Delayed post-dialysis recovery times are associated with relative changes in intracellular and extracellular fluid ratios between different body compartments.

INTRODUCTION: Hemodialysis patient groups have advocated reducing dialysis fatigue and symptoms. We investigated whether compartmental fluid shifts were associated with peri-dialytic fatigue and symptoms. METHODS: Sessional dialysis records of patients reporting both a short and delayed recovery (<1 h and ≥1 h) with corresponding bioimpedance measurements were reviewed. RESULTS: One hundred and twenty-four patients reported both short and delayed recovery times, mean age 66.0 ± 14.8 years, 66.1% male. Differences between sessions included higher distress thermometer [4 (1-6) vs. 3 (0-5)], fatigue [4 (0-9) vs. 2 (0-7)], total symptom scores [20.5 (12.3-34.5) vs. 16 (7-28)], change in extracellular water to total body water ratios between body compartments [right leg/left arm 2.36 (1.23-4.19) vs. 1.28 (0.12-2.01), all p < 0.01] with delayed recovery, and more hemodialysis than hemodiafiltration sessions (χ2 4.6, p = 0.02). CONCLUSION: Sessions with prolonged recovery times were associated with more peri-dialytic symptoms, psychological distress, and hemodialysis mode, and greater changes in compartmental fluid shifts.

Do patients dialysing with higher ultrafiltration rates report more intradialytic symptoms and longer postdialysis recovery times?

BACKGROUND: Many hemodialysis (HD) patients report intradialytic symptoms, and take time to recover postdialysis. To improve quality of life, patient groups have highlighted the need to reduce postdialysis fatigue and other peridialytic symptoms. As compartmental shifts of fluid during dialysis have been proposed to cause peridialytic symptoms we investigated whether patients dialysing with higher ultrafiltration rates (UFR) reported more intradialytic symptoms and recovery times. METHODS: We reviewed the hospital records of HD patients who completed a self-reported intradialytic symptom questionnaire, using a visual analogue scale, who had contemporaneous midweek pre- and postdialysis segmental bioimpedance measurements. RESULTS: Six hundred and five patients returned the peridialytic symptom questionnaire with pre- and postdialysis bioimpedance measurements. The majority were male (64.8%), mean age 64.2 ± 15.6 years, duration of dialysis treatment 26.8 (10.7-59.2) months, 85% treated by hemodiafiltration and mean dialysate temperature 35.4 ± 0.4°C. We divided patients into terciles according to UFR adjusted for weight, and there was a greater fall in the ratio of extracellular water (ECW) to total body water (TBW) postdialysis in the nonfistula arm from the lower to middle to higher tercile (0.8 (0-1.54) vs. 1.28 (0.52-1.85) vs. 1.54 (0.78-2.52)), trunk (1.5 (0.74-2.27) vs. 1.53 (0.99-2.2) vs. 1.98 (1.18-2.66)), left leg (1.56 (0.49-2.25) vs. 1.77 (1.24-2.43) vs. 2.08 (1.18-2.95)), lower versus higher tercile p < 0.05. However, no differences in intradialytic symptoms or postdialysis recovery times between the UFR terciles were observed. CONCLUSION: There were no differences in self-reported intradialytic symptoms or postdialysis recovery times with differing UFRs, despite changes in intracompartmental fluid shifts as measured by changes in ECW/TBW.

Hemodialysis patients with less extracellular water overload and smaller cardiac atrial chamber sizes are at greater risk of a fall in blood pressure during dialysis.

Intradialytic hypotension is the most common complication of hemodialysis (HD) treatments. Excessive ultrafiltration results in reduced cardiac preload. We aimed to determine whether a fall in systolic blood pressure during HD was greater in patients starting HD with (a) less overhydration measured by extracellular water (ECW) and (b) lower cardiac preload by cardiac magnetic resonance imaging (MRI). Pre-HD measurements of ECW and total body water (TBW) were performed using multifrequency bioimpedance (MFBIA). Cardiac chamber sizes and functions were determined by MRI. Twenty-six patients, 18 males (69.2%), 11 (42.3%) with diabetes, mean age 63.9 ± 15.9 years were studied. Systolic blood pressure (SBP) fell in 15 (57.7%) patients, and either did not change or increased in 9. There was no difference in demographics between groups. Patients with a fall in SBP had lower pre-HD ECW/TBW (0.400 ± 0.018 vs 0.418 ± 0.021), indexed right ventricular end-diastolic volume (81.2 ± 37.6 vs 100.8 ± 33.7 mL/m2 ), and indexed left atrial size (13.7 ± 3.9 vs 18.3 ± 5.0 mL/m2 ), all P < .05, respectively. There were univariate correlations between the change in SBP and pre-HD ECW/TBW for the trunk (r = .50, P = .009) and indexed left atrial volume (r = .54, P = .005). A fall in blood pressure occurred more commonly in patients starting HD with lower overhydration as measured by bioimpedance, and those with smaller cardiac chamber sizes. Patients with the lowest ECW/TBW and smallest cardiac chamber sizes had the greatest falls in SBP. This study reinforces the importance of determining physiological target weights and avoiding inappropriately low target weights for HD patients.

Pilot Study to Detect Changes in Blood Flow in the External Auditory Meatus During Hemodialysis.

Blood flow to internal organs is reported to fall during hemodialysis (HD). As such, noninvasive monitoring devices are required to detect changes in perfusion, which could then be used for therapeutic interventions. We report on a pilot study monitoring blood flow in the outer auditory meatus. We measured the maximum pulse wave amplitude and indicators of blood flow by analyzing red and green color changes in the outer auditory meatus from video recordings made using an otoscope fitted with a digital camera during HD treatments. We studied 61 patients, 43 (71.5%) male, mean age 64.9 ± 12.7 years. Weight fell from 72.8 ± 22.5 kg predialysis to 71.5 ± 22.1 kg postdialysis (P < 0.001). BP did not significantly change (predialysis 142 ± 29/67 ± 18 to 143 ± 25/68 ± 17 mm Hg postdialysis). The maximum pulse wave amplitude in the external auditory meatus fell from 0.21 (0.1-0.55) to 0.14 (0.04-0.4) after 90 min, P < 0.001, and remained low thereafter, and the change at the end of the dialysis session was associated with percentage weight loss (r = -0.37, P = 0.003). Green and red pixel values did not change (predialysis 0.339 [0.333-0.345] to 0.302 [0.291-0.33] post, and 0.301 [0.293-0.328] predialysis to 0.339 [0.334-0.347] post, respectively). This pilot study showed that the maximum pulse wave amplitude measured in the external auditory meatus fell during the dialysis session, and that the fall was associated with fluid removal. This could potentially lead to the development of a monitoring device, which could fit in the ear and record during the dialysis session.

Acute changes in cardiac structural and tissue characterisation parameters following haemodialysis measured using cardiovascular magnetic resonance.

In patients with chronic kidney disease (CKD), reverse left ventricular (LV) remodelling, including reduction in LV mass, can be observed following long-term haemodialysis (HD) and has been attributed to regression of LV hypertrophy. However, LV mass can vary in response to changes in myocyte volume, edema, or fibrosis. The aims of this study were to investigate the acute changes in structural (myocardial mass and biventricular volumes) and tissue characterization parameters (native T1 and T2) following HD using cardiovascular magnetic resonance (CMR). Twenty-five stable HD patients underwent non-contrast CMR including volumetric assessment and native T1 and T2 mapping immediately pre- and post-HD. The mean time between the first and second scan was 9.1 ± 1.1 hours and mean time from completion of dialysis to the second scan was 3.5 ± 1.3 hours. Post-HD, there was reduction in LV mass (pre-dialysis 98.9 ± 36.9 g/m2 vs post-dialysis 93.3 ± 35.8 g/m2, p = 0.003), which correlated with change in body weight (r = 0.717, p < 0.001). Both native T1 and T2 reduced significantly following HD (Native T1: pre-dialysis 1085 ± 43 ms, post-dialysis 1072 ± 43 ms; T2: pre-dialysis 53.3 ± 3.0 ms, post-dialysis 51.8 ± 3.1 ms, both p < 0.05). These changes presumably reflect acute reduction in myocardial water content rather than regression of LV hypertrophy. CMR with multiparametric mapping is a promising tool to assess the cardiac changes associated with HD.

Relationships Between Peritoneal Protein Clearance and Parameters of Fluid Status Agree with Clinical Observations in Other Diseases that Venous Congestion Increases Microvascular Protein Escape.

BACKGROUND: Peritoneal effluent from peritoneal dialysis (PD) patients contains proteins, mainly transported from the circulation through large pores in the venular part of the peritoneal microvessels. Hydrostatic convection is the major driver for peritoneal protein transport, although in PD there is additional diffusion. Consequently, venous pressure may have a role in peritoneal protein transport. The aim of the study was to investigate the importance of venous congestion on the magnitude of peritoneal protein clearance in incident PD patients using non-invasive measurements. METHODS: A total of 316 adult PD patients, on PD for 8 - 12 weeks and collecting 24-hour urine and dialysate for total protein determination, underwent standard peritoneal equilibration testing (PET) along with measurement of N terminal pro-brain natriuretic peptide (NT-proBNP) and C-reactive protein (CRP), multifrequency bioimpedance analysis, and a transthoracic echocardiogram. RESULTS: Statistically significant univariate relationships for peritoneal protein clearance with a Spearman correlation coefficient > 0.25 were present for 4-hour dialysate/plasma (D/P) creatinine, NT-proBNP, extracellular/total body water, extracellular water excess, left ventricular mass, and right atrial area. Negative correlations were found with serum total protein and residual renal function. On multivariate analysis, logNTproBNP (ß 0.11, p = 0.007) and right atrial area (ß 0.01, p = 0.03) were significant independent predictors of peritoneal protein clearance. CONCLUSION: Indicators of venous congestion showed the most important relationships with peritoneal protein clearance. These indicators have not been assessed in previous studies on the presence or absence of relationships between peritoneal protein clearance and mortality.

Do Pre-Hemodialysis Estimates of Extracellular Volume Excess Using Bioimpedance and N-Terminal Brain Natriuretic Peptide Correlate With Cardiac Chamber Size Measured by Magnetic Resonance Imaging?

Bioimpedance can be used to measure extracellular water (ECW) and total body water in hemodialysis (HD) patients and estimate ECW excess. However, ECW excess potentially includes both an increase in the plasma volume and also the extravascular volume. Overestimating the amount of fluid to be removed during HD risks intra-dialytic hypotension. We wished to determine the association between estimates of ECW excess comparing several different equations using bioimpedance, brain N-terminal pro-brain natriuretic peptide (NT-proBNP) with cardiac chamber volumes and function as determined by cardiac magnetic resonance imaging pre-HD measurements of ECW and total body water were made using multifrequency bioimpedance and cardiac chamber sizes and function were determined by magnetic resonance imaging. Thirty patients, 20 males (66.7%), mean age 64.4 ± 15.3 years were studied. ECW and ECW/height were positively associated with indexed right ventricular end-systolic (RVESVi) and end-diastolic volume (RVEDVi) (RVESi r = 0.46, r = 0.43; RVEDi r = 0.50, r = 0.44, all P < 0.05), but not with left sided cardiac volumes. Whereas NT-proBNP was associated with indexed left atrial and ventricular size (r = 0.47, r = 0.58, P < 0.05), but not right sided cardiac volumes. Pre-HD NT-proBNP was associated with left sided cardiac chamber sizes, but not with right sided chamber sizes, whereas ECW/height was associated with right sided cardiac chamber sizes. As right-sided cardiac chamber size is more responsive to and reflective of changes in intravascular volume than the left atrium and ventricle, then bioimpedance measured ECW is potentially more reliable in estimating plasma volume expansion.

Estimation of lean body mass by creatinine kinetics increases the prevalence of muscle wasting in peritoneal dialysis patients compared to bioimpedance.

Dialysis patients are at increased risk for muscle wasting, and time efficient screening tests are required for to allow for early detection. Creatinine kinetics have been advocated to estimate lean body mass (LBM) in peritoneal dialysis (PD) patients, and can be readily calculated in clinical practice from peritoneal dialysate effluent and urine collections. Bioimpedance is increasingly available, and we compared methods in 434 PD patients (55% men, 33.3% diabetics), mean age 55.2 ± 16.2 years. LBM was lower by creatinine kinetics (47.8 ± 16.6 kg men, 37.8 ± 11.2 kg women) vs. bioimpedance (53.2 ± 11.5 kg men, 39.2 ± 7.2 kg women), p < 0.01. The prevalence of muscle wasting was much greater using creatinine kinetics (72.4% men, 52.4% women) vs. bioimpedance (55.2% men, 37.3%), p < 0.05. Estimates of LBM were much lower using creatinine kinetics compared to bioimpedance. Studies reporting the prevalence of muscle loss in PD patients will differ depending upon the method used to estimate muscle mass.

Peritoneal Protein Losses Depend on More Than Just Peritoneal Dialysis Modality and Peritoneal Membrane Transporter Status.

Peritoneal protein clearance (PPCl) depends upon vascular supply and size selective permeability. Some previous reports suggested PPCl can distinguish fast peritoneal membrane transport due to local or systemic inflammation. However, as studies have been discordant, we wished to determine factors associated with an increased PPCl. Consecutive patients starting peritoneal dialysis (PD) who were peritonitis-free were studied. Data included a baseline peritoneal equilibration test (PET), measurement of dialysis adequacy, 24-h dialysate PPCl and body composition measured by multifrequency bioimpedance. 411 patients, mean age 57.2 ± 16.6 years, 60.8% male, 39.4% diabetic, 20.2% treated by continuous ambulatory peritoneal dialysis (CAPD) were studied. Mean PET 4-h Dialysate/Serum creatinine was 0.73 ± 0.13, with daily peritoneal protein loss 4.6 (3.3-6.4) g, and median PPCl 69.6 (49.1-99.6) mL/day. On multivariate analysis, PPCl was most strongly associated with CAPD (ß 0.25, P < 0.001), extracellular water (ECW)/total body water (TBW) ratio (ß 0.21, P < 0.001), skeletal muscle mass index (ß 0.21, P < 0.001), log N-terminal brain natriuretic peptide (NT-proBNP) (ß 0.17, P = 0.001), faster PET transport (ß 0.15, P = 0.005), and normalized nitrogen appearance rate (ß 0.13, P = 0.008). In addition to the longer dwell times of CAPD, greater peritoneal creatinine clearance and faster PET transporter status, we observed an association between increased PPCl and ECW expansion, increased NT-proBNP, estimated dietary protein intake and muscle mass, suggesting a link to sodium intake and sodium balance, increasing both ECW and conduit artery hydrostatic pressure resulting in greater vascular protein permeability. This latter association may explain reports linking PPCl to patient mortality.

The prevalence of muscle wasting (sarcopenia) in peritoneal dialysis patients varies with ethnicity due to differences in muscle mass measured by bioimpedance.

BACKGROUND/OBJECTIVES: Sarcopenia is associated with increased mortality. European and North American recommended screening for low muscle mass uses gender specific cut points, with no adjustment for ethnicity. We wished to determine whether the prevalence of sarcopenia was altered by ethnicity in peritoneal dialysis (PD) patients. SUBJECTS/METHODS: We measured appendicular lean mass indexed to height (ALMI) in PD patients by segmental bioimpedance and determined sarcopenia using different cut off points for reduced muscle mass. RESULTS: We measured ALMI in 434 PD patients, 55.1% males, mean age 55.3 ± 16.2 years, 32.3% diabetic, 54.1% white, 23.7% Asian, 19.1% black. ALMI was lower in Asian women, compared to white and black women (6.4 ± 1.1 vs. 6.6 ± 1.0 and 6.9 ± 1.4 kg/m2), and lower in Asian men (7.5 ± 1.3 vs. 8.5 ± 1.2 and 8.7 ± 1.3 kg/m2), p < 0.001. Depending on the ALM/ALMI cut point; the prevalence of sarcopenia was greater in Asian patients (25.6-41.2% using North American or European cut points) compared to white (12.3-18.7%) and black patients (3.8-15.7%), p < 0.001, but <11% when using Asian-specific cut points. The prevalence of sarcopenia obesity (BMI ≥ 30 kg/m2) was <3%, for all groups. There was no association with duration of PD, dialysis prescription, residual renal function or small solute clearances. CONCLUSIONS: There is no universally agreed consensus definition for loss of muscle mass (sarcopenia) and current European and North American recommended cut points for screening are adjusted only for gender. As body composition differs also with age and ethnicity, then ideally cut points should be based on age, gender and ethnicity normative values.

Effect of Self-Reported Distress Thermometer Score on the Maximal Handgrip and Pinch Strength Measurements in Hemodialysis Patients.

BACKGROUND: Muscle weakness is a risk factor for mortality in hemodialysis (HD) patients. Muscle strength measurements are routinely used as a screening tool but depend on patient cooperation and motivation. We wished to determine whether measuring maximal voluntary muscle strength was affected by patient self-reported distress. METHODS: We measured pinch strength (PS) and handgrip strength (HGS) in 382 adult HD patients with a corresponding self-reported distress thermometer (DT) scores. Postdialysis body composition measurements were made using multifrequency bioelectrical assessments and patients assessed for frailty. RESULTS: Mean age was 66.4 ± 14.9 years, with 238 males (62%), 48% diabetic, and dialysis vintage 36 (15-75) months. The mean DT score was 4.4 ± 3.3, with a frailty score of 4.6 ± 1.5. On multivariable analysis, DT scores were associated with frailty (ß = 0.35, P = .003), prescription of aspirin for cardiac disease (ß = 1.0, P = .004), lean body mass (ß = 0.04, P = .004), and negatively with age (ß = -0.05, P < .001), hematocrit (ß = -8.2, P = .004), and maximum PS (ß = -1.4, P = .003). CONCLUSION: Paradoxically higher self-reported DT scores were associated with younger age and lean body mass. As such, younger healthier, rather than more comorbid, patients may have greater expectations for their health and therefore report more distress. We found no association between DT scores and HGS, and as such, although HGS is a voluntary test, it appears to be a robust test independent of patient stresses. However, PS was lower in patients with higher DT scores, and as such, greater care may be required in interpreting these measurements.