Dialysis Clinic Research Articles

Barriers and Facilitators to Home Dialysis Among Latinx Patients with Kidney Disease

Latinx people have a high burden of kidney disease but are less likely to receive home dialysis compared to non-Latinx White people. The disparity in home dialysis therapy has not been completely explained by demographic, medical, or social factors. To understand the barriers and facilitators to home dialysis therapy experienced by Latinx individuals with kidney failure receiving home dialysis. This qualitative study used semistructured interviews with Latinx adults with kidney failure receiving home dialysis therapy in Denver, Colorado, and Houston, Texas, between November 2021 and March 2023. Patients were recruited from home dialysis clinics affiliated with academic medical centers. Of 39 individuals approached, 27 were included in the study. Interviews were audio-recorded, transcribed verbatim, and analyzed using thematic analysis. Themes and subthemes regarding barriers and facilitators to home dialysis therapy. A total of 27 Latinx adults (17 [63%] female and 10 [37%] male) with kidney failure who were receiving home dialysis participated. Themes and subthemes were identified, 3 related to challenges with home dialysis and 2 related to facilitators. Challenges to home dialysis included misinformation and immigration-related barriers to care (including cultural stigma of dialysis, misinformation regarding chronic disease care, and lack of health insurance due to immigration status), limited dialysis education (including lack of predialysis care, no-nephrologist education, and shared decision-making), and maintenance of home dialysis (including equipment issues, lifestyle restrictions, and anxiety about complications). Facilitators to home dialysis included improved lifestyle (including convenience, autonomy, physical symptoms, and dietary flexibility) and support (including family involvement, relationships with staff, self-efficacy, and language concordance). Latinx participants in this study who were receiving home dialysis received misinformation and limited education regarding home dialysis, yet were engaged in self-advocacy and reported strong family and clinic support. These findings may inform new strategies aimed at improving access to home dialysis education and uptake for Latinx individuals with kidney disease.

Stakeholder Perspectives on Factors Related to Deprescribing Potentially Inappropriate Medications in Older Adults Receiving Dialysis.

Potentially inappropriate medications, or medications that generally carry more risk of harm than benefit in older adults, are commonly prescribed to older adults receiving dialysis. Deprescribing, a systematic approach to reducing or stopping a medication, is a potential solution to limit potentially inappropriate medications use. Our objective was to identify clinicians and patient perspectives on factors related to deprescribing to inform design of a deprescribing program for dialysis clinics. We conducted rapid qualitative analysis of semistructured interviews and focus groups with clinicians (dialysis clinicians, primary care providers, and pharmacists) and patients (adults receiving hemodialysis aged 65 years or older and those aged 55-64 years who were prefrail or frail) from March 2019 to December 2020. We interviewed 76 participants (53 clinicians [eight focus groups and 11 interviews] and 23 patients). Among clinicians, 24 worked in dialysis clinics, 18 worked in primary care, and 11 were pharmacists. Among patients, 13 (56%) were aged 65 years or older, 14 (61%) were Black race, and 16 (70%) reported taking at least one potentially inappropriate medication. We identified four themes (and corresponding subthemes) of contextual factors related to deprescribing potentially inappropriate medications: ( 1 ) system-level barriers to deprescribing (limited electronic medical record interoperability, time constraints and competing priorities), ( 2 ) undefined comanagement among clinicians (unclear role delineation, clinician caution about prescriber boundaries), ( 3 ) limited knowledge about potentially inappropriate medications (knowledge limitations among clinicians and patients), and ( 4 ) patients prioritize symptom control over potential harm (clinicians expect resistance to deprescribing, patient weigh risks and benefits). Challenges to integration of deprescribing into dialysis clinics included siloed health systems, time constraints, comanagement behaviors, and clinician and patient knowledge and attitudes toward deprescribing.

Who have a better-kidney-related quality of life: peritoneal dialysis or hemodialysis patients? A cross sectional study from Saudi Arabia

BackgroundEnd-stage kidney disease (ESKD) substantially impacts different aspects of patients' lives, including mental and physical health, and overall quality of life. The aim of our study is to assess the quality of life (QoL) and the associated predictors in ESKD Saudi Arabian patients receiving either hemodialysis (HD) or peritoneal dialysis (PD). Saudi Ministry of health (MOH) is advancing dialysis care in the country with more focus on patients’ satisfaction and QoL. However, the data regarding QoL in Saudi Arabian dialysis patients is limited.MethodsA cross sectional study was carried out using Kidney Disease Quality of Life scale (KDQOL-36) to assess the QoL. We disturbed a validated formal arabic version of the questionnaire. Patients older than 18-year-old and attending dialysis clinics in Aseer region, Saudi Arabia, were invited to participate in the study.ResultsA total of 152 responses were analyzed, which were separated into two primary groups: the HD group (98 patients) and the PD group (54 patients). Our results showed no significant differences between the two groups except for the KDQOL-SF-36 physical composite score at which the PD group had a higher mean than the HD group 44.75 vs 37.84, respectively (p < 0.001). However, more PD patients reported feeling depressed compared to HD patients.ConclusionsKidney Disease Quality of Life scale scores were comparable between HD and PD groups except for the physical composite score. On the other hand, PD patients tend to suffer from depression more than HD patients. Interventions to attenuate the physical deconditioning and depressive symptoms in HD and PD patients, respectively, are crucial. Future prospective studies with larger sample sizes are warranted.

Seasonal variation in predialysis systolic blood pressure and cardiovascular events in patients on maintenance hemodialysis.

Predialysis systolic blood pressure (SBP) in patients on hemodialysis (HD) consistently followed a seasonal pattern, reaching a peak in winter and nadir in summer, similar to blood pressure in the general population. However, the relationship between seasonal variations in predialysis SBP and clinical outcomes is still under-investigated in Japanese patients on HD. This retrospective cohort study included 307 Japanese patients undergoing HD for >1 year in three dialysis clinics and evaluated the association between the standard deviation (SD) of predialysis SBP and clinical outcomes, including major adverse cardiovascular events (MACEs; cardiovascular death, nonfatal myocardial infarction or unstable angina, stroke, heart failure, and other severe cardiovascular events requiring hospitalization) with 2.5 years follow-up. The SD of predialysis SBP was 8.2 (6.4-10.9) mmHg. In the model fully adjusted for the SD of predialysis SBP, predialysis SBP, age, sex, HD vintage, Charlson comorbidity index, ultrafiltration rate, renin-angiotensin system inhibitors, corrected calcium, phosphorus, human atrial natriuretic peptide, C-reactive protein, albumin, hemoglobin, body mass index, normalized protein catabolism rate, and intradialytic SBP decline, Cox regression analyses showed that a higher SD of predialysis SBP (per 10 mmHg) was significantly associated with increased MACE risk (hazard ratio [HR], 1.89; 95% confidence interval [95% CI], 1.07-3.36) and all-cause hospitalization (HR, 1.57; 95% CI, 1.07-2.30). Therefore, greater seasonal variations in predialysis SBP were associated with worse clinical outcomes, including MACEs and all-cause hospitalization. Whether interventions to reduce seasonal variations in predialysis SBP will improve the prognosis of Japanese patients on HD must be investigated further.

Effects of sacubitril-valsartan in patients undergoing maintenance dialysis

Objectives Data on angiotensin receptor-neprilysin inhibitor (ARNI) sacubitril-valsartan (SV) in patients undergoing maintenance dialysis is scarce. Our study aimed to investigate the effect of SV on patients undergoing dialysis. Methods We retrospectively reviewed the data of end-stage kidney disease (ESRD) patients undergoing either peritoneal dialysis (PD) or hemodialysis (HD) in our center. A total of 51 patients receiving SV treatment were enrolled in the SV group. Another 51 age and sex-matched patients on dialysis without SV treatment were selected as the control group. All the patients were regularly followed up in the dialysis clinic. Their clinical, biochemical, and echocardiographic parameters were all recorded at baseline and during follow-up. The effect and safety of SV were further analyzed. Results A total of 102 ESRD patients on dialysis (51 patients in the SV group and 51 patients in the control group) were finally enrolled. The median follow-up time was 349 days (interquartile range [IQR]: 217–535 days). The level of B-type natriuretic peptide (BNP) (median [IQR] before and after SV treatment: 596.35 pg/ml [190.6–1714.85] vs. 188.7 pg/ml [83.34–600.35], p < 0.001) or N-terminal pro-B-type natriuretic peptide (NT-proBNP) (median [IQR]: 6316.00 pg/ml [4552.00–28598.00] vs. 5074.00 pg/ml [2229.00–9851.00], p = 0.022) were significantly decreased after treatment with SV. The variant rate of left ventricular ejection fraction (LVEF) was significantly higher in the SV group compared to the control group, especially in the PD subgroup. No significant difference was found in other echocardiographic parameters between SV and control group. Subgroup analysis of the PD group showed an increase in daily PD ultrafiltration (median [IQR]: 400 ml/d [200-500] vs. 500 ml/d [200–850], p = 0.114) after SV treatment. Variant rate of overhydration (OH) measured by the body composition monitor (BCM) of the SV group were significantly different from the control group (median [IQR]: −13.13% [−42.85%–27.84%] vs. 0% [−17.95%–53.85%], p = 0.049). The rate of hyperkalemia was slightly higher but without significant difference before and after the introduction of SV (19.6% vs. 27.5%, p = 0.350). No event of hypotension and angioedema were observed. Conclusions SV might have a cardio-protective role in ESRD patients undergoing dialysis, especially in PD patients. Serum potassium should be monitored during the treatment.

#3281 SAFETY AND EFFICACY OF VIRTUAL OUTPATIENT NEPHROLOGY CONSULTATION IN THE NORTHERN ALBERTA RENAL PROGRAM

Abstract Background and Aims There is a growing awareness among Canadian health care providers of the need to incorporate virtual consultations safely and effectively post pandemic. With the onset of the Covid-19 pandemic in March 2020, outpatient consultation in Northern Alberta Renal Program (NARP) was rapidly transitioned to virtual delivery (telephone or videoconferencing) in place of face-to-face visits. To scale up and sustain virtual consultation in kidney care programs, its safety and effectiveness in improving processes of care (reduced wait time and access to care) and patient-related outcomes must be established. Data establishing safety and effectiveness of virtual consultation in kidney care has been limited. We therefore aimed to evaluate the safety and effectiveness of virtual consultation in patients with advanced CKD or peritoneal dialysis (PD) being cared for in NARP. Method The study was conducted in NARP (one of the largest kidney care programs in Canada). The study populations comprised two categories of patients with kidney disease: 1) CKD (non-dialytic) being followed in the ambulatory care clinics and 2) chronic PD patients being followed up in a dedicated home dialysis clinic at 3-monthly intervals. Data were collected over two-time points, pre and post implementation of virtual kidney following the COVID-19 pandemic: March 2019-February 2020 (pre-implementation), and March 2020- February 2021 (post implementation). We were only allowed to collate data on the processes of care outcomes for CKD (clinic cancellations or no-shows, wait times to see a nephrologist from the point of referral and number of visits), and adverse clinical outcomes (peritonitis rates, all-cause hospitalizations, technique failure, defined as PD failure with transition to hemodialysis) for the patients on PD. Summary statistics and tests of associations applied as appropriate. Interrupted time series analyses were used to evaluate trends. All analyses were conducted using (STATA 15 software (Stata Corporation, 2017). The study was approved by the University of Alberta Research Ethics Board. Results In patients on PD, the studied outcome measures were not significantly impacted (no changes in the trend) pre and post virtual care implementation (Figs 1a-c). The absolute number of clinic visits in patients on PD did not change (data not shown). In the patients with CKD, there were significant reductions in the rate of clinic cancellations/no-show rates (Fig. 2a), and a reduction in wait time (by a median of two weeks) following virtual care implementation (Fig. 2b). The rates of clinic visits pre and post implementation did not change (Fig. 2c) Conclusion The implementation of virtual consultation with the onset of COVID-19 pandemic (and the attendant reduction in face-to-face contacts with patients) did not negatively impact the care of patients on PD regarding risk for adverse clinical outcomes (peritonitis rates, all-cause hospitalizations, and technique failure). In patients with CKD, implementation of virtual care has led to significant improvements in the processes of care (reduction in wait times and enhanced access to care). These findings have implications in the design of sustainable virtual care programs for delivery of specialized kidney care in both dialysis and non-dialytic CKD in Canada and beyond.

#5803 ARTERIOVENOUS FISTULA BLOOD FLOW ESTIMATION THROUGH AI MODEL EXPLOITING THE PATIENT'S ROUTINELY COLLECTED DATA

Abstract Background and Aims Clinical monitoring and surveillance are key pillars of Arteriovenous Fistula (AVF) management in hemodialysis patients. They are aimed at limiting the risk of suboptimal dialysis dose and Vascular Access (VA) failure. AVF blood flow (Qa) is commonly used to assess VA function. Several methods have been proposed for the measurement of Qa including doppler ultrasound, and Body Thermal Monitor, among others. All these diagnostic tests are, in general, time-consuming for clinical staff, operator dependent, and costly for healthcare providers. To overcome limitations in the uptake of current Qa measurement techniques, we used data automatically recorded by dialysis machine sensors and medical information captured in electronic charts records to estimate Qa using a machine learning technique. Method For this historical cohort study, we analyzed electronic health records (EHR) of adult patients from four different European countries (Czech Republic, Portugal, Slovakia, and Spain), receiving in-center hemodialysis therapy in Fresenius Medical Care dialysis clinics between January 1st, 2015 and June 30th, 2022 registered in the European Clinical Database (EuCliD®). All patients consented their pseudo-anonymized data be used for secondary data analysis. The input dataset included 49 variables representing the health status of the patients, functional parameters of AVF function and the HD treatment parameters. The input variables were collected in the 90 days before the Qa measure. We constructed metrics representing the 90-day average and trend of each functional and medical parameter. Qa was classified in three levels: &amp;lt; 525 ml/h (very low), 525 ml/h - 925 ml/h (low), &amp;gt; 925 ml/h (normal). We estimated Qa as ordinal classification problem. Therefore, we used 2 binary classifiers based on the XGBoost algorithm. The estimation of the first-class, P(Qa&amp;lt;525), is given by the first classifier and the estimation of the third class, P(Qa≥925), is given by the second classifier. The probability of the middle class is computed as P(Qa≥525)⋅(1-P(Qa≥925)). The Qa estimation accuracy was assessed computing mean absolute error (MAE), precision and recall, F1-score and confusion matrix. Results Our dataset included 46,292 Qa measurements referred to 5,940 different hemodialysis patients. We obtained an overall precision of 0.77, a recall of 0.76, a F1-score of 0.76, a MAE of 0.27. The same metrics for each class are shown in Table 1. The model was able to detect fistula with “very low flow” with a precision of 0.9 and 16% of the missed “very low flow” AVFs are predicted as “low flow” and 4.7% are predicted as normal flow. The Confusion Matrix for each class is shown in Figure 1. Conclusion In this study we showed that clinically relevant Qa classes can be accurately predicted by resorting to routinely collected clinical data extracted from a electronic health record without any additional effort from healthcare professionals, training or instrumentation. Qa assessment is an important parameter in the evaluation of AVF function. Our algorithm accurately discriminated patients with “very low flow” that may be referred to vascular surgeon evaluation. It might help the AVF surveillance process, without adding time-consuming procedures for clinical staff or costs for healthcare provider.

#4401 IMPACT OF POLYPHARMACY ON QUALITY OF LIFE IN DUTCH DIALYSIS PATIENTS: A QUALITATIVE STUDY

Abstract Background and Aims Almost all dialysis patients have polypharmacy but little is known about their experiences with medication and perception towards it. In this study, we aim to gain insight in dialysis patients’ experiences with polypharmacy the ways they integrate their medication in their daily lives and how it affects their quality of life. Method We conducted a qualitative study among dialysis patients from two Dutch university hospitals and affiliated dialysis clinics. Participants were interviewed in semi-structured interviews based on a pre-selected topic list. Interviews were transcribed verbatim and analysed independently by two researchers through thematic content analysis. Results Overall, 28 participants were interviewed (29% women, mean age 63±16 years, median dialysis vintage 25.5 [IQR 15-48] months, mean number of medications 14±3). Important themes were (1) participants’ own definition of what constitutes ‘medication’, (2) their perception of medication, (3) medication routines and its impact on daily life, and (4) interactions with healthcare professionals and others regarding medication. Participants generally perceived medication as burdensome but less burdensome than dialysis. Medication was accepted as an essential condition for their health even though participants could not always directly notice these health benefits and often relied on their physicians to determine the effectiveness of medication. Medication routines and other coping mechanisms helped participants to reduce the perceived negative effects of medication. In fact, for some participants, medication increased their freedom. Participants generally had constructive relationships with their physicians discussing their medication. Conclusion Polypharmacy negatively affected dialysis patients’ quality of life. These effects were, however, overshadowed by the burden of dialysis. Patients’ realization that medication is of importance for their health and effective coping strategies mitigated the negative impact of polypharmacy on quality of life. Physicians should continuously work together with their patients to evaluate the impact of treatments, not only on health but also on other aspects of patients’ daily lives.

#4261 RELATIONSHIP BETWEEN FLUID OVERLOAD AND AVERAGE PLASMA REFILL RATE IN HEMODIALYSIS PATIENTS

Abstract Background and Aims Attaining the optimal balance between achieving adequate volume removal while preserving organ perfusion remains challenging in patients on maintenance hemodialysis (HD). Quantification of fluid status using bioimpedance spectroscopy (BIS) has become routine in many countries. Inadequate vascular space refill from the interstitial tissue (plasma refill rate, PRR) is the main contributing factor of hemodynamic instability during HD. We aimed to explore the association between fluid overload (FO) and plasma refill rate (PRR) in chronic HD patients. Method Pre-HD FO [l] was assessed once per subject by BIS (Body Composition Monitor; Fresenius Medical Care) in four urban HD dialysis clinics in the U.S. For each treatment within 30 days before and after the BIS measurement, we calculated the respective pre-HD FO by assuming that differences in pre-HD body weight were equivalent to differences in FO. We then used intradialytic hematocrit (measured with the Crit-Line® Monitor, Fresenius Medical Care) and ultrafiltration data to quantify the average PRR, normalized by body weight (Wang et al. Kidney360, 2023): To calculate the starting blood volume (BV), we first calculated the ending BV using the Nadler equation, followed by back-calculating the starting BV based on the cumulative change in relative BV. Plasma refill volume was calculated as the sum of the changes in blood volume and ultrafiltration volume; plasma refill volume was then divided by treatment time and estimated clinical dry weight to calculate the PRR [ml/kg/hr]. Results We analyzed 746 HD sessions from 79 patients (age 61 ± 15 years; 52 (66%) males; 41 (52%) black and 33 (42%) white). Across all HD sessions, PRR was positively associated with FO [slope estimate 0.92 (95% confidence interval 0.83 to 1.02) ml/kg/hr per 1 l of FO, P value &amp;lt; 0.0001] (Figure 1). This was also the case in subgroup analyses of fluid depleted (r = 0.94, P&amp;lt;0.001), normohydrated (r = 1.03, P&amp;lt;0.0001), and fluid overloaded subjects (r = 0.83, P&amp;lt;0.0001). Conclusion Across the entire fluid status spectrum, from fluid depletion to fluid overload, higher FO was associated with higher PRR on average (overall, an increase of 0.92 ml/kg/hr in PRR for each additional liter of FO). While patients with greater FO would be expected to better tolerate higher ultrafiltration rates, there is large inter-individual variability in PRR. Further investigation of the utility of PRR throughout HD may offer novel insights into fluid management and intradialytic symptom mitigation.

Can Dialysis Patients Identify and Diagnose Pulmonary Congestion Using Self-Lung Ultrasound?

With the recent developments in automated tools, smaller and cheaper machines for lung ultrasound (LUS) are leading us toward the potential to conduct POCUS tele-guidance for the early detection of pulmonary congestion. This study aims to evaluate the feasibility and accuracy of a self-lung ultrasound study conducted by hemodialysis (HD) patients to detect pulmonary congestion, with and without artificial intelligence (AI)-based automatic tools. This prospective pilot study was conducted between November 2020 and September 2021. Nineteen chronic HD patients were enrolled in the Soroka University Medical Center (SUMC) Dialysis Clinic. First, we examined the patient's ability to obtain a self-lung US. Then, we used interrater reliability (IRR) to compare the self-detection results reported by the patients to the observation of POCUS experts and an ultrasound (US) machine with an AI-based automatic B-line counting tool. All the videos were reviewed by a specialist blinded to the performer. We examined their agreement degree using the weighted Cohen's kappa (Kw) index. A total of 19 patients were included in our analysis. We found moderate to substantial agreement between the POCUS expert review and the automatic counting both when the patient performed the LUS (Kw = 0.49 [95% CI: 0.05-0.93]) and when the researcher performed it (Kw = 0.67 [95% CI: 0.67-0.67]). Patients were able to place the probe in the correct position and present a lung image well even weeks from the teaching session, but did not show good abilities in correctly saving or counting B-lines compared to an expert or an automatic counting tool. Our results suggest that LUS self-monitoring for pulmonary congestion can be a reliable option if the patient's count is combined with an AI application for the B-line count. This study provides insight into the possibility of utilizing home US devices to detect pulmonary congestion, enabling patients to have a more active role in their health care.

Predicting SARS-CoV-2 infection among hemodialysis patients using multimodal data.

The coronavirus disease 2019 (COVID-19) pandemic has created more devastation among dialysis patients than among the general population. Patient-level prediction models for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are crucial for the early identification of patients to prevent and mitigate outbreaks within dialysis clinics. As the COVID-19 pandemic evolves, it is unclear whether or not previously built prediction models are still sufficiently effective. We developed a machine learning (XGBoost) model to predict during the incubation period a SARS-CoV-2 infection that is subsequently diagnosed after 3 or more days. We used data from multiple sources, including demographic, clinical, treatment, laboratory, and vaccination information from a national network of hemodialysis clinics, socioeconomic information from the Census Bureau, and county-level COVID-19 infection and mortality information from state and local health agencies. We created prediction models and evaluated their performances on a rolling basis to investigate the evolution of prediction power and risk factors. From April 2020 to August 2020, our machine learning model achieved an area under the receiver operating characteristic curve (AUROC) of 0.75, an improvement of over 0.07 from a previously developed machine learning model published by Kidney360 in 2021. As the pandemic evolved, the prediction performance deteriorated and fluctuated more, with the lowest AUROC of 0.6 in December 2021 and January 2022. Over the whole study period, that is, from April 2020 to February 2022, fixing the false-positive rate at 20%, our model was able to detect 40% of the positive patients. We found that features derived from local infection information reported by the Centers for Disease Control and Prevention (CDC) were the most important predictors, and vaccination status was a useful predictor as well. Whether or not a patient lives in a nursing home was an effective predictor before vaccination, but became less predictive after vaccination. As found in our study, the dynamics of the prediction model are frequently changing as the pandemic evolves. County-level infection information and vaccination information are crucial for the success of early COVID-19 prediction models. Our results show that the proposed model can effectively identify SARS-CoV-2 infections during the incubation period. Prospective studies are warranted to explore the application of such prediction models in daily clinical practice.

Walking aids and complicated orthopedic diseases are risk factors for falls in hemodialysis patients: an observational study

BackgroundAging and an increased fall risk have been demonstrated in hemodialysis patients at home and in a facility. However, studies investigating the cause of falls to prevent fractures in dialysis rooms are scarce. This study aimed to explore the related factors for accidental falls statistically in dialysis facilities for future fall prevention.MethodsThis study included 629 hemodialysis patients with end-stage renal disease. The patients were divided into two groups: the fall and non-fall groups. The main outcome was the presence or absence of falls in the dialysis room. Univariate and multivariate logistic analyses were performed; multivariate analysis was conducted using covariates significantly correlated in the univariate analysis.ResultsA total of 133 patients experienced falling accidents during the study period. The multivariate analysis indicated that the use of walking aid (p < 0.001), orthopedic diseases (p < 0.05), cerebrovascular disease, and age were significantly correlated with falls.ConclusionsIn the dialysis clinic, patients who use walking aids and have complicated orthopedic or cerebrovascular conditions are at a high risk of falling in the dialysis room. Therefore, establishing a safe environment may help prevent falls, not only for these patients but also among other patients with similar conditions.

A collaborative model between dialysis clinics and a hospital center improves the quality of vascular access care and intervention for hemodialysis patients.

This study reports the outcomes of a collaborative program between dialysis clinics and a referral hospital, which consisted of clinical monitoring and supplementary routine surveillance, for improving the quality of vascular access care. This retrospective observational study was performed at five dialysis clinics as part of a 2-year collaborative program (2019-2020) in conjunction with a hospital-based dialysis access management center. A total of 392 hemodialysis patients (arteriovenous fistula [AVF], n = 339 and arteriovenous graft [AVG], n = 53) were included. Outcome measures included the prognosis of vascular access, clinic satisfaction, and referral rate to the hospital. Increased vascular access flow was observed and critical flow events decreased from the first to the second year (AVF: 18.3% vs. 12.7%, p &lt; 0.001; AVG: 26.2% vs. 20.1%, p = 0.30). There were fewer percutaneous transluminal angioplasty events in the AVG group (0.77 per person-year vs. 0.51 per person-year, p = 0.005). New AVF or AVG creation events also remained low. All dialysis clinics were satisfied with the program. The overall referral rate from the participating clinics increased (65.7% vs. 72.0%) during the study period independently of the physical distance between the dialysis clinic and the hospital. The collaboration between dialysis clinics and a referral hospital for improving the quality of vascular access care was successful in this study, and the model can be used by other clinics and hospitals looking to improve care coordination in dialysis patients.

Beta-arrestin-biased agonism promotes TRPC6-mediated calcium influx in human podocytes

Background: Angiotensin Receptor blockers (ARBs) are the first-line treatment for hypertension and other chronic kidney diseases and act by inhibiting signaling through the angiotensin 1 receptor (AT1R). AT1R activation initiates signaling through G protein-coupled receptor (GPCR) effector signaling and β-arrestins. Recently, a novel AT1R agonist TRV120027 (TRV) that selectively activates the β-arrestin cascade without impacting the GCPR pathway has become available. Therefore, we hypothesized that β-arrestin and G-protein signaling pathways via AT1R have distinct downstream effects in podocytes. Furthermore, we propose that β-arrestin signaling initiates TRPC6-mediated Ca 2+ entry. Methods: We used a conditionally immortalized human podocyte cell line to determine β-arrestin’s involvement in podocyte calcium signaling and cytoskeletal reorganization. Intracellular Ca 2+ influx (Fluo-4 AM) and NO response (DAF-FM) to Ang II or TRV applications were analyzed with confocal microscopy. The role of TRPC channels was tested by single-channel electrophysiology and confocal imaging using a variety of commercially available inhibitors (AC1903 for TRPC5 and GSK283350A, SAR7334 for TRPC6). Western blotting for apoptosis-associated proteins, TUNEL staining to detect DNA cleavage, and actin cytoskeleton rearrangements were performed in podocytes exposed to TRV or Ang II treatment. Results: Our experiments determined that TRV-mediated β-arrestin pathway activation in podocytes promotes rapid elevation of intracellular Ca 2+ in a dose-dependent manner (IC 50 =15μM, ligand-receptor binding fit modeled with Levenberg–Marquardt algorithm, adj. R 2 =0.93). Interestingly, the amplitude of β-arrestin-mediated Ca 2+ influx was four times higher than the response to similar Ang II concentrations (t-test, n≥30, p&lt;0.05). Moreover, the TRV response was significantly increased under hyperglycemic stress conditions, and promoted rapid apoptosis in podocytes (one-way ANOVA, n≥21, p=0.003). The pharmacological blockade of TRPC6, but not TRPC5, significantly attenuated Ca 2+ influx in response to β-arrestin. In contrast to Ang II, TRV does not induce AT1R-mediated NO production, suggesting that β-arrestin activation only targets AT1R, and not AT2R. Single-channel analyses show rapid activation of TRPC activity in response to acute TRV application in podocytes (one-way ANOVA, n=8, p=0.004). Overall prolonged activation of the β-arrestin pathway in podocytes results in enhanced actin bundle thickness, abnormal actin cytoskeleton distribution, and increased apoptotic cell markers. Conclusions: TRV-mediated β-arrestin signaling in podocytes promotes high ionotropic TRPC6 channel-mediated Ca 2+ influx, cytoskeleton rearrangement, and apoptosis, possibly leading to severe defects in glomerular filtration barrier integrity and kidney health. Under these circumstances, the potential therapeutic application of TRV for hypertension treatment is controversial and requires further investigation. DK126720 (to OP), DK129227 (to AS and OP), and NIH/NCATS/SCTR UL1TR001450/SCTR 2214 (to OP), endowed funds from the SC SmartState Centers of Excellence (to OP), Veterans Affairs Support Veterans Affairs (Merit Award I01 BX000820 to JL), research grant from Dialysis Clinic, Inc (to JL). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Protease-activated receptor-1 mediated calcium oscillations in renal mesangial cells

INTRODUCTION. Mesangial cells provide structural support to the glomerular tuft and modulate the glomerular capillary flow via their contractile properties. Mesangial cells undergo phenotypic changes into myofibroblast-like cells, such as proliferation, mesangial expansion, abnormal glomerular tuft formation, and reduced numbers of capillary loops, are present in several glomerular diseases, including diabetic nephropathy and glomerulonephritis. In addition, thrombin-induced mesangial remodeling was found in diabetic patients, and expression of the corresponding protease-activated receptors (PARs) in the renal mesangium was reported. However, the functional PAR-mediated signaling and mechanisms in mesangial cells were not examined. This study aims to investigate protease-activated mechanisms regulating mesangial cell contraction and glomerular capillary flow. METHODS. We used primary human renal mesangial cells (HRMC) to determine the signaling mechanisms mediated by PAR1 thrombin-activated receptors. Confocal fluorescent microscopy was utilized to detect changes in intracellular Ca 2+ response to specific PAR1 modulators. Pharmacology and patch clamp electrophysiology was further applied to reveal downstream signaling mechanisms responsible for intracellular Ca 2+ oscillations. RESULTS. PAR1-mediated Ca 2+ response displayed high sensitivity to specific agonist (TFLLR-NH 2 ) with EC 50 values of 3 and 6.3 nM for male and female-derived cultured cells, respectively (the competition of a ligand for receptor binding fit converged; adj. R 2 =0.98). The response to PAR1 activation promoted initial cytosolic Ca 2+ increase followed by synchronized, damped Ca 2+ oscillations with a lag of 6.74±0.84 min between peaks. The pre-application of a specific inhibitor (RWJ56110) eliminated PAR1-mediated response, and oscillations were blocked by the changes of an extracellular solution to zero Ca 2+ . The specific inhibitors for store-operated calcium (SOCs) (Pyr6) and TRPC3 (GSK 2833503A) channels strongly attenuated oscillation behavior (up to 40% when added separately and up to 65% when both were applied; two-way ANOVA, * p&lt;0.0001). In addition, the effect of a specific inhibitor of TRPC6 channels (BI-749327) had a minimal impact on Ca 2+ flux. Further single-channel electrophysiology experiments in HRMC cells confirmed the involvement of SOC and TRPC3 channels in PAR1-mediated GPCR activation. CONCLUSION. Our results indicate that coagulation proteases like thrombin may strongly regulate mesangial cell contraction and corresponding glomerular capillary flow by PAR1 GPCRs-related activation. The contraction mechanism is mediated presumably through SOCs entry and TRPC3 channels. Since high thrombin levels are linked to poor diabetic control, the described signaling may play a crucial role in the development of diabetic glomerular disease. DK126720 (to OP), DK129227 (to AS and OP), Veterans Affairs Support Veterans Affairs (Merit Award I01 BX000820 to JL), research grant from Dialysis Clinic, Inc (to JL). This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Work Experiences of the Interdisciplinary Dialysis Workforce in the United States: A Cross-Sectional Survey

Introduction: Suboptimal dialysis care may be in part due to staff issues such as job dissatisfaction, burnout, work overload, high staff turnover, and inconsistent training. Here, we leveraged data collected in a recent national survey to provide an initial, comprehensive description of current work experiences of US dialysis care providers. Methods: We conducted a cross-sectional survey of 1,240 active US dialysis clinic staff members (physicians, advanced practice providers, nurse managers/clinic coordinators, nurses, social workers, dietitians, and patient care technicians), who were recruited via emails to society membership lists. Respondents were asked about a wide variety of work experiences, including job satisfaction, professional fulfillment, and burnout (Stanford Professional Fulfillment Index), work culture, experiences of hostility and violence, and self-reported medical errors. Responses were summarized overall and compared by clinic role. Results: Most of the survey respondents, representing all 50 US states, were aged 35–49 years (58.3%) or ≥50 years (23.5%), female (60.7%), and white (59.8%; 23.1% black, and 10.0% Asian); 82.1% had been in their current role for at least 1 year. Most US dialysis staff responding to our survey reported being generally satisfied with their jobs (mean rating of 7.9 on 0–10 scale), but only 54.4% met criteria for professional fulfillment, and 32.8% met criteria for burnout, driven by high scores in the work exhaustion domain. Related issues, including high workloads, lack of respect (including experiences of violence and hostility), lack of autonomy, and suboptimal patient environments (in terms of both safety and patient centeredness), were commonly reported among dialysis care providers, although their prevalence often differed by provider type. Conclusion: Our results suggest that the dialysis workforce may be at a critical point. Preventing further staff burnout, which could lead to even greater staffing shortages and worse working conditions among those who continue to provide dialysis care, is essential.

A pilot trial of Thymalfasin (Ta1) to prevent covid-19 infection and morbidities in renal dialysis patients: Preliminary report.

Patients with end-stage renal disease (ESRD) on hemodialysis (HD) are considered particularly susceptible to infection with SARS-CoV2 on the basis of the immunodeficiency associated with advanced age, comorbidity burden, medication use, and need for frequent visits to dialysis clinics. In prior studies, thymalfasin (thymosin alpha 1, Ta1) has been shown to enhance antibody response to influenza vaccine and reduce influenza infection in geriatric populations, including hemodialysis patients, when used as an adjunct to influenza vaccine. Early in the COVID-19 pandemic we speculated that administration of Ta1 to HD patients would result in reduced rate and severity of COVID-19 infection. We also hypothesized that HD patients treated with Ta1 who did become infected with COVID-19 would have a milder course of infection in terms of hospitalization rates, requirement for and length of ICU stays, requirement for mechanical ventilation, and survival. Further, we proposed that patients who avoided COVID-19 infection during the study would have decreased non-COVID-19 infections and hospitalizations compared to controls. The study launched in January 2021 and, as of July 1, 2022, 254 ESRD/ HD patients from five dialysis centers in Kansas City, MO have been screened. Of these, 194 patients have been randomized 1:1 to either Group A (1.6mg Ta1 given subcutaneously twice weekly for 8weeks), or Group B (control group not receiving Ta1). After the 8-week treatment period, subjects were followed for an additional 4months and monitored for safety and efficacy. A data safely monitoring board reviewed all reported adverse effects and commented on study progress. To date, only 3 deaths have occurred in subjects treated with Ta1 (Group A), compared to 7 in the control (Group B). There have been 12 COVID-19 related serious adverse effects (SAEs; 5 in Group A, and 7 in Group B). The majority of patients have received a COVID-19 vaccine (91 patients in group A, and 76 patients in Group B) at various times throughout the study. Nearing completion of the study, blood samples have been collected and antibody responses to COVID-19 will be analyzed along with safety and efficacy endpoints when all subjects have completed the study.

Blunted humoral immune response to the fourth dose of BNT162b2 COVID-19 vaccine in patients undergoing hemodialysis.

We aimed to investigate the impact of a fourth dose of BNT162b2 vaccine (Comirnaty®, Pfizer-BioNTech) on anti-SARS-CoV-2 (anti-S IgG) antibody titers in patients receiving hemodialysis (HD) and healthcare workers (HCWs). A multi-institutional retrospective study at five dialysis clinics in Japan was conducted using 238 HD patients and 58 HCW controls who received four doses of the BNT162b2 mRNA vaccine. Anti-S IgG titers were measured at 1, 3, and 6months after the second dose, at 1 and 5/6months after the third dose, and at 1month after the fourth dose of vaccine. The log anti-S IgG titers of the HD patients after the second vaccination were significantly lower than those of the control group, but equalized 1month after the third vaccination: 9.94 (95% CI 9.82-10.10) vs. 9.81 (95% CI 9.66-9.96), (P = 0.32). In both groups, the fold-increase in anti-S IgG titers was significantly lower after the fourth dose than after the third dose of vaccine. In addition, there was a strong negative correlation between antibody titers 1month after the fourth vaccination and antibody titers immediately before the vaccination. In both groups, the waning rate of anti-S IgG titers from the post-vaccination peak level after the third vaccine dose was significantly slower than that after the second dose. These findings suggest that the humoral immune response was blunted after the fourth dose of the conventional BNT162b2 vaccine. However, multiple vaccinations could extend the window of humoral immune protection.

Impact of different automated peritoneal dialysis modalities on the inflammatory profile of elderly patients with chronic kidney disease.

Chronic kidney disease, more prevalent in the elderly, is considered a public health issue worldwide. To evaluate the impact of automated, peritoneal dialysis modalities, intermittent and continuous, on the inflammatory profile of elderly people with chronic kidney disease. Prospective, cross-sectional and analytical study carried out in a dialysis clinic in Brasília - Brazil, with 74 elderly people aged 60 years or older. The patients underwent rapid Peritoneal Equilibration Test, clinical assessment, blood collection for biochemical and cytokine assessments, interleukin 6 and transforming growth factor beta 1, and answered a quality-of-life questionnaire (KDQOL-SF36). We used a 5% significance level for data analysis, associations and correlations. Patients in the continuous modality had higher serum values of transforming growth factor beta 1 than those in the intermittent modality, which had higher peritoneal transforming growth factor beta 1, age and residual renal function than those in continuous mode. Interleukin 6 dosage in the peritoneum was associated with age, while serum IL-6 was associated with IL-6 in the peritoneum, time on dialysis and age. There was no association between the modality and the presence of diabetes, blood volume or nutritional status. Both modalities enable good adaptation to the dialysis treatment. Inflammation in automated peritoneal dialysis is mainly associated with low residual renal function, advanced age and longer time on therapy, and not to the type of dialysis performed.

High prevalence of hyperkalemia in Brazilian chronic dialysis patients and differences across geographic regions.

Hyperkalemia is a common multifactorial condition of people on chronic dialysis and is associated with mortality. We aimed to inform and discuss the prevalence of hyperkalemia in a large population of chronic dialysis patients in Brazil and its geographic regions. Prevalence of hyperkalemia (serum potassium ≥6.0 mEq/L) was assessed in the Brazilian Dialysis Survey (BDS) in July 2019, an online survey of voluntary participation in which all dialysis centers registered at the Brazilian Society of Nephrology were invited. Approximately one-third (n=263 of 805) of the Brazilian dialysis clinics participated. The prevalence of hyperkalemia in the whole population was 16.1% (n=7,457 of 46,193; 95%CI=15.8-16.5%,), and varied from 12.1% in the North to 18.7% in the Northeast. We found a high prevalence of hyperkalemia in a large Brazilian chronic dialysis population. A nationwide investigation of risk factors, treatment options, and whether this high prevalence contributes to dialysis mortality is warranted.