Molecular Insights and Novel Approaches toward Individualized Arteriovenous Fistula Care.

The aim of the paper is to summarize the current understanding of the molecular biology of arteriovenous fistula (AVF). It intends to encourage vascular access teams, care providers, and scientists, to explore new molecular tools for assessing the suitability of patients for AVF as vascular access for maintenance hemodialysis (HD). This review also highlights most recent discoveries and may serve as a guide to explore biomarkers and technologies for the assessment of kidney disease patients choosing to start kidney replacement therapy. Objective criteria for AVF eligibility are lacking partly because the underlying physiology of AVF maturation is poorly understood. Several molecular processes during a life cycle of an AVF, even before creation, can be characterized by measuring molecular fingerprints using newest "omics" technologies. In addition to hypothesis-driven strategies, untargeted approaches have the potential to reveal the interplay of hundreds of metabolites, transcripts, proteins, and genes underlying cardiovascular adaptation and vascular access-related adjustments at any given timepoint of a patient with kidney disease. As a result, regular monitoring of modifiable, molecular risk factors together with clinical assessment could help to reduce AVF failure rates, increase patency, and improve long-term outcomes. For the future, identification of vulnerable patients based on the assessment of biological markers of AVF maturation at different stages of the life cycle may aid in individualizing vascular access recommendations.

Proportional integral feedback control of ultrafiltration rate in hemodialysis.

BACKGROUND: Most hemodialysis patients without residual kidney function accumulate fluid between dialysis session that needs to be removed by ultrafiltration. Ultrafiltration usually results in a decline in relative blood volume (RBV). Recent epidemiological research has identified RBV ranges that were associated with significantly better survival. The objective of this work was to develop an ultrafiltration controller to steer a patient's RBV trajectory into these favorable RBV ranges. METHODS: We designed a proportional-integral feedback ultrafiltration controller that utilizes signals from a device that reports RBV. The control goal is to attain the RBV trajectory associated with improved patient survival. Additional constraints such as upper and lower bounds of ultrafiltration volume and rate were realized. The controller was evaluated in in silico and ex vivo bench experiments, and in a clinical proof-of-concept study in two maintenance dialysis patients. RESULTS: In all tests, the ultrafiltration controller performed as expected. In the in silico and ex vivo bench experiments, the controller showed robust reaction toward deliberate disruptive interventions (e.g. signal noise; extreme plasma refill rates). No adverse events were observed in the clinical study. CONCLUSIONS: The ultrafiltration controller can steer RBV trajectories toward desired RBV ranges while obeying to a set of constraints. Prospective studies in hemodialysis patients with diverse clinical characteristics are warranted to further explore the controllers impact on intradialytic hemodynamic stability, quality of life, and long-term outcomes.

Arterial oxygen saturation and hypoxemia in hemodialysis patients with COVID-19.

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.

Effect of Statewide Lockdown in Response to COVID-19 Pandemic on Physical Activity Levels of Hemodialysis Patients.

BACKGROUND/OBJECTIVES: On March 22, 2020, a statewide stay-at-home order for nonessential tasks was implemented in New York State. We aimed to determine the impact of the lockdown on physical activity levels (PAL) in hemodialysis patients. METHODS: Starting in May 2018, we are conducting an observational study with a 1-year follow-up on PAL in patients from 4 hemodialysis clinics in New York City. Patients active in the study as of March 22, 2020, were included. PAL was defined by steps taken per day measured by a wrist-based monitoring device (Fitbit Charge 2). Average steps/day were calculated for January 1 to February 13, 2020, and then weekly from February 14 to June 30. RESULTS: 42 patients were included. Their mean age was 55 years, 79% were males, and 69% were African Americans. Between January 1 and February 13, 2020, patients took on average 5,963 (95% CI 4,909-7,017) steps/day. In the week prior to the mandated lockdown, when a national emergency was declared, and in the week of the shutdown, the average number of daily steps had decreased by 868 steps/day (95% CI 213-1,722) and 1,222 steps/day (95% CI 668-2300), respectively. Six patients were diagnosed with COVID-19 during the study period. Five of them exhibited significantly higher PAL in the 2 weeks prior to showing COVID-19 symptoms compared to COVID-19 negative patients. CONCLUSION: Lockdown measures were associated with a significant decrease in PAL in hemodialysis patients. Patients who contracted COVID-19 had higher PAL during the incubation period. Methods to increase PAL while allowing for social distancing should be explored and implemented.

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.