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In January 2021, there were 9648 patients in Ukraine on kidney replacement therapy, including 8717 on extracorporeal therapies and 931 on peritoneal dialysis. On 24 February 2022, foreign troops entered the territory of Ukraine. Before the war, the Fresenius Medical Care dialysis network in Ukraine operated three medical centres. These medical centres provided haemodialysis therapy to 349 end-stage kidney disease patients. In addition, Fresenius Medical Care Ukraine delivered medical supplies to almost all regions of Ukraine. Even though Fresenius Medical Care's share of end-stage kidney disease patients on dialysis is small, a brief narrative account of the managerial challenges that Fresenius Medical Care Ukraine and the clinical directors of the Fresenius Medical Care centres had to face, as well as the suffering of the dialysis population, is a useful testimony of the burden imposed by war on these frail, high-risk patients dependent on a complex technology such as dialysis. The war in Ukraine is causing immense suffering for the dialysis population of this country and has called for heroic efforts from dialysis personnel. The experience of a small dialysis network treating a minority of dialysis patients in Ukraine is described. Guaranteeing dialysis treatment has been and remains an enormous challenge in Ukraine and we are confident that the generosity and the courage of Ukrainian dialysis staff and international aid will help to mitigate this tragic suffering.

Background The five-year mortality rate for haemodialysis patients is over 50%. Acute and chronic disturbances in salt and fluid homeostasis contribute to poor survival and are established as individual mortality risk factors. However, their interaction in relation to mortality is unclear. Methods We used the European Clinical Database 5 to investigate in a retrospective cohort analysis the relationship between transient hypo- and hypernatremia, fluid status and mortality risk of 72 163 haemodialysis patients from 25 countries. Incident haemodialysis patients with at least one valid measurement of bioimpedance spectroscopy were followed until death or administrative censoring from 1 January 2010 to 4 December 2020. Fluid overload and depletion were defined as > 2.5 Liters above, and −1.1 liters below normal fluid status, respectively. N = 2 272 041 recorded plasma sodium and fluid status measurements were available over a monthly time grid and analysed in a Cox regression model for time-to-death. Results Mortality risk of hyponatremia (plasma sodium Conclusions Plasma sodium and fluid status act independently as risk factors on mortality. Patient surveillance of fluid status is especially important in the high-risk subpopulation of patients with hyponatremia. Prospective patient-level studies should examine the effects of chronic hypo-, and hypernatremia, risk determinants, and their outcome risk.

Background Cold hemodialysis (HD) prevented intradialysis hypotension (IDH) in small, short-term, randomized trials in selected patients with IDH. Whether this treatments prevents IDH and mortality in the HD population at large is unknown. Methods We investigated the relationship between dialysate temperature and the risk of IDH, i.e. nadir blood pressure Results Twenty-seven percent of patients in the study cohort were systematically treated with a dialysate temperature ≤35.5°C. Over a median follow-up of 13.6 months (interquartile range 5.2–26.1 months), a 0.5°C reduction of the dialysate temperature was associated with a small (–2.4%) reduction of the risk of IDH [odds ratio (OR) 0.976, 95% confidence interval (CI) 0.957–0.995, P = .013]. In case-mix, facility-level adjusted analysis, the association became much stronger (OR 0.67, 95% CI 0.63–0.72, risk reduction = 33%, P Conclusions Cold HD was associated with IDH in the HD population but had no association with all-cause mortality.

The extent of removal of the uremic toxins in hemodialysis (HD) therapies depends primarily on the dialysis membrane characteristics and the solute transport mechanisms involved. While designation of ‘flux’ of membranes as well toxicity of compounds that need to be targeted for removal remain unresolved issues, the relative role, efficiency and utilization of solute removal principles to optimize HD treatment are better delineated. Through the combination and intensity of diffusive and convective removal forces, levels of concentrations of a broad spectrum of uremic toxins can be lowered significantly and successfully. Extended clinical experience as well as data from several clinical trials attest to the benefits of convection-based HD treatment modalities. However, the mode of delivery of HD can further enhance the effectiveness of therapies. Other than treatment time, frequency and location that offer clinical benefits and increase patient well-being, treatment- and patient-specific criteria may be tailored for the therapy delivered: electrolytic composition, dialysate buffer and concentration and choice of anticoagulating agent are crucial for dialysis tolerance and efficacy. Evidence-based medicine (EBM) relies on three tenets, i.e. clinical expertise (i.e. doctor), patient-centered values (i.e. patient) and relevant scientific evidence (i.e. science), that have deviated from their initial aim and summarized to scientific evidence, leading to tyranny of randomized controlled trials. One must recognize that practice patterns as shown by Dialysis Outcomes and Practice Patterns Study and personalization of HD care are the main driving force for improving outcomes. Based on a combination of the three pillars of EBM, and particularly on bedside patient–clinician interaction, we summarize what we have learned over the last 6 decades in terms of best practices to improve outcomes in HD patients. Management of initiation of dialysis, vascular access, preservation of kidney function, selection of biocompatible dialysers and use of dialysis fluids of high microbiological purity to restrict inflammation are just some of the approaches where clinical experience is vital in the absence of definitive scientific evidence. Further, HD adequacy needs to be considered as a broad and multitarget approach covering not just the dose of dialysis provided, but meeting individual patient needs (e.g. fluid volume, acid–base, blood pressure, bone disease metabolism control) through regular assessment—and adjustment—of a series of indicators of treatment efficiency. Finally, in whichever way new technologies (i.e. artificial intelligence, connected health) are embraced in the future to improve the delivery of dialysis, the human dimension of the patient–doctor interaction is irreplaceable. Kidney medicine should remain ‘an art’ and will never be just ‘a science’.

BackgroundHemodialysis patients have high-risk of severe SARS-CoV-2 infection but were unrepresented in randomized controlled trials evaluating the safety and efficacy of COVID-19 vaccines. We estimated the real-world effectiveness of COVID-19 vaccines in a large international cohort of hemodialysis patients.MethodsIn this historical, 1:1 matched cohort study, we included adult hemodialysis patients receiving treatment from December 1, 2020, to May 31, 2021. For each vaccinated patient, an unvaccinated control was selected among patients registered in the same country and attending a dialysis session around the first vaccination date. Matching was based on demographics, clinical characteristics, past COVID-19 infections and a risk score representing the local background risk of infection at vaccination dates. We estimated the effectiveness of mRNA and viral-carrier COVID-19 vaccines in preventing infection and mortality rates from a time-dependent Cox regression stratified by country.ResultsIn the effectiveness analysis concerning mRNA vaccines, we observed 850 SARS-CoV-2 infections and 201 COVID-19 related deaths among the 28110 patients during a mean follow up of 44 ± 40 days. In the effectiveness analysis concerning viral-carrier vaccines, we observed 297 SARS-CoV-2 infections and 64 COVID-19 related deaths among 12888 patients during a mean follow up of 48 ± 32 days. We observed 18.5/100-patient-year and 8.5/100-patient-year fewer infections and 5.4/100-patient-year and 5.2/100-patient-year fewer COVID-19 related deaths among patients vaccinated with mRNA and viral-carrier vaccines respectively, compared to matched unvaccinated controls. Estimated vaccine effectiveness at days 15, 30, 60 and 90 after the first dose of a mRNA vaccine was: for infection, 41.3%, 54.5%, 72.6% and 83.5% and, for death, 33.1%, 55.4%, 80.1% and 91.2%. Estimated vaccine effectiveness after the first dose of a viral-carrier vaccine was: for infection, 38.3% without increasing over time and, for death, 56.6%, 75.3%, 92.0% and 97.4%.ConclusionIn this large, real-world cohort of hemodialyzed patients, mRNA and viral-carrier COVID-19 vaccines were associated with reduced COVID-19 related mortality. Additionally, we observed a strong reduction of SARS-CoV-2 infection in hemodialysis patients receiving mRNA vaccines.

IntroductionPatients with end-stage kidney disease face a higher risk of severe outcomes from SARS-CoV-2 infection. Moreover, it is not well known to what extent potentially modifiable risk factors contribute to mortality risk. In this historical cohort study, we investigated the incidence and risk factors for 30-day mortality among hemodialysis patients with SARS-CoV-2 infection treated in the European Fresenius Medical Care NephroCare network using conventional and machine learning techniques.MethodsWe included adult hemodialysis patients with the first documented SARS-CoV-2 infection between February 1, 2020, and March 31, 2021, registered in the clinical database. The index date for the analysis was the first SARS-CoV-2 suspicion date. Patients were followed for up to 30 days until April 30, 2021. Demographics, comorbidities, and various modifiable risk factors, expressed as continuous parameters and as key performance indicators (KPIs), were considered to tap multiple dimensions including hemodynamic control, nutritional state, and mineral metabolism in the 6 months before the index date. We used logistic regression (LR) and XGBoost models to assess risk factors for 30-day mortality.ResultsWe included 9,211 patients (age 65.4 ± 13.7 years, dialysis vintage 4.2 ± 3.7 years) eligible for the study. The 30-day mortality rate was 20.8%. In LR models, several potentially modifiable factors were associated with higher mortality: body mass index (BMI) 30–40 kg/m2 (OR: 1.28, CI: 1.10–1.50), single-pool Kt/V (OR off-target vs on-target: 1.19, CI: 1.02–1.38), overhydration (OR: 1.15, CI: 1.01–1.32), and both low (ConclusionBoth conventional and machine learning techniques showed that KPIs and modifiable risk factors in different dimensions ascertained 6 months before the COVID-19 suspicion date were associated with 30-day COVID-19-related mortality. Our results suggest that adequate dialysis and achieving KPI targets remain of major importance during the COVID-19 pandemic as well.

Background and ObjectivesCardiovascular (CV) disease is the main cause of morbidity and mortality in patients suffering from chronic kidney disease (CKD). Although it is widely recognized that CV risk assessment represents an essential prerequisite for clinical management, existing prognostic models appear not to be entirely adequate for CKD patients. We derived a literature-based, naïve-bayes model predicting the yearly risk of CV hospitalizations among patients suffering from CKD, referred as the CArdiovascular, LIterature-Based, Risk Algorithm (CALIBRA).MethodsCALIBRA incorporates 31 variables including traditional and CKD-specific risk factors. It was validated in two independent CKD populations: the FMC NephroCare cohort (European Clinical Database, EuCliD®) and the German Chronic Kidney Disease (GCKD) study prospective cohort. CALIBRA performance was evaluated by c-statistics and calibration charts. In addition, CALIBRA discrimination was compared with that of three validated tools currently used for CV prediction in CKD, namely the Framingham Heart Study (FHS) risk score, the atherosclerotic cardiovascular disease risk score (ASCVD), and the Individual Data Analysis of Antihypertensive Intervention Trials (INDANA) calculator. Superiority was defined as a ΔAUC>0.05.ResultsCALIBRA showed good discrimination in both the EuCliD® medical registry (AUC 0.79, 95%CI 0.76-0.81) and the GCKD cohort (AUC 0.73, 95%CI 0.70-0.76). CALIBRA demonstrated improved accuracy compared to the benchmark models in EuCliD® (FHS: ΔAUC=-0.22, pConclusionCALIBRA provides accurate and robust stratification of CKD patients according to CV risk and allows score calculations with improved accuracy compared to established CV risk scores also in real-world clinical cohorts with considerable missingness rates. Our results support the generalizability of CALIBRA across different CKD populations and clinical settings.

BACKGROUND AND AIMS The Kidney Disease Quality of Life (KDQOL™-36) is widely used to assess the quality of life of dialysis patients worldwide. It combines disease-specific and generic scales capturing unique facets of patients’ adaptation to the physical and mental burden of renal disease and dialysis treatment. the KDQOL™-36 psychometric properties and cross-national validation have been subject to intense review in latest years suggesting mixed replicability in different populations. Furthermore, its length may hamper its wider use in clinical practice as respondent burden may be substantial if used longitudinally within continuous quality improvement programs. Therefore, we sought to evaluate its measurement properties and develop an item response theory model enabling personalized survey administration while maximizing measurement efficiency. METHOD This is a retrospective, observational analysis of Patient-Reported Outcomes Measures (PROM) collected in Spanish NephroCare clinics during 2019 as part of a continuous quality improvement program launched by the country medical director of Spain. We used Multidimensional Item Response Theory (MIRT) models to confirm the theoretical factor structure underlying the measurement model of KDQOL™-36. MIRT extends classical IRT in that it allows complex factor structures in the multifactorial space. A critical advantage of scoring systems based on MIRT models over classical test theory models is the ability to personalize survey administration based on patient's characteristics and previous responses, reduction of measurement error, objective calibration, evaluation of test and item bias, greater accuracy in the assessment of change due to therapeutic intervention, and evaluation of model and person fit. We specified 4 competitive theoretical models for the SF-12 and the disease-specific KDQOL items (Figure 1). First, we fitted a unidimensional model, to exclude that one single factor could explain the response pattern of the questionnaire. Second, we tested a two-factor (or three-factor) orthogonal model for the SF-12 (and disease-specific KDQOL) to account for the standard scoring structure of the KDQOL™-36 questionnaire. Third, we tested the hypothesis of correlated two-factor (or three-factor) structure. Fourth, we tested a bifactor model structure, which accounts for a general HRQOL latent construct as well as lower order dimensions tapping specific dimensions of health. We expect the bifactor model would capture the pleiotropic effect of ESKD on patients’ life adjustment. We compared model fit with RMSEA, CFI and TLI statistics. For illustrative purposes, we simulated MIRT-based adaptive testing using different Delta Thetas as stopping rules to assesses measurement efficiency for the SF-12 component of the questionnaire. RESULTS Among patients completing the survey in the 2019 ePROM Spanish wave, 1838 (80.6%) dialysis prevalent patients met the inclusion criteria for the present analysis. Mean age was 68.8 ± 14.4, 60% were men, 65% had an arteriovenous fistula, and 66% were on HDF. For both generic and disease-specific KDQOL-36 components, the bifactor model significantly improved empirical fit (Figure 1). Despite slightly inferior compared with the bifactor model solutions, a simpler correlated second-order factor solution showed acceptable model fit. CAT simulation of the SF-12 showed reduction in the amount of administered item while preserving measurement reliability (Figure 2). CONCLUSION As previously reported, a correlated two factor structure and three-factor structure for the SF-12 and disease-specific KDQOL, respectively, showed acceptable fit to the observed response pattern. However, a bifactor model structure improved model fit. CAT simulation based on delta theta rules for the SF-12 questionnaire demonstrated promising results as an item selection strategy.

BACKGROUND AND AIMS Chronic HD-patients have a 50% 5-year survival and unphysiological fluid and sodium shifts are key pathophysiological contributors. Several studies have shown that hyponatremia is associated with worse outcomes in haemodialysis patients. However, the association of all-cause mortality with volume status in hyponatremic patients is uncertain. Body composition monitoring has provided a more precise tool to estimate fluid status in dialysis patients. The primary aim of this international observational study performed in a large patient database (EUCLID5) was to quantify the association between salt exposure, fluid overload (FO) and mortality risk in haemodialysis patients. METHOD We included 71 706 incident haemodialysis patients from 1 January 2010 to 4 December 2020 in an extended Cox regression model for a time to death analysis. Exposure variables were defined as predialysis serum sodium and fluid overload (in liters as determined by the BCM—Body Composition Monitor using bioimpedance spectroscopy) on a monthly time grid. Effect modifiers, mediators, confounders and predictors were defined a priori. Adults were included with at least one valid BCM measurement within 3 months from first haemodialysis treatment and followed up until death or administrative censoring. All patients included in the study cohort were treated in the NephroCare–FMC dialysis centre network operating in 26 countries. Data were retrieved from the central EuCliD5 database. RESULTS In hyponatremic patients (serum sodium 90th percentile of physiological hydration), was increased by 56% [HR = 1.56 (1.27–1.93)] in underhydrated patients (142 mmol/L), (Table 1). Generally, the risk increased with rising FO and declining sodium concentration. CONCLUSION The observed associations to the risk of death reflecting the interplay between states of hypo-, iso- and hypernatremia and states of under, normal and over hydration deserve further study to understand the underlying complex mechanisms and identify therapeutic approaches. When assessing the risk level of different sodium concentrations, fluid status should be taken into account.

BACKGROUND AND AIMS Health-Related Quality of Life (HRQOL) is a key outcome in dialysis as it stands at the vertex of the outcomes pyramid. The Kidney Disease Quality of Life (KDQOL™-36) questionnaire has been specifically developed for patients affected by kidney disease and it combines both generic and disease-specific scales capturing unique facets of patients’ adaptation to the physical and mental burden of renal disease and dialysis treatment. We sought to evaluate the association between HRQOL scores and the prevalence of adverse outcomes such as mortality and hospitalization events among prevalent dialysis patients. METHOD This is a retrospective, observational analysis of patient-reported outcomes measures (PROMs) collected in NephroCare clinics in Spain in 2019. Clinical and socio-demographic patients’ information were abstracted from EuCliD® (the European Clinical Database) and merged to PROMs HRQOL was assessed by KDQOL™-36 questionnaire and its scores for physical and mental composite (PCS and MCS) as well as for specific-disease dimensions (effects, burden and symptoms) were computed. A renal factor score (RFS) was calculated through principal component analysis to summarize the score of these latter. Mortality and hospitalizations events in the year following the survey administration date were collected and the possible association of these events with HRQOL scores was then explored. Cox and logistic regression models evaluated the relationship between KDQOL™-36 scores and survival and hospitalization events, respectively. A hierarchical model building strategy was adopted to test the incremental discrimination provided by HRQOL scores. First, two outcome risk scores (ORS) were constructed to predict the likelihood of hospitalization and mortality within 12 months given traditional clinical and socio-demographic confounders. Second, KDQOL™-36 scores were added to ORS in the fully adjusted model. We assessed both individual ORS-adjusted coefficient estimates for the KDQOL-36 scales and the KDQOL-36 associated increment in model ROC-AUC. RESULTS We enrolled 1838 prevalent dialysis patients in the present analysis with a response rate of 80.6% (study flowchart is reported in Figure 1). Mean age was 68.8 ± 14.4, 60% were men, 65% presented arteriovenous fistula as vascular access and 66% were on HDF modality. We observed a graded relationship between almost all KDQOL™-36 scores and adverse patient-centred outcomes (average KDQOL-36™ scores are reported in Figure 2). These associations were robust to adjustment for potential confounders. ROC-AUC describe the discrimination accuracy of models predicting hospitalization and mortality events, where both improved after including KDQOL-36™ scores beyond traditional clinical and socio-demographic factors. CONCLUSION We observed a monotonic, clinically important association denoting increased hospitalization and mortality risk among patients with worse KDQOL-36™ scores. The association was robust to adjustment for potential confounders. The KDQOL-36™ score captures unique facets of health, which are not sufficiently accounted for by traditional clinical and socio-demographic correlates of hospitalization and survival. Careful assessment of HRQOL in routine practice can uncover important health trajectories otherwise overlooked by standard clinical care.

BACKGROUND AND AIMS Electronic patient-reported outcome measures (ePROMs) may help personalize healthcare for dialysis patients. ePROMs allow patients to self-report their symptoms and disease burden remotely and make the data available to healthcare professionals (HCP) in real-time. Such information can be used for digital phenotyping, symptoms and disease burden monitoring and to enable personalized healthcare through improved outcomes prediction, as well as Screen and Act, N-of-1 trials and treat-to-target approaches. However, routine use of ePROM in clinical practice presents several challenges, including respondent burden and a lack of clear guidance on medical and psycho-educational intervention in response to patients’ complains. We sought to implement a quality improvement programme based on ePROM management in a large network of dialysis patients. METHOD ePROM were collected as part of a screen and act programme launched for the first time in all centres belonging to the Fresenius Medical Care (FMC) Nephrocare network in France (FR), Italy (IT), Spain (SP), UK and Ireland (IR) starting on 20 September 2021. The screening phase ended on 4 December 2021. The action phase is still ongoing. The programme aims at screening all dialysis patients for undetected quality of life and adjustment problems and allow physicians, at their sole discretion, to provide remediation actions potentially including adjustment of treatment plan based on revision of patients’ clinical charts and administration of health education modules. The questionnaire included KDQOL-36, the 5D-Itch questionnaire and an ad hoc module on intradialytic symptoms, and its content was mapped to SONG-HD initiative endpoints. ePROM were collected at the bedside or at patients’ home with a web application available for tablet and smartphones either as self-report or assisted self-report. All ePROM data were recorded in EuCLiD®, the clinical information systems adopted by FMC Nephrocare clinics, as part of patients’ clinical chart. A dashboard displaying patients’ scores was shown to the attending healthcare professional upon survey completion. Statistics about patients’ engagement, scores and action alerts are presented in clinical reports. In the present analysis, we report a retrospective analysis of data abstracted from the EuCliD® database. RESULTS Overall, 152 centres (93%) joined the campaign. Participation statistics across countries are reported in Fig. 1. Among 11 537 active patients treated in the five participating countries, 1553 were ineligible because belonging to non-participating centres, temporarily transferred to other centres outside the network (i.e. vacation, rehabilitation, etc.), hospitalized, or because they were considered unable to respond to the survey (i.e. language barrier, inability to read and write or cognitive impairment). Around 23% (IT) to 30% (FR) were considered eligible with assisted administration only. Attrition rate ranged from 3% (IT) to 15% (FR). Item missingness was 10% in all countries). KDQOL-36 scores are reported in Fig. 2; 22.5% reported moderate to very severe pruritus mostly distributed on the head/scalp, chest, abdomen, back, lower legs and thighs, forearm and upper arm (all >30% prevalence). Between 10% (IT) and 20% (UK) reported any complications during their last dialysis session, and between 6% (SP) and 12% (IR) suspended or interrupted treatment because of their symptoms. Prevalence of recovery time >3 h ranged from 34.8% (FR) to 46.4% (IR). CONCLUSION The ePROM quality improvement campaign attained wide participation and low attrition. We found no evidence of respondent burden given the low missingness rate throughout the survey items. The screening phase allowed to collect and organize a wealth of patient-reported outcomes amenable of medical or psycho-educational interventions.

BACKGROUND AND AIMS Patients with end-stage kidney disease (ESKD) face higher risk for severe outcomes from COVID-19 infection. Moreover, it is not well known to which extent potentially modifiable risk factors contribute to mortality risk. In this study, we investigated the incidence and risk factors for 30-day case-fatality of COVID-19 in haemodialysis patients treated in the European Fresenius Medical Care (FMC) Nephrocare network. METHOD In this historical cohort study, we included unvaccinated adult dialysis patients with a first documented SARS-CoV-2 infection between 1 February 2020 and 31 March 2021 (study period) registered in the European Clinical Database (EuCliD®). The first SARS-CoV-2 suspicion date for all documented infections was considered the index date for the analysis. Patients were followed for up to 30 days. Follow-up time was defined from the index date until the date of death, end of follow-up period or lost to follow-up, whichever occurred first. We ascertained patients’ characteristics in the 6-month period prior to index date. We used logistic regression and XGBoost to assess risk factors for 30-day mortality. RESULTS We included 9211 patients meeting the inclusion criteria for the study (Table 1). Age was 65.4 ± 13.7 years, dialysis vintage was 4.2 ± 3.7 years. In the follow up period, 1912 patients died within 30 days (20.8%, 95% confidence interval: 19.9%–21.6%). Correlates of COVID-19 related mortality are summarized in Table 2. Several potentially modifiable factors were associated with increased risk of death: patients on HD compared with online haemodiafiltration had shorter survival after presentation with COVID-19 as well as those who did not achieve the therapeutic targets for serum albumin, erythropoietin resistance index, protein catabolic rate, haemodynamic status, C-reactive protein, single-pool Kt/V, hydration status and serum sodium in the months before infection. The discrimination accuracy of prediction models developed with XGBoost was similar to that observed for main-effect logistic regression (AUC 0.69 and 0.71, respectively) suggesting that no major cross-interaction and non-linear effect could improve prediction accuracy. CONCLUSION We observed high 30-day COVID-19 related mortality among unvaccinated dialysis patients. Older patients, men and those with greater comorbidities had higher risk of death after COVID-19 infection. Derangement in potentially modifiable factors in the 6 months prior to COVID-19 infection was independently associated with increased mortality. Whether achievement of clinical therapeutic targets is associated with improved survival after COVID-19 infection is a matter of further research.

BACKGROUND AND AIMS Complications during hemodialysis (HD) sessions remain one of the main challenges in the dialytic patients’ management. Intradialytic hypotension (IDH) is among the most frequent adverse events in HD treatments. However, the IDH incidence varies widely across studies from 7.5% up to 68% of HD sessions, because of the lack of a univocal IDH definition. Besides, inadequate IDH management can lead to adverse outcome including increased mortality risk, hospitalization and vascular access thrombosis. IDH can be partially prevented by improved hydration management, as well as fine tuning of dialysis and pharmacological prescriptions. Nevertheless, a personalized approach to IDH prevention is still challenging. Therefore, new, cutting-edge approaches to predict these events is of critical importance to advance dialysis practice. We sought to develop and validate an AI-based classification model to predict the risk of IDH in the next HD treatment. METHOD The IDH was defined as any treatments with IDH symptoms reported in the clinical chart with a fall of ≥20 mmHg in systolic blood pressure (SBP) from pre-dialysis to nadir intradialytic levels plus ≥2 responsive measures. The aim of IDH model is to predict the risk of IDH in the next HD session exploiting a high-performance machine learning classifier called XGBoost. A feature selection strategy based on a tradeoff between prediction accuracy and model complexity was performed to determine the set of input variables. All the model's variables are routinely collected in clinical practice or they are automatically recorded from dialysis machine: no additional effort is required by the clinical staff to use the risk model. The accuracy of the prediction was evaluated as the average of the Area Under the ROC Curve (AUC-ROC) on 10 different random sampling of the dataset. In each randomization 70% of the dataset has been used for training and 30% for testing. The appropriateness of the model was also assessed computing the Risk Rate Ratio of the incidence of the IDH in 4 risk classes. RESULTS The final dataset comprised 8217 adult patients for a total of 1.7 million of HD sessions collected in EuCliD database by Fresenius Medical Care (FMC) clinics in Portugal and Spain between January 2018 and November 2021. The IDH incidence was of 10%. Baseline patients’ characteristics are the following: male: n = 5361 (65%); age (year): 67.93 ± 14.39; dialysis vintage (days): 752.58 ± 1742.7; BMI: 27.08 ± 5.76; and 3532 (43%) patients affected by diabetes. The average of AUC-ROCs was 0.80 [95% confidence interval (95% CI) 0.79–0.81]. Variables associated with the greatest impact on risk estimates were different metrics on intra-dialytic blood pressures, fluid overload, treatment time, clinic IDH rate and use of diuretics (Figure 1). We defined three thresholds determining four distinct risk groups, ranging from low-risk patients to high-risk patients. The relative Risk Rate Ratio for each class is reported in Table 1. CONCLUSION The developed AI model showed a good discrimination and excellent calibration. Moreover, the definition of four risk groups together with new continuous and interactive monitoring protocols, will promote the application of new personalized digital therapeutic program to prevent IDH. The great advantage of this strategy is that the triad ‘patient-nurse-physician’ will tightly cooperate to prevent IDH achieving a concrete improvement of the patient's quality of life.

BACKGROUND AND AIMS Chronic kidney disease–associated pruritus (CKD-aP) is common, yet underrecognized condition among end-stage kidney disease patients. We sought to evaluate the prevalence of CKD-aP and its impact on health-related quality of life (HRQOL) among dialysis patients across five European countries. METHOD This is a retrospective, observational analysis of data abstracted from the EuCliD® database (European Clinical database), the clinical information system adopted in Fresenius Medical Care (FMC) outpatient dialysis facilities in several European countries. Patient-Reported Outcomes Measures (PROM) were collected as part of a continuous quality improvement program launched for the first time in all centres belonging to the Nephrocare network in France, Italy, Spain, United Kingdom and Ireland. The presence and severity of CKD-aP were documented based on information captured by both the Kidney Disease Quality of Life (KDQOL™-36) and the 5-D Itch questionnaires. HRQOL was assessed with KDQOL™-36. Clinical and demographic data have been extracted from EuCliD®. The relationship between CKD-aP and HRQOL was evaluated with generalized linear models. RESULTS The ePROM campaign attained a large participation rate with very low attrition. Among 9974 who were actively treated in the clinics and were able to fill in a self-reported questionnaire, 8157 responded to the survey and only 1033 (11.2%) refused to participate. We enrolled 6221 patients in the present secondary analysis. The study flowchart is reported in Figure 1. Slightly more than half of patients (52%) reported no CKD-aP, 25% mild, whereas roughly 23% reported moderate-to-severe CKD-aP. Patients reporting more severe CKD-aP had shorter dialysis vintage, higher phosphate and parathormone, and more frequently diabetes. Average KDQOL-36 scores are reported in Figure 2a. We observed a strong, graded relationship between CKD-aP severity and KDQOL-36 scores (Figure 2b). The association was robust to adjustment for potential confounders. The quality of life penalty associated with more severe pruritus was clinically significant based on distribution based minimal clinically important difference threshold for the KDQOL-36 scales. CONCLUSION CKD-aP was common in a large, representative sample of the dialysis population in five European countries. We observed a large, clinically important, quality of life penalty associated with CKD-aP even after adjusting for potential confounders.

BACKGROUND AND AIMS Renal anemia management remains challenging for the nephrologist. Chronic inflammation, EPO resistance, uremia, malnutrition, iron deficiency, dialysis modalities, bleeding, infections, hydration status all interfere with erythropoiesis and erythrocytes half-life. Since 2013, >100 clinics in the FMC Nephrocare network have been using the Anemia Control Model (ACM), an artificial-intelligence based, certified medical device, decision support tool, to assist nephrologists in optimizing the monthly ESA and iron dose based on the specific characteristics of the patient and the amount of ESA dose already taken in the last 90 days. Based on this widespread experience, we sought to evaluate the real-world effectiveness of the use of ACM to facilitate hemoglobin target achievement among dialysis patients. METHOD In this historical cohort study, we analyzed electronic health records (EHR) of adult patients receiving in-center hemodialysis therapy in Fresenius Medical Care European dialysis clinics between 1 January 2015 and 31 December 2018 registered in the European Clinical Database (EuCliD®). We compared the rate of target achievement between patients treated with the ESA dose, suggested by ACM, against three control groups of patients treated in clinics without ACM and stratified by different target achievement rates for hemoglobin (Hb in the range of 10–12 g/dL or > 12 g/dL without ESA administration) (Fig. 1). To decrease indication bias, we matched patients belonging to the four comparison groups by a propensity-score assessing the likelihood of receiving the same dose suggested by ACM based on patients’ characteristics (i.e. demographic, comorbidities, anemia-related biomarkers and dialysis vintage). Centers where Hb target achievement 80% were classified as Tier 3 centers. Performance was evaluated in the month before the index date for all the patients in any given clinic. For each matched group, the index date corresponds to the date of dose suggestion (ACM group) or to the last Hb assessment date (for all matched patients belonging to other three control groups). The study endpoints were Hb target achievement, inappropriate ESA administration (ESA administration despite Hb > 12 g/dL) and severe anemia (Hb RESULTS After matching, we obtained four groups accounting for 8 5512 patient-months each. There were negligible differences in patients’ characteristics across the four matched groups (Table 1). In the ACM group, the Hb target achievement rate was 87.52/100 patient-months 95% confidence interval (95% CI): 86.89–88.15], inappropriate ESA use rate was 4.13/100 patient-months (95% CI: 3.99–4.27) and the incidence of severe anemia was 2.14/100 patient-months (95% CI: 2.04–2.24); the Hb target achievement rate ratio (95% CI) was 1.18 (1.17–1.2), 1.08 (1.07–1.09), 1.01 (1–1.02) for ACM versus Tier 1 centers, ACM versus Tier 2 centers and ACM versus Tier 3 centers, respectively. Rate ratio for inappropriate ESA administration were 0.37 (0.36–0.39), 0.49 (0.47–0.51), 0.66 (0.64–0.69) for ACM versus Tier 1 centers, ACM versus Tier 2 centers and ACM versus Tier 3 centers, respectively. The risk ratios for severe anemia were 0.43 (0.41–0.46), 0.65 (0.62–0.7), 0.95 (0.89–1.02) for ACM versus Tier 1 centers, ACM versus Tier 2 centers and ACM versus Tier 3 centers, respectively. CONCLUSION In this matched historical cohort study, we observed an increased hemoglobin target achievement rate, decreased inappropriate ESA usage and a decreased incidence of severe anemia among patients treated according to ACM suggestions. Target achievement rate among patients treated according to ACM suggestions was 87%. The magnitude of the effect in favor of ACM was larger in centers with a lower target achievement rate.

BACKGROUND AND AIMS To date, no large-scale study has evaluated the effectiveness of COVID-19 vaccines in hemodialysis patients. We sought to evaluate the effectiveness of vaccines against SARS-CoV-2 infections and death in haemodialysis patients registered in the Fresenius Medical Care (FMC) Nephrocare network. METHOD In this historical, 1:1 matched cohort study, we analysed electronic health records (EHR) of individuals receiving in-center haemodialysis therapy in FMC European dialysis clinics from 1 December 2020, to 31 May 2021 (study period). For each vaccinated patient, an unvaccinated patient was selected among patients registered in the same country and attending a dialysis session within +/–3 days from the vaccination date. Matching without replacement was based on demographics, clinical characteristics, past COVID-19 infections and a risk score representing the local (dialysis centre) background risk of infection at each vaccination date. The infection risk score was calculated from an artificial Intelligence model predicting the risk of COVID-19 outbreak in each clinic over a 2-week prediction horizon. The infection risk score was based on trends in regional COVID-19 epidemic metrics, FMC COVID-19 reporting system and clinical practice patterns. The index date was the date of the first vaccination for the vaccinated and the matching treatment date for the unvaccinated controls. To overcome violation of the proportional hazard assumption, we estimated the effectiveness of the COVID-19 vaccines in preventing infection and mortality rates as 1—hazard ratio estimated from a time-dependent extended Cox regression stratified by country and vaccine type. RESULTS We included 44 458 patients, 22 229 vaccinated and matched 22 229 unvaccinated. Distribution of covariates was balanced across study arms after matching (Figure 1A). In the effectiveness analysis on mRNA vaccines, we observed 850 SARS-CoV-2 infections and 201 COVID19-related deaths among the 28 110 patients (14 055 vaccinated and 14 055 unvaccinated) during a mean follow up time of 44 ± 40 days. In the effectiveness analysis of viral-vector vaccines, we observed 297 SARS-CoV-2 infections and 64 COVID19-related deaths among 12 888 patients (6444 vaccinated and 6444 unvaccinated) during a mean a follow-up time of 48 ± 32 days (Figure 1B). We observed 18.5/100 patient-year and 8.5/100 patient-year fewer infections and 5.4/100 patient-year and 5.2/100 patient-year fewer COVID-19-related deaths among patients vaccinated with mRNA and viral-vector vaccines respectively, as compared to matched unvaccinated controls. The effectiveness of COVID-19 vaccines concerning both symptomatic infections and COVID-related death along the follow up period is shown in Figure 2. CONCLUSION In this matched, historical cohort study, we observed a strong reduction in both SARS-CoV-2 symptomatic infection and COVID-19-related death among dialysis patients receiving an mRNA vaccine. Despite seemingly less protective against symptomatic infections, we observed similar reduction in COVID-19 mortality rate among patients receiving a viral-carrier vaccine.

BACKGROUND AND AIMS Haemodiafiltration on-line (HDF-ol), an effective mode of replacement therapy for stage 5 chronic kidney disease (CKD 5D), cannot be considered sufficiently studied in terms of its effect on the outcomes. Our main aim was to identify a possible association between individual anthropometric, laboratory data and parameters of the prescribed treatment regimen with the best survival rate when using the HDF-ol mode. METHOD A retrospective1 year analysis of the EuCliD database of 9986 patients treated with HDF-ol in 27 Fresenius Medical Care centres in Russia was carried out. All patients got post-dilution HDF-ol procedures at least 3 times a week, for at least 12 h a week with Kt/V at least 1.4. Data on alive (9616) and deceased (370) patients were compared by gender, age, treatment experience, body weight (BW), body mass index (BMI), body surface area (BSA), total body water volume (TBW), volume of urea distribution (V Urea BCM), presence of diabetes mellitus (DM), ischemic heart disease (CHD), chronic heart failure (CHF), as well as parameters of the procedure: effective weekly dialysis time, Kt/V, effective infusion volume (EIV) and effective convection volume (ECV). RESULTS Differences in groups were found only for a part of parameters (Table 1). CONCLUSION Association of risk of death in patients with CKD 5D treated with HDF-ol included male gender, older age, concomitant diseases (CHD, CHF, DM), lower BW and BMI, shorter effective weekly dialysis time, lower values of EIV and ECV, Kt/V, higher values of hypercalcemia, hypoalbuminemia, lower haemoglobin levels, higher levels of b2-microglobulin and CRP. Such indicators as TBW, VUrea BCM, BSA and the length of treatment on dialysis did not reached statistical significance when comparing alivе and deceased patients.

Background Treatment of end-stage kidney disease patients is extremely challenging given the interconnected functional derangements and comorbidities characterizing the disease. Continuous quality improvement (CQI) in healthcare is a structured clinical governance process helping physicians adhere to best clinical practices. The digitization of patient medical records and data warehousing technologies has standardized and enhanced the efficiency of the CQI’s evidence generation process. There is limited evidence that ameliorating intermediate outcomes would translate into better patient-centred outcomes. We sought to evaluate the relationship between Fresenius Medical Care medical patient review CQI (MPR-CQI) implementation and patients’ survival in a large historical cohort study. Methods We included all incident adult patients with 6-months survival on chronic dialysis registered in the Europe, Middle East and Africa region between 2011 and 2018. We compared medical key performance indicator (KPI) target achievements and 2-year mortality for patients enrolled prior to and after MPR-CQI policy onset (Cohorts A and B). We adopted a structural equation model where MPR-CQI policy was the exogenous explanatory variable, KPI target achievements was the mediator variable and survival was the outcome of interest. Results About 4270 patients (Cohort A: 2397; Cohort B: 1873) met the inclusion criteria. We observed an increase in KPI target achievements after MPR-CQI policy implementation. Mediation analysis demonstrated a significant reduction in mortality due to an indirect effect of MPR-CQI implementation through improvement in KPI target achievement occurring in the post-implementation era [odds ratio 0.70 (95% confidence interval 0.65–0.76); P Conclusions Our study suggests that MPR-CQI achieved by standardized clinical practice and periodic structured MPR may improve patients’ survival through improvement in medical KPIs.

Background It has been a long-standing clinical concern that haemodialysis (HD) patients on afternoon shifts (ASs) are more prone to protein-energy wasting (PEW) than those on morning shifts (MSs), as their dialysis scheme and post-dialysis symptoms may interfere with meal intake. We evaluated the effect of time of day of HD on the evolution of body composition changes and PEW surrogates. Methods We conducted a retrospective study among 9.963 incident HD patients treated in NephroCare centres (2011–16); data were routinely collected in the European Clinical Database. The course of multi-frequency bioimpedance determined lean and fat tissue indices (LTI and FTI) between patients in MSs/ASs over 2 years were compared with linear mixed models. Secondary PEW indicators were body mass index, albumin, creatinine index and normalized protein catabolic rate. Models included fixed (age, sex, vascular access and diabetes mellitus) and random effects (country and patient). Results Mean baseline LTI and FTI were comparable between MSs (LTI: 12.5 ± 2.9 kg/m2 and FTI: 13.7 ± 6.0 kg/m2) and ASs (LTI: 12.4 ± 2.9 kg/m2 and FTI: 13.2 ± 6.1 kg/m2). During follow-up, LTI decreased and FTI increased similarly, with a mean absolute change (baseline to 24 months) of −0.3 kg/m2 for LTI and +1.0 kg/m2 for FTI. The course of these malnutrition indicators did not differ between dialysis shifts (P for interaction ≥0.10). We also did not observe differences between groups for secondary PEW indicators. Conclusions This study suggests that a dialysis shift in the morning or in the afternoon does not impact the long-term nutritional status of HD patients. Regardless of time of day of HD, patients progressively lose muscle mass and increase body fat.

BackgroundThe iron-based phosphate binder (PB), sucroferric oxyhydroxide (SFOH), demonstrated its effectiveness for lowering serum phosphate levels, with low daily pill burden, in clinical trials of dialysis patients with hyperphosphatemia. This retrospective database analysis evaluated the real-world effectiveness of SFOH for controlling serum phosphate in European hemodialysis patients.MethodsDe-identified patient data were extracted from a clinical database (EuCliD®) for adult hemodialysis patients from France, Italy, Portugal, Russia and Spain who were newly prescribed SFOH for up to 1 year as part of routine clinical care. Serum phosphate and pill burden were compared between baseline (3-month period before starting SFOH) and four consecutive quarterly periods of SFOH therapy (Q1−Q4; 12 months) in the overall cohort and three subgroups: PB-naïve patients treated with SFOH monotherapy (mSFOH), and PB-pretreated patients who were either switched to SFOH monotherapy (PB → mSFOH), or received SFOH in addition to another PB (PB + SFOH).Results1096 hemodialysis patients (mean age: 60.6 years; 65.8% male) were analyzed, including 796, 188 and 53 patients in, respectively, the PB + SFOH, mSFOH, and PB → mSFOH groups. In the overall cohort, serum phosphate decreased significantly from 1.88 mmol/L at baseline to 1.77–1.69 mmol/L during Q1–Q4, and the proportion of patients achieving serum phosphate ≤1.78 mmol/L increased from 41.3% at baseline to 56.2–62.7% during SFOH treatment. Mean PB pill burden decreased from 6.3 pills/day at baseline to 5.0–5.3 pills/day during Q1–Q4. The subgroup analysis found the proportion of patients achieving serum phosphate ≤1.78 mmol/L increased significantly from baseline during SFOH treatment in the PB + SFOH group (from 38.1% up to 60.9% [Q2]) and the mSFOH group (from 49.5% up to 75.2% [Q2]), but there were no significant changes in the PB → mSFOH group. For the PB + SFOH group, serum phosphate reductions were achieved with a similar number of PB pills prescribed at baseline prior to SFOH treatment (6.5 vs 6.2 pills/day at Q4). SFOH daily pill burden was low across all 3 subgroups (2.1–2.8 pills/day).ConclusionIn this real-world study of European hemodialysis patients, prescription of SFOH as monotherapy to PB-naïve patients, or in addition to existing PB therapy, was associated with significant improvements in serum phosphate control and a low daily pill burden.

Patients with kidney failure have multifaced clinical needs. Continuous quality improvement (CQI) programs initiated by large healthcare provider networks bear the promise of improving guideline adherence and improving patient-centered outcome, including health-related quality of life (HRQOL). We aimed at evaluating the association between key performance indicators (KPI) adopted for our CQI and HRQOL in a large network of dialysis providers. We conducted a survey study in 39 centers belonging to the Portuguese Fresenius Medical Care (FME) network, in September 2017. For each participant, we retrospectively extracted clinical information during the 6-month period preceding survey administration. We used this information to calculate KPI as defined by the FME-CQI policy. Those KPI were selected in the FME-CQI policy as modifiable intermediate endpoints for which previous evidence suggested a causal relationship with patients’ morbidity and mortality. HRQOL was assessed by the Kidney Disease Quality of Life Short Form 36 (KDQOL-36) questionnaire. Among 4691 eligible patients who were invited to participate in the survey, 2263 (48.2%) answered the self-administered survey. Based on KPI standards, patients had 1.5 (± 1.2) off-target clinical parameters on average. KDQOL-36 score were generally higher than those observed in European reference population. We found a significant linear association between KPI parameters and HRQOL. This pattern was robust to adjustment for satisfaction scores. Our data demonstrated a graded, monotonic, dose–response relationship between the number of off-target KPIs and HRQOL. Such relationship was not mediated by patients’ satisfaction and may be attributed to amelioration of disease-specific symptoms and functional capacity.

BackgroundCitric acid-based bicarbonate dialysate (CiD) is increasingly used in haemodialysis (HD) to improve haemodynamic tolerance and haemocompatibility associated with acetic acid-based bicarbonate dialysate. Safety concerns over CiD have been raised recently after a French ecological study reported higher mortality hazard in HD clinics with high CiD consumption. Therefore, we evaluated the mortality risk associated with various acidifiers (AcD, CiD) of bicarbonate dialysate.MethodsIn this multicentre, historical cohort study, we included adult incident HD patients (European, Middle-East and Africa Fresenius Medical Care network; 1 January 2014 to 31 October 2018). We recorded acidifiers of bicarbonate dialysis and dialysate composition for each dialysis session. In the primary intention-to-treat analysis, patients were assigned to the exposed group if they received CiD in >70% of sessions during the first 3 months (CiD70%), whereas the non-exposed group received no CiD at all. In the secondary analysis, exposure was assessed on a monthly basis for the whole duration of the follow-up.ResultsWe enrolled 10 121 incident patients during the study period. Of them, 371 met the criteria for inclusion in CiD70%. After propensity score matching, mortality was 11.43 [95% confidence interval (CI) 8.86–14.75] and 12.04 (95% CI 9.44–15.35) deaths/100 person-years in the CiD0% and CiD70% groups, respectively (P = 0.80). A similar association trend was observed in the secondary analysis.ConclusionsWe did not observe evidence of increased mortality among patients exposed to CiD in a large European cohort of dialysis patients despite the fact that physicians were more inclined to prescribe CiD to subjects with worse medical conditions.

Chronic volume overload is pervasive in patients on chronic haemodialysis and substantially increases the risk of cardiovascular death. The rediscovery of the three-compartment model in sodium metabolism revolutionizes our understanding of sodium (patho-)physiology and is an effect modifier that still needs to be understood in the context of hypertension and end-stage kidney disease. Assessment of fluid overload in haemodialysis patients is central yet difficult to achieve, because traditional clinical signs of volume overload lack sensitivity and specificity. The highest all-cause mortality risk may be found in haemodialysis patients presenting with high fluid overload but low blood pressure before haemodialysis treatment. The second highest risk may be found in patients with both high blood pressure and fluid overload, while high blood pressure but normal fluid overload may only relate to moderate risk. Optimization of fluid overload in haemodialysis patients should be guided by combining the traditional clinical evaluation with objective measurements such as bioimpedance spectroscopy in assessing the risk of fluid overload. To overcome the tide of extracellular fluid, the concept of time-averaged fluid overload during the interdialytic period has been established and requires possible readjustment of a negative target post-dialysis weight. 23Na-magnetic resonance imaging studies will help to quantitate sodium accumulation and keep prescribed haemodialytic sodium mass balance on the radar. Cluster-randomization trials (e.g. on sodium removal) are underway to improve our therapeutic approach to cardioprotective haemodialysis management.

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

Background: Vascular access surveillance of dialysis patients is a challenging task for clinicians. We derived and validated an arteriovenous fistula failure model (AVF-FM) based on machine learning. Methods: The AVF-FM is an XG-Boost algorithm aimed at predicting AVF failure within three months among in-centre dialysis patients. The model was trained in the derivation set (70% of initial cohort) by exploiting the information routinely collected in the Nephrocare European Clinical Database (EuCliD®). Model performance was tested by concordance statistic and calibration charts in the remaining 30% of records. Features importance was computed using the SHAP method. Results: We included 13,369 patients, overall. The Area Under the ROC Curve (AUC-ROC) of AVF-FM was 0.80 (95% CI 0.79–0.81). Model calibration showed excellent representation of observed failure risk. Variables associated with the greatest impact on risk estimates were previous history of AVF complications, followed by access recirculation and other functional parameters including metrics describing temporal pattern of dialysis dose, blood flow, dynamic venous and arterial pressures. Conclusions: The AVF-FM achieved good discrimination and calibration properties by combining routinely collected clinical and sensor data that require no additional effort by healthcare staff. Therefore, it can potentially enable risk-based personalization of AVF surveillance strategies.

Current equation-based risk stratification algorithms for kidney failure (KF) may have limited applicability in real world settings, where missing information may impede their computation for a large share of patients, hampering one from taking full advantage of the wealth of information collected in electronic health records. To overcome such limitations, we trained and validated the Prognostic Reasoning System for Chronic Kidney Disease (PROGRES-CKD), a novel algorithm predicting end-stage kidney disease (ESKD). PROGRES-CKD is a naïve Bayes classifier predicting ESKD onset within 6 and 24 months in adult, stage 3-to-5 CKD patients. PROGRES-CKD trained on 17,775 CKD patients treated in the Fresenius Medical Care (FMC) NephroCare network. The algorithm was validated in a second independent FMC cohort (n = 6760) and in the German Chronic Kidney Disease (GCKD) study cohort (n = 4058). We contrasted PROGRES-CKD accuracy against the performance of the Kidney Failure Risk Equation (KFRE). Discrimination accuracy in the validation cohorts was excellent for both short-term (stage 4–5 CKD, FMC: AUC = 0.90, 95%CI 0.88–0.91; GCKD: AUC = 0.91, 95% CI 0.86–0.97) and long-term (stage 3–5 CKD, FMC: AUC = 0.85, 95%CI 0.83–0.88; GCKD: AUC = 0.85, 95%CI 0.83–0.88) forecasting horizons. The performance of PROGRES-CKD was non-inferior to KFRE for the 24-month horizon and proved more accurate for the 6-month horizon forecast in both validation cohorts. In the real world setting captured in the FMC validation cohort, PROGRES-CKD was computable for all patients, whereas KFRE could be computed for complete cases only (i.e., 30% and 16% of the cohort in 6- and 24-month horizons). PROGRES-CKD accurately predicts KF onset among CKD patients. Contrary to equation-based scores, PROGRES-CKD extends to patients with incomplete data and allows explicit assessment of prediction robustness in case of missing values. PROGRES-CKD may efficiently assist physicians’ prognostic reasoning in real-life applications.

Background The successful application of Machine Learning (ML) to many clinical problems can lead to its implementation as medical devices (MD), being important to assess the associated risks. Methods An anemia control model (ACM), certified as MD may face adverse events as the result of wrong predictions that are translated into suggestions of doses of erythropoietic stimulating agents to dialysis patients. Risks are assessed as the combination of severity and probability of a given hazard. While severities are typically assessed by clinicians, probabilities are tightly related to the performance of the predictive model. Results A post-marketing dataset formed by all adult patients registered in French, Portuguese and Spanish clinics, belonging to an international network was considered; 3876 patients and 11508 suggestions were eventually included. The achieved results show that there are no statistical differences between the probabilities of adverse events that are estimated in the ACM test set (using only Spanish clinics) and those actually observed in the post-marketing cohort. Conclusions The risks of an ACM-MD can be accurately and robustly estimated, thus enhancing patients' safety. The proposed methodology is applicable to other clinical decisions based on predictive models since our proposal does not depend on the particular predictive model.

Accurate predictions of COVID-19 epidemic dynamics may enable timely organizational interventions in high-risk regions. We exploited the interconnection of the Fresenius Medical Care (FMC) European dialysis clinic network to develop a sentinel surveillance system for outbreak prediction. We developed an artificial intelligence-based model considering the information related to all clinics belonging to the European Nephrocare Network. The prediction tool provides risk scores of the occurrence of a COVID-19 outbreak in each dialysis center within a 2-week forecasting horizon. The model input variables include information related to the epidemic status and trends in clinical practice patterns of the target clinic, regional epidemic metrics, and the distance-weighted risk estimates of adjacent dialysis units. On the validation dates, there were 30 (5.09%), 39 (6.52%), and 218 (36.03%) clinics with two or more patients with COVID-19 infection during the 2-week prediction window. The performance of the model was suitable in all testing windows: AUC = 0.77, 0.80, and 0.81, respectively. The occurrence of new cases in a clinic propagates distance-weighted risk estimates to proximal dialysis units. Our machine learning sentinel surveillance system may allow for a prompt risk assessment and timely response to COVID-19 surges throughout networked European clinics.

Background and Aims Peritonitis is a common and potentially severe complication for peritoneal dialysis (PD) patients. It is associated with mortality and technique failure risk and contributes significantly to their healthcare cost. Despite several peritonitis prevention programs based on education and training have been implemented worldwide, it has been reported a large variability of efficacy across patients groups and healthcare settings. In order to avoid unnecessary treatment of low risk patients, healthcare prevention programs should be personalized based on accurate patients’ risk profiling, so that high risk patients may be addressed with intensified prevention programs. However, referral strategy (i.e. defining when risk is too much and deserves special attention) depends the availability, efficacy and cost of medical interventions. In this study, we demonstrate through a program implementation simulator, how different referral strategies to inform peritonitis prevention program among PD patients informed by AI-based risk stratification tools, produce different healthcare and health economics outcomes. In particular, the simulation considers a prevention program characterized by standard of care, which affects all patients as well as an intensive intervention for a subset of high-risk patients (e.g. special training or medical treatment). Method The Peritonitis Risk Score model was trained and validated among 9325 PD patients treated in FMC network (Model accuracy, AUC=0.86). The pharmaco-economic model simulation was performed considering a cohort of 22,900 adult PD patients, treated in Fresenius Medical Care dialysis network between January 1, 2011 and December 31, 2018, for which the Peritonitis Risk Score was computed at a given date. The occurrence of an acute peritonitis in the month after prediction has been registered. We simulated the program outcomes in terms of proportion of referrals to the intensified prevention program, false omission rate, peritonitis risk reduction, overall cost-savings, number needed to treat. We considered the following scenario based on previous cost-effectiveness analysis on peritonitis risk prevention: Results Given the action threshold selected, 5.3% of patients entered the intensified intervention program (PPV=9.5%); the false omission rate was 2.2%. Cost savings for the intensified healthcare where generated when the effect size of the intensified intervention exceeded 1.4 (figure 1A). For that effect size the number needed to treat for each prevented peritonitis was NNT=23.4. Overall, 162 peritonitis/month could be prevented in the whole network (peritonitis with no intervention=592; Peritonitis after intervention=430). When a less conservative threshold was selected, 12.2% of patients entered the intensified prevention program (PPV=7.3%), generating a false omission rate=1.9%. Cost savings were never generated (i.e. the intensified program needed investment to be sustained) but with the same effect size of 1.4 additional 24 peritonitis/months could be saved in the whole network (peritonitis with no intervention=592; Peritonitis after intervention=406). The number needed to treat for the intensified program was NTT=30.4 (figure 1B). Conclusion Cost-effectiveness simulating tool provides a rational evaluation framework for AI-based referral to peritonitis preventive programs. This tool can be easily adapted for any healthcare program based on patient risk score.

Background Fluid overload is frequent among hemodialysis (HD) patients. Dialysis therapy itself may favor sodium imbalance from sodium dialysate prescription. As on-line hemodiafiltration (OL-HDF) requires large amounts of dialysate infusion, this technique can expose to fluid accumulation in case of a positive sodium gradient between dialysate and plasma. To evaluate this risk, we have analyzed and compared the fluid status of patients treated with HD or OL-HDF in French NephroCare centers. Method This is a cross-sectional and retrospective analysis of prevalent dialysis patients. Data were extracted from the EUCLID5 data base. Patients were split in 2 groups (HD and OL-HDF) and compared as whole group or matched patients for fluid status criteria including predialysis relative fluid overload (RelFO%) status from the BCM®. Results 2242 patients (age 71 years; female: 39%; vintage: 38 months; Charlson index: 6) were studied. 58% of the cohort were prescribed post-dilution OL-HDF. Comparing the HD and OL-HDF groups, there was no difference between HD and OL-HDF patients regarding the predialysis systolic BP, the interdialytic weight gain, the dialysate-plasma sodium gradient, and the predialysis RelFO%. The stepwise logistic regression did not find dialysis modality (HD or OL-HDF) associated with fluid overload or high predialysis systolic blood pressure. In OL-HDF patients, monthly average convective or weekly infusion volumes per session were not related with the presence of fluid overload. Conclusions In this cross-sectional study we did not find association between the use of post-dilution OL-HDF and markers of fluid volume excess. Aligned dialysis fluid sodium concentrations to patient predialysis plasma sodium and regular monitoring of fluid volume status by bioimpedance spectroscopy may have been helpful to manage adequately the fluid status in both OL-HDF and HD patients.

INTRODUCTION Numerous studies showed that higher body mass index (BMI) is associated with better survival in hemodialysis (HD) patients. Most of them evaluated short-term mortality. It has been suggested that presence of inflammation may be a key modifier of relationship between BMI and mortality in incident HD patients. We examined whether presence of inflammation modifies the association between BMI and mortality in both short-term and long-term follow-up in a large group of prevalent HD patients. METHODS A total of 3.252 HD patients from 41 HD centers were enrolled; the patients were divided into quartiles based on time-averaged BMI (Q1

Background Innovative care models such as public-private partnerships (PPPs) may help meet the challenge of providing cost-effective high-quality care for the steadily growing and complex chronic kidney disease population since they combine the expertise and efficiency of a specialized dialysis provider with the population care approach of a public entity. We report the five-years main clinical outcomes of a population of patients treated on hemodialysis within a PPP-care model in Italy. Methods This descriptive retrospective cohort study consisted of all consecutive hemodialysis patients treated in the NephroCare-operated Nephrology and Dialysis unit of the Seriate Hospital in 2012–2016, which exercises a PPP-care model. Clinical and treatment information was obtained from the European Clinical Database. Hospitalization outcomes and cumulative all-cause mortality incidences that accounted for competing risks were calculated. Results We included 401 hemodialysis patients (197 prevalent and 204 incident patients) in our study. The mean cohort age and age-adjusted Charlson Comorbidity Index were 67.0 years and 6.7, respectively. Patients were treated with online high-volume hemodiafiltration or high-flux hemodialysis. Parameters of treatment efficiency were above the recommended targets throughout the study period. Patients in the PPP experienced benefits in terms of hospitalization (average number of hospital admissions/patient-year: 0.79 and 1.13 for prevalent and incident patients, respectively; average length of hospitalization: 8.9 days for both groups) and had low cumulative all-cause mortality rates (12 months: 10.6 and 7.8%, 5 years: 42.0 and 35.9%, for prevalent and incident patients, respectively). Conclusions Results of our descriptive study suggest that hemodialysis patients treated within a PPP-care model framework received care complying with recommended treatment targets and may benefit in terms of hospitalization and mortality outcomes. Electronic supplementary material The online version of this article (10.1186/s12882-019-1224-2) contains supplementary material, which is available to authorized users.

Background Both baseline fluid overload (FO) and fluid depletion are associated with increased mortality risk and cardiovascular complications in haemodialysis patients. Fluid status may vary substantially over time, and this variability could also be associated with poor outcomes. Methods In our retrospective cohort study, including 4114 haemodialysis patients from 34 Romanian dialysis units, we investigated both all-cause and cardiovascular mortality risk according to baseline pre- and post-dialysis volume status, changes in pre- and post-dialysis fluid status during follow-up (time-varying survival analysis), pre–post changes in volume status during dialysis and pre-dialysis fluid status variability during the first 6 months of evaluation. Results According to their pre-dialysis fluid status, patients were stratified in the following groups: normovolaemic with an absolute FO (AFO) compartment between −1.1 and 1.1 L, fluid depletion with an AFO below −1.1 L, moderate FO with an AFO compartment >1.1 but 2.5 L. Baseline pre-dialysis FO and fluid depletion patients had a significantly elevated risk of all-cause mortality risk {hazard ratio [HR] 1.53 [95% confidence interval (CI) 1.22–1.93], HR 2.04 (95% CI 1.59–2.60) and HR 1.88 (95% CI 1.07–3.39) for moderate FO, severe FO and fluid depletion, respectively}. In contrast, post-dialysis fluid depletion was associated with better survival [HR 0.71 (95% CI 0.57–0.89)]. Similar results were found when using changes in pre- or post-dialysis fluid status during follow-up (time-varying values): FO patients had an increased risk of all-cause [moderate FO: HR 1.39 (95% CI 1.11–1.75); severe FO: HR 2.29 (95% CI 2.01–3.31] and cardiovascular (CV) mortality [moderate FO: HR 1.34 (95% CI 1.05–1.70); severe FO: HR 2.34 (95% CI 1.67–3.28)] as compared with normohydrated patients. Using pre–post changes in volume status during dialysis, we categorized the patients into six groups: Group 1, AFO 1.1 L pre-dialysis and 1.1 L pre-dialysis and between −1.1 and 1.1 L post-dialysis; Group 6, AFO >1.1 L pre- and post-dialysis. Using the baseline values, only patients in Groups 1, 5 and 6 maintained an increased risk for all-cause mortality as compared with the reference group. Additionally, CV mortality risk was significantly higher for patients in Groups 5 and 6. When we applied the time-varying analysis, patients in Groups 1, 5 and 6 had a significantly higher risk for both all-cause and CV mortality risk. In the last approach, the highest risk for the all-cause mortality outcome was observed for patients with high-amplitude fluctuation during the first 6 months of evaluation [HR 2.75 (95% CI 1.29–5.84)]. Conclusion We reconfirm the association between baseline pre- and post-dialysis volume status and mortality in dialysis patients; additionally, we showed that greater fluid status variability is independently associated with higher mortality.

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

Background: Fluid volume and blood pressure (BP) management are crucial endpoints for end-stage kidney disease patients. BP control in clinical practice mainly relies on reducing extracellular fluid volume overload by diminishing targeted postdialysis weight. This approach exposes dialysis patients to intradialytic hypotensive episodes. Summary: Both chronic hypertension and intradialytic hypotension lead to adverse long-term outcomes. Achieving the optimal trade-off between adequate fluid removal and the risk of intradialytic adverse events is a complex task in clinical practice given the multiple patient-related and dialysis-related factors affecting the hemodynamic response to treatment. State-of-the-art artificial intelligence has been adopted in other complex decision-making tasks for dialysis patients and may help personalize the multiple dialysis-related prescriptions affecting patients’ intradialytic hemodynamics. As a proof of concept, we developed a multiple-endpoint model predicting session-specific Kt/V, fluid volume removal, heart rate, and BP based on patient characteristics, historic hemodynamic responses, and dialysis-related prescriptions. Key Messages: The accuracy and precision of this preliminary model is extremely encouraging. Such analytic tools may be used to anticipate patients’ reactions through simulation so that the best strategy can be chosen based on clinical judgment or formal utility functions.

Background: Chronic hemodialysis (HD) patients are at high risk of severe COVID-19 with a high risk of death. The organization of dialysis units to treat chronic HD patients with COVID-19 is demanding to prevent virus transmission both in COVID-free patients and the staff. These constraints may have an impact on the dialysis delivery to COVID-free HD patients. We report our experience in French NephroCare (NC) centers. Methods: We report retrospectively dialysis and nutritional indicators among COVID-free prevalent chronic HD patients’ cohort treated in French NC units from February 2020 to April 2020. The COVID-free HD patients were split into 2 subgroups for the analysis, Paris region and other regions because the incidence of COVID-19 was different according to the French regions. Results: The Paris region was the most impacted by COVID-19 with 73% of all the contaminations that occurred in French NC units (n = 118). The dialysis frequency was not reduced all over the NC regions. 2,110 COVID-free HD patients were split into 2 subgroups including Paris region (748 patients) and other regions (1,362 patients). The weekly treatment time decreased significantly in Paris region from February to April (723–696 min [p < 0.00001]) but remained stable in the other regions. The processed blood volume, KT/V, and convective volume declined significantly in the Paris region subgroup but not in other regions. The 3-month weight loss significantly increased in the whole group of patients whatever the region from 0.0 to 0.2% between February 2020 and April 2020 (p < 0.00001). Ultrafiltration rate (UFR) and the normalized proteic catabolic rate remained stable all along the period. The stepwise regression analysis identified February serum albumin level and April UFR as negatively associated with 3-month weight loss. Conclusion: HD delivery to COVID-free HD patients was negatively impacted in the Paris region because of the strong constraints on units’ organization related to the treatment of COVID-19+ HD patients and with a higher proportion of limited care/self-care units with less staff resources. The 3-month weight loss increase may be related to the suppression of intradialytic snack that impacted mostly the more malnourished patients or patients with lower interdialytic weight gain. These consequences of the COVID-19 crisis on COVID-free HD patients must be recognized and corrected to prevent further deleterious effects on patients’ outcomes.

Background The high rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreading represents a challenge to haemodialysis (HD) units. While fast isolation of suspected cases plays an essential role to avoid disease outbreaks, significant rates of asymptomatic cases have recently been described. After detecting an outbreak in one of our HD clinics, wide SARS-CoV-2 screening and segregation of confirmed cases were performed. Methods The entire clinic population, 192 patients, underwent testing for SARS-CoV-2 detection by real-time reverse-transcriptase polymerase chain reaction . We used univariate and multivariate logistic regression to define variables involved in SARS-CoV-2 infection in our dialysis unit. Later, we analysed differences between symptomatic and asymptomatic SARS-CoV-2-positive patients. Results In total, 22 symptomatic and 14 of the 170 asymptomatic patients had a SARS-CoV-2-positive result. Living in a nursing home/homeless [odds ratio (OR) 3.54; P = 0.026], having been admitted to the reference hospital within the previous 2 weeks (OR 5.19; P = 0.002) and sharing health-care transportation with future symptomatic (OR 3.33; P = 0.013) and asymptomatic (OR 4.73; P = 0.002) positive patients were independent risk factors for a positive test. Nine positive patients (25.7%) remained asymptomatic after a 3-week follow-up. We found no significant differences between symptomatic and asymptomatic SARS-CoV-2-positive patients. Conclusions Detection of asymptomatic SARS-CoV-2-positive patients is probably one of the key points to controlling an outbreak in an HD unit. Sharing health-care transportation to the dialysis unit, living in a nursing home and having been admitted to the reference hospital within the previous 2 weeks, are major risk factors for SARS-CoV-2 infection.

Background and Aims Ferritin, is commonly used as a surrogate marker of iron storage in haemodialysis (HD) patients. However, besides being an indicator of iron storage, serum ferritin levels are closely influenced by non-iron related factors, such as systemic inflammation. The aim of this study is to assess the combined effect of serum ferritin and C-reactive protein (CRP) levels on all-cause and cardiovascular (CV) mortality in a large national cohort of HD patients. Method This is a retrospective study which included all patients that were on standard HD therapy in 34 Romanian Fresenius dialysis units at January 1st 2014. The main outcomes were all-cause and CV mortality. Patients were censored at December 31st 2016. Results Our study included 1255 patients. The mean age of the population at baseline was 59 years. The median values for CRP and ferritin levels were 4.8 (IQR 1.9-11.0) mg/dL and 696.0 (IQR 448.5-996.8) ng/mL, respectively. Using the tertiles categories for CRP (8.1 mg/dL) and ferritin (876.1 ng/mL) our population was categorized into 9 groups of patients: Group 1 CRP Group 2 CRP Group 3 CRP 2.7-8.1mg/dL, ferritin >876.1 ng/mL; Group 4 CRP 2.7-8.1 mg/dL, ferritin Group 5 CRP 2.7-8.1 mg/dL, ferritin 536.6-876.1ng/mL; Group 6 2.7-8.1 mg/dL, ferritin >876.1 ng/mL; Group 7 CRP>8.1 mg/dL, ferritin Group 8 CRP>8.1 mg/dL, ferritin 536.6-876.1ng/mL; Group 9 CRP>8.1 mg/dL, ferritin >876.1 ng/mL; During the follow-up (mean 1.75, median 1.94 years), 204 patients (16.25%) died with 103 (8.21%) from CV disease. The central point of our investigation was to assess the combined effect of CRP and ferritin levels on the two outcomes (Table 1). For the all-cause mortality, after adjustment for different demographic, clinical and biological risk factors, only patients with CRP levels in the highest tertile (CRP>8.1 mg/dL), irrespectively of ferritin levels (Groups 7, 8 and 9), remained significantly associated with this outcome. When considering the CV mortality, in the adjusted analysis, only patients from Groups 4 (2nd tertile CRP, 1st tertile ferritin) and 7 (3rd tertile CRP, 1st tertile ferritin) remained associated with a higher risk for the outcome as compared with patients from Group 1. Conclusion We show that increased levels of CRP are associated with an increased risk for all-cause mortality in the HD population, irrespective of ferritin levels. However, increasing CRP levels are associated with CV mortality only for the lowest tertile of ferritin levels. This work was supported by a grant of the Ministery of Research and Innovation, CNCS-UEFISCDI, project number PN-III-P1-1.1-PD-2016-0287, within PNCDI III and by grants of the “Grigore T. Popa” University of Medicine and Pharmacy, contract numbers 27495/2018 and 27505/2018.

Background Citric Acid Based Bicarbonate Dialysate (CiD) is increasingly used in hemodialysis to improve hemodynamic tolerance and hemocompatibility associated with Acetic Acid Based Bicarbonate dialysis (AcD). We sought to evaluate the mortality risk associated with different dialysate acidifiers. Methods We conducted a multicenter, historical cohort study; all adult incident hemodialysis patients registered in EMEA Fresenius Medical Care network since January 1st 2014 to October 31st 2018 were enrolled. We recorded dialysate acidifier composition for each dialysis session. In the primary analysis (intention-to-treat population), patients were assigned to the exposed group if they received CiD in more than 70% of sessions during the first three months (CiD70%), whereas non-exposed received no CiD at all. In the secondary analysis, exposure was assessed on a monthly basis for the whole duration of the follow up. Results We enrolled 10,121 incident patients during the study period. Of them, 371 met criteria for inclusion in CiD70%. After propensity score matching mortality was 11.43 (95%CI: 8.86 - 14.75) and 12.04 (95%CI: 9.44 - 15.35) deaths/100 person-years, in the CiD0% and CiD70% groups respectively (p=0.80). A similar association trend was observed in the secondary analysis. Conclusions We did not observe evidence of increased mortality among patients exposed to CiD in a large European cohort of dialysis patients despite physicians were more inclined to prescribe CiD to subjects with worse medical conditions.