Identification of fluid overload in elderly patients with chronic kidney disease using bioimpedance techniques.

Diagnosis of fluid overload (FO) in early stage is essential to manage fluid balance of patients with chronic kidney disease (CKD) and to prevent cardiovascular disease (CVD). However, the identification of fluid status in patients with CKD is largely dependent on the physician's clinical acumen. The ratio of fluid overload to extracellular volume (FO/ECV) has been used as a reference to assess fluid status. The primary aim of this study was to compare FO/ECV with other bioimpedance methods and clinical assessments in patients with CKD. Whole body ECV, intracellular volume (ICV), total body water (TBW), and calf normalized resistivity (CNR) were measured (Hydra 4200). Thresholds of FO utilizing CNR and ECV/TBW were derived by receiver operator characteristic (ROC) analysis based on data from pooled patients with CKD and healthy subjects (HSs). Clinical assessments of FO in patients with CKD were performed by nephrologists. Patients with CKD (stage 3 and stage 4) (n = 50) and HSs (n = 189) were studied. The thresholds of FO were ≤14.3 (10-2 Ωm3/kg) for females and ≤13.1 (10-2 Ωm3/kg) for males using CNR and ≥0.445 in females and ≥0.434 in males using ECV/TBW. FO was diagnosed in 78%, 62%, and 52% of patients with CKD by CNR, FO/ECV, and ECV/TBW, respectively, whereas only 24% of patients with CKD were diagnosed to be FO by clinical assessment. The proportion of FO in patients with nondialysis CKD was largely underestimated by clinical assessment compared with FO/ECV, CNR, and ECV/TBW. CNR and FO/ECV methods were more sensitive than ECV/TBW in identifying fluid overload in these patients with CKD.NEW & NOTEWORTHY We found that fluid overload (FO) in patients with nondialysis CKD was largely underestimated by clinical assessment compared with bioimpedance methods, which was majorly due to lack of appropriate techniques to assess FO. In addition, although degree of FO by bioimpedance markers positively correlated with the age in healthy subjects (HSs), no difference was observed in the three hydration markers between groups of 50 ≤ age <70 yr and age ≥70 yr in the patients with CKD.

Monitoring of Intraperitoneal Fluid Volume during Peritoneal Equilibration Testing using Segmental Bioimpedance.

BACKGROUND: Ultrafiltration failure and fluid overload are common in peritoneal dialysis (PD) patients. Knowledge of intraperitoneal volume (IPV) and time to peak IPV during a dwell would permit improved PD prescription. This study aimed to utilize trunk segmental bioimpedance analysis (SBIA) to quasi-continuously monitor IPV (IPVSBIA) during the peritoneal dwell. METHODS: IPVSBIA was measured every minute using lower-trunk SBIA (Hydra 4200; Xitron Technologies Inc., CA, USA) in 10 PD patients during a standard 240-min peritoneal equilibration test (PET). The known dialysate volume (2 L) rendered IPVSBIA calibration and calculation of instantaneous ultrafiltration volume (UFVSBIA) possible. UFVSBIA was defined as IPVSBIA - 2 L. RESULTS: Based on dialysate-to-plasma creatinine ratio, 2 patients were high, 7 high-average, and 1 low-average transporters. Technically sound IPVSBIA measurements were obtained in 9 patients (age 59.0 ± 8.8 years, 7 females, 5 African Americans). Drained ultrafiltration volume (UFVdrain) was 0.47 ± 0.21 L and correlated (r = 0.74; p < 0.05) with end-dwell UFVSBIA (0.55 ± 0.17 L). Peak UFVSBIA was 1.04 ± 0.32 L, it was reached 177 ± 61 min into the dwell and exceeded end-dwell UFVSBIA by 0.49 ± 0.28 L (95% CI: 0.27-0.7) and UFVdrain by 0.52 ± 0.31 L (95% CI: 0.29-0.76), respectively. CONCLUSION: This pilot study demonstrates the feasibility of trunk segmental bioimpedance to quasi-continuously monitor IPVSBIA and identify the time to peak UFVSBIA during a standard PET. Such new insights into the dynamics of intraperitoneal fluid volume during the dwell may advance our understanding of the underlying transport physiology and eventually assist in improving PD treatment prescriptions.

The effect of increased frequency of hemodialysis on vitamin C concentrations: an ancillary study of the randomized Frequent Hemodialysis Network (FHN) daily trial.

BACKGROUND: Reports on vitamin C in HD patients have shown effects of vitamin C deficiency in association with scurvy symptoms. Dialyzability of water soluble vitamins is high, and substantial losses in those who are dialyzed more frequently were hypothesized. The randomized FHN Daily Trial compared the effects of in-center HD six versus three times per week. We studied baseline correlations between vitamin C and potentially associated parameters, and the effect of more frequent HD on circulating vitamin C concentrations. METHODS: We studied vitamin C levels at baseline and months, 3, 5 and 11. Patients enrolled between 2007 and 2009 into the randomized FHN Daily trial in the East Coast consortium were approached for participation. Predialysis plasma samples were processed with metaphosphoric acid and frozen at - 70 °C for measurement with HPLC. Regression models between baseline log-transformed vitamin C and hemoglobin, CRP, eKt/V, ePCR and PTH, and a linear mixed-effects model to estimate the effect size of more frequent HD on plasma vitamin C, were constructed. RESULTS: We studied 44 subjects enrolled in the FHN Daily trial (50 ± 12 years, 36% female, 29% Hispanics and 64% blacks, 60% anuric). Vitamin C correlated significantly with predialysis hemoglobin (r = 0.3; P = 0.03) and PTH (r = - 0.3, P = 0.04), respectively. Vitamin C did not significantly differ at baseline (6×/week, 25.8 ± 25.9 versus 3×/week, 32.6 ± 39.4 µmol/L) and no significant treatment effect on plasma vitamin C concentrations was found [- 26.2 (95%CI -57.5 to 5.1) µmol/L at Month 4 and - 2.5 (95%CI -15.6 to 10.6) µmol/L at Month 12. CONCLUSIONS: Based on data from this large randomized-controlled trial no significant effect of the intervention on circulating plasma vitamin C concentrations was found, allaying the concerns that more frequent HD would affect the concentrations of water-soluble vitamins and adversely affect patient's well-being. Correlations between vitamin C and hemoglobin and PTH support the importance of vitamin C for normal bone and mineral metabolism, and anemia management.

Effect of Change in Fluid Status Evaluated by Bioimpedance Techniques on Body Composition in Hemodialysis Patients.

OBJECTIVE: This prospective study uses calf bioimpedance spectroscopy (cBIS) to guide the attainment of dry weight (DWcBIS) in chronic hemodialysis (HD) patients. The primary aim of this study was to evaluate whether body composition is altered when fluid status is reduced to DWcBIS. METHODS: Target post-HD weight was gradually reduced from baseline (BL) until DWcBIS was achieved. DWcBIS was defined as the presence of both flattening of the curve of extracellular resistance and the attainment calf normalized resistivity in the normal range during the dialysis treatment. Extracellular volume (ECV), intracellular volume, and total body water (TBW) were measured using whole body BIS (Hydra 4200). Fluid overload, lean body mass, and fat mass were calculated according to a body composition model. RESULTS: Seventy-three patients enrolled and 60 completed the study (55 ± 13 years, 49% male). Twenty-eight patients (25% diabetes) achieved DWcBIS, whereas 32 patients (47% diabetes) did not. Number of treatment measurements were 16 ± 10 and 12 ± 13 studies per patient in the DWcBIS and non-DWcBIS groups, respectively. Although significant decreases in body weight and ECV were observed, lean body mass and FM did not differ significantly in both groups from BL to the end of study. ECV, ECV/TBW, and fluid overload were higher in the non-DWcBIS than in the DWcBIS group both at BL and at the end of study. Ratios of intradialytic changes in calf normalized resistivity, ECV, and ECV/TBW to ultrafiltration volume were significantly lower in diabetic than in non-diabetic patients. CONCLUSIONS: This study shows that decreasing fluid status by gradual reduction of post-HD weight in both DWcBIS and Non-DWcBIS groups did not affect body composition significantly over a period of about 4 weeks.

Effect of age and blood pressure on determination of normal fluid status in a general population using whole body and calf bioimpedance techniques.

Normal fluid status (dry weight) can be identified by hydration markers established in the healthy population. The general population average could be influenced by age with its accompanying physiological changes and/or illness. The aims of this study were (1) to evaluate the effect of age and systolic blood pressure (SBP) on these markers; (2) to compare mean values of hydration markers as assessed by different bioimpedance techniques. Subjects from the general population (n = 212, males 105, 57.1% White, 31.6% Black, and 11.3% others) were studied. Body weight, height and SBP were measured. Whole body and calf bioimpedance (Hydra 4200) methods were utilized with subjects in the supine position. Calf normalized resistivity (CNR), fluid overload (FO), extracellular (ECV) and intracellular (ICV) volume measurements ECV/total body water (TBW) were calculated. Subjects were stratified by age; young (Group1): 18-35 years; middle (Group2): 36-60 years, senior (Group3): 61-80 years. Body mass index (BMI), CNR, and ECV/TBW differed significantly between age groups, and genders. ECV and FO increased with age in males. Decreased CNR (indicating relative increased fluid load) (p < 0.001) and increased SBP (p < 0.001) were associated with age in all three groups. CNR in Group1 was the same as in 36.0% of subjects in Group2 and 12.5% of subjects in Group3. In those subjects in Group2 and Group3, with CNR levels comparable to Group1 subjects, SBP was lower than in their peers in each respective age group. In conclusion average CNR in Group1 represents the range of healthy subjects. Since CNR is correlated with age, subjects in Group2 and Group3 are more likely to have fluid overload. Although about a third of subjects in Group2 and Group3 were in the range of Group1, the age and associated factors should be considered when CNR is used to identify fluid status in senior patients.

A Randomized Crossover Trial of Dietary Sodium Restriction in Stage 3-4 CKD.

BACKGROUND AND OBJECTIVES: Patients with chronic kidney disease (CKD) are often volume expanded and hypertensive. Few controlled studies have assessed the effects of a sodium-restricted diet (SRD) in CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a randomized crossover trial to evaluate the effect of SRD (target <2 g sodium per day) versus usual diet on hydration status (by bioelectrical impedance spectroscopy) and blood pressure (BP) between May of 2009 and May of 2013. A total of 58 adults with stage 3-4 CKD were enrolled from two academic sites: University of Michigan (n=37) and University of North Carolina at Chapel Hill (n=21); 60% were men, 43% were diabetic, 93% were hypertensive, and mean age was 61 years. Participants followed SRD or usual diet for 4 weeks, followed by a 2-week washout period and a 4-week crossover phase. During the SRD, dieticians provided counseling every 2 weeks, using motivational interviewing techniques. RESULTS: Whole-body extracellular volume and calf intracellular volume decreased by 1.02 L (95% confidence interval [95% CI], -1.48 to -0.56; P<0.001) and -0.06 L (95% CI, -0.12 to -0.01; P=0.02), respectively, implying decreased fluid content on the SRD compared with usual diet. Significant reductions in urinary sodium (-57.3 mEq/24 h; 95% CI, -81.8 to -32.9), weight (-2.3 kg; 95% CI, -3.2 to -1.5), and 24-hour systolic BP (-10.8 mmHg; 95% CI, -17.0 to -4.6) were also observed (all P<0.01). Albumin-to-creatinine ratio did not change significantly and mean serum creatinine increased slightly (0.1 mg/dl; 95% CI, -0.01 to 0.2; P=0.06). No period or carryover effects were observed. Results were similar when analyzed from phase 1 only before crossover, although P values were modestly larger because of the loss of power. CONCLUSIONS: In this randomized crossover trial, implementation of SRD in patients with CKD stage 3-4 resulted in clinically and statistically significant improvement in BP and hydration status. This simple dietary intervention merits a larger trial in CKD to evaluate effects on major clinical outcomes.

Bioimpedance can solve problems of fluid overload.

Bioimpedance (BI) techniques for measuring normal hydration status (NHS) can be generally classified as (1) by frequency as single frequency at 50 kHz, BI analysis, and multifrequency BI spectroscopy and (2) by method as whole body (wrist to ankle) measurement and calf BI spectroscopy. The aim of this article was to review current BI methods for clinical practice in patients with end-stage of kidney disease. BI vector analysis using whole-body single-frequency BI at 50 kHz may be useful for population studies to indicate a range of degree of fluid loading and of nutritional status. Whole body multifrequency BI spectroscopy is used to estimate extracellular (ECV), intracellular fluid volume, and total body water in dialysis patients. The whole-body BI model is used in the body composition monitor (BCM). The whole-body BI model is established with ECV, intracellular fluid volume, and body weight based on parameters from regression analysis in healthy subjects to calculate fluid overload in dialysis patients. Calf BI methods have been developed to measure NHS by 2 ways: (1) continuous measurement of the intradialytic resistance curve until flattening occurs; (2) calf normalized resistivity in the range of healthy subjects (18.5 × 10(-2) Ω m(3)/kg in male and 19.1 × 10(-2) Ω m(3)/kg in female). In general, for population studies, BI vector analysis or ECV/total body water may be useful; BCM is a commercially available device that can certainly guide volume reduction safely over time. For more exact measure of fluid overload, calf BI methods appear to be most accurate, but these are at present research tools. BI techniques are not only useful in assessing NHS but also in the study of nutrition and body composition.

Agreement of single- and multi-frequency bioimpedance measurements in hemodialysis patients: an ancillary study of the Frequent Hemodialysis Network Daily Trial.

BACKGROUND: Bioimpedance analysis (BIA) is well established to assess body composition. Agreements between single- and multi-frequency bioimpedance (SF-BIA, MF-BIS) measurements in subjects undergoing 6 or 3 times/week hemodialysis (HD) were analyzed. METHODS: Total body water (TBW) and intra- and extracellular fluid (ICF, ECF) of subjects enrolled in the Frequent Hemodialysis Network (FHN) Daily Trial (www.clinicaltrials.gov No. NCT00264758) were measured with a Hydra 4200 at baseline (BL) and at 5 months (M5). Volumes were computed using SF (at 50 kHz) and MF approaches. Agreement was assessed by means of linear regression and Bland-Altman analysis and treatment effects by t test. RESULTS: 35 subjects (17 on the more frequent regimen, 26 males, 20 African-American, 48 ± 9 years, pre-HD weight 84 ± 19 kg) were studied. Assessments with SF-BIA and MF-BIS correlated significantly at BL and M5 in both arms. No proportional errors, but systematic biases over the entire range of values were found at BL and M5. Agreement did not differ between subjects randomized to either HD treatment arm at both time points. MF-BIS appears to have better precision than SF-BIA allowing the observation of a significant treatment effect by the intervention [-1.5 (95% CI -2.5 to -0.5) l] on ECF, not found for ECF SF-BIA. Precision also affected the statistical power of the SF-BIA data in the current analysis. CONCLUSION: Both methods showed agreement without significant proportional errors regardless of HD frequency and can be used for longitudinal analyses. SF-BIA has lower precision which needs thorough consideration in the design of future trials with similar outcomes.

Effect of change in fluid distribution in segments in hemodialysis patients at different ultrafiltration rates on accuracy of whole body bioimpedance measurement.

This study explored divergence (error) between ultrafiltration volumes (UFV) and intradialytic changes in extracellular volume (ΔECV) in hemodialysis (HD) patients measured by whole body (wBIS) and sum of segmental bioimpedance spectroscopy (sBIS). The primary aim of the study was to evaluate the effect of different ultrafiltration rates (UFR) on error of estimation of ΔECV by changes in their distribution in body segments (arm, trunk, and leg). Forty-four HD patients (26 men, age 63.5 ± 14.3 yr) were studied twice in the same week following high and low UFR treatments. ΔECV and distributions (segmental ΔECV/Σsegmental ΔECV, %) in arm, trunk, and leg were measured. ΔECV by wBIS underestimated UFV (0.58 ± 0.43 in high vs. 0.36 ± 0.5 liters at low UFR; P < 0.001, respectively); however, using sBIS no significant difference between UFV and ΔECV was present. Divergence using wBIS but not sBIS correlated positively with UFR. ΔECV distribution in trunk and leg at high UFR (44.1 ± 8.3, 47.2 ± 8.5, %) differed significantly (P < 0.01) from low UFR (36 ± 15.7, 53.8 ± 14.7) respectively, but in arm did not differ between UFR. Primary sources of whole body resistance are arms and legs. Due to different cross-sectional areas between trunk and limbs, wBIS is insensitive to detection of changes in trunk volume. At higher UFR, plasma water was rapidly and largely removed from the trunk but with only a small change in whole body resistance. As a result, accuracy of estimation of ECV by wBIS is further decreased by high UFR, while sBIS remains accurate using separate measurements of segmental volumes.

Comparison of bioimpedance techniques to detect changes in fluid status in hemodialysis patients.

UNLABELLED: Bioimpedance (BI) is maturing as a clinical technique for assessing fluid volume status. The aim of this study was to compare the sensitivity of four BI methods to detect changes in fluid status in hemodialysis patients. METHODS: Forty-five patients were studied twice in the same week, i.e. once after the long and short interdialytic intervals, respectively. The four BI methods used were: (a) calf normalized resistivity (CNR) at a 5-kHz frequency, (b) whole-body multifrequency BI spectroscopy (MF-BIS) to estimate the normal hydration weight (NHWWBM), (c) whole-body MF-BIS to estimate the ratio of extracellular volume to total body water (wECV/wTBW), and (d) whole-body single-frequency (50 kHz) BI analysis to compute the ratio of ECV (sfECV) to TBW (sfTBW). RESULTS: The relationship (slope of the regressive line) between relative changes (%) in the above mentioned four BI parameters and differences in weight (kg) was most pronounced with CNR (5.2 ± 1.6%/kg), followed by wECV/wTBW (1.7 ± 0.7%/kg) and NHWWBM (0.73 ± 0.2%/kg). Changes in sfECV/sfTBW and differences in weight were not correlated. CONCLUSIONS: CNR is more sensitive than whole-body BIS for detecting differences in fluid status.

The association between arterial stiffness and fluid status in peritoneal dialysis patients.

OBJECTIVES: In this study our aim was to evaluate the relationship between degree of fluid status and arterial stiffness measured by pulse wave velocity (PWV) in peritoneal dialysis (PD) patients. Fluid status was determined by different methods including fluid overload measured by bioimpedance (Body Composition Monitor, BCM), calf normalized resistivity (CNR), plasma N-terminal fragment of B-type natriuretic peptide (NT-proBNP) and extracellular to intracellular water ratio (ECW/ICW). METHODS: Sixty PD patients were evaluated. They were stratified into normo- and hypervolemic groups according to their fluid overload (FO). CNR was calculated from resistance at 5 kHz using calf bioimpedance spectroscopy. Arterial stiffness was assessed by PWV. Additionally, all patients underwent transthoracic echocardiography and had levels of NT-proBNP measured. RESULTS: PWV was higher in the hypervolemic compared to normovolemic patients (9.99 ± 2.4 m/sec vs 7.48 ± 2.3 m/sec, p < 0.001). Hypervolemic patients had higher NT-proBNP levels (3065 ± 981 pg/mL vs 1095 ± 502 pg/mL, p < 0.001), a higher ratio of ECW/ICW; (0.93 ± 0.11 vs 0.81 ± 0.08, p < 0.001) and lower CNR (13.7 ± 2.4 vs 16.0 ± 3.3 W m(3)/kg(*)10(-2), p = 0.005). NT-pro BNP level, ECW/ICW ratio, relative FO, and left ventricular (LV) mass index were positively and CNR negatively correlated with PWV. Relative FO and CNR independently predicted PWV in multivariate analysis adjusted for age, duration of PD, body mass index and mean arterial pressure. CONCLUSIONS: Arterial stiffness is increased in fluid-overloaded PD patients. Our results indicated that fluid status is an independent predictor of PWV.

Early systolic blood pressure changes in incident hemodialysis patients are associated with mortality in the first year.

BACKGROUND: In incident hemodialysis (HD) patients, the relationship between early systolic blood pressure (SBP) dynamics and mortality is unknown. METHODS: Baseline SBP levels were stratified into 5 categories ranging from <120 and ≥180 mm Hg. Early pre-HD SBP change was defined as the slope of pre-HD SBP from week 1 to 12 and categorized in quartiles (Q1, lowest slope). SBP slopes were computed for each patient by simple linear regression. RESULTS: In 3,446 incident HD patients (42% females, 44% black, age 62 ± 15 years), the median pre-HD SBP slope was -1.7 (Q1) to +2.3 (Q4) mm Hg/week. In an adjusted multivariate Cox regression analysis, patients with declining SBP (slope Q1) had higher mortality compared to patients with increasing pre-HD SBP (slope Q4) at 12 months (hazard ratio 2.01, 95% confidence interval 1.35-3.01). In addition, patients with baseline pre-HD SBP <120 mm Hg showed higher mortality compared to the reference group (SBP ≥180 mm Hg) at 12 months (hazard ratio 1.89, 95% confidence interval 1.03-3.45). CONCLUSION: Baseline pre-HD SBP and early SBP dynamics are associated with mortality in the first year of dialysis. Patients who had low (pre-HD SBP <120 mm Hg) or declining SBP had the highest mortality rates. Particular attention is warranted in incident HD patients with low or declining SBP.