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Chronic kidney disease (CKD) is classified into five stages with kidney failure being the most severe stage (stage G5). CKD conveys a high risk for coronary artery disease, heart failure, arrhythmias, and sudden cardiac death. Cardiovascular complications are the most common causes of death in patients with kidney failure (stage G5) who are maintained on regular dialysis treatment. Because of the high death rate attributable to cardiovascular (CV) disease, most patients with progressive CKD die before reaching kidney failure. Classical risk factors implicated in CV disease are involved in the early stages of CKD. In intermediate and late stages, non-traditional risk factors, including iso-osmotic and non-osmotic sodium retention, volume expansion, anaemia, inflammation, malnutrition, sympathetic overactivity, mineral bone disorders, accumulation of a class of endogenous compounds called 'uremic toxins', and a variety of hormonal disorders are the main factors that accelerate the progression of CV disease in these patients. Arterial disease in CKD patients is characterized by an almost unique propensity to calcification and vascular stiffness. Left ventricular hypertrophy, a major risk factor for heart failure, occurs early in CKD and reaches a prevalence of 70–80% in patients with kidney failure. Recent clinical trials have shown the potential benefits of hypoxia-inducible factor prolyl hydroxylase inhibitors, especially as an oral agent in CKD patients. Likewise, the value of proactively administered intravenous iron for safely treating anaemia in dialysis patients has been shown. Sodium/glucose cotransporter-2 inhibitors are now fully emerged as a class of drugs that substantially reduces the risk for CV complications in patients who are already being treated with adequate doses of inhibitors of the renin-angiotensin system. Concerted efforts are being made by major scientific societies to advance basic and clinical research on CV disease in patients with CKD, a research area that remains insufficiently explored. [ABSTRACT FROM AUTHOR]

Background In maintenance hemodialysis patients, intradialytic hypotension (IDH) is a frequent complication that has been associated with poor clinical outcomes. Prediction of IDH may facilitate timely interventions and eventually reduce IDH rates. Methods We developed a machine learning model to predict IDH in in-center hemodialysis patients 15–75 min in advance. IDH was defined as systolic blood pressure (SBP) <90 mmHg. Demographic, clinical, treatment-related and laboratory data were retrieved from electronic health records and merged with intradialytic machine data that were sent in real-time to the cloud. For model development, dialysis sessions were randomly split into training (80%) and testing (20%) sets. The area under the receiver operating characteristic curve (AUROC) was used as a measure of the model's predictive performance. Results We utilized data from 693 patients who contributed 42   656 hemodialysis sessions and 355   693 intradialytic SBP measurements. IDH occurred in 16.2% of hemodialysis treatments. Our model predicted IDH 15–75 min in advance with an AUROC of 0.89. Top IDH predictors were the most recent intradialytic SBP and IDH rate, as well as mean nadir SBP of the previous 10 dialysis sessions. Conclusions Real-time prediction of IDH during an ongoing hemodialysis session is feasible and has a clinically actionable predictive performance. If and to what degree this predictive information facilitates the timely deployment of preventive interventions and translates into lower IDH rates and improved patient outcomes warrants prospective studies. [ABSTRACT FROM AUTHOR]

Informed decision-making is paramount to the improvement of dialysis therapies and patient outcomes. A cornerstone of delivery of optimal dialysis therapy is to delineate which substances (uraemic retention solutes or 'uraemic toxins') contribute to the condition of uraemia in terms of deleterious biochemical effects they may exert. Thereafter, decisions can be made as to which of the accumulated compounds need to be targeted for removal and by which strategies. For haemodialysis (HD), the non-selectivity of membranes is sometimes considered a limitation. Yet, considering that dozens of substances with potential toxicity need to be eliminated, and targeting removal of individual toxins explicitly is not recommended, current dialysis membranes enable elimination of several molecules of a broad size range within a single therapy session. However, because HD solute removal is based on size-exclusion principles, i.e. the size of the substances to be removed relative to the mean size of the 'pores' of the membrane, only a limited degree of selectivity of removal is possible. Removal of unwanted substances during HD needs to be weighed against the unavoidable loss of substances that are recognized to be necessary for bodily functions and physiology. In striving to improve the efficiency of HD by increasing the porosity of membranes, there is a greater potential for the loss of substances that are of benefit. Based on this elementary trade-off and availability of recent guidance on the relative toxicity of substances retained in uraemia, we propose a new evidence-linked uraemic toxin elimination (ELUTE) approach whereby only those clusters of substances for which there is a sufficient body of evidence linking them to deleterious biological effects need to be targeted for removal. Our approach involves correlating the physical properties of retention solutes (deemed to express toxicity) with key determinants of membranes and separation processes. Our analysis revealed that in attempting to remove the relatively small number of 'larger' substances graded as having only moderate toxicity, uncontrolled (and efficient) removal of several useful compounds would take place simultaneously and may compromise the well-being or outcomes of patients. The bulk of the uraemic toxin load comprises uraemic toxins below <30 000 Da and are adequately removed by standard membranes. Further, removal of a few difficult-to-remove-by-dialysis (protein-bound) compounds that express toxicity cannot be achieved by manipulation of pore size alone. The trade-off between the benefits of effective removal of the bulk of the uraemic toxin load and risks (increased loss of useful substances) associated with targeting the removal of a few larger substances in 'high-efficiency' HD treatment strategies needs to be recognized and better understood. The removability during HD of substances, be they toxic, inert or beneficial, needs be revised to establish the pros and cons of current dialytic elimination strategies. [ABSTRACT FROM AUTHOR]

Background Dialysis patients are typically inactive and their physical activity (PA) decreases over time. Uremic toxicity has been suggested as a potential causal factor of low PA in dialysis patients. Post-dilution high-volume online hemodiafiltration (HDF) provides greater higher molecular weight removal and studies suggest better clinical/patient-reported outcomes compared with hemodialysis (HD). Methods HDFIT was a randomized controlled trial at 13 clinics in Brazil that aimed to investigate the effects of HDF on measured PA (step counts) as a primary outcome. Stable HD patients (vintage 3–24 months) were randomized to receive HDF or high-flux HD. Treatment effect of HDF on the primary outcome from baseline to 3 and 6 months was estimated using a linear mixed-effects model. Results We randomized 195 patients (HDF 97; HD 98) between August 2016 and October 2017. Despite the achievement of a high convective volume in the majority of sessions and a positive impact on solute removal, the treatment effect HDF on the primary outcome was +538 [95% confidence interval (CI) −330 to 1407] steps/24 h after dialysis compared with HD, and was not statistically significant. Despite a lack of statistical significance, the observed size of the treatment effect was modest and driven by steps taken between 1.5 and 24.0 h after dialysis, in particular between 20 and 24 h (+197 steps; 95% CI −95 to 488). Conclusions HDF did not have a statistically significant treatment effect on PA 24 h following dialysis, albeit effect sizes may be clinically meaningful and deserve further investigation. [ABSTRACT FROM AUTHOR]

Background Maintenance hemodialysis (MHD) patients are particularly vulnerable to coronavirus disease 2019 (COVID-19), a viral disease that may cause interstitial pneumonia, impaired alveolar gas exchange and hypoxemia. We ascertained the time course of intradialytic arterial oxygen saturation (SaO2) in MHD patients between 4 weeks pre-diagnosis and the week post-diagnosis of COVID-19. Methods We conducted a quality improvement project in confirmed COVID-19 in-center MHD patients from 11 dialysis facilities. In patients with an arterio-venous access, SaO2 was measured 1×/min during dialysis using the Crit-Line monitor (Fresenius Medical Care, Waltham, MA, USA). We extracted demographic, clinical, treatment and laboratory data, and COVID-19-related symptoms from the patients' electronic health records. Results Intradialytic SaO2 was available in 52 patients (29 males; mean ± standard deviation age 66.5 ± 15.7 years) contributing 338 HD treatments. Mean time between onset of symptoms indicative of COVID-19 and diagnosis was 1.1 days (median 0; range 0–9). Prior to COVID-19 diagnosis the rate of HD treatments with hypoxemia, defined as treatment-level average SaO2 <90%, increased from 2.8% (2–4 weeks pre-diagnosis) to 12.2% (1 week) and 20.7% (3 days pre-diagnosis). Intradialytic O2 supplementation increased sharply post-diagnosis. Eleven patients died from COVID-19 within 5 weeks. Compared with patients who recovered from COVID-19, demised patients showed a more pronounced decline in SaO2 prior to COVID-19 diagnosis. Conclusions In HD patients, hypoxemia may precede the onset of clinical symptoms and the diagnosis of COVID-19. A steep decline of SaO2 is associated with poor patient outcomes. Measurements of SaO2 may aid the pre-symptomatic identification of patients with COVID-19. [ABSTRACT FROM AUTHOR]

Background Evidence indicates that the inverse relationships between phosphate levels and mortality maybe modified by age. Furthermore, malnutrition and inflammation could strengthen the risk associated with phosphate abnormalities. This study aimed to assess the associations between phosphate levels and mortality while accounting for the interactions with age and parameters associated with malnutrition and inflammation in hemodialysis (HD) patients. Methods Adult HD patients (n  = 245 853) treated in Fresenius Medical Care North America clinics from January 2010 to October 2018 were enrolled. Baseline was defined as Months 4–6 on dialysis, with the subsequent 12 months as the follow-up period. Univariate and multivariate Cox proportional hazard models with spline terms were applied to study the nonlinear relationships between serum phosphate levels and mortality. The interactions of phosphate levels with albumin, creatinine, normalized protein catabolic rate (nPCR) and neutrophil–lymphocyte ratio (NLR) were assessed with smoothing spline analysis of variance Cox proportional hazard models. Results Older patients tended to have lower levels of serum phosphate, albumin, creatinine and nPCR. Additionally, both low (<4.0 mg/dL) and high (>5.5 mg/dL) phosphate levels were associated with higher risk of mortality across all age strata. The U-shaped relationships between phosphate levels and outcome persisted even for patients with low or high levels of serum albumin, creatinine, nPCR and NLR, respectively. Conclusion The consistent U-shaped relationships between serum phosphate and mortality across age strata and levels of inflammatory and nutritional status should prompt the search for underlying causes and potentially nutritional intervention in clinical practice. [ABSTRACT FROM AUTHOR]

Background Protein-energy wasting, muscle mass (MM) loss and sarcopenia are highly prevalent and associated with poor outcome in haemodialysis (HD) patients. Monitoring of MM and/or muscle metabolism in HD patients is of paramount importance for timely detection of muscle loss and to intervene adequately. In this study we assessed the reliability and reproducibility of a simplified creatinine index (SCI) as a surrogate marker of MM and explored its predictive value on outcome. Method We included all in-centre HD patients from 16 European countries with at least one SCI. The baseline period was defined as 30 days before and after the first multifrequency bioimpedance spectroscopy measurement; the subsequent 7 years constituted the follow-up. SCI was calculated by the Canaud equation. Multivariate Cox proportional hazards models were applied to assess the association of SCI with all-cause mortality. Using backward analysis, we explored the trends of SCI before death. Bland–Altman analysis was performed to analyse the agreement between estimated and measured MM. Results We included 23 495 HD patients; 3662 were incident. Females and older patients have lower baseline SCI. Higher SCI was associated with a lower risk of mortality [hazard ratio 0.81 (95% confidence interval 0.79–0.82)]. SCI decline accelerated ∼5–7 months before death. Lean tissue index (LTI) estimated by SCI was correlated with measured LTI in both sexes (males: R 2 = 0.94; females: R 2 = 0.92; both P < 0.001). Bland–Altman analysis showed that measured LTI was 4.71 kg/m2 (±2 SD: −12.54–3.12) lower than estimated LTI. Conclusion SCI is a simple, easily obtainable and clinically relevant surrogate marker of MM in HD patients. [ABSTRACT FROM AUTHOR]

Background Pre-dialysis systolic blood pressure (pre-HD SBP) and peridialytic SBP change have been associated with morbidity and mortality among hemodialysis (HD) patients in previous studies, but the nature of their interaction is not well understood. Methods We analyzed pre-HD SBP and peridialytic SBP change (calculated as post-HD SBP minus pre-HD SBP) between January 2001 and December 2012 in HD patients treated in US Fresenius Medical Care facilities. The baseline period was defined as Months 4–6 after HD initiation, and all-cause mortality was noted during follow-up. Only patients who survived baseline and had no missing covariates were included. Censoring events were renal transplantation, modality change or study end. We fitted a Cox proportional hazard model with a bivariate spline functions for the primary predictors (pre-HD SBP and peridialytic SBP change) with adjustment for age, gender, race, diabetes, access-type, relative interdialytic weight gain, body mass index, albumin, equilibrated normalized protein catabolic rate and ultrafiltration rate. Results A total of 172 199 patients were included. Mean age was 62.1 years, 61.6% were white and 55% were male. During a median follow-up of 25.0 months, 73 529 patients (42.7%) died. We found that a peridialytic SBP rise combined with high pre-HD SBP was associated with higher mortality. In contrast, when concurrent with low pre-HD SBP, a peridialytic SBP rise was associated with better survival. Conclusion The association of pre-HD and peridialytic SBP change with mortality is complex. Our findings call for a joint, not isolated, interpretation of pre-HD SBP and peridialytic SBP change. [ABSTRACT FROM AUTHOR]

Digitization of healthcare will be a major innovation driver in the coming decade. Also, enabled by technological advancements and electronics miniaturization, wearable health device (WHD) applications are expected to grow exponentially. This, in turn, may make 4P medicine (predictive, precise, preventive and personalized) a more attainable goal within dialysis patient care. This article discusses different use cases where WHD could be of relevance for dialysis patient care, i.e. measurement of heart rate, arrhythmia detection, blood pressure, hyperkalaemia, fluid overload and physical activity. After adequate validation of the different WHD in this specific population, data obtained from WHD could form part of a body area network (BAN), which could serve different purposes such as feedback on actionable parameters like physical inactivity, fluid overload, danger signalling or event prediction. For a BAN to become clinical reality, not only must technical issues, cybersecurity and data privacy be addressed, but also adequate models based on artificial intelligence and mathematical analysis need to be developed for signal optimization, data representation, data reliability labelling and interpretation. Moreover, the potential of WHD and BAN can only be fulfilled if they are part of a transformative healthcare system with a shared responsibility between patients, healthcare providers and the payors, using a step-up approach that may include digital assistants and dedicated 'digital clinics'. The coming decade will be critical in observing how these developments will impact and transform dialysis patient care and will undoubtedly ask for an increased 'digital literacy' for all those implicated in their care. [ABSTRACT FROM AUTHOR]

Background Relative blood volume (RBV) monitoring is widely used in hemodialysis (HD) patients, yet the association between intradialytic RBV and mortality is unknown. Methods Intradialytic RBV was recorded once/min during a 6-month baseline period; all-cause mortality was noted during follow-up. RBV at 1, 2 and 3 h into HD served as a predictor of all-cause mortality during follow-up. We employed Kaplan–Meier analysis, univariate and adjusted Cox proportional hazards models for survival analysis. Results We studied 842 patients. During follow-up (median 30.8 months), 249 patients (29.6%) died. The following hourly RBV ranges were associated with improved survival: first hour, 93–96% [hazard ratio (HR) 0.58 (95% confidence interval (CI) 0.42–0.79)]; second hour, 89–94% [HR 0.54 (95% CI 0.39–0.75)]; third hour, 86–92% [HR 0.46 (95% CI 0.33–0.65)]. In about one-third of patients the RBV was within these ranges and in two-thirds it was above. Subgroup analysis by median age (≤/> 61 years), sex, race (white/nonwhite), predialysis systolic blood pressure (SBP; ≤/> 130 mmHg) and median interdialytic weight gain (≤/> 2.3 kg) showed comparable favorable RBV ranges. Patients with a 3-h RBV between 86 and 92% were younger, had higher ultrafiltration volumes and rates, similar intradialytic average and nadir SBPs and hypotension rates, lower postdialysis SBP and a lower prevalence of congestive heart failure when compared with patients with an RBV >92%. In the multivariate Cox analysis, RBV ranges remained independent and significant outcome predictors. Conclusion Specific hourly intradialytic RBV ranges are associated with lower all-cause mortality in chronic HD patients. [ABSTRACT FROM AUTHOR]

Background Cardiac disease is highly prevalent in hemodialysis (HD) patients. Decreased tissue perfusion, including cardiac, due to high ultrafiltration volumes (UFVs) is considered to be one of the drivers of cardiac dysfunction. While central venous oxygen saturation (ScvO2) is frequently used as an indicator of cardiac output in non-uremic populations, the relationship of ScvO2 and UFV in HD patients remains unclear. Our aim was to determine how intradialytic ScvO2 changes associate with UFV. Methods We conducted a 6-month retrospective cohort study in maintenance HD patients with central venous catheters as vascular access. Intradialytic ScvO2 was measured with the Critline monitor. We computed treatment-level slopes of intradialytic ScvO2 over time (ScvO2 trend) and applied linear mixed effects models to assess the association between patient-level ScvO2 trends and UFV corrected for body weight (cUFV). Results We studied 6042 dialysis sessions in 232 patients. In about 62.4% of treatments, ScvO2 decreased. We observed in nearly 80% of patients an inverse relationship between cUFV and ScvO2 trend, indicating that higher cUFV is associated with steeper decline in ScvO2 during dialysis. Conclusions In most patients, higher cUFV volumes are associated with steeper intradialytic ScvO2 drops. We hypothesize that in a majority of patients the intradialytic cardiac function is fluid dependent, so that in the face of high ultrafiltration rates or volume, cardiac pre-load and consequently cardiac output decreases. Direct measurements of cardiac hemodynamics are warranted to further test this hypothesis. [ABSTRACT FROM AUTHOR]

Background. The pathophysiology of a paradoxical systolic blood pressure (SBP) rise during hemodialysis (HD) is not yet fully understood. Recent research indicated that 10% of chronic HD patients suffer from prolonged intradialytic hypoxemia. Since hypoxemia induces a sympathetic response we entertained the hypothesis that peridialytic SBP change is associated with arterial oxygen saturation (SaO2). Methods. We retrospectively analyzed intradialytic SaO2 and peridialytic SBP change in chronic HD patients with arteriovenous vascular access. Patients were followed for 6months. We defined persistent intradialytic hypertension (piHTN) as average peridialytic SBP increase ≥10mmHg over 6months. Linear mixed effects (LME) models were used to explore associations between peridialytic SBP change and intradialytic SaO2 in univariate and adjusted analyses. Results. We assessed 982 patients (29 872 HD treatments; 59% males; 53% whites). Pre-dialysis SBP was 146.7±26.5mmHg and decreased on average by 10.1#177;24.5mmHg. Fifty-three (5.7%) patients had piHTN. piHTN patients had lower intradialytic SaO2, body weight and interdialytic weight gain. LME models revealed that with every percentage point lower mean SaO2, the peridialytic SBP change increased by 0.46mmHg (P<0.001). This finding was corroborated in multivariate analyses. Conclusion. We observed an inverse relationship between intradialytic SaO2 and the blood pressure response to HD. These findings support the notion that hypoxemia activates mechanisms that partially blunt the intradialytic blood pressure decline, possibly by sympathetic activation and endothelin-1 secretion. To further explore that hypothesis, specifically designed prospective studies are required. [ABSTRACT FROM AUTHOR]

Background: The aim of this studywas to describe the experience of pediatric and young adult hemodialysis (HD) patients from a global cohort. Methods: The Pediatric Investigation and Close Collaborative Consortium for Ongoing Life Outcomes for MONitoring Dialysis Outcomes (PICCOLO MONDO) study provided de-identified electronic information of 3244 patients, ages 0-30 years from2000 to 2012 in four regions: Asia, Europe, North America and South America. The study samplewas categorized into pediatric (⩽18 years old) and young adult (19-30 years old) groups based on the age at dialysis initiation. Results: For those with known end-stage renal disease etiology, glomerular disease was the most common diagnosis in children and young adults. Using Europe as a reference group, North America [odds ratio (OR) 2.69; CI 1.29, 5.63] and South America (OR 4.21; CI 2.32, 7.63) had the greatest mortality among young adults. North America also had higher rates of overweight, obesity, hypertension, cardiovascular disease, hospitalizations and secondary diabetes compared with all other regions. Initial catheter use was greater for North American (86.4% in pediatric patients and 75.2% in young adults) and South America (80.6% in pediatric patients and 75.9% in young adults). Catheter use at 1-year follow-up was most common in North American children (77.3%) and young adults (62.9%). Asia had the lowest rate of catheter use. For both age groups, dialysis adequacy (equilibrated Kt/V) ranged between 1.4 and 1.5. In Asia, patients in both age groups had significantly longer treatment times than in any other region. Conclusions: The PICCOLO MONDO study has provided unique baseline and 1-year follow-up information on children and young adults receiving HD around the globe. This cohort has brought to light aspects of care in these age groups that warrant further investigation. [ABSTRACT FROM AUTHOR]

Background. Seasonal variations in blood pressure (BP) and inter-dialytic weight gain (IDWG) are well established in dialysis patients. However, no study has assessed changes in body composition (BC) in this population. Methods. In this survey, seasonal variations in fat mass (FM), lean tissue mass (LTM), extracellular water (ECW) and fluid overload (FO) were assessed in 42 099 dialysis patients (mean age 61.2 years, 58% males) from the Fresenius Medical Care Europe database, as part of the MONitoring Dialysis Outcomes (MONDO) consortium, in relation to other nutritional parameters, IDWG and BP. BC was assessed by a body composition monitor (BCM®, Fresenius Medical Care, Bad Homburg, Germany). Results. FM was highest in winter and lowest in summer (ΔFM -1.17 kg; P < 0.001), whereas LTM was lowest during winter and highest in summer (ΔLTM 0.86 kg; P < 0.0001). ECW and FO were lowest in winter, and highest in spring (ΔECW: 0.13 L; P < 0.0001, ΔFO: 0.31L; P<0.0001) and summer (ΔECW: 0.15 L; P < 0.0001 and ΔFO: 0.2 L; P < 0.0001), despite a higher systolic blood pressure (SBP; 136.7 ± 17.4 mmHg) and IDWG (3.0 ± 1.1 kg) during winter. C-reactive protein (CRP), serum sodium and haemoglobin levels were highest in winter, whereas serum albumin was lowest in fall. Normalized protein catabolic rate (nPCR) was lowest in winter and matched variations in BC only to a minor degree. Conclusions. BC and hydration state, assessed by bioimpedance spectroscopy, follows a seasonal pattern which may be of relevance for the estimation of target weight, and for the interpretation of longitudinal studies including estimates of BC. Whether these changes should lead to therapeutic interventions could be the focus of future studies. [ABSTRACT FROM AUTHOR]

There is increasing evidence that we should be putting this information to use elsewhere: in identifying patients at risk of morbidity associated hospitalization and prompting intervention, improving the patient experience and reducing the healthcare cost.Background and objectives In chronic hemodialysis (HD), patients’ hospitalizations result in significant costs and affect the quality of life. We aimed at understanding hospitalization rates before death and to identify patterns in clinical and laboratory parameters that precede the first hospitalization. Design, setting, participants and measurements We conducted two separate analyses in patients treated in the 51 US Renal Research Institute HD facilities. The first analysis involved hospitalizations before death in all HD patients who died between 1 January 2007 and 31 December 2011. In the second analysis, we studied the evolution of laboratory and treatment parameters before hospitalization in all patients with, at least, one hospital admission between 1 January 2007 and 31 December 2011. Patients were followed from up to 6 months prior to their first hospital admission. For comparison, we selected non-hospitalized patients and observed the evolution of their laboratory and treatment parameters. Results We studied 6262 patients in total. The first analysis encompassed 2058 deaths. In these patients, hospitalization increased from 0.32 admissions per patient-month 4 months before death to 1.85 in the month of death. In the second analysis, we studied the first hospitalizations in 4204 patients. Irrespective of the cause of hospitalization, all hospitalizations were preceded by an increase in the neutrophil-to-lymphocyte ratio, a decline in hemoglobin and a reduction in effective treatment time and inter-dialytic weight gain. We noted no comparable trends in non-hospitalized patients. Conclusions Hospitalization rates increase sharply before death. Months before the first hospitalization changes in clinical and laboratory parameters ensued. These results suggest that models aiming at predicting hospitalization should include indicators capturing the dynamics of relevant parameters. [ABSTRACT FROM AUTHOR]

…we are starting to acknowledge the ability of modified dialysis procedures (in particular extended dialysis schedules) over the current conventional norms of frequency and duration to provide a range of benefits cutting across the range of relevant domains…”Background End-stage renal disease is associated with reduced heart rate variability (HRV), components of which generally are associated with advanced age, diabetes mellitus and left ventricular hypertrophy. We hypothesized that daily in-center hemodialysis (HD) would increase HRV. Methods The Frequent Hemodialysis Network (FHN) Daily Trial randomized 245 patients to receive 12 months of six versus three times per week in-center HD. Two hundred and seven patients had baseline Holter recordings. HRV measures were calculated from 24-h Holter electrocardiograms at both baseline and 12 months in 131 patients and included low-frequency power (LF, a measure of sympathetic modulation), high-frequency power (HF, a measure of parasympathetic modulation) and standard deviation (SD) of the R–R interval (SDNN, a measure of beat-to-beat variation). Results Baseline to Month 12 change in LF was augmented by 50% [95% confidence interval (95% CI) 6.1–112%, P =0.022] and LF + HF was augmented by 40% (95% CI 3.3–88.4%, P = 0.03) in patients assigned to daily hemodialysis (DHD) compared with conventional HD. Changes in HF and SDNN were similar between the randomized groups. The effects of DHD on LF were attenuated by advanced age and diabetes mellitus (predefined subgroups). Changes in HF (r = −0.20, P = 0.02) and SDNN (r = −0.18, P = 0.04) were inversely associated with changes in left ventricular mass (LVM). Conclusions DHD increased the LF component of HRV. Reduction of LVM by DHD was associated with increased vagal modulation of heart rate (HF) and with increased beat-to-beat heart rate variation (SDNN), suggesting an important functional correlate to the structural effects of DHD on the heart in uremia. [ABSTRACT FROM PUBLISHER]

Next to a high morbidity, patients with end-stage renal failure (ESRD) suffer from a complex spectrum of clinical manifestations. Both the phenotype of patients with ESRD as well as the pathophysiology of uremia show interesting parallels with the general aging process. Phenotypically, patients with ESRD have an increased susceptibility for both cardiovascular as well as infectious disease and show a reduction in functional capacity as well as muscular mass (sarcopenia), translating into a high prevalence of frailty also in younger patients. Pathophysiologically, the immune dysfunction, telomere attrition and the presence of low-grade inflammation in uremic patients also show parallels with the aging process. System models of aging, such as the homeodynamic model and reliability theory of Gavrilov may also have relevance for ESRD. The reduction in the redundancy of compensatory mechanisms and the multisystem impairment in ESRD explain the rapid loss of homeodynamic/homeostatic balance and the increased susceptibility to external stressors in these patients. System theories may also explain the relative lack of success of interventions focusing on single aspects of renal disease. The concept of accelerated aging, which also shares similarities with other organ diseases, may be of relevance both for a better understanding of the uremic process, as well as for the design of multidimensional interventions in ESRD patients, including an important role for early rehabilitation. Research into processes akin to both aging and uremia may result in novel therapeutic approaches. [ABSTRACT FROM PUBLISHER]

Background Continuous intradialytic bioelectrical impedance spectroscopy of the calf (cBIS) monitors changes in calf extracellular fluid volume (cECV), thus allowing estimation of hydration in end-stage renal disease patients. Blood volume monitoring (BVM) during hemodialysis (HD) provides information about relative changes in intravascular volume, which indirectly reflects plasma refilling. We hypothesize that the rate of plasma refilling changes when cBIS-determined dry weight (BIS-DW) is reached. Methods Post-HD weight was reduced from baseline (BL) in 15 patients until dry weight was reached according to cBIS criteria (BIS-DW). The slopes of cBIS and BVM curves were analysed during the first 30 and last 20 min in 31 BL treatments, which were compared to the slopes during 31 treatments when BIS-DW was reached. Results During BL treatments, BVM slopes did not differ between the first 30 and last 20 min (−0.112 ± 0.157%/min versus −0.089 ± 0.036, P = n.s.), while cBIS slopes were generally steeper at the beginning than at the end of HD (−0.184 ± 0.139%/min versus 0.10 ± 0.127, P < 0.01). During BIS-DW treatments, BVM and cBIS slopes were steeper at the beginning than at the end (BVM: −0.131 ± 0.122 versus −0.064 ± 0.051, P < 0.01; cBIS: −0.192 ± 0.129 versus −0.035 ± 0.012, P < 0.001) and the cBIS slopes were steeper than BVM slopes at the beginning of HD. This relationship is inverted at the end of HD, when BIS-DW is reached (beginning: −0.192 ± 0.129 versus −0.131 ± 0.122, P < 0.05, end: −0.035 ± 0.012 versus −0.064 ± 0.051, P = 0.05). Conclusions This study demonstrates that cECV changes faster at the beginning than at the end of HD. A reversal steepness of the cBIS slope in relation to BVM slope is observed at the time when BIS-DW is reached. Therefore, combined analysis of cBIS and BVM aiming at clinical end points may be useful to assess the relationship between plasma refilling and tissue hydration during dialysis. [ABSTRACT FROM PUBLISHER]

Background Various biochemical and physiological variables are related to outcome in hemodialysis (HD) patients. However, the prognostic implications of trends in body temperature (BT) in this population have not yet been studied. The aim of this study was to assess the relationship between trends in BT and outcome in incident HD patients. Methods Six thousand seven hundred and forty-two incident HD patients without thyroid disease from the Renal Research Institute were followed for 1 year. Patients were divided into tertiles of initial pre-dialysis BT (Tertile 1: ≤ 36.47°C, Tertile 2: > 36.47 to 36.71°C and Tertile 3: > 36.7°C) and further classified according to the change in BT (increased: > 0.01°C/month, decreased: less than −0.01°C/month and stable, with change between − 0.01 and + 0.01°C/month) during the first year of treatment. The reference group is Tertile 2 of initial temperature with stable BT. Cox regression was used for survival analyses. Analyses were repeated for patients who survived the first year and were treated for ≥ 1 month in Year 2. Results BT decreased in 2903 patients, remained stable in 2238 patients and increased in 1601 patients. After adjustment for multiple risk factors, hazard ratios (HRs) for mortality were higher for those groups in whom, irrespective of the initial BT, BT increased or declined, as compared to the reference group during follow-up (HR between 1.46 and 2.27). Conclusions The best survival was observed in the group with the highest BT at baseline and stable BT during the follow-up period (HR 0.50). [ABSTRACT FROM AUTHOR]

Background. There is no agreement concerning dialyzate glucose concentration in hemodialysis (HD) and 100 and 200 mg/dL (G100 and G200) are frequently used. G200 may result in diffusive glucose flux into the patient, with consequent hyperglycemia and hyperinsulinism, and electrolyte alterations, in particular potassium (K) and phosphorus (P). This trial compared metabolic effects of G100 versus G200.Methods. Chronic HD patients participated in this randomized, single masked, controlled crossover trial (www.clinicaltrials.gov: #NCT00618033) consisting of two consecutive 3-week segments with G100 and G200, respectively. Intradialytic serum glucose (SG) and insulin concentrations (SI) were measured at 0, 30, 60, 120, 180, 240 min and immediately post-HD; P and K were measured at 0, 120, 180 min and post-HD. Hypoglycemia was defined as an SG <70 mg/dL. Mean SG and SI were computed as area under the curve divided by treatment time.Results. Fourteen diabetic and 15 non-diabetic subjects were studied. SG was significantly higher with G200 as compared to G100, both in diabetic {G200: 192.8 ± 48.1 mg/dL; G100: 154.0 ± 27.3 mg/dL; difference 38.8 [95% confidence interval (CI): 21.2–56.4] mg/dL; P < 0.001} and non-diabetic subjects [G200: 127.0 ± 11.2 mg/dL; G100 106.5 ± 10.8 mg/dL; difference 20.6 (95% CI: 15.3–25.9) mg/dL; P < 0.001]. SI was significantly higher with G200 in non-diabetic subjects. Frequency of hypoglycemia, P and K serum levels, interdialytic weight gain and adverse intradialytic events did not differ significantly between G100 and G200.Conclusion. G200 may exert unfavorable metabolic effects in chronic HD patients, in particular hyperglycemia and hyperinsulinism, the latter in non-diabetic subjects. [ABSTRACT FROM PUBLISHER]

Background. Thermal changes during dialysis strongly influence intra-dialytic hemodynamics. The mechanisms behind the increase in body temperature during hemodialysis (HD) are still not completely understood. The objective of this retrospective observational cohort study is to assess the effect of circadian variation on body temperature changes during HD by comparing results in patients treated on different treatment shifts. Methods. Data from the Renal Research Institute, New York, clinical database encompassing patients treated in six states in the USA were used. Data from January and August 2008 were used for analysis. Results. Pre-dialysis body temperatures were significantly different among the different shifts [morning, 36.41 (95% confidence interval: 36.39–36.43°C), afternoon, 36.47 (36.45–36.49°C), evening, 36.67 (36.64–36.70°C), P < 0.001]. In August, but not in January, intra-dialytic increases in body temperature were significantly different between patients treated during morning [0.07 (0.058–0.082°C)], afternoon [0.03 (0.016–0.044°C)] and evening shifts [−0.01 (−0.032 to 0.012°C); P < 0.001 analysis of variance], although in January, treatment shift was a significant predictor of the intra-dialytic increase in body temperature. The intra-dialytic change in body temperature was related not only to the pre-dialysis body temperature (r2 = 0.31; P < 0.001) but also to microbiological dialysate quality, treatment time and dialysate temperature. The intra-dialytic change in blood pressure (BP) was significantly related to changes in intra-dialytic body temperature irrespective of the study month. Conclusions. Both pre-dialytic body temperature as well as changes in body temperature are significantly related to the timing of the dialysis shifts, in phase with the circadian body temperature rhythm. Due to the relationship between body temperature changes and changes in intra-dialytic BP, these findings might be of additional relevance in the pathogenesis of intra-dialytic hypotension. [ABSTRACT FROM PUBLISHER]

Background. Heart rate variability (HRV), a noninvasive measure of autonomic dysfunction and a risk factor for cardiovascular disease (CVD), has not been systematically studied in nondialysis chronic kidney disease (CKD). Methods. HRV was assessed using 24-h Holter monitoring in 305 subjects from the Renal Research Institute-CKD Study, a four-center prospective cohort of CKD (Stages 3–5). Multiple linear regression was used to assess predictors of HRV (both time and frequency domain) and Cox regression used to predict outcomes of CVD, composite of CVD/death and end-stage renal disease (ESRD). Results. A total of 47 CVD, 67 ESRD and 24 death events occurred over a median follow-up of 2.7 years. Lower HRV was significantly associated with older age, female gender, diabetes, higher heart rate, C-reactive protein and phosphorus, lower serum albumin and Stage 5 CKD. Lower HRV (mostly frequency domain) was significantly associated with higher risk of CVD and the composite end point of CVD or death. Significantly, lower HRV (frequency domain) was associated with higher risk of progression to ESRD, although this effect was relatively weaker. Conclusions. This study draws attention to the importance of HRV as a relatively under recognized predictor of adverse cardiovascular and renal outcomes in patients with nondialysis CKD. Whether interventions that improve HRV will improve these outcomes in this high-risk population deserves further study. [ABSTRACT FROM AUTHOR]

Background. Intra-dialytic morbid events (IDME) such as intra-dialytic hypotension (IDH) and muscle cramps frequently complicate haemodialysis (HD). Cardiac dysfunction is highly prevalent in HD patients. We investigated the relationship between proto-dialytic (i.e. early intra-dialytic) cardiac function and IDME in HD patients.Methods. Heart rate, beat-to-beat blood pressure (BP) and cardiac output were continuously measured during the first 30 min of dialysis treatment using the Task Force™ Monitor. Total peripheral resistance index (TPRI) was calculated from cardiac index (CI) and BP. Univariate, multivariate and logistic regression analyses were employed to relate IDME to haemodynamic predictors; Kaplan–Meier method was employed for time-to-event analysis.Results. Fourteen HD patients (age 67 ± 15 years; 7 females) were studied. Dialysis treatment was complicated by IDH and muscle cramps in 4 and 8 out of 30 sessions, respectively. CI was higher in patients without IDME (2.6 ± 0.5 L/min/m2) as compared to those with muscle cramps (2.0 ± 0.3 L/min/m2) or IDH (1.8 ± 0.2 L/min/m2; all P < 0.05). CI and TPRI at baseline independently predicted IDME in a multivariate regression analysis (odds ratio: 0.043 per unit of CI, 95% confidence interval: 0.003–0.611; odds ratio: 1.124 per unit of TPRI, 95% confidence interval: 1.25–1.01). Patients were stratified by tertiles of CI. IDME occurred in the two lower tertiles, whereas patients in the upper tertile were event free (log-rank test, P < 0.002).Conclusions. Low CI and high TPRI in the first 30 min of HD are associated with an increased risk of IDME. [ABSTRACT FROM AUTHOR]

Background. Uromodulin (also known as Tamm–Horsfall protein) is the most abundant urinary protein in healthy individuals and exhibits diverse functions including prevention of ascending urinary tract infections by binding type I-fimbriated Escherichia coli. Although uromodulin is targeted to the apical membrane of thick ascending limb (TAL) cells and secreted into the lumen, detectable levels are also found in venous blood. Uromodulin has been shown to interact with and activate specific components of the immune system, and thus, may act as a signalling molecule for renal tubular damage. [ABSTRACT FROM PUBLISHER]

Background. Little is known about the epidemiology of chronic kidney disease (CKD) in patients with suspected sleep apnoea (SA). [ABSTRACT FROM PUBLISHER]

Background. Observational studies demonstrate poor clinical outcomes in chronic haemodialysis patients with venous catheters as vascular access. This longitudinal study examines the impact of vascular access change on key clinical and laboratory parameters. [ABSTRACT FROM PUBLISHER]

Background. Chronic metabolic acidosis may increase alkali mobilization from the bone and thus promote the development of osteoporosis. The objective of the current study was to compare urinary acidification in patients with reduced bone mineral content with that in control subjects with normal bone density. [ABSTRACT FROM PUBLISHER]