The Use of Anemia Control Model Is Associated with Improved Hemoglobin Target Achievement, Lower Rates of Inappropriate Erythropoietin Stimulating Agents, and Severe Anemia among Dialysis Patients.

INTRODUCTION: The Anemia Control Model (ACM) is a certified medical device suggesting the optimal ESA and iron dosage for patients on hemodialysis. We sought to assess the effectiveness and safety of ACM in a large cohort of hemodialysis patients. METHODS: This is a retrospective study of dialysis patients treated in NephroCare centers between June 1, 2013 and December 31, 2019. We compared patients treated according to ACM suggestions and patients treated in clinics where ACM was not activated. We stratified patients belonging to the reference group by historical target achievement rates in their referral centers (tier 1: <70%; tier 2: 70-80%; tier 3: >80%). Groups were matched by propensity score. RESULTS: After matching, we obtained four groups with 85,512 patient-months each. ACM had 18% higher target achievement rate, 63% smaller inappropriate ESA administration rate, and 59% smaller severe anemia risk compared to Tier 1 centers (all p < 0.01). The corresponding risk ratios for ACM compared to Tier 2 centers were 1.08 (95% CI: 1.08-1.09), 0.49 (95% CI: 0.47-0.51), and 0.64 (95% CI: 0.61-0.68); for ACM compared to Tier 3 centers, 1.01 (95% CI: 1.01-1.02), 0.66 (95% CI: 0.63-0.69), and 0.94 (95% CI: 0.88-1.00), respectively. ACM was associated with statistically significant reductions in ESA dose administration. CONCLUSION: ACM was associated with increased hemoglobin target achievement rate, decreased inappropriate ESA usage and a decreased incidence of severe anemia among patients treated according to ACM suggestion.

Effect of Dialysate and Plasma Sodium on Mortality in a Global Historical Hemodialysis Cohort.

SIGNIFICANCE STATEMENT: This large observational cohort study aimed to investigate the relationship between dialysate and plasma sodium concentrations and mortality among maintenance hemodialysis patients. Using a large multinational cohort of 68,196 patients, we found that lower dialysate sodium concentrations (≤138 mmol/L) were independently associated with higher mortality compared with higher dialysate sodium concentrations (>138 mmol/L). The risk of death was lower among patients exposed to higher dialysate sodium concentrations, regardless of plasma sodium levels. These results challenge the prevailing assumption that lower dialysate sodium concentrations improve outcomes in hemodialysis patients. The study confirms that until robust evidence from randomized trials that are underway is available, nephrologists should remain cautious in reconsideration of dialysate sodium prescribing practices to optimize cardiovascular outcomes and reduce mortality in this population. BACKGROUND: Excess mortality in hemodialysis (HD) patients is largely due to cardiovascular disease and is associated with abnormal fluid status and plasma sodium concentrations. Ultrafiltration facilitates the removal of fluid and sodium, whereas diffusive exchange of sodium plays a pivotal role in sodium removal and tonicity adjustment. Lower dialysate sodium may increase sodium removal at the expense of hypotonicity, reduced blood volume refilling, and intradialytic hypotension risk. Higher dialysate sodium preserves blood volume and hemodynamic stability but reduces sodium removal. In this retrospective cohort, we aimed to assess whether prescribing a dialysate sodium ≤138 mmol/L has an effect on survival outcomes compared with dialysate sodium >138 mmol/L after adjusting for plasma sodium concentration. METHODS: The study population included incident HD patients from 875 Fresenius Medical Care Nephrocare clinics in 25 countries between 2010 and 2019. Baseline dialysate sodium (≤138 or >138 mmol/L) and plasma sodium (<135, 135-142, >142 mmol/L) concentrations defined exposure status. We used multivariable Cox regression model stratified by country to model the association between time-varying dialysate and plasma sodium exposure and all-cause mortality, adjusted for demographic and treatment variables, including bioimpedance measures of fluid status. RESULTS: In 2,123,957 patient-months from 68,196 incident HD patients with on average three HD sessions per week dialysate sodium of 138 mmol/L was prescribed in 63.2%, 139 mmol/L in 15.8%, 140 mmol/L in 20.7%, and other concentrations in 0.4% of patients. Most clinical centers (78.6%) used a standardized concentration. During a median follow-up of 40 months, one third of patients ( n =21,644) died. Dialysate sodium ≤138 mmol/L was associated with higher mortality (multivariate hazard ratio for the total population (1.57, 95% confidence interval, 1.25 to 1.98), adjusted for plasma sodium concentrations and other confounding variables. Subgroup analysis did not show any evidence of effect modification by plasma sodium concentrations or other patient-specific variables. CONCLUSIONS: These observational findings stress the need for randomized evidence to reliably define optimal standard dialysate sodium prescribing practices.

European Nephrologists' Attitudes toward the Application of Artificial Intelligence in Clinical Practice: A Comprehensive Survey.

INTRODUCTION: The rapid advancement of artificial intelligence and big data analytics, including descriptive, diagnostic, predictive, and prescriptive analytics, has the potential to revolutionize many areas of medicine, including nephrology and dialysis. Artificial intelligence and big data analytics can be used to analyze large amounts of patient medical records, including laboratory results and imaging studies, to improve the accuracy of diagnosis, enhance early detection, identify patterns and trends, and personalize treatment plans for patients with kidney disease. Additionally, artificial intelligence and big data analytics can be used to identify patients' treatment who are not receiving adequate care, highlighting care inefficiencies in the dialysis provider, optimizing patient outcomes, reducing healthcare costs, and consequently creating values for all the involved stakeholders. OBJECTIVES: We present the results of a comprehensive survey aimed at exploring the attitudes of European physicians from eight countries working within a major hemodialysis network (Fresenius Medical Care NephroCare) toward the application of artificial intelligence in clinical practice. METHODS: An electronic survey on the implementation of artificial intelligence in hemodialysis clinics was distributed to 1,067 physicians. Of the 1,067 individuals invited to participate in the study, 404 (37.9%) professionals agreed to participate in the survey. RESULTS: The survey showed that a substantial proportion of respondents believe that artificial intelligence has the potential to support physicians in reducing medical malpractice or mistakes. CONCLUSION: While artificial intelligence's potential benefits are recognized in reducing medical errors and improving decision-making, concerns about treatment plan consistency, personalization, privacy, and the human aspects of patient care persist. Addressing these concerns will be crucial for successfully integrating artificial intelligence solutions in nephrology practice.

Patient Survival With Extended Home Hemodialysis Compared to In-Center Conventional Hemodialysis.

Introduction: More frequent and/or longer hemodialysis (HD) has been associated with improvements in numerous clinical outcomes in patients on dialysis. Home HD (HHD), which allows more frequent and/or longer dialysis with lower cost and flexibility in treatment planning, is not widely used worldwide. Although, retrospective studies have indicated better survival with HHD, this issue remains controversial. In this multicenter study, we compared thrice-weekly extended HHD with in-center conventional HD (ICHD) in a large patient population with a long-term follow-up. Methods: We matched 349 patients starting HHD between 2010 and 2014 with 1047 concurrent patients on ICHD by using propensity scores. Patients were followed-up with from their respective baseline until September 30, 2018. The primary outcome was overall survival. Secondary outcomes were technique survival; hospitalization; and changes in clinical, laboratory, and medication parameters. Results: The mean duration of dialysis session was 418 ± 54 minutes in HHD and 242 ± 10 minutes in patients on ICHD. All-cause mortality rate was 3.76 and 6.27 per 100 patient-years in the HHD and the ICHD groups, respectively. In the intention-to-treat analysis, HHD was associated with a 40% lower risk for all-cause mortality than ICHD (hazard ratio [HR] = 0.60; 95% confidence interval [CI] 0.45 to 0.80; P < 0.001). In HHD, the 5-year technical survival was 86.5%. HHD treatment provided better phosphate and blood pressure (BP) control, improvements in nutrition and inflammation, and reduction in hospitalization days and medication requirement. Conclusion: These results indicate that extended HHD is associated with higher survival and better outcomes compared to ICHD.

From electronic health records to clinical management systems: how the digital transformation can support healthcare services.

Healthcare systems worldwide are currently undergoing significant transformations in response to increasing costs, a shortage of healthcare professionals and the growing complexity of medical needs among the population. Value-based healthcare reimbursement systems are emerging as an attempt to incentivize patient-centricity and cost containment. From a technological perspective, the transition to digitalized services is intended to support these transformations. A Health Information System (HIS) is a technological solution designed to govern the data flow generated and consumed by healthcare professionals and administrative staff during the delivery of healthcare services. However, the exponential growth of digital capabilities and applied advanced analytics has expanded their traditional functionalities and brought the promise of automating administrative procedures and simple repetitive tasks, while enhancing the efficiency and outcomes of healthcare services by incorporating decision support tools for clinical management. The future of HIS is headed towards modular architectures that can facilitate implementation and adaptation to different environments and systems, as well as the integration of various tools, such as artificial intelligence (AI) models, in a seamless way. As an example, we present the experience and future developments of the European Clinical Database (EuCliD®). EuCliD is a multilingual HIS used by 20 000 nurses and physicians on a daily basis to manage 105 000 patients treated in 1100 clinics in 43 different countries. EuCliD encompasses patients' follow-up, automatic reporting and mobile applications while enabling efficient management of clinical processes. It is also designed to incorporate multiagent systems to automate repetitive tasks, AI modules and advanced dynamic dashboards.

Development and validation of AI-based triage support algorithms for prevention of intradialytic hypotension.

BACKGROUND: Intradialytic hypotension remains one of the most recurrent complications of dialysis sessions. Inadequate management can lead to adverse outcomes, highlighting the need to develop personalized approaches for the prevention of intradialytic hypotension. Here, we sought to develop and validate two AI-based risk models predicting the occurrence of symptomatic intradialytic hypotension at different time points. METHODS: The models were built using the XGBoost algorithm and they predict the occurrence of intradialytic hypotension in the next dialysis session and in the next month. The initial dataset, obtained from routinely collected data in the EuCliD® Database, was split to perform model derivation, training and validation. Model performance was evaluated by concordance statistic and calibration charts; the importance of features was assessed with the Shapley Additive Explanation (SHAP) methodology. RESULTS: The final dataset included 1,249,813 dialysis sessions, and the incidence rate of intradialytic hypotension was 10.07% (95% CI 10.02-10.13). Our models retained good discrimination (AUC around 0.8) and a suitable calibration yielding to the selection of three classification thresholds identifying four distinct risk groups. Variables providing the most significant impact on risk estimates were blood pressure dynamics and other metrics mirroring hemodynamic instability over time. CONCLUSIONS: Recurrent symptomatic intradialytic hypotension could be reliably and accurately predicted using routinely collected data during dialysis treatment and standard clinical care. Clinical application of these prediction models would allow for personalized risk-based interventions for preventing and managing intradialytic hypotension.

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

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Distribution, preparedness and management of Ukrainian adult refugees on dialysis-an international survey by the Renal Disaster Relief Task Force of the European Renal Association.

BACKGROUND: Due to the Russian-Ukrainian war, some of the about 10 000 adults requiring dialysis in Ukraine fled their country to continue dialysis abroad. To better understand the needs of conflict-affected dialysis patients, the Renal Disaster Relief Task Force of the European Renal Association conducted a survey on distribution, preparedness and management of adults requiring dialysis who were displaced due to the war. METHODS: A cross-sectional online survey was sent via National Nephrology Societies across Europe and disseminated to their dialysis centers. Fresenius Medical Care shared a set of aggregated data. RESULTS: Data were received on 602 patients dialyzed in 24 countries. Most patients were dialyzed in Poland (45.0%), followed by Slovakia (18.1%), Czech Republic (7.8%) and Romania (6.3%). The interval between last dialysis and the first in the reporting center was 3.1 ± 1.6 days, but was ≥4 days in 28.1% of patients. Mean age was 48.1 ± 13.4 years, 43.5% were females. Medical records were carried by 63.9% of patients, 63.3% carried a list of medications, 60.4% carried the medications themselves and 44.0% carried their dialysis prescription, with 26.1% carrying all of these items and 16.1% carrying none. Upon presentation outside Ukraine, 33.9% of patients needed hospitalization. Dialysis therapy was not continued in the reporting center by 28.2% of patients until the end of the observation period. CONCLUSIONS: We received information about approximately 6% of Ukrainian dialysis patients, who had fled their country by the end of August 2022. A substantial proportion were temporarily underdialyzed, carried incomplete medical information and needed hospitalization. The results of our survey may help to inform policies and targeted interventions to respond to the special needs of this vulnerable population during wars and other disasters in the future.

War in Ukraine and dialysis treatment: human suffering and organizational challenges.

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.

Hyponatraemia and fluid overload are associated with higher risk of mortality in dialysis patients.

BACKGROUND: The 5-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 2019. Fluid overload and depletion were defined as >2.5 L above, and -1.1 L 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 <135 mmol/L) was slightly increased when fluid status was normal [hazard ratio (HR) 1.26, 95% confidence interval (CI) 1.18-1.35], increased by half when patients were fluid depleted (HR 1.56, 95% CI 1.27-1.93) and accelerated during fluid overload (HR 1.97, 95% CI 1.82-2.12). 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.

Assessment of a serum calcification propensity test for the prediction of all-cause mortality among hemodialysis patients.

BACKGROUND: Vascular calcification is a major contributor to the high cardiac burden among hemodialysis patients. A novel in vitro T50-test, which determines calcification propensity of human serum, may identify patients at high risk for cardiovascular (CV) disease and mortality. We evaluated whether T50 predicts mortality and hospitalizations among an unselected cohort of hemodialysis patients. METHODS: This prospective clinical study included 776 incident and prevalent hemodialysis patients from 8 dialysis centers in Spain. T50 and fetuin-A were determined at Calciscon AG, all other clinical data were retrieved from the European Clinical Database. After their baseline T50 measurement, patients were followed for two years for the occurrence of all-cause mortality, CV-related mortality, all-cause and CV-related hospitalizations. Outcome assessment was performed with proportional subdistribution hazards regression modelling. RESULTS: Patients who died during follow-up had a significantly lower T50 at baseline as compared to those who survived (269.6 vs. 287.7 min, p = 0.001). A cross-validated model (mean c statistic: 0.5767) identified T50 as a linear predictor of all-cause-mortality (subdistribution hazard ratio (per min): 0.9957, 95% CI [0.9933;0.9981]). T50 remained significant after inclusion of known predictors. There was no evidence for prediction of CV-related outcomes, but for all-cause hospitalizations (mean c statistic: 0.5284). CONCLUSION: T50 was identified as an independent predictor of all-cause mortality among an unselected cohort of hemodialysis patients. However, the additional predictive value of T50 added to known mortality predictors was limited. Future studies are needed to assess the predictive value of T50 for CV-related events in unselected hemodialysis patients.

Biphasic Dynamics of Inflammatory Markers Following Hemodialysis Initiation: Results From the International MONitoring Dialysis Outcome Initiative.

Introduction: Inflammation is highly prevalent among patients with end-stage kidney disease and is associated with adverse outcomes. We aimed to investigate longitudinal changes in inflammatory markers in a diverse international incident hemodialysis patient population. Methods: The MONitoring Dialysis Outcomes (MONDO) Consortium encompasses hemodialysis databases from 31 countries in Europe, North America, South America, and Asia. The MONDO database was queried for inflammatory markers (total white blood cell count [WBC], neutrophil count, lymphocyte count, serum albumin, and C-reactive protein [CRP]) and hemoglobin levels in incident hemodialysis patients. Laboratory parameters were measured every month. Patients were stratified by survival time (≤6 months, >6 to 12 months, >12 to 18 months, >18 to 24 months, >24 to 30 months, >30 to 36 months, and >36 months) following dialysis initiation. We used cubic B-spline basis function to evaluate temporal changes in inflammatory parameters in relationship with patient survival. Results: We studied 18,726 incident hemodialysis patients. Their age at dialysis initiation was 71.3 ± 11.9 years; 10,802 (58%) were males. Within the first 6 months, 2068 (11%) patients died, and 12,295 patients (67%) survived >36 months (survivor cohort). Hemodialysis patients who died showed a distinct biphasic pattern of change in inflammatory markers where an initial decline of inflammation was followed by a rapid rise that was consistently evident approximately 6 months before death. This pattern was similar in all patients who died and was consistent across the survival time intervals. In contrast, in the survivor cohort, we observed initial decline of inflammation followed by sustained low levels of inflammatory biomarkers. Conclusion: Our international study of incident hemodialysis patients highlights a temporal relationship between serial measurements of inflammatory markers and patient survival. This finding may inform the development of prognostic models, such as the integration of dynamic changes in inflammatory markers for individual risk profiling and guiding preventive and therapeutic interventions.

Effectiveness of cold HD for the prevention of HD hypotension and mortality in the general HD population.

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 <90 mmHg (generalized estimating equation model) and all-cause mortality (Cox's regression) in an incident cohort of HD patients (n = 8071). To control for confounding by bias by indication and other factors we applied instrumental variables adjusting for case mix at facility level. 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 < .001). In contrast, colder dialysate temperature had no effect on mortality both in the unadjusted [hazard ratio (HR) (0.5°C decrease) 1.074, 95% CI 0.972-1.187, P = .16] and case-mix-adjusted analysis at facility level (HR 1.01, 95% CI 0.88-1.16, P = .84). Similar results were registered in additional analyses by instrumental variables applying the median dialysate temperature or the facility percentage of patients prescribed a dialysate temperature <36°C. Further analyses restricted to patients with recurrent IDH fully confirmed these findings. CONCLUSIONS: Cold HD was associated with IDH in the HD population but had no association with all-cause mortality.

Remote Patient Management May Reduce All-Cause Mortality in Patients With Heart-Failure and Renal Impairment.

Background: Remote patient management (RPM) in heart failure (HF) patients has been investigated in several prospective randomized trials. The Telemedical Interventional Management in Heart Failure II (TIM-HF2)-trial showed reduced all-cause mortality and hospitalizations in heart failure (HF) patients using remote patient management (RPM) vs. usual care (UC). We report the trial's results for prespecified eGFR-subgroups. Methods: TIM-HF2 was a prospective, randomized, controlled, parallel-group, unmasked (with randomization concealment), multicenter trial. A total of 1,538 patients with stable HF were enrolled in Germany from 2013 to 2017 and randomized to RPM (+UC) or UC. Using CKD-EPI-formula at baseline, prespecified subgroups were defined. In RPM, patients transmitted their vital parameters daily. The telemedical center reviewed and co-operated with the patient's General Practitioner (GP) and cardiologist. In UC, patients were treated by their GPs or cardiologist applying the current guidelines for HF management and treatment. The primary endpoint was the percentage of days lost due to unplanned cardiovascular hospitalizations or death, secondary outcomes included hospitalizations, all-cause, and cardiovascular mortality. Results: Our sub analysis showed no difference between RPM and UC in both eGFR-subgroups for the primary endpoint (<60 ml/min/1.73 m2: 40.9% vs. 43.6%, p = 0.1, ≥60 ml/min/1.73 m2 26.5 vs. 29.3%, p = 0.36). In patients with eGFR < 60 ml/min/1.73 m2, 1-year-survival was higher in RPM than UC (89.4 vs. 84.6%, p = 0.02) with an incident rate ratio (IRR) 0.67 (p = 0.03). In the recurrent event analysis, HF hospitalizations and all-cause death were lower in RPM than UC in both eGFR-subgroups (<60 ml/min/1.73 m2: IRR 0.70, p = 0.02; ≥60 ml/min/1.73 m2: IRR 0.64, p = 0.04). In a cox regression analysis, age, NT-pro BNP, eGFR, and BMI were associated with all-cause mortality. Conclusion: RPM may reduce all-cause mortality and HF hospitalizations in patients with HF and eGFR < 60 ml/min/1.73 m2. HF hospitalizations and all-cause death were lower in RPM in both eGFR-subgroups in the recurrent event analysis. Further studies are needed to investigate and confirm this finding.

Modifiable Risk Factors Are Important Predictors of COVID-19-Related Mortality in Patients on Hemodialysis.

Introduction: Patients 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. Methods: We 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. Results: We 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 (<2.5 mg/dl) and high (≥5.5 mg/dl) serum phosphate levels (OR: 1.52, CI: 1.07-2.16 and OR: 1.17, CI: 1.01-1.35). On-line hemodiafiltration was protective in the model using KPIs (OR: 0.86, CI: 0.76-0.97). SHapley Additive exPlanations analysis in XGBoost models shows a high influence on prediction for several modifiable factors as well, including inflammatory parameters, high BMI, and fluid overload. In both LR and XGBoost models, age, gender, and comorbidities were strongly associated with mortality. Conclusion: Both 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.

The Cardiovascular Literature-Based Risk Algorithm (CALIBRA): Predicting Cardiovascular Events in Patients With Non-Dialysis Dependent Chronic Kidney Disease.

Background and Objectives: Cardiovascular (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). Methods: CALIBRA 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. Results: CALIBRA 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, p<0.001; ASCVD: ΔAUC=-0.17, p<0.001; INDANA: ΔAUC=-0.14, p<0.001) and GCKD (FHS: ΔAUC=-0.16, p<0.001; ASCVD: ΔAUC=-0.12, p<0.001; INDANA: ΔAUC=-0.04, p<0.001) populations. Accuracy of the CALIBRA score was stable also for patients showing missing variables. Conclusion: CALIBRA 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.

Effectiveness of COVID-19 vaccines in a large European hemodialysis cohort.

Background: Hemodialysis 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. Methods: In 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. Results: In 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%. Conclusion: In 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.

Impact of First Wave COVID-19 Crisis on Dialysis Parameters of COVID-Free Hemodialysis Patients: A NephoCare France Longitudinal Retrospective Cohort Study.

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.

Prolonged patient survival after implementation of a continuous quality improvement programme empowered by digital transformation in a large dialysis network.

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 < 0.0001]. 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.

Development and Validation of a Machine Learning Model Predicting Arteriovenous Fistula Failure in a Large Network of Dialysis Clinics.

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.