Intradialytic Protein Ingestion and Exercise do Not Compromise Uremic Toxin Removal Throughout Hemodialysis.

OBJECTIVE: Dietary protein and physical activity interventions are increasingly implemented during hemodialysis to support muscle maintenance in patients with end-stage renal disease (ESRD). Although muscle maintenance is important, adequate removal of uremic toxins throughout hemodialysis is the primary concern for patients. It remains to be established whether intradialytic protein ingestion and/or exercise modulate uremic toxin removal during hemodialysis. METHODS: We recruited 10 patients with ESRD (age: 65 ± 16 y, BMI: 24.2 ± 4.8 kg/m2) on chronic hemodialysis treatment to participate in this randomized cross-over trial. During hemodialysis, patients were assigned to ingest 40 g protein or a nonprotein placebo both at rest (protein [PRO] and placebo [PLA], respectively) and following 30 min of exercise (PRO + exercise [EX] and PLA + EX, respectively). Blood and spent dialysate samples were collected throughout hemodialysis to assess reduction ratios and removal of urea, creatinine, phosphate, cystatin C, and indoxyl sulfate. RESULTS: The reduction ratios of urea and indoxyl sulfate were higher during PLA (76 ± 6% and 46 ± 9%, respectively) and PLA + EX interventions (77 ± 5% and 45 ± 10%, respectively) when compared to PRO (72 ± 4% and 40 ± 8%, respectively) and PRO + EX interventions (73 ± 4% and 43 ± 7%, respectively; protein effect: P = .001 and P = .023, respectively; exercise effect: P = .25 and P = .52, respectively). Nonetheless, protein ingestion resulted in greater urea removal (P = .046) during hemodialysis. Reduction ratios and removal of creatinine, phosphate, and cystatin C during hemodialysis did not differ following intradialytic protein ingestion or exercise (protein effect: P > .05; exercise effect: P>.05). Urea, creatinine, and phosphate removal were greater throughout the period with intradialytic exercise during PLA + EX and PRO + EX interventions when compared to the same period during PLA and PRO interventions (exercise effect: P = .034, P = .039, and P = .022, respectively). CONCLUSION: The removal of uremic toxins is not compromised by protein feeding and/or exercise implementation during hemodialysis in patients with ESRD.

Artificial intelligence enabled applications in kidney disease.

Artificial intelligence (AI) is considered as the next natural progression of traditional statistical techniques. Advances in analytical methods and infrastructure enable AI to be applied in health care. While AI applications are relatively common in fields like ophthalmology and cardiology, its use is scarcely reported in nephrology. We present the current status of AI in research toward kidney disease and discuss future pathways for AI. The clinical applications of AI in progression to end-stage kidney disease and dialysis can be broadly subdivided into three main topics: (a) predicting events in the future such as mortality and hospitalization; (b) providing treatment and decision aids such as automating drug prescription; and (c) identifying patterns such as phenotypical clusters and arteriovenous fistula aneurysm. At present, the use of prediction models in treating patients with kidney disease is still in its infancy and further evidence is needed to identify its relative value. Policies and regulations need to be addressed before implementing AI solutions at the point of care in clinics. AI is not anticipated to replace the nephrologists' medical decision-making, but instead assist them in providing optimal personalized care for their patients.

COVID-19 in ESRD and Acute Kidney Injury.

The COVID-19 pandemic has greatly affected nephrology. Firstly, dialysis patients appear to be at increased risk for infection due to viral transmission next to an enhanced risk for mortality as compared to the general population, even in the face of an often apparently mild clinical presentation. Derangements in the innate and adaptive immune systems may be responsible for a reduced antiviral response, whereas chronic activation of the innate immune system and endothelial dysfunction provide a background for a more severe course. The presence of severe comorbidity, older age, and a reduction of organ reserve may lead to a rapid deterioration of the clinical situation of the patients in case of severe infection. Secondly, patients with COVID-19 are at increased risk of acute kidney injury (AKI), which is related to the severity of the clinical disease. The presence of AKI, and especially the need for renal replacement therapy (RRT), is associated with an increased risk of mortality. AKI in COVID-19 has a multifactorial origin, in which direct viral invasion of kidney cells, activation of the renin-angiotensin aldosterone system, a hyperinflammatory response, hypercoagulability, and nonspecific factors such as hypotension and hypoxemia may be involved. Apart from logistic challenges and the need for strict hygiene within units, treatment of patients with ESRD and COVID-19 is not different from that of the general population. Extracorporeal treatment of patients with AKI with RRT can be complicated by frequent filter clotting due to the hypercoagulable state, for which regional citrate coagulation provides a reasonable solution. Also, acute peritoneal dialysis may be a reasonable option in these patients. Whether adjuncts to extracorporeal therapies, such as hemoadsorption, provide additional benefits in the case of severely ill COVID-19 patients needs to be addressed in controlled studies.

End-Stage Renal Disease Patients Lose a Substantial Amount of Amino Acids during Hemodialysis.

BACKGROUND: Poor nutritional status is frequently observed in end-stage renal disease patients and associated with adverse clinical outcomes and increased mortality. Loss of amino acids (AAs) during hemodialysis (HD) may contribute to protein malnutrition in these patients. OBJECTIVE: We aimed to assess the extent of AA loss during HD in end-stage renal disease patients consuming their habitual diet. METHODS: Ten anuric chronic HD patients (mean ± SD age: 67.9 ± 19.3 y, BMI: 23.2 ± 3.5 kg/m2), undergoing HD 3 times per week, were selected to participate in this study. Spent dialysate was collected continuously and plasma samples were obtained directly before and after a single HD session in each participant. AA profiles in spent dialysate and in pre-HD and post-HD plasma were measured through ultra-performance liquid chromatography to determine AA concentrations and, as such, net loss of AAs. In addition, dietary intake before and throughout HD was assessed using a 24-h food recall questionnaire during HD. Paired-sample t tests were conducted to compare pre-HD and post-HD plasma AA concentrations. RESULTS: During an HD session, 11.95 ± 0.69 g AAs were lost via the dialysate, of which 8.26 ± 0.46 g were nonessential AAs, 3.69 ± 0.31 g were essential AAs, and 1.64 ± 0.17 g were branched-chain AAs. As a consequence, plasma total and essential AA concentrations declined significantly from 2.88 ± 0.15 and 0.80 ± 0.05 mmol/L to 2.27 ± 0.11 and 0.66 ± 0.05 mmol/L, respectively (P < 0.05). AA profiles of pre-HD plasma and spent dialysate were similar. Moreover, AA concentrations in pre-HD plasma and spent dialysate were strongly correlated (Spearman's ρ = 0.92, P < 0.001). CONCLUSIONS: During a single HD session, ∼12 g AAs are lost into the dialysate, causing a significant decline in plasma AA concentrations. AA loss during HD can contribute substantially to protein malnutrition in end-stage renal disease patients. This study was registered at the Netherlands Trial Registry (NTR7101).

Wearable health devices and personal area networks: can they improve outcomes in haemodialysis patients?

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.

Association of all-cause mortality with pre-dialysis systolic blood pressure and its peridialytic change in chronic hemodialysis patients.

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.

Intradialytic Hypotension: Mechanisms and Outcome.

Intradialytic hypotension (IDH) occurs in approximately 10-12% of treatments. Whereas several definitions for IDH are available, a nadir systolic blood pressure carries the strongest relation with outcome. Whereas the relation between IDH may partly be based on patient characteristics, it is likely that also impaired organ perfusion leading to permanent damage, plays a role in this relationship. The pathogenesis of IDH is multifactorial and is based on a combination of a decline in blood volume (BV) and impaired vascular resistance at a background of a reduced cardiovascular reserve. Measurements of absolute BV based on an on-line dilution method appear more promising than relative BV measurements in the prediction of IDH. Also, feedback treatments in which ultrafiltration rate is automatically adjusted based on changes in relative BV have not yet resulted in improvement. Frequent assessment of dry weight, attempting to reduce interdialytic weight gain and prescribing more frequent or longer dialysis treatments may aid in preventing IDH. The impaired vascular response can be improved using isothermic or cool dialysis treatment which has also been associated with a reduction in end organ damage, although their effect on mortality has not yet been assessed. For the future, identification of vulnerable patients based on artificial intelligence and on-line assessment of markers of organ perfusion may aid in individualizing treatment prescription, which will always remain dependent on the clinical context of the patient.

Using Bioimpedance Spectroscopy to Assess Volume Status in Dialysis Patients.

The aim of the paper is to reflect on the current status of bioimpedance spectroscopy (BIS) in fluid management in dialysis patients. BIS identifies fluid overload (FO) as a virtual (overhydration) compartment, which is calculated from the difference between the measured extracellular volume and the predicted values based on a fixed hydration of lean and adipose tissue mass. FO is highly prevalent in both hemodialysis (HD) and peritoneal dialysis (PD) patients, while levels of FO are at a population level comparable between PD patients and HD patients when measured before the dialysis treatment. Even mild levels of FO are independently related to outcome in patients on HD, PD as well as in nondialysis patients with advanced chronic kidney disease. FO is not only related to left ventricular hypertrophy (LVH) but also forms part of a multidimensional spectrum with noncardiovascular risk factors such as malnutrition and inflammation. Even after multiple adjustments, FO remains an independent predictor of mortality. BIS-assisted adjustment of dry weight in HD patients has been shown to improve hypertension control and LVH and has resulted in a decline in intradialytic symptomatology. On the other hand, with increased fluid removal, target weight may not always be reached due to an increase in intradialytic symptomatology, and care should be applied in target weight adjustment in fluid overloaded patients with severe malnutrition and/or inflammation. Although a reduction in hospitalization rate was suggested, the effect of BIS-guided dry weight adjustment on mortality has not yet been shown, however, although available studies are underpowered. In PD patients, results have been more equivocal, which may be partly related to differences in treatment protocols or study populations. Future large-scale studies are needed to assess the full potential of BIS.

Increased Mortality Associated with Higher Pre-Dialysis Serum Sodium Variability: Results of the International MONitoring Dialysis Outcome Initiative.

BACKGROUND: Low serum sodium (SNa) is associated with an increased mortality in chronic hemodialysis (HD) patients. Dialysis patients are thought to have an individual pre-dialysis SNa set-point, yet there is evidence for variability of pre-dialysis SNa in individual patient. In this study, we explored the association of several SNa variability metrics with all-cause mortality in a large patient population from the international MONitoring Dialysis Outcomes (MONDO) Initiative. METHODS: All adult incident patients from the MONDO database with more than 5 SNa measurements during the first year on HD were included. All patients were required to survive the first year on HD (defined as the baseline). During the subsequent 2 years of follow-up, all-cause mortality was recorded. The following variability indicators were calculated during baseline: mean SNa and its SD; average real variability (ARV, average the absolute distance of the 2 consecutive SNa measurements), and average directional range (DR, the difference between minimum and maximum values). We used Cox Proportional hazard model with bivariate spline terms to analyze the joint association of SNa and SD, ARV and DR, respectively, with all-cause mortality. While conducting the multivariate Cox regression analyses, patients were stratified into 3 groups of DR (Negative DR: -20≤ DR ≤ -6, Null DR: -6< DR < 6 and Positive DR: 6≤ DR ≤20) with the Null DR as the reference group. RESULTS: We included 20,216 patients in the study. A SNa ≤135 mEq/L was observed to be the strongest predictor of evaluated mortality risk. Higher SNa variability (quantified as SD, ARV, and DR) was also associated with an increased mortality irrespective of SNa levels. When compared with higher SD or ARV, greater DR showed a stronger association with an elevated risk of death. Controlling the Cox Proportional hazard models for additional parameters showed consistent results. CONCLUSION: Higher SNa variability associated with increased all-cause mortality at all levels of SNa. DR of SNa showed the strongest association with mortality and may constitute a Simple and novel prognostic indicator, easily applicable at the bedside.

All-cause mortality in relation to changes in relative blood volume during hemodialysis.

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.

Body Fluids in End-Stage Renal Disease: Statics and Dynamics.

BACKGROUND: Abnormalities in fluid status in hemodialysis (HD) patients are highly prevalent and are related to adverse outcomes. SUMMARY: The inherent discontinuity of the HD procedure in combination with an often compromised cardiovascular response is a major contributor to this phenomenon. In addition, systemic inflammation and endothelial dysfunction are related to extracellular fluid overload (FO). Underlying this relation may be factors such as hypoalbuminemia and an increased capillary permeability, leading to an altered fluid distribution between the blood volume (BV) and the interstitial fluid compartments, compromising fluid removal during dialysis. Indeed, whereas estimates of extracellular volume by bioimpedance spectroscopy are highly predictive of mortality, absolute BV assessed by the saline dilution technique was predictive of intra-dialytic morbidity. Changes in relative BV during HD are positively related to ultrafiltration rate (UFR) and, at least in some studies, negatively to FO. High UFR is also related to changes in central venous oxygen saturation (ScvO2), a marker for tissue perfusion. On the one hand, high UFR and more pronounced declines in ScvO2, but on the other hand, flat relative BV curves are also predictive of mortality; the relation between outcome which statics and dynamics of fluid status appears to be complex. Key Message: While technological developments enable the clinician to monitor statics and dynamics of fluid status and hemodynamics during HD in an accessible way, the role of technology-based interventions needs further study.

Dialysate Calcium Levels: Do They Matter?

BACKGROUND: Calcium (Ca) is an essential element that plays a critical role in many biological processes. In dialysis patients, the regulation of Ca balance is highly complex, given the absence of kidney function, endocrine disturbances and the use of drugs such as phosphate binders, vitamin D analogues, and calcimimetics. Also, the use of different dialysate Ca (DCa) baths has profound effect on Ca balance, which depends both on the difference between the Ca concentration in the bath and the serum of the patients, as on the ultrafiltration volume. SUMMARY: The choice of DCa may have important short- and long-term consequences. While lower DCa (especially < 2.5 mEq/L) concentrations have been associated with an increased risk of sudden cardiac death in observational studies, DCa in the higher ranges (3.0 mEq/L and above) may contribute to vascular pathology. Intra-dialytic hemodynamics may also be affected by the choice of DCa. In general, lower DCa concentrations are associated with an increase, and higher DCa concentrations with a decrease in parathyroid hormone (PTH) levels. Preliminary data has suggested that a DCa of 2.75 mEq/L may help in obtaining a net zero intradialytic Ca balance in individual patients, but clinical experience is still limited. Key Message: The optimal Ca balance depends on multiple parameters including blood Ca levels, PTH and the use of phosphate binders and vitamin D analogues, as well as on the risk of hemodynamic stability and cardiac arrhythmias. Therefore, DCa prescription should be individualised. A DCa of 2.75 mEq/L may be useful adjunct for dialysis providers.

Cycles, Arrows and Turbulence: Time Patterns in Renal Disease, a Path from Epidemiology to Personalized Medicine?

Patients with end-stage renal disease (ESRD) experience unique patterns in their lifetime, such as the start of dialysis and renal transplantation. In addition, there is also an intricate link between ESRD and biological time patterns. In terms of cyclic patterns, the circadian blood pressure (BP) rhythm can be flattened, contributing to allostatic load, whereas the circadian temperature rhythm is related to the decline in BP during hemodialysis (HD). Seasonal variations in BP and interdialytic-weight gain have been observed in ESRD patients in addition to a profound relative increase in mortality during the winter period. Moreover, nonphysiological treatment patters are imposed in HD patients, leading to an excess mortality at the end of the long interdialytic interval. Recently, new evidence has emerged on the prognostic impact of trajectories of common clinical and laboratory parameters such as BP, body temperature, and serum albumin, in addition to single point in time measurements. Backward analysis of changes in cardiovascular, nutritional, and inflammatory parameters before the occurrence as hospitalization or death has shown that changes may already occur within months to even 1-2 years before the event, possibly providing a window of opportunity for earlier interventions. Disturbances in physiological variability, such as in heart rate, characterized by a loss of fractal patterns, are associated with increased mortality. In addition, an increase in random variability in different parameters such as BP and sodium is also associated with adverse outcomes. Novel techniques, based on time-dependent analysis of variability and trends and interactions of multiple physiological and laboratory parameters, for which machine-learning -approaches may be necessary, are likely of help to the clinician in the future. However, upcoming research should also evaluate whether dynamic patterns observed in large epidemiological studies have relevance for the individual risk profile of the patient.

Association of Central Venous Oxygen Saturation Variability and Mortality in Hemodialysis Patients.

BACKGROUND: Central venous oxygen saturation (ScvO2) is correlated with cardiac output. In most patients, ScvO2 declines during hemodialysis (HD) due to factors such as reduced preload, myocardial stunning, and intermittent arrhythmias. Previous research has shown that low ScvO2 is associated with higher mortality in chronic HD patients. In this research, we tested the hypothesis that ScvO2 variability is associated with all-cause mortality. METHODS: We conducted a retrospective study in 232 chronic HD patients with central venous catheter as vascular access. ScvO2 was recorded 1× per minute during dialysis using the Crit-Line monitor. A 6-month baseline comprising at least 10 dialysis treatments with ScvO2 recordings preceded a follow-up period of up to 3 years. The coefficient of variation (CV) of ScvO2 (100 times the ratio of the standard deviation and mean of ScvO2) served as a measure of ScvO2 stability during baseline. Patients were stratified by median population CV of ScvO2 during baseline, and survival during follow-up was compared between the 2 groups by Kaplan Meier and multivariate Cox analysis. The association between CV of ScvO2 and all-cause mortality during follow-up was further assessed by Cox analysis with a spline term for CV of ScvO2. RESULTS: The mean CV ± standard deviation of ScvO2 in our population was 6.1 ± 2.7% and the median was 5.3%. Univariate Kaplan-Meier analysis (p = 0.043) and multivariate Cox analysis (hazard ratio [HR] 1.16; p = 0.0005) indicated that a CV of ScvO2 > 5.3% was significantly associated with increased mortality. In Cox analysis with spline term, a CV of ScvO2 >  11% was associated with a significantly increased HR for all-cause mortality. CONCLUSION: High ScvO2 variability during dialysis is associated with increased all-cause mortality.

Longitudinal patterns of health-related quality of life and dialysis modality: a national cohort study.

BACKGROUND: Health-related quality of life (HrQoL) varies among dialysis patients. However, little is known about the association of dialysis modality with HrQoL over time. We describe longitudinal patterns of HrQoL among chronic dialysis patients by treatment modality. METHODS: National retrospective cohort study of adult patients who initiated in-center dialysis or a home modality (peritoneal or home hemodialysis) between 1/2013 and 6/2015. Patients remained on the same modality for the first 120 days of the first two years. HrQoL was assessed by the Kidney Disease and Quality of Life-36 (KDQOL) survey in the first 120 days of the first two years after dialysis initiation. Home modality patients were matched to in-center patients in a 1:5 fashion. RESULTS: In-center (n=4234) and home modality (n=880) patients had similar demographic and clinical characteristics. In-center dialysis patients had lower mean KDQOL scores across several domains compared to home modality patients. For patients who remained on the same modality, there was no change in HrQoL. However, there were trends towards clinically meaningful changes in several aspects of HrQoL for patients who switched modalities. Specifically, physical functioning decreased for patients who switched from home to in-center dialysis (p< 0.05). CONCLUSIONS: Among a national cohort of chronic dialysis patients, there was a trend towards different patterns of HrQoL life that were only observed among patients who changed modality. Patients who switched from home to in-center modalities had significant lower physical functioning over time. Providers and patients should be mindful of HrQoL changes that may occur with dialysis modality change.

Lipid levels are inversely associated with infectious and all-cause mortality: international MONDO study results.

Cardiovascular (CV) events are increased 36-fold in patients with end-stage renal disease. However, randomized controlled trials to lower LDL cholesterol (LDL-C) and serum total cholesterol (TC) have not shown significant mortality improvements. An inverse association of TC and LDL-C with all-cause and CV mortality has been observed in patients on chronic dialysis. Lipoproteins also may protect against infectious diseases. We used data from 37,250 patients in the international Monitoring Dialysis Outcomes (MONDO) database to evaluate the association between lipids and infection-related or CV mortality. The study began on the first day of lipid measurement and continued for up to 4 years. We applied Cox proportional models with time-varying covariates to study associations of LDL-C, HDL cholesterol (HDL-C), and triglycerides (TGs) with all-cause, CV, infectious, and other causes of death. Overall, 6,147 patients died (19.2% from CV, 13.2% from infection, and 67.6% from other causes). After multivariable adjustment, higher LDL-C, HDL-C, and TGs were independently associated with lower all-cause death risk. Neither LDL-C nor TGs were associated with CV death, and HDL-C was associated with lower CV risk. Higher LDL-C and HDL-C were associated with a lower risk of death from infection or other non-CV causes. LDL-C was associated with reduced all-cause and infectious, but not CV mortality, which resulted in the inverse association with all-cause mortality.

Association between intradialytic central venous oxygen saturation and ultrafiltration volume in chronic hemodialysis patients.

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.

Albuminuria is associated with a higher prevalence of depression in a population-based cohort study: the Maastricht Study.

Background: Depression is common in individuals with chronic kidney disease (CKD). However, data on the association of albuminuria, which together with reduced estimated glomerular filtration rate (eGFR) defines CKD, with depression are scarce and conflicting. In addition, it is not clear when in the course from normal kidney function to CKD the association with depression appears. Methods: We examined the cross-sectional associations of albuminuria and eGFR with depressive symptoms and depressive episodes in 2872 and 3083 40- to 75-year-old individuals, respectively, who completed the baseline survey of an ongoing population-based cohort study conducted in the southern part of The Netherlands between November 2010 and September 2013. Urinary albumin excretion (UAE) was the average UAE in two 24-h urine collections and eGFR was calculated with the Chronic Kidney Disease Epidemiology Collaboration equation based on creatinine and cystatin C. Depressive symptoms were assessed with the 9-item Patient Health Questionnaire (PHQ-9) and the presence of a minor or major depressive episode was assessed with the MINI-International Neuropsychiatric Interview. Results: In total, 5.4% had a minor or major depressive episode. UAE was <15 mg/24 h in 81.2%, 15-<30 mg/24 h in 10.3% and ≥30 mg/24 h in 8.6%. In a multivariable logistic regression analysis adjusted for potential confounders, and with UAE <15 mg/24 h as reference category, the odds ratio for a minor or major depressive episode was 2.13 [95% confidence interval (CI) 1.36-3.36] for UAE 15-<30 mg/24 h and 1.81 (95% CI 1.10-2.98) for UAE ≥30 mg/24 h. The average eGFR was 88.2 ± 14.7 mL/min/1.73 m2. eGFR was not associated with the presence of a minor or major depressive episode. Results were similar when we assessed associations with depressive symptoms or clinically relevant depressive symptoms (PHQ-9 score ≥10). Conclusions: Albuminuria was associated with depressive symptoms and depressive episodes, even at levels of UAE that do not fulfil the CKD criteria. Future longitudinal studies should examine the direction of this association and whether albuminuria could serve as a biomarker to identify individuals at risk of depression.

Hemodialysis: A model for extreme physiology in a vulnerable patient population.

Hemodialysis (HD) is a lifesaving treatment for patients with end-stage renal disease, which is very efficient in the correction of abnormalities of the internal environment. However, this efficiency also induces significant hemodynamic, thermal, and respiratory stressors. These have parallels with the extreme physiologic demands which are normally mainly experienced by healthy subjects under adverse environmental conditions, with the difference that they must be endured by a vulnerable patient population. Hemodynamic stress induced by ultrafiltration leads to a decline in circulating blood volume, which may result in intradialytic hypotension (IDH) and changes in tissue perfusion, which may have long-term consequences for the function of vital organs such as the brain and the heart. Pronounced declines in central venous oxygen saturation have been observed during routine HD, which are related to the circulatory stress imposed upon the patient. Apart from patient-related factors, thermal stress induced by HD may lead to skin vasodilation, counteracting the normal hemodynamic response to hypovolemia, which has important pathophysiologic correlates in heat syncope. Lastly, respiratory stress is reflected by prolonged arterial hypoxemia during HD, which is both related to patient-related factors, but may also be partly because of the treatment itself, especially during the first 30-60 minutes. Whereas hypoxemia during HD is related to increased mortality, its role in the reduced tissue oxygen delivery during HD should be further defined. Treatment modifications, such as cool or temperature-controlled HD, may reduce circulatory and thermal stress, which also may translate into a reduced risk of long-term cardiac or cerebral damage. However, as circulatory stress is mainly time-dependent, prolonged, or more dialysis treatment may reduce the homeostatic burden on the patient.

The Association of Weekly pre-Hemodialysis Systolic Blood Pressure and Following Week Mortality.

BACKGROUND/AIMS: Few studies examine the impact of systolic blood pressure (SBP) on mortality in the incident hemodialysis (HD) period, and throughout the first HD year. This large retrospective observational study analyzes the impact of "current" and cumulative low preSBP <110 mmHg (L), and variations in preSBP on short-term (1 week) mortality over the first HD year. METHODS: Weekly mean preSBP for HD weeks 1 to 51 was categorized into L or high preSBP>=110 mmHg (H) for each patient. A generalized linear model (GLM) was used to compute the probability of death in the following week. The model includes age, gender, race and three preSBP-related parameters: (a) percent of prior weeks with L preSBP; (b) percent of prior weeks with switching between L to H; (c) "current" week's preSBP as a binary variable. Separate models were constructed that include demographics and BP-related parameters (a), (b), and (c) separately. RESULTS: In a model combining (a), (b), and (c) above, "current" week L preSBP is associated with increased odds ratio for following week mortality throughout the first HD year. The percent of prior week's L and more switching between L and H are less significantly associated with short-term mortality. In models including (a), (b), and (c) separately, "current" L preSBP is associated with higher mortality. CONCLUSION: This study confirms an association of L preSBP with increased short-term mortality which is maintained over the first HD year. Percent of L preSBP in prior weeks, switching between L and H, and "current" week L are all associated with short-term mortality risk, but "current" week L preSBP is most significant.