Assessment of bioimpedance spectroscopy devices: a comparative study and error analysis of gold-plated copper electrodes.

Objective. Bioimpedance spectroscopy (BIS) is a non-invasive diagnostic tool to derive fluid volume compartments from frequency dependent voltage drops in alternating currents by extrapolating to the extracellular resistance (R0) and intracellular resistance (Ri). Here we tested whether a novel BIS device with reusable and adhesive single-use electrodes produces results which are (in various body positions) equivalent to an established system employing only single-use adhesive electrodes.Approach. Two BIS devices ('Cella' and the 'Body Composition Monitor' [BCM]) were compared using four dedicated resistance testboxes and by measuring 40 healthy volunteers.Invivocomparisons included supine wrist-to-ankle (WA) reference measurements and wrist-to-wrist (WW) measurements with pre-gelled silver/silver-chloride (Ag/AgCl) electrodes and WW measurements with reusable gold-plated copper electrodes.Main results. Coefficient of variation were <1% for all testbox measurements with both BIS devices. Accuracy was within ±1% of true resistance variability, a threshold which was only exceeded by the Cella device for all resistances in a testbox designed with a lowR0/Riratio.Invivo, WA-BIS differed significantly between BIS devices (p< 0.001). Reusable WW electrodes exhibited larger resistances than WW-BIS with Ag/AgCl electrodes (R0: 738.36 and 628.69 Ω;Ri: 1508.18 and 1390 Ω) and the relative error varied from 7.6% to 31.1% (R0) and -15.6% to 37.3% (Ri).Significance. Both BIS devices produced equivalent resistances measurements but different estimates of body composition bothinsilicoand in WA setupsinvivo, suggesting that the devices should not be used interchangeably. Employing WW reusable electrodes as opposed to WA and WW measurement setups with pre-gelled Ag/AgCl electrodes seems to be associated with measurement variations that are too large for safe clinical use. We recommend further investigations of measurement errors originating from electrode material and current path.

Day-to-day variability in euvolemic body mass.

Short-term variability in body mass is a common, everyday phenomenon; however, data on body mass variability are scarce. While the physiological variability of body mass is negligible in healthy individuals, it could have implications for therapy in patients with impaired volume homeostasis, for example, patients with kidney failure undergoing kidney replacement therapy. We analyzed a long-term dataset comprising 9521 days of standardized body mass measurements from one healthy male individual and assessed the variability in body mass as a positive or negative relative difference in body mass measured on subsequent days. The average and median relative differences were zero, with a standard deviation (SD) of 0.53% for the one-day interval, increasing to 0.69% for the 7-day interval, and this variability was constant throughout the observation period. A body mass variability of approximately 0.6% (±450 mL in a 75-kg patient) should be taken into consideration when weight-dependent treatment prescriptions, e.g. the ultrafiltration rates in patients on hemodialysis, are being set. Consequently, a "soft target weight", considering the longitudinal variation of volume markers, such as body mass, might improve treatment quality.

Differences in bioimpedance-derived fluid status between two versions of the Body Composition Monitor.

OBJECTIVES: The Body Composition Monitor (BCM) (Fresenius Medical Care) measures body impedances in alternating currents to subsequently calculate fat and lean tissue mass, fluid compartments, and overhydration (OH). The aim of this study was to investigate differences between two versions of the BCM (an older version, 3.2.5, and a newer version, 3.3.3). METHODS: Between September 2021 and December 2021, 28 hemodialysis patients were included to undergo BCM measurements before each of 14 consecutive dialysis sessions with versions 3.2.5 and 3.3.3 devices. Measurements were performed according to instructions provided by the manufacturer. Differences between BCM devices were tested for statistical significance using paired Wilcoxon tests, neglecting clustering. RESULTS: A total of 288 measurement pairs of 27 patients were left after exclusion of 43 flawed data points. The mean difference in OH between both BCM devices was 0.548 L (higher for version 3.2.5). Analysis of impedance data revealed differences in the high-frequency spectrum, quantifiable by the intracellular resistance, Ri (median Ri version 3.2.5 = 1750.3 Ω; Ri version 3.3.3 = 1612.45 Ω; P < 0.001), and the time delay, Td (median Td version 3.2.5 = 1.85 ns; Td version 3.3.3 = 8.88 nanoseconds; P < 0.001). CONCLUSIONS: This study finds that results between the two versions of the BCM differed in a clinically meaningful fashion and that the newer version 3.3.3 device had a bias toward less OH. Circulating BCM devices should be checked for versions and only devices of the same version should be used for each patient to ensure better within-patient consistency.

Ultrafiltration-induced decrease in relative blood volume is larger in hemodialysis patients with low specific blood volume: Results from a dialysate bolus administration study.

INTRODUCTION: Prescribing the ultrafiltration in hemodialysis patients remains challenging and might benefit from the information on absolute blood volume, estimated by intradialytic dialysate bolus administration. Here, we aimed at determining the relationship between absolute blood volume, normalized for body mass (specific blood volume, Vs), and ultrafiltration-induced decrease in relative blood volume (∆RBV) as well as clinical parameters including body mass index (BMI). METHODS: This retrospective analysis comprised 77 patients who had their dialysate bolus-based absolute blood volume extracted routinely with an automated method. Patient-specific characteristics and ∆RBV were analyzed as a function of Vs, dichotomizing the data above or below a previously proposed threshold of 65 ml/kg for Vs. Statistical methodology comprised descriptive analyses, two-group comparisons, and correlation analyses. FINDINGS: Median Vs was 68.6 ml/kg (54.9 ml/kg [Quartile 1], 83.4 ml/kg [Quartile 3]). Relative blood volume decreased by 6.3% (2.6%, 12.2%) over the entire hemodialysis session. Vs correlated inversely with BMI (rs  = -0.688, p < 0.001). ∆RBV was 9.8% in the group of patients with Vs <65 ml/kg versus 6.0% in the group of patients with Vs ≥65 ml/kg (p = 0.024). The two groups did not differ significantly regarding their specific ultrafiltration volume, normalized for body mass, which amounted to 34.1 ml/kg and 36.0 ml/kg in both groups, respectively (p = 0.630). ∆RBV correlated inversely with Vs (rs  = -0.299, p = 0.008). DISCUSSION: The present study suggests that patients with higher BMI and lower Vs experience larger blood volume changes, despite similar ultrafiltration requirements. These results underline the clinical plausibility and importance of dialysate bolus-based absolute blood volume determination in the assessment of target weight, especially in view of a previous study where intradialytic morbid events could be decreased when the target weight was adjusted, based on Vs.

Revisiting the concept of constant tissue conductivities for volume estimation in dialysis patients using bioimpedance spectroscopy.

RATIONALE: Current estimation of body fluid volumes in hemodialysis patients using bioimpedance analysis assumes constant specific electrical characteristics of biological tissues despite a large variation in plasma Na+ concentrations [Na+], ranging from 130 to 150 mmol/L. Here, we examined the potential effect of variable [Na+] on bioimpedance-derived volume overload. METHOD: Volumes were calculated from published whole-body extra- and intracellular resistance data and relationships using either "standard" or "revised" specific electrical characteristics modeled as functions of [Na+]. RESULT: With "standard" assumptions, volumes increased with increasing [Na+]. The increase in volume overload was about 0.5 dm3 and 3% of extracellular volume per 10 mmol/dm3 of [Na+] in a 75 kg patient. This increase was abolished when the same bioimpedance data were analyzed under "revised" conditions. DISCUSSION: The overestimation in extracellular volume overload in the range of 0.5 dm3 per 10 mmol/dm3 [Na+] perfectly matches the positive relationship determined in a large cohort of hemodialysis patients. The bias may be considered moderate when interpreting data of individual patients, but may become important when comparing data of larger patient groups. The bias disappears when analysis of bioimpedance data accounts for differences in tissue electrical properties, using individual [Na+].

Chronic kidney disease is more prevalent among women but more men than women are under nephrological care : Analysis from six outpatient clinics in Austria 2019.

BACKGROUND: A discrepancy between sex-specific treatment of kidney failure by dialysis (higher in men) and the prevalence of chronic kidney disease in the general population (higher in women) has been reported internationally, but the prevalence by sex has not been described for Austria. Sex disparity among nephrology outpatients has not been studied. METHODS: We employed two formulae (2009 CKD-EPI suppressing the race factor, and race-free 2021 CKD-EPI) to estimate the sex distribution of CKD in Austrian primary care, based on creatinine measurements recorded in a medical sample of 39,800 patients from general practitioners' offices (1989-2008). Further, we collected information from all clinic appointments scheduled at nephrology departments of 6 Austrian hospitals (Wien, Linz, Wels, St. Pölten, Villach, Innsbruck) during 2019 and calculated visit frequencies by sex. RESULTS: Using the 2009 CKD-EPI formula, the prevalence of CKD in stages G3-G5 (estimated glomerular filtration rate < 60 mL/min/1.73 m2) was 16.4% among women and 8.5% among men aged > 18 years who had attended general practitioners' offices in Austria between 1989 and 2008 and had at least one creatinine measurement performed. Using the 2021 CKD-EPI formula, the respective CKD prevalence was 12.3% among women and 6.1% among men. In 2019, 45% of all outpatients at 6 participating nephrology departments were women. The median of nephrology clinic visits in 2019 was two (per year) for both sexes. CONCLUSION: CKD is more prevalent among Austrian women than men. Men are more prevalent in nephrology outpatient services. Research into causes of this sex disparity is urgently needed.

The systemic renin-angiotensin system in COVID-19.

SARS-CoV-2 gains cell entry via angiotensin-converting enzyme (ACE) 2, a membrane-bound enzyme of the "alternative" (alt) renin-angiotensin system (RAS). ACE2 counteracts angiotensin II by converting it to potentially protective angiotensin 1-7. Using mass spectrometry, we assessed key metabolites of the classical RAS (angiotensins I-II) and alt-RAS (angiotensins 1-7 and 1-5) pathways as well as ACE and ACE2 concentrations in 159 patients hospitalized with COVID-19, stratified by disease severity (severe, n = 76; non-severe: n = 83). Plasma renin activity (PRA-S) was calculated as the sum of RAS metabolites. We estimated ACE activity using the angiotensin II:I ratio (ACE-S) and estimated systemic alt-RAS activation using the ratio of alt-RAS axis metabolites to PRA-S (ALT-S). We applied mixed linear models to assess how PRA-S and ACE/ACE2 concentrations affected ALT-S, ACE-S, and angiotensins II and 1-7. Median angiotensin I and II levels were higher with severe versus non-severe COVID-19 (angiotensin I: 86 versus 30 pmol/L, p < 0.01; angiotensin II: 114 versus 58 pmol/L, p < 0.05), demonstrating activation of classical RAS. The difference disappeared with analysis limited to patients not taking a RAS inhibitor (angiotensin I: 40 versus 31 pmol/L, p = 0.251; angiotensin II: 76 versus 99 pmol/L, p = 0.833). ALT-S in severe COVID-19 increased with time (days 1-6: 0.12; days 11-16: 0.22) and correlated with ACE2 concentration (r = 0.831). ACE-S was lower in severe versus non-severe COVID-19 (1.6 versus 2.6; p < 0.001), but ACE concentrations were similar between groups and correlated weakly with ACE-S (r = 0.232). ACE2 and ACE-S trajectories in severe COVID-19, however, did not differ between survivors and non-survivors. Overall RAS alteration in severe COVID-19 resembled severity of disease-matched patients with influenza. In mixed linear models, renin activity most strongly predicted angiotensin II and 1-7 levels. ACE2 also predicted angiotensin 1-7 levels and ALT-S. No single factor or the combined model, however, could fully explain ACE-S. ACE2 and ACE-S trajectories in severe COVID-19 did not differ between survivors and non-survivors. In conclusion, angiotensin II was elevated in severe COVID-19 but was markedly influenced by RAS inhibitors and driven by overall RAS activation. ACE-S was significantly lower with severe COVID-19 and did not correlate with ACE concentrations. A shift to the alt-RAS axis because of increased ACE2 could partially explain the relative reduction in angiotensin II levels.

Criteria for prediabetes and posttransplant diabetes mellitus after kidney transplantation: A 2-year diagnostic accuracy study of participants from a randomized controlled trial.

Posttransplant diabetes mellitus (PTDM) and prediabetes (impaired glucose tolerance [IGT] and impaired fasting glucose [IFG]) are associated with cardiovascular events. We assessed the diagnostic performance of fasting plasma glucose (FPG) and HbA1c as alternatives to oral glucose tolerance test (OGTT)-derived 2-hour plasma glucose (2hPG) using sensitivity and specificity in 263 kidney transplant recipients (KTRs) from a clinical trial. Between visits at 6, 12, and 24 months after transplantation, 28%-31% of patients switched glycemic category (normal glucose tolerance [NGT], IGT/IFG, PTDM). Correlations of FPG and HbA1c against 2hPG were lower at 6 months (r = 0.59 [FPG against 2hPG]; r = 0.45 [HbA1c against 2hPG]) vs. 24 months (r = 0.73 [FPG against 2hPG]; r = 0.74 [HbA1c against 2hPG]). Up to 69% of 2hPG-defined PTDM cases were missed by conventional HbA1c and FPG thresholds. For prediabetes, concordance of FPG and HbA1c with 2hPG ranged from 6%-9%. In conclusion, in our well-defined randomized trial cohort, one-third of KTRs switched glycemic category over 2 years and although the correlations of FPG and HbA1c with 2hPG improved with time, their diagnostic concordance was poor for PTDM and, especially, prediabetes. Considering posttransplant metabolic instability, FPG's and HbA1c 's diagnostic performance, the OGTT remains indispensable to diagnose PTDM and prediabetes after kidney transplantation.

Feasibility of Dialysate Bolus-Based Absolute Blood Volume Estimation in Maintenance Hemodialysis Patients.

BACKGROUND: Absolute blood volume (ABV) is a critical component of fluid status, which may inform target weight prescriptions and hemodynamic vulnerability of dialysis patients. Here, we utilized the changes in relative blood volume (RBV), monitored by ultrasound (BVM) upon intradialytic 240 mL dialysate fluid bolus-infusion 1 h after hemodialysis start, to calculate the session-specific ABV. With the main goal of assessing clinical feasibility, our sub-aims were to (i) standardize the BVM-data read-out; (ii) determine optimal time-points for ABV-calculation, "before-" and "after-bolus"; (iii) assess ABV-variation. METHODS: We used high-level programming language and basic descriptive statistics in a retrospective study of routinely measured BVM-data from 274 hemodialysis sessions in 98 patients. RESULTS: Regarding (i) and (ii), we automatized the processing of RBV-data, and determined an algorithm to select the adequate RBV-data points for ABV-calculations. Regarding (iii), we found in 144 BVM-curves from 75 patients, that the average ABV ± standard deviation was 5.2 ± 1.5 L and that among those 51 patients who still had ≥2 valid estimates, the average intra-patient standard deviation in ABV was 0.8 L. Twenty-seven of these patients had an average intra-patient standard deviation in ABV <0.5 L. CONCLUSIONS: We demonstrate feasibility of ABV-calculation by an automated algorithm after dialysate bolus-administration, based on the BVM-curve. Based on our results from this simple "abridged" calculation approach with routine clinical measurements, we encourage the use of multi-compartment modeling and comparison with reference methods of ABV-determination. Hopes are high that clinicians will be able to use ABV to inform target weight prescription, improving hemodynamic stability.

Early Postoperative Basal Insulin Therapy versus Standard of Care for the Prevention of Diabetes Mellitus after Kidney Transplantation: A Multicenter Randomized Trial.

BACKGROUND: Post-transplantation diabetes mellitus (PTDM) might be preventable. METHODS: This open-label, multicenter randomized trial compared 133 kidney transplant recipients given intermediate-acting insulin isophane for postoperative afternoon glucose ≥140 mg/dl with 130 patients given short-acting insulin for fasting glucose ≥200 mg/dl (control). The primary end point was PTDM (antidiabetic treatment or oral glucose tolerance test-derived 2 hour glucose ≥200 mg/dl) at month 12 post-transplant. RESULTS: In the intention-to-treat population, PTDM rates at 12 months were 12.2% and 14.7% in treatment versus control groups, respectively (odds ratio [OR], 0.82; 95% confidence interval [95% CI], 0.39 to 1.76) and 13.4% versus 17.4%, respectively, at 24 months (OR, 0.71; 95% CI, 0.34 to 1.49). In the per-protocol population, treatment resulted in reduced odds for PTDM at 12 months (OR, 0.40; 95% CI, 0.16 to 1.01) and 24 months (OR, 0.54; 95% CI, 0.24 to 1.20). After adjustment for polycystic kidney disease, per-protocol ORs for PTDM (treatment versus controls) were 0.21 (95% CI, 0.07 to 0.62) at 12 months and 0.35 (95% CI, 0.14 to 0.87) at 24 months. Significantly more hypoglycemic events (mostly asymptomatic or mildly symptomatic) occurred in the treatment group versus the control group. Within the treatment group, nonadherence to the insulin initiation protocol was associated with significantly higher odds for PTDM at months 12 and 24. CONCLUSIONS: At low overt PTDM incidence, the primary end point in the intention-to-treat population did not differ significantly between treatment and control groups. In the per-protocol analysis, early basal insulin therapy resulted in significantly higher hypoglycemia rates but reduced odds for overt PTDM-a significant reduction after adjustment for baseline differences-suggesting the intervention merits further study.Clinical Trial registration number: NCT03507829.

Sex Differences in Kidney Transplantation: Austria and the United States, 1978-2018.

BACKGROUND: Systematic analyses about sex differences in wait-listing and kidney transplantation after dialysis initiation are scarce. We aimed at identifying sex-specific disparities along the path of kidney disease treatment, comparing two countries with distinctive health care systems, the US and Austria, over time. METHODS: We analyzed subjects who initiated dialysis from 1979-2018, in observational cohort studies from the US and Austria. We used Cox regression to model male-to-female cause-specific hazard ratios (csHRs, 95% confidence intervals) for transitions along the consecutive states dialysis initiation, wait-listing, kidney transplantation and death, adjusted for age and stratified by country and decade of dialysis initiation. RESULTS: Among 3,053,206 US and 36,608 Austrian patients starting dialysis, men had higher chances to enter the wait-list, which however decreased over time [male-to-female csHRs for wait-listing, 1978-1987: US 1.94 (1.71, 2.20), AUT 1.61 (1.20, 2.17); 2008-2018: US 1.35 (1.32, 1.38), AUT 1.11 (0.94, 1.32)]. Once wait-listed, the advantage of the men became smaller, but persisted in the US [male-to-female csHR for transplantation after wait-listing, 2008-2018: 1.08 (1.05, 1.11)]. The greatest disparity between men and women occurred in older age groups in both countries [male-to-female csHR for wait-listing after dialysis, adjusted to 75% age quantile, 2008-2018: US 1.83 (1.74, 1.92), AUT 1.48 (1.02, 2.13)]. Male-to-female csHRs for death were close to one, but higher after transplantation than after dialysis. CONCLUSIONS: We found evidence for sex disparities in both countries. Historically, men in the US and Austria had 90%, respectively, 60% higher chances of being wait-listed for kidney transplantation, although these gaps decreased over time. Efforts should be continued to render kidney transplantation equally accessible for both sexes, especially for older women.

Sex differences in chronic kidney disease awareness among US adults, 1999 to 2018.

BACKGROUND: Chronic kidney disease (CKD) is less prevalent among men than women, but more men than women initiate kidney replacement therapy. Differences in CKD awareness may contribute to this gender gap, which may further vary by race/ethnicity. We aimed to investigate trends in CKD awareness and the association between individual characteristics and CKD awareness among US men versus women. METHODS AND FINDINGS: We conducted a serial, cross-sectional analysis of 10 cycles (1999-2018) from the National Health and Nutrition Examination Survey (NHANES). Adult participants with CKD stages G3-G5 (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73m2) were included, unless they were on dialysis or medical information was missing. Serum creatinine was measured during NHANES medical exams. CKD stage was classified by eGFR, based on the CKD-EPI formula. CKD awareness was assessed with the question: "Have you ever been told by a health care professional you had weak or failing kidneys", asked in standardized NHANES questionnaires on each survey. Using logistic regression models, we evaluated the association between sex and CKD awareness, adjusting for potential confounders including age, race/ethnicity and comorbidities. We stratified CKD awareness by 5 pre-defined calendar-year periods and conducted all analyses for the complete study population as well as the Caucasian and African American subpopulations. We found that among 101871 US persons participating in NHANES, 4411 (2232 women) had CKD in stages G3-G5. These participants were, on average, 73±10 years old, 25.3% reported diabetes, 78.0% reported hypertension or had elevated blood pressure during medical examinations and 39.8% were obese (percentages were survey-weighted). CKD awareness was more prevalent among those with higher CKD stage, younger age, diabetes, hypertension and higher body mass index. CKD awareness was generally low (<22.5%), though it increased throughout the study period, remaining consistently higher among men compared to women, with a decreasing gender gap over time (adjusted odds ratio [men-to-women] for CKD awareness = 2.71 [1.31-5.64] in period 1; = 1.32 [0.82-2.12] in period 5). The sex difference in CKD awareness was smaller in African American participants, in whom CKD awareness was generally higher. Using serum creatinine rather than eGFR as the CKD-defining exposure, CKD awareness increased with rising serum creatinine, in a close to identical fashion among both sexes during 1999-2008, while during 2009-2018, CKD awareness among women increased earlier than among men (i.e. with lower serum creatinine levels). CONCLUSIONS: CKD awareness is lower among US women than men. The narrowing gap between the sexes in more recent years and the results on CKD awareness by serum creatinine indicate that health care professionals have previously been relying on serum creatinine to inform patients about their condition, but in more recent years have been using eGFR, which accounts for women's lower serum creatinine levels due to their lower muscle mass. Additional efforts should be made to increase CKD awareness among both sexes.

Supramacroparticulate PE in 6 different joint endoprostheses localisations: An indicator for PE damage?

In the histopathological particle algorithm polyethylene (PE) particles with maximum lengths of more than 100µm - called PE supramacroparticles - are identified exclusively for knee joint and hip prostheses. However, a definitive characterisation, detection in all joint localisations and a causal clarification of the pathogenesis are lacking. In this study a total of 175 SLIM (synovial-like interface membrane) cases with PE supramacroparticles of knee joint prostheses (n=89), hip joint prostheses (n=44), ankle joint prostheses (n=36) and prostheses in three localisations of the upper extremities (n=6) were systematically investigated. The arithmetic mean of the particle length varied greatly within the prosthesis types. This had a significant positive correlation with the prosthesis lifetime and negative correlation with the date of implantation. It can be concluded that both the lifetime and the time of implantation have an influence on the particle length. The prostheses with supramacroparticulate damage moreover showed a clearly reduced survival rate compared with other data published on the prosthesis lifetime. The material wear therefore could not be attributed solely to the usual fatigue factors. Since loosening of the prostheses, decentring of the PE components or damage to the PE inlay existed in all cases, mechanical dysloading seems to be the most probable cause of PE supramacroparticle genesis. Due to the striking length and for demarcation from PE macroparticles, the term supramacroparticulate PE is proposed for a length of more than 100µm. In the extended histopathological particle algorithm supramacroparticulate PE has been included in the macroparticles category and should be taken into account and interpreted causally in histopathological diagnostics of joint prosthesis failure.