Adult Hemodialysis Patients Research Articles

#3648 INDIVIDUALIZED ANEMIA THERAPY IMPROVES HEMOGLOBIN OUTCOMES AND DECREASES EPOETIN BETA DRUG EXPOSURE IN HEMODIALYSIS PATIENTS

Abstract Background and Aims Anemia is a common complication in hemodialysis (HD) patients. Its treatment with erythropoiesis-stimulating agents (ESAs) is challenging due to a nonlinear dose-response relationship and time delays between ESA administration and hemoglobin (Hgb) response. Anemia treatment protocols are frequently used in clinical settings. However, high variability of patient-specific disease characteristics complicate attainment and maintenance of desired Hgb levels. We developed a novel fully personalized ESA dose recommendation tool and present clinical results of a multi-center, randomized controlled trial (RCT) using this software. Method We conducted an RCT in adult HD patients in six dialysis facilities in the US. Patients were randomized 1:1 and treated with our personalized ESA dose recommendation tool for twenty-six weeks (intervention group) or continued to be treated using an anemia protocol that was used as part of standard of care in those clinics (control group). The recommendation tool utilized a physiology-based model of anemia to estimate patient-specific physiological key characteristics, such as red blood cell lifespan, to create a patient-individual model from recent routine clinical data (gender, height, weight, Hgb measurements, and ESA treatment). These key characteristics and model-based outcome predictions were used to generate patient-specific ESA dose recommendations to stabilize Hgb levels in a target window of 10–11 g/dL. Dose recommendations were disseminated to the anemia managers of patients enrolled in the study for evaluation and further decision-making (Figure 1). This procedure was repeated biweekly with updated clinical data. Results Ninety-six patients were enrolled in the RCT. Patients were included in the statistical analysis when they remained in the clinical study for at least 30 days (n = 45 control group, n = 46 intervention group). We evaluated outcome measures showing efficacy and efficiency of the treatment in achieving target Hgb levels. Hgb-related outcomes were significantly different between the two study groups, with an improved Hgb control in the intervention arm, manifesting in a reduction of the Hgb distance to target by more than 30%. Epoetin-beta utilization in the intervention group was decreased by over 20%, while iron-related parameters showed no difference between the two arms (Table 1). Acceptance rate of dose recommendations was high; roughly 95% of the recommendations were accepted and implemented by the clinical staff. Conclusion A therapy software for personalized anemia management was developed for use with epoetin beta. The model-based ESA dose recommendation tool was evaluated in a clinical RCT in HD patients. Hgb control improved significantly in the group using the novel software tool, while ESA usage decreased, thus providing more efficient anemia management for the individual patient while reducing epoetin-beta drug exposure.

#6348 HFR USING A HIGH-FLUX DIALYZER (SUPRA-H) AS NEW EFFECTIVE ALTERNATIVE TO ON-LINE HEMODIAFILTRATION: A SINGLE SESSION ANALYSIS

Abstract Background and Aims Hemodiafiltration with regeneration of the ultrafiltrate (HFR) is a highly biocompatible dialysis technique that combines convection, diffusion, and adsorption. SUPRA-H is a new HFR system which uses a high-flux dialyzer in the diffusive stage to improve large uremic toxin removal. The aim of our study was to compare the toxin removal of the SUPRA-H system with high-volume online-hemodiafiltration (OL-HDF). Method In an open, randomized, cross-over, single-center, controlled study, 16 adult chronic hemodialysis patients were treated with SUPRA-H or OL-HDF. Hemodialysis sessions were delivered with Flexya dialysis monitor (Medtronic) in the middle-week session, lasting four hours. OL-HDF session was performed in post-dilution mode with the same high-flux dialyzer (Phylter HF17G, Medtronic) as that used in the diffusive stage of the SUPRA-H system. All other dialysis parameters were kept constant in both study arms. The reduction rate (RR) of urea, creatinine, phosphate, β2-microglobulin (β2mglob), kappa (κFLC) and lambda (λFLC) free light chains, interleukin-6 (IL-6) p-Cresyl sulfate, indoxyl sulfate and albumin, was intraindividually compared for the two dialysis types with linear mixed models. Results Whereas urea RR was significantly lower, SUPRA-H had significantly higher RR for κFLC (Median: 58.63%, IQR: 49.91-70.24) than those obtained with OL-HDF (Median: 51.97%, IQR: 37.12-62.71); p = 0.03). The RRs for the other large and protein-bound uremic toxins tended to be higher with the SUPRA-H system (Figure 1). There were no significant differences in the RRs for creatinine, phosphate, IL-6, and albumin. Conclusion The new HFR system SUPRA-H, appears to be a potential technologic step ahead in terms of improved large molecule removal for dialysis patients, and might contribute to a more adequate dialysis therapy.

#4894 EFFICIENCY AND SAFETY OF AN ASSISTED HOME HEMODIALYSIS PROGRAM IN THE STATE OF QATAR: A RETROSPECTIVE STUDY

Abstract Background and Aims Home hemodialysis (HHD) usually done as self-care by patient themselves through a portable haemodialysis (HD) machine under training and monitoring by dialysis team. HHD offers greater patient autonomy, cost benefits, treatment-related flexibility, and improved quality of life compared to traditional in-centre HD. Uptake of HHD is limited by patient motivation, cognitive and/or physical barriers, as well as lack of support of family and community. Assisted HHD (AHHD) is a new concept where dialysis team provides HD at home. Usually, it is done by a visiting dialysis nurse using mobile HD machine. Its use is limited due to financial and logistical restriction. We like to present our unique experience in providing AHHD in the State of Qatar. Planning for our AHHD program started in July 2020. Because of COVID-19 pandemic, it faced many challenges and delays. We started first patient in July of 2021. In our program, we use traditional HD machine (not portable) with connection set up in the house in a dedicated room. Special training was provided to AHHD staff regarding the special care needed for home setting (including social, complication of home dialysis settings, decision making, follow up of protocols and policies, etc.) Method We performed a retrospective study between July 1st, 2021 - December 31st, 2022. Our primary objectives were efficiency and safety of AHHD, and secondary objective was cost effectiveness. We included adult chronic HD patients (on HD >3 months) using ambulance (or eligible for it) with functional dialysis access. We excluded patients who are not suitable for home environment (psychiatric illness, aggressive behaviour, etc.). Data were collected from our national electronic health record system. Results 946 patients screened for the program. 237 were eligible (exclusion mostly due to lack of national insurance coverage or not meeting mobility/transport criteria). 121 patients refused to participate (mostly for feeling safer in the clinic setting or improper home environment), 40 patients were undecided, and 76 patients accepted and started AHHD. Age was 73+/-11 years. We had 32 males and 44 females. Mean follow up period were 7 months. 12 patients died and 2 patients returned to dialysis centre during follow up period. Only 15 out of the total 126 hospitalizations were related to dialysis (mostly due to volume overload and non-compliance with dialysis schedule and time). We had 55 patients with permcath and 21 with AV fistulas. We had 8 incidents of dialysis catheter malfunction (6 required tissue plasminogen activator installation in the house setting and only two needed catheter exchange (one had catheter related infection)). No reported significant access bleeding or hypotension episodes. We had 20 technical incidents during the study related to electricity or water supply failures. All incidents were resolved without much interruption of treatment. The program overall was cost effective and reduced cost by over 25% (mostly related to saving of ambulance cost). Patients and their families were very satisfied with the program overall. Conclusion We present a unique successful program related to providing AHHD. Targeting certain dialysis population showed great care, safety, cost saving, better QOL and satisfaction.

#4465 NO DIFFERENCES IN ALL-CAUSE OR CARDIOVASCULAR MORTALITY BETWEEN DIALYSATE CALCIUM OF 1.25 AND 1.50 MMOL/L: RESULTS FROM A EUROPEAN HEMODIALYSIS COHORT

Abstract Background and Aims The appropriate prescription of dialysate calcium (DCa) concentration for hemodialysis (HD) patients is debated and guidelines are inconsistent. We investigated the association between DCa and all-cause, cardiovascular mortality and sudden cardiac death (SCD). Moreover, we examined the association between serum dialysate calcium gradient (SCa-DCa) and the study outcomes. Method In this historical cohort study, we included adult incident HD patients registered in the clinical database EuCliD® with dialysis initiation between January 1, 2010, and June 30, 2017 (recruitment period) who survived for at least 6 months after starting dialysis (grace period). We observed patients’ outcomes for up to 2 years after the end of the grace period (Figure 1). We categorized patients into 2 groups according to the prescribed DCa in the last 3 months of the grace period (ascertainment period): 1.25 (DCa 1.25) or 1.50 mmol/l (DCa 1.50). We calculated hazard ratio (HR) with 95% confidence intervals (CI) for all study outcomes with Cox Regression. The fully adjusted model included age, sex, ethnicity, diabetes mellitus, cardiovascular disease, liver disease, cancer, vascular access, treatment time, Kt/V, total ultrafiltered volume per session, serum hemoglobin, serum albumin, calcium containing phosphate binders, active vitamin D, Cinacalcet. We added country indicators as random effects. The SCa-DCa (in mEq/l) was calculated as (albumin-correct serum calcium (in mg⁄dl) × 0.5) – (DCa (in mmol/l) × 2) (1). Results We included 12,897 patients with DCa 1.25 and 26,989 patients with DCa 1.50 from 22 countries. The median age was 65 years and the percentage of men was 61% in both groups. In the unadjusted model, patients treated with DCa 1.50 had higher risk of all-cause mortality compared to those treated with DCa 1.25 (HR 1.07 [95% CI 1.01-1.12]. However, this association was not robust when adjusting for potential confounding (HR 1.04 [95% CI 0.97-1.10]). Similarly, we found no evidence of significant adjusted association between DCa and cardiovascular mortality (HR 1.01 [95% CI 0.92-1.11]). We observed a significant adjusted lower association between DCa 1.50 and SCD (HR 0.78 [95% CI 0.65-0.94]). We found significant associations between larger SCa-DCa gradient and all outcomes: all-cause (HR 1.16 per 1 mEq/L increase [95% CI 1.09-1.24]), cardiovascular mortality (HR 1.23 [95% CI 1.12-1.35]) and SCD (HR 1.69 [95% CI 1.41-2.03]). To explore the contribution of gradient components to patients’ risk, we included both DCa and serum calcium level (SCa) in the models. We observed significant associations with all outcomes and SCa, but not with DCa and the interaction between them. In a subgroup analysis of patients with iPTH levels below 130 pg/ml (n = 7,438), we did not find any significant association between DCa and the outcomes. Conclusion In this observational study, no differences in all-cause or cardiovascular mortality were observed with the prescription of DCa 1.50 as compared to 1.25 after adjustment for confounders, whereas the risk of SCD appeared to be lower in the group of DCa 1.50. The association between the SCa-DCa gradient and outcomes appears to be predominantly related to the effect of SCa.

#2868 PREDICTION OF MAJOR GASTROINTESTINAL BLEEDING EVENTS IN HEMODIALYSIS

Abstract Background and Aims INitiativeS on advancing Patients’ outcomes In REnal disease (INSPIRE) is an academia and industry collaboration set forth to identify critical investigations needed to advance the practice of medicine in nephrology. At the inaugural INSPIRE meeting, the group came to a consensus that major bleeding events represent potentially preventable complications that occur more frequently in people with kidney disease versus the general population [1]. Given the most common class of bleeding event is gastrointestinal bleeding (GIB) [2], the INSPIRE group assessed if a machine learning model could be developed to assist with determining a hemodialysis (HD) patient's 180-day GIB hospitalization risk. Method Model was developed using adult HD patient data from United States (2017-2020). Patient data was randomly split (50% training, 30% validation, and 20% testing). HD treatments ≤180 days before GIB hospitalization were classified as positive observations, and others were negative observations. Datasets were randomly sampled to build an XGBoost model that considered 386 exposures initially and was refined to the top 50 exposures. Unseen testing dataset was used to determine final model performance. Results The incidence of 180-day GIB hospitalization was 1.18% in the HD population (n = 451,579), and 1.16% among patients in the testing dataset (n = 27,991). The model showed an area under the curve = 0.69, sensitivity = 57.9%, specificity = 68.9%, accuracy = 68.8% and balanced accuracy = 63.4%. Exposures with largest effect size observed via Shapley values were older age (group mean GIB event = 68.2 years vs no GIB event = 63.4 years), shorter days since last all-cause hospital admission (group mean GIB event = 203.2 days vs no GIB event = 253.2 days), and higher serum 25-hydroxy (OH) vitamin D levels from most recent lab (group mean GIB event = 33.4 ng/mL vs no GIB event = 30.5 ng/mL). Other important predictors included lower hemoglobin and iron indices, longer dialysis vintage, and proton pump inhibitor use (Fig. 1). Conclusion The machine learning model appears suitable for early detection of GIB event risk in HD, yet prospective testing is needed. The association between higher 25OH vitamin D and GIB events was unexpected and warrants investigation. A consistent signal has been observed in warfarin users without kidney disease among which 25OH vitamin D levels of 30–100 ng/mL were shown to associate with the highest GIB risk [3].

#3388 ASSOCIATIONS BETWEEN PHYSICAL ACTIVITY, PHYSICAL FUNCTION AND BONE METABOLISM MARKERS IN HAEMODIALYSIS PATIENTS: A PRELIMINARY CROSS-SECTIONAL STUDY

Abstract Background and Aims Chronic kidney disease (CKD) patients suffering from end-stage renal disease often undergo dialysis treatment. Haemodialysis (HD) patients spend most of their time in sedentary behaviour, having therefore poor physical function, as well as frequently develop mineral and bone disorders due to disease-induced systemic alterations such as abnormally high bone resorption rates exceeding bone formation. In healthy individuals, there is considerable evidence highlighting the associations between physical activity (PA), physical function (PF), and bone health. In HD patients, however, evidence on the association between these variables is still scarce. Therefore, the present preliminary study seeks to characterise HD patients in terms of their PA and PF, and to identify any associations between these and markers of bone metabolism. Method A cross-sectional design study recruited 88 adult HD patients (males: 68%, age: 66±14 years, dialysis vintage: 42±52 months) from three clinics in Portugal. Resting blood samples were collected from the patients’ fistula at the start of the second dialysis session of the week. Plasma levels of the bone markers tartrate-resistant acid phosphatase 5b (TRAP-5b) (IDS, Tyne and Wear, UK), and sclerostin (SOST) and receptor activator of nuclear factor kappa-Β ligand (RANKL) (Biomedica Immunoassays, Vienna, Austria) were measured by commercially-available enzyme-linked immunosorbent assays (ELISA), and osteocalcin (OCN) (Biogen, Madrid, Spain) and osteoprotegerin (OPG) (R&D Systems, Abingdon, UK) via DuoSet ELISA kits. PF was assessed by completing the Sit to Stand 60 (STS60), the STS5, the Incremental Shuttle Walk Test (ISWT), the Timed Up and Go (TUG), and handgrip strength (HGS). All participants worn tri-axial accelerometers continuously for a week to estimate PA levels. Results Accelerometers were worn for an average 13±2h/day and data showed that 81±11% of the time was spent in sedentary behaviour, and 18±10% in light PA. Associations between PA, PF and markers of bone metabolism are described in Table 1. Weekly sedentary time was associated with reduced agility (TUG), muscle endurance (STS60, ISWT), and muscle power and strength (STS5), whereas light PA levels were associated with an increment in overall PF. Also, light PA levels were associated with decreased TRAP-5b and OPG, but elevated circulating OCN, supporting a potential modulatory effect of PA on bone turnover. Decreased overall PF were associated with increased concentrations of OPG, with muscle endurance and strength associated with increased circulating TRAP-5b. Conclusion Our data suggests that sedentarism may be responsible for a reduced PF, which in turn was associated with increased inhibition of osteoclastogenesis via OPG activity. Yet, a rather small increase in PA levels may lead to PF gains and could be a trigger for OCN activity and TRAP-5b inhibition. Therefore, increasing PA levels may modulate bone metabolism through mechanisms that favor bone formation.

#3689 RELATIONSHIP BETWEEN STAPHYLOCOCCUS AUREUS NASAL CARRIAGE AND URAEMIC PRURITUS IN HAEMODIALYSIS PATIENTS AND ITS INFLUENCE ON INFECTION

Abstract Background and Aims Uraemic pruritus is a common and distressing comorbid disease among patients undergoing haemodialysis (HD). The aetiology of uraemic pruritus is multifactorial and not fully understood. The role of skin microbiota in chronic inflammatory skin disease has long been discussed, but evidence regarding the relationship between uraemic pruritus and Staphylococcus aureus (SA) colonization is limited. The rate of SA nasal carriage in HD patients was more than double that of healthy individuals, and the phage type of SA infection was often the same as the type of SA carried in the HD patients' nares. SA colonization is associated with greater skin barrier disruption, which suggests a possibility to increase the risk of infection in patients with uraemic pruritus. This study aimed to assess the role of SA nasal carriage in uraemic pruritus, as well as the interplay among SA colonization, uraemic pruritus, and SA infection in HD patients. Method We conducted a prospective cohort study to enrol adult HD patients in the Far Eastern Memorial Hospital, a tertiary medical centre in Taiwan, in April 2019. Eligible patients should had received maintenance HD for more than three months. Patients were excluded if they had active infection or primary skin diseases. The intensity of uraemic pruritus was assessed using a visual analogue scale (VAS) from 0 to 10 (0 = no pruritus, 10 = the worst pruritus imaginable). Nasal swab culture was performed to examine the status of SA nasal carriage. Patients were followed until SA infection, death, or January 2020, whichever had occurred earlier. The definition of SA infection should fulfil both the clinical diagnosis and the results of microbiological culture. Multivariate linear regression models were used to assess the potential predictors for a higher pruritus intensity. Multivariate Cox proportional hazard models were used to analyse the risk of SA nasal carriage on SA infection among the HD patients. Results A total of 100 HD patients were enrolled, the mean age was 61.7 years and 69% were men. The mean dialysis vintage was 6.7 years. Among the participants, 55% had uraemic pruritus and the mean VAS score of pruritus intensity was 4.0. The prevalence of SA nasal carriage was higher in patients with uraemic pruritus than that in patients without uraemic pruritus (33% vs 13%, P = 0.024). The multivariate linear regression model showed that SA nasal carriage was an independent predictor of a higher VAS score of pruritus intensity (parameter estimate, 1.18; 95% CI 0.05-2.30; P = 0.04) (Table 1). After follow-up for 10 months, there were four SA infection events in the pruritus patients and one event in the non-pruritus patients. The multivariate Cox proportional hazard model showed that patients with SA nasal carriage had a borderline higher risk for SA infection (adjusted hazard ratio, 50.9; 95% CI, 0.62-3689; P = 0.08) (Table 2). Conclusion SA nasal carriage is independently associated with uraemic pruritus, and is also an independent predictor for a higher pruritus intensity among HD patients. Moreover, SA colonization might predict SA infection in later follow-up period. This study provide evidence for future studies regarding the survey for SA colonization and application of nasal decolonization among HD patients with uraemic pruritus.

#3055 ASSOCIATION OF MORTALITY WITH INTRADIALYTIC EXERCISE IN HEMODIALYSIS PATIENTS

Abstract Background and Aims Patients with hemodialysis (HD) have an increased risk of mortality, which can be minimized by physical activity (PA). Intradialytic exercises (IDE) are very convenient, potentially increasing adherence to PA and allowing for a sedentary lifestyle. Thus, the purpose of this study was to analyze the association of IDE with mortality in patients with HD. Method A single center, prospective study in adult HD patients eligible for IDE (cycling 3 times a week) was performed. After 1 year of IDE introduction, patients were followed up for up to 3 years. Three groups were created based on the impact of IDE (minutes of exercise per week): no exercise (patients who refused IDE); low load (<87 min/week); high load (≥87 min/week). Kaplan-Meier models (unadjusted analysis) and Cox proportional hazard models (adjusted for age, dialysis experience, vascular access, comorbidity index, CVD, muscle tissue, overhydration, and hospitalizations) were used with a non-exercise group as a reference. In addition, a sub-analysis was conducted, limited to IDE participants, with exposure as a continuous variable. Results 106 patients (no exercise: 58; low exercise: 26; high exercise: 22) were followed for an average of 24.5 months. Uncorrected mortality differed between the three groups: (no exercise: 24.1%; low load: 23.0%; high load: 9.0%; p<0.01). In the adjusted analysis, the high load group had a lower risk of mortality than the no exercise group (RR = 0.42, 95% CI 0.23–0.76, p<0.05), while in the low load group this was not observed (RR). = 1.07, 95% CI 0.66–1.52, p = 0.568). In addition, mortality risk decreased for every 55 minutes of exercise per week in unadjusted (HR = 0.46, 95% CI 0.29–0.76, p = 0.01) and adjusted analyzes (HR = 0.54, 95% CI 0.32–0.91, p<0.05). Conclusion Our findings show that IDE is associated with a reduced risk of mortality in HD patients, but a significant amount of exercise is required. Thus, patients who achieve low load doses may require non-clinical approaches to PA in addition to IDE. These findings complement those of earlier studies and highlight the need for a tailored approach to the exercise.

Chronic kidney disease-associated pruritus (CKD-aP) is associated with worse quality of life and increased healthcare utilization among dialysis patients.

Chronic pruritus significantly impairs hemodialysis patients' health status and quality of life (QOL) and it is associated with higher mortality rate, more frequent hospitalizations, poorer dialysis and medication adherence, and deteriorated mental status. However, pruritus is still underestimated, underdiagnosed, and undertreated in the real-life clinical scenario. We investigated prevalence, clinical characteristics, clinical correlates, severity as well as physical and psychological burden of chronic pruritus among adult hemodialysis patients in a large international real-world cohort. We conducted a retrospective cross-sectional study of patients registered in 152 Fresenius Medical Care (FMC) NephroCare clinics located in Italy, France, Ireland, United Kingdom, and Spain. Demographic and medical data were retrieved from the EuCliD® (European Clinical) database, while information on pruritus and QoL were abstracted from KDQOL™-36 and 5-D Itch questionnaire scores. A total of 6221 patients were included, of which 1238 were from France, 163 Ireland, 1469 Italy, 2633 Spain, and 718 UK. The prevalence of mild-to-severe pruritus was 47.9% (n = 2977 patients). Increased pruritus severity was associated with increased use of antidepressants, antihistamines, and gabapentin. Patients with severe pruritus more likely suffered from diabetes, more frequently missed dialysis sessions, and underwent more hospitalizations due to infections. Both mental and physical QOL scores were progressively lower as the severity of pruritus increased; this association was robust to adjustment for potential confounders. This international real-world analysis confirms that chronic pruritus is a highly prevalent condition among dialysis patients and highlights its considerable burden on several dimensions of patients' life.

HEMODYNAMICS STRESS TEST USING FINGER-TO-TOE PULSE WAVE VELOCITY IN SUPINE AND SITTING POSITION IN END-STAGE KIDNEY DISEASE

Objective: Aortic pulse wave velocity (PWV), a measure of arterial stiffness can either be measured by the ratio of distance to pulse transit time or, estimated based on the pulse wave profile (ePWV). Aortic PWV measurements are performed in the supine position as there is no added hydrostatic pressure along the arterial path, and the recording of the arterial pressure waveform of the femoral arterial is easier to perform. However, finger-to-toe PWV (ftPWV), a surrogate for aortic PWV, can easily be performed in other positions, such as the sitting position, giving the opportunity to examine arterial wall properties in a dynamic manner. The aim of the study was to observe the impact of the position (supine vs sitting) on the ePWV and on the measured ftPWV in patients with end-stage kidney disease. Design and method: In a cross-sectional study involving adult hemodialysis patients, we performed vascular assessments in the supine and the sitting position within the first 2 hours of their hemodialysis session. The ePWV was obtained using the Mobil-O-Graph and ftPWV was obtained using the pOpmètre®. Three measures were taken with each device. Generalized estimated equations were then used to calculate the average of ePWV and ftPWV with respect to each position. Results: In 46 patients (17 females), the average age was 71±12 years and the blood pressure was 136±24 /77±15 mmHg. The ePWV was 10.8 m/s (IC95% :10.1-11.4 m/s) in the supine position and 10.7 m/s (IC95%: 10.0-11.3 m/s) in the sitting position. However, the ftPWV was 12.1 m/s (IC95%: 9.6-14.7 m/s) in the supine position but it increased to 22.0 m/s (IC95%: 15.0-29.0 m/s) in the sitting position. This increase of 9.8 m/s was highly significant (P = 0.006) even though the brachial blood pressure and the heart rate had barely changed. Conclusions: This study shows that finger-to-toe PWV increases in the sitting position, offering us the opportunity to explore this postural changes in PWV as a possible vascular stress test.

Polyclonal Burkholderia cepacia complex outbreak caused by contaminated chlorhexidine gluconate solution

Background:Burkholderia cepacia complex is an opportunistic environmental pathogen that has been linked to nosocomial outbreaks. We describe an outbreak of bacteremia caused by Burkholderia cenocepacia from a contaminated chlorhexidine gluconate solution. Methods: The hospital infection control team carried out an outbreak investigation on February 21, 2021, when 3 adult hemodialysis patients developed B. cenocepacia bacteremia. Patient demographics and clinical profile were reviewed retrospectively. Potential sources of infection were identified, and environmental screening was performed in several units. Processes of catheter care in the hemodialysis unit were reviewed. Water samples from the hemodialysis unit, and samples of solutions used in patient care were sent for culture. Isolates from patients and from environmental samples were sent for 16S rRNA gene sequencing to determine genetic relatedness. Results: In total, 16 patients, 8 of whom were male, developed B. cenocepacia bacteremia during the investigated period. The median age was 68 years (range, 19–83), and 15 of 16 had at least 1 comorbidity. All patients used a central venous catheter (CVC) for hemodialysis, and 11 (70%) of these 16 were temporary. Chlorhexidine gluconate solution was routinely used as part of CVC care and 1 bottle was shared among 4 hemodialysis stations. On suspicion of contamination, all identified chlorhexidine bottles were recalled on February 26, 2021, and random samples from 15 opened and 19 unopened bottles were sent for culture from the following units: hemodialysis (n = 2), ICU (n = 14), wards (n = 6), and 4 each from transplant surgery, and delivery suites. O0f 34 sampled bottles, 17 grew B. cenocepacia: 8 opened and 9 unopened bottles. The Bayesian inference tree (Fig. 1) supports the hypothesis that patient samples and the samples from the chlorhexidine solutions were most probably related to each other based on the 16S rRNA sequences. However, the individual identities of the specific sample sequences could not be determined using the analyzed region of the gene, possibly due to low quality of the sequences received. No new cases of B. cenocepacia were identified after recall of the chlorhexidine solution, and the outbreak was deemed resolved on March 24, 2021. Conclusions: Medical solutions routinely used in patient care can cause outbreaks and should be suspected as a potential source of infection by infection control teams.Disclosures: None

Associations of metabolic syndrome, its severity with cognitive impairment among hemodialysis patients

BackgroundIn the general population, metabolic syndrome (MetS) is associated with increased risk of cognitive impairment, including global and specific cognitive domains. These associations are not well studied in patients undergoing hemodialysis and were the focus of the current investigation.MethodsIn this multicenter cross-sectional study, 5492 adult hemodialysis patients (3351 men; mean age: 54.4 ± 15.2 years) treated in twenty-two dialysis centers of Guizhou, China were included. The Mini-Mental State Examination (MMSE) was utilized to assess mild cognitive impairment (MCI). MetS was diagnosed with abdominal obesity, hypertension, hyperglycemia, and dyslipidemia. Multivariate logistic and linear regression models were used to examine the associations of MetS, its components, and metabolic scores with the risk of MCI. Restricted cubic spline analyses were performed to explore the dose–response associations.ResultsHemodialysis patients had a high prevalence of MetS (62.3%) and MCI (34.3%). MetS was positively associated with MCI risk with adjusted ORs of 1.22 [95% confidence interval (CI) 1.08–1.37, P = 0.001]. Compared to no MetS, adjusted ORs for MCI were 2.03 (95% CI 1.04–3.98) for 22.51 (95% CI 1.28–4.90) for 3, 2.35 (95% CI 1.20–4.62) for 4, and 2.94 (95% CI 1.48–5.84) for 5 components. Metabolic syndrome score, cardiometabolic index, and metabolic syndrome severity score were associated with increased risk of MCI. Further analysis showed that MetS was negatively associated with MMSE score, orientation, registration, recall and language (P < 0.05). Significant interaction effect of sex (P for interaction = 0.012) on the MetS-MCI was observed.ConclusionMetabolic syndrome was associated with MCI in hemodialysis patients in a positive dose–response effect.

Lung Ultrasound and Caval Indices to Assess Volume Status in Maintenance Hemodialysis Patients.

Background: Volume overload is common in end stage kidney disease (ESKD) and dialysis patients. Hence, the need for objective tools to detect such volume excess. Point of care ultrasound (POCUS) is a goal-directed, bedside examination to answer such a specific diagnostic question. Methods: One hundred Iraqi adult hemodialysis patients were recruited from February 1 to May 31, 2022. Primary clinical, dialysis data, and prescriptions were recorded. A nephrologist performed a POCUS examination after the last dialysis session of the week. In addition, an ultrasound examination of the chest was performed to detect B-lines and pleural effusion. Caval parameters included inferior vena cava (IVC) diameter and collapsibility index. Results: The mean age of the study group was 51.48 ± 14.6 years, with 53% males. The mean interdialytic weight gain was 2.74 ± 1.15 Kg. Lower limb edema and pleural effusion were present in 33% and 27%, respectively. Forty-seven percent of patients had >3 B-lines on lung ultrasound with a range of 12. Forty-three percent of patients had an IVC diameter of >2 cm, and 93% had <50% IVC collapsibility. In total, 97% of patients had evidence of excess volume by ultrasound criteria. IVC collapsibility index was the most prevalent sign of excess volume (93%). Patients without lower limb edema and pleural effusion had positive B-lines in 38.8% and 38.3%, an IVC diameter >2 cm in 46.2% and 38.3%, and IVC collapsibility <50% in 89.5% and 95.8% respectively. Conclusion: Iraqi maintenance hemodialysis patients are volume overloaded, which warrants proper intervention for detection and dialysis management. POCUS is a useful and easily performed technique to assess the volume status.

A phase IV, randomised, double-blind, controlled, parallel group trial to evaluate the effectiveness and safety of Balneum Plus versus emollient in the treatment of chronic kidney disease-associated pruritus in haemodialysis patients.

Chronic kidney disease-associated pruritus (CKD-aP) is a common, distressing complaint in patients with advanced renal disease that is frequently overlooked. Treatment is often unsatisfactory. Balneum Plus (Almirall, Barcelona, Spain) is a cream containing 3% lauromacrogols and 5% urea, commonly used to treat atopic dermatitis. It has not been studied in CKD-aP to date. Adult haemodialysis patients were randomised 1:1 to apply Balneum Plus or E45 (Reckitt Beckiser, Slough, UK) to compare the active ingredients of lauromacrogol and urea with a control cream. Itch was defined as three episodes of itching during the last 2weeks, appearing a few times a day, lasting a few minutes and troubling the patient [1]. Patients with other causes of itch, e.g. eczema and liver disease, were excluded. The primary outcome was a reduction in itch as measured by the visual analogue scale (VAS) score at 4weeks and analysed using an analysis of covariance approach. A total of 314 patients were screened and 58 patients were randomised, 29 in each group. Three patients dropped out in each group. The median baseline VAS scores were 6.5 [interquartile range (IQR) 4.4-8.0] in the Balneum Plus group and 6.3 (IQR 5.1-7.3) in the E45 group. After 4weeks, VAS scores decreased to 2.6 (IQR 0.9-4.5) and 2.0 (IQR 0.5-4.8) in the Balneum Plus and E45 groups respectively (P=0.64 for the difference). Using a validated questionnaire to assess secondary outcomes, we found that the Balneum Plus group had longer itching episodes, more difficulty staying asleep and itching was more annoying than in the E45 group. There was no significant difference in adverse events between the two groups. One patient reported inflamed spots on the abdominal skin in the Balneum Plus group. This is the first randomised controlled study of two different emollients for the treatment of CKD-aP and is a negative study. We found no significant difference in itch scores between Balneum Plus and E45.

Variability of Serum Phosphate in Incident Hemodialysis Patients: Association with All-Cause Mortality.

Key Points An increase in serum phosphate variability is an independent risk factor of mortality.The effects of a positive directional range (DR) is most pronounced in patients with high serum phosphate levels whereas the effects of a negative DR is most pronounced in patients with low serum phosphate and/or serum albumin. Background In maintenance hemodialysis (HD) patients, previous studies have shown that serum phosphate levels have a bidirectional relation to outcome. Less is known about the relation between temporal dynamics of serum phosphate in relation to outcome. We aimed to further explore the relation between serum phosphate variability and all-cause mortality. Methods All adult incident HD patients treated in US Fresenius Kidney Care clinics between January 2010 and October 2018 were included. Baseline period was defined as 6 months after initiation of HD and months 7–18 as follow-up period. All-cause mortality was recorded during the follow-up period. The primary metric of variability used was directional range (DR) that is the difference between the largest and smallest values within a time period; DR was positive when the smallest value preceded the largest and negative otherwise. Cox proportional hazards models with spline terms were applied to explore the association between phosphate, DR, and all-cause mortality. In addition, tensor product smoothing splines were computed to further elucidate the interactions of phosphate, DR, and all-cause mortality. Results We included 302,613 patients. Baseline phosphate was 5.1±1.2 mg/dl, and mean DR was +0.6±3.3 mg/dl. Across different levels of phosphate, higher levels of DR of phosphate were associated with higher risk of all-cause mortality. In patients with lower levels of phosphate and serum albumin, the effect of a negative DR was most pronounced, whereas in patients with higher phosphate levels, a positive DR was related to increased mortality. Conclusions Higher variability of serum phosphate is related to mortality at all levels of phosphate, especially in lower levels with a negative DR and in low serum albumin levels. This could possibly reflect dietary intake in patients who are already inflamed or malnourished, where a further reduction in serum phosphate should prompt for nutritional evaluation.

QT-Prolonging Antibiotics, Serum-to-Dialysate Potassium Gradient, and Risk of Sudden Cardiac Death Among Patients Receiving Maintenance Hemodialysis

Treatment with certain QT interval-prolonging antibiotics is associated with a higher risk of sudden cardiac death among individuals with hemodialysis-dependent kidney failure. Concurrent exposure to large serum-to-dialysate potassium gradients, which promote large potassium shifts, may augment the proarrhythmic effects of these medications. The primary objective of this study was to examine whether the serum-to-dialysate gradient modifies the cardiac safety of azithromycin, and separately, levofloxacin/moxifloxacin. Retrospective observational cohort study using a new-user study design. Adult in-center hemodialysis patients with Medicare coverage in the US Renal Data System (2007-2017). Initiation of azithromycin (or levofloxacin/moxifloxacin) as compared to amoxicillin-based antibiotics (exposure). Serum-to-dialysate potassium gradient (effect modifier). Individual patients could contribute multiple study antibiotic treatment episodes to the analyses. Sudden cardiac death (14 days). Inverse probability of treatment-weighted survival models to estimate HRs and robust 95% CIs. The azithromycin versus amoxicillin-based antibiotic cohort included 89,379 unique patients with 113,516 azithromycin and103,493 amoxicillin-based treatment episodes. Azithromycin versus amoxicillin-based antibiotic treatment was associated with a higher risk ofsudden cardiac death overall, HR, 1.68; 95% CI, 1.31-2.16. The risk was numerically higher when the baseline serum-to-dialysate potassium gradient was≥3 mEq/L compared with<3 mEq/L (HR, 2.22; 95% CI, 1.46-3.40 vs HR, 1.43; 95% CI. 1.04-1.96, P interaction=0.07). Analogous analyses in a respiratory fluoroquinolone (levofloxacin/moxifloxacin) versus amoxicillin-based antibiotic cohort with 79,449 unique patients and 65,959 respiratory fluoroquinolone and 103,776 amoxicillin-based treatment episodes yielded similar results. Residual confounding. Although treatment with azithromycin and, separately, respiratory fluoroquinolones were each associated with a heightened risk of sudden cardiac death, this risk was augmented in the setting of larger serum-to-dialysate potassium gradients. Minimizing the potassium gradient may be an approach to reduce the cardiac risk of these antibiotics.

Frailty status improvement after kidney transplantation.

Frailty is a clinical syndrome characterized by a decrease in strength, resistance and body physiological condition, making the individual more vulnerable, and increasing his/her risk of dependence and death. Kidney transplant (KT) is currently the best end-stage renal disease therapeutic alternative for certain individuals. Frailty status occurs in approximately 20% of KT patients. Thus, it was evaluated if there would be any change in frailty status level in a population of adult patients on chronic HD after receiving KT. A cross-sectional study was conducted on a population of adult hemodialysis patients (n: 57), with the objective of evaluating if there was a significant change in their clinical frailty score (CFS) after 6months of KT. For the statistical analysis, the Student's t-test, and the test of statistical significance between two proportions were applied. Mean CFS before KT was 4 (vulnerable), and after KT was 3 (robust). CFS value was significantly lower after KT (p value < 0.01). A significant improvement was found between pre- and post-transplant clinical frailty scores in hemodialysis adult patients.

Impact of Water Treatment on Anemia in Hemodialysis Patients.

The microbiological quality of water in the dialysate used in hemodialysis has been suggested as a contributor to inflammation, and a link between dialysate purity, inflammation, and responsiveness to erythropoietin therapy has been suggested in many studies. The level of endotoxin might induce inflammation and resistance to erythropoietin therapy in dialysis patients. We aimed to compare the effect of using the central dialysis fluid delivery system (CDDS) versus the single-patient dialysis fluid delivery system (SPDDS) on anemia in prevalent hemodialysis patients. In a prospective cohort study, 100 adult prevalent hemodialysis patients with T-SAT ≥20% were divided into two equal groups: CDDS and SPDDS. Endotoxin in water sample and routine investigations (hemoglobin, serum Ca+, serum Po4-, PTH, and urea level) were done. CRP, erythropoietin resistivity index (ERI), and erythropoietin stimulating agents (ESAs) doses were assessed repeatedly to assess inflammatory and anemia states. Endotoxin level in the dialysis fluid of the CDDS group was significantly lower compared to the SPDDS group (0.05 vs. 0.11 EU/ml, P = 0.001). CRP level decreased significantly after 3 months in the CDDS group (P < 0.001) compared to the SPDDS group (P = 0.54), with significant improvement in the hemoglobin level and ERI at 3 months in the CDDS group and decrease in ESA requirements. Improvement in dialysis liquid purity reduces inflammatory markers in prevalent hemodialysis patients, improves ERI, and decreases ESA requirements in renal anemia.

Intensive Nutritional Counseling and Education for Management of Hyperphosphatemia in Hemodialysis Patients at Al-Khor Hospital- Hamad Medical Corporation - State of Qatar

Objectives: To assess the dietary phosphate intake of hemodialysis patients with hyperphosphatemia and the effects of a dietetic intervention focused on limiting dietary phosphate load. Design: Cross-sectional dietary phosphate intake assessment and prospective intervention study. Setting: Hospital hemodialysis units of AL-Khor hospital – Hamad Medical Corporation, Qatar. Subjects: sixteen stable adult hemodialysis patients, who had phosphorus serum levels ≥1.6 mmol/L. Intervention: Analysis of dietary composition and of the effects of individual dietetic counseling to reduce phosphorus intake while preserving the same or improving protein intake. Main outcome measures: Differences in nutrient intake between pre and post-dietary intervention among hyperphosphatemia patients, and changes in phosphorus–protein ratio, and serum phosphate, after the dietetic intervention. Results: Significant differences in nutrient intake including energy, protein, and phosphorus were detected after the intervention. After dietetic intervention in the hyperphosphatemia patients, a decrease in the dietary phosphate–protein ratio (28.9 -13.4 mg/g, P &lt;0.05) also occurred. Serum phosphate showed a trend of a significant decrease after the dietary intervention (2.2mmol/L-1.68mmol/L), P &lt; 0.05). Conclusion: Individual intensive nutritional education and counseling may be useful in reducing phosphate load and improving serum phosphorus with a positive effect on nutrient intake. A phosphate-controlled diet has a role in an integrated therapeutic approach to hyperphosphatemia and positive calcium-phosphorus balance in hemodialysis patients.

Association of aortic arch and aortic valve calcifications with cardiovascular risk in patients on maintenance hemodialysis.

This study aimed to investigate the association of aortic arch calcification (AoAC) and aortic valve calcification (AVC) with major adverse cardiovascular events (MACE) and cardiovascular and all-cause mortality in patients on maintenance hemodialysis (MHD). This study enrolled 297 adult patients with end-stage kidney disease who were on MHD. They were divided into those with an AoAC score <2 without AVC (n = 70, 23.6%), those with an AoAC score <2 with AVC (n = 96, 32.3%), and those with an AoAC score ≥2 regardless of AVC status (n = 131, 44.1%). We analyzed the risks of MACE, cardiovascular and overall mortality among the three groups using Cox proportional hazard analyses. Survival probabilities were estimated using the log-rank test via the Kaplan-Meier method. Kaplan-Meier analysis revealed that the MACE-free rate and the survival rates of cardiovascular and overall mortality were significantly higher in adult chronic hemodialysis patients with AoAC score <2 without AVC, followed by those with AoAC score <2 with AVC, and then those with AoAC score ≥2 (log-rank test; all p < 0.01). The grade of AoAC is a significant risk factor for MACE, cardiovascular mortality, and overall mortality after adjusting for age and gender Relative to AoAC score <2 without AVC, adult chronic hemodialysis patients with AoAC score ≥2 remained an independently significantly risk factor of MACE (adjusted hazard ratio, 2.17; 95% confidence interval 1.11-4.20; p = 0.023) after adjusting for age, sex, and all significant variables in baseline characteristics. AoAC grade was positively correlated with a higher risk of MACE and cardiovascular and overall mortality. Furthermore, the presence of AVC modified the adverse cardiovascular risk associated with AoAC in patients on MHD.