Denominator adjusted for the number of interventions in nonanuric patients. Open table in a new tab BI, bioimpedance; BP, blood pressure; Ccr, creatinine clearance; Kt/V, urea clearance (weekly); NC, not collected; UF, ultrafiltration from peritoneal equilibration test. NA, not applicable as it is unavailable in China. There was no apparent difference in the pattern of interventions between active and control groups, and the proportion of assessments does not necessarily reflect the magnitude—e.g., there were more recorded episodes of increasing the glucose prescription in the UK, but the actual average increase in prescription in Shanghai was greater. A key aspect of the study design was to capture decisions at the point of fluid management assessments so as to better understand how clinicians were using the additional information from BI. Of a potential 1274 visits and 1394 assessments (additional assessments were allowed in the active BI group) of fluid status, data were captured and recorded for analysis at 1106 visits (89.6%): 568 for Shanghai with >95% data validity and 538 for the UK with 85% validity; the proportions are not significantly different by randomization group. Frequency of intervention type was highly variable by patient, usually multiple and often repeated (see Table 5), but not demonstrably different according to randomization, with the exception of significantly higher glucose prescription in the Shanghai-anuric BI group (Table 4). By taking a change in target weight of ≥1 kg in either direction as a cutoff value for a clinically significant decision, it can be seen (Table 6) that the weight was more likely to be reduced in the intervention compared with the control groups in all three substudies, with the primary reason given as 'to improve control of high blood pressure', whereas hydration status on clinical examination was less likely to be a factor (although reduction of weight in the Shanghai-anuric BI group was borderline significant). Overall, this effect on decision-making was most marked in the UK-nonanuric BI patients, thus explaining the overall greater likelihood of weight reduction in this intervention group, as already discussed (Figure 3a).Table 6Analysis of interventions according to changes in target dry weight defining ≥ ± 1 kg as being clinically significantClinical decisionRandomizationUK-NAS-NAS-AAll groupsChange in target weight↓=↑P-value↓=↑P-value↓=↑P-value↓=↑P-valueReason given for changing weightBI intervention103016271629322865to achieve lower blood pressureControls1331120.004113640.0322610.0022693170.008Reason given for changing weight to achieveBI intervention62019331821223744better fluid status based on clinical examinationControls72340.248370ND42820.056198860.15Overall decision to change weight in eitherBI intervention3815919271351324110138940445direction regardless of reasonControls31177360.00325142160.5819109130.5175428650.006A, anurie; NA, nonanuric; ND, not done; S, Shanghai.↓, target weight decreased by ≥1 kg; =, change in target weight <1 kg; t, target weight increased by ≥1 kg.P-values are for the Χ2-test. Open table in a new tab A, anurie; NA, nonanuric; ND, not done; S, Shanghai. ↓, target weight decreased by ≥1 kg; =, change in target weight <1 kg; t, target weight increased by ≥1 kg. P-values are for the Χ2-test. The most important finding of