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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.

Background and Aims Vascular calcification as cause of vascular stiffness is a major contributor to the high cardiac burden among stage 5 chronic kidney disease dialysis (CKD5HD) patients. Early identification of patients with high calcification propensity is crucial for proper risk stratification and management of these patients. Recently, a novel in vitro test (T50-test) was developed which determines calcification propensity of human serum and predicts mortality among ND-CKD (non-dialysis chronic kidney disease) patients, kidney transplant recipients and CKD5HD patients suffering from secondary hyperparathyroidism. We now evaluated whether these results can be confirmed in an unselected cohort of CKD5HD patients and can be used in the future for improving care of these patients. Method This prospective clinical study included 776 incident and prevalent hemodialysis patients from 8 Fresenius Medical Care NephroCare centers in Cataluña (Spain). T50 was determined at Calciscon AG, all other clinical data were retrieved from the European Clinical Database (EuCliD®). After their baseline T50 measurement, patients were followed for two years for the occurrence of the primary endpoint all-cause mortality. The association between T50 and all-cause mortality was examined by using proportional subdistribution hazards regression modelling accounting for kidney transplantation as competing event. In sensitivity analyses we adjusted for age, sex, vascular access (fistula/graft, catheter), treatment modality (HD, HDF), Charlson comorbidity index and dialysis vintage. Results Mean age of the study population was 72.2 years and 63.8% were male. 42.5% had diabetes and 55.0% past history of cardiovascular disease. Mean T50 was 283.4 min among the total cohort. During follow-up, 185 (23.8%) patients died. Patients who reached the endpoint had a significantly lower T50 at baseline as compared to those who survived during follow-up (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 a significant predictor of all-cause mortality after adjusting for relevant confounding in sensitivity analyses. Conclusion In this prospective study, we confirmed that T50 is an independent predictor of all-cause mortality among a large unselected cohort of hemodialysis patients. T50 may be used to identify patients with high vascular calcification propensity and mortality risks and may help physicians to implement a personalized and more precise renal replacement therapy option.

Background and Aims Anemia management is still challenging in a large share of dialysis patients. ESA resistance show wide variations across patients as well as fluctuations along time within the same patient. The Anemia Control Model (ACM) is a software application which can be integrated in electronic health record systems. ACM is based on an artificial neural network system trained on 1 million health records which simulates patient’s personalized dose-response relationship to ESA and Iron. Based on patients’ response forecast, ACM suggests the optimal drug dose recommendations to reach or maintain the hemoglobin level within target and to minimize the drug consumption. The ACM has earned medical device certification and it is currently used in 13 countries within the EMEA FMC network. Effectiveness and safety of ACM has been demonstrated in previous real-world evidence studies. We report ACM use and its clinical outcomes among hemodialysis patients registered in the Spanish FME Network Method We recorded all medical prescriptions and their clinical outcome for which an ACM recommendation was computed (ACM prescription). prescription occurred in 9 clinics located in Catalunya (Spain) from September 2017 to September 2018. We report dynamics of ACM suggestion acceptance rate, ESA consumption and Hb target achievement in the study period. Results There were 1189 active patients per month during the study period on average. ACM suggestion acceptance rate was 73,3%. ESA monthly consumption ranged from 234:7±281:9 – 310.2 ± 310:8 UI/Kg; 86% of patients receiving ESA doses according to ACM recommendations achieved or remained within Hb target range; on the contrary, when physicians rejected ACM recommendations and prescribed a different dosage, only 77% of patients reached or maintained the Hb level on target (p Conclusion Our study demonstrated that ACM suggestions were frequently accepted by physicians. Acceptance of ACM suggestion was associated with higher Hb target achievement.

Background and Aims This retrospective analysis of data from the European Clinical Database (EuCliD®) evaluated changes in iron-related parameters and use of concomitant anti-anaemic therapies in European haemodialysis (HD) patients treated with sucroferric oxyhydroxide (SFOH). Previous Phase 3 clinical studies and non-clinical studies have indicated that there is minimal iron absorption from SFOH. This study aimed to evaluate the changes in iron-related parameters among patients treated with SFOH in the real-world setting. Method De-identified patient data were extracted from a clinical database (EuCliD®) for adult HD patients newly prescribed SFOH routinely for up to 1 year (1 Jan 2015–1 Jan 2019). Levels of serum ferritin, transferrin saturation (TSAT) and haemoglobin were compared between baseline (BL; 3-month period before starting SFOH) and each quarterly period in the year after starting SFOH treatment (Q1–Q4). Proportions of patients receiving intravenous (IV) iron and erythropoiesis-stimulating agent (ESA) therapies, in addition to their mean weekly doses, during each quarter were recorded. Results The cohort included 1,096 patients with recorded SFOH prescriptions (mean age: 60.6 years; 65.8% male). There were small, but significant increases in ferritin from BL to Q1–Q4 (P Conclusion This real-world study showed that SFOH treatment in routine clinical practice for up to 1 year was associated with small increases in iron-related parameters and decreases in the use and mean dose of concomitant anti-anaemic therapies in European HD patients. The results from this study indicate that SFOH treatment may be associated with the reduction in concomitant IV iron and ESA use in HD patients, in line with previous findings from the Phase 3 study.

Background and Aims Mineral bone disease in dialysis patients is an important predictor of morbimortality.iPTH levels had been previously associated with different parameters, but not clearly to diabetic disease (DBT). We aim to analyze relationship between DBT and iPTH levels in a large cohort of dialysis patients from Fresenius Medical Care LatinAmerica (FMC LA). Method Prevalent dialysis patients (more than 90 days on renal replacement therapy) by November 2019 in FMC LA dialysis units (Argentina, Brasil, Chile, Colombia, Ecuador, Perú) were included into the dataset. We obtained demographic, treatment and laboratory data by November 2019. Patients were identified as DBT when DBT was informed as etiology of renal disease or any DBT related ICD10 code was recorded as comorbid condition into the database. Use of insulin, calcitriol, paricalcitol and cinacalcet was also obtained.To evaluate association between DBT and iPTH level, Student t test for independent samples was used. Kruskal-Wallis and Mann-Whitney tests were also performed as confirmatory non-parametric tests for iPTH. Categorical variables were compared using Chi Square test. Linear regression was used to predict iPTH and analyze association with DBT. All procedures were performed on IBM SPSS Statistics© 21. Results A total of 31,709 prevalent patients were included. DBT prevalence was 29.7%. Main differences found between DBT and non-DBT patients are shown in table 1: Linear regression model to predict iPTH showed variables associated with increase in iPTH: Ca, P, K, use of calcitriol, use of cinacalcet; while others were associated with decrease in iPTH: age, dialyzate Ca, Hb, glucose, albumin, use of calcium carbonate as supplementation and DBT (table 2): Conclusion In our population diabetic patients were older, showed higher male prevalence and higher rate of catheter use. Kt/V, Ca and P serum levels were slightly lower than non-diabetic, but not clinically significant.Remarkable differences in laboratory were higher glucose and lower K and alb in DBT. While these differences were expected and already known and well described, lower iPTH in DBT is not.Diabetic disease affects iPTH level independently from other factors increasing the risk for hypoparathyroidism. Those findings should be analyzed to determine if DBT should be considered as a different group when targeting in mineral bone disease or P-binder prescription.

Introduction. In order to help facilitate the uptake of best clinical practices, improve outcomes, enhance efficiency and reduce costs, few healthcare organizations have introduced Continuous Quality Improvement (CQI) programs. Since September 2014, dialysis centers belonging to the EMEA Fresenius Medical Care (FME) network have introduced a CQI policy called Medical Peer Review (MPR) based on key performance indicators (KPI) related to patient’s clinical status. We exploit the quasi-experimental setting generated by the introduction of FMC CQI policy, to evaluate the association between improvement in intermediate outcomes (key performance indicators) and prolonged survival among dialysis patients registered in the EMEA FME network. Methods. We conducted a historical cohort study. We included adult patients on chronic dialysis with less than 90 days between renal replacement therapy (RRT) initiation date and first treatment date in FME clinics. We compared KPI target achievement (P-BSC score) and 2-year mortality for patients enrolled prior to MPR-CQI policy onset (Cohort A) and a cohort of patients enrolled after MPR-CQI policy onset (Cohort B). Structural Equation model was adopted to estimate the association of MPR-CQI policy on patients’ survival through changes in intermediate outcomes (P-BSC score). Results. The Cohort A and Cohort B consisted of 2397 and 1873 patients, respectively. We observed no difference across groups concerning the distribution of age (63.1 vs 62.8 years), gender (59% vs 60% males) and body mass index (27.6 vs 26.4 kg/m2); Cohort A showed lower Charlson’s comorbidity index (3.3±1.5 vs 3.8±1.9, p Conclusion. We showed that, after discounting for potential unmodifiable confounding factors and potential unmeasured selection/chronological bias, improvement of intermediate outcomes and performance indicators occurred after MPR-CQI policy implementation, was associated to a strong improvement in survival. Figure

Background: Evidence suggests that online hemodiafiltration (OL-HDF) is associated with improved survival. Whether the dose-response relationship between convective volume and mortality may be confounded by selection bias or descends from practice patterns is not clear. We sought to evaluate the role of patients’ characteristics and practice patterns on OL-HDF dose and mortality in a large private dialysis network in the Republic of Russia. Methods: In this multicenter, historical cohort study, we included adult incident patients on OL-HDF with at least 90 days of survival on renal replacement therapy in centers belonging to the Russian Federation Fresenius Medical Care network (January 1, 2011, to December 31, 2016). We evaluated predictors and outcomes (survival) of substitution volume target achievement (Qsub > 21 L/session). Results: Among 1,081 enrolled patients, the average Qsub was 22.9 (±3.2) L/session; the mean ultrafiltration volume was 1.6 (±0.8) L/session. The mean age was 55.8 ± 13.2; 42% were woman. Most common comorbidities were congestive heart failure (39.7%) and peripheral vascular disease (21.7%). The average hemoglobin was 9.3 ± 1.3. The case-mix adjusted center effect accounted for 20% of variance in Qsub. The top 10 most important variables associated with higher Qsub were effective Qb, serum protein, Charlson’s comorbidity index, hemoglobin, year of dialysis initiation (proxy of high Qsub treatment policy in the clinic network), predialysis heart rate, serum bicarbonate, serum phosphate, age, serum sodium, and dry body weight. In addition, we found that the association of Qb with Qsub is moderated by year of enrollment, intradialytic weight gain, and coronary artery disease, whereas higher hemoglobin concentration moderated the relationship between treatment time and Qsub. Finally, Qsub between 21 and 25 L/session was associated with longer 5-year survival. Conclusions: Both center-dependent clinical practice standards and patient clinical conditions substantially contributed to the risk of low Qsub. We confirmed previous evidence indicating better survival among patients with Qsub ≥ 21 L/session.

Introduction Although high serum uric acid (SUA) has been consistently associated with an increased risk of death in the general population and in persons with nondialysis chronic kidney disease (CKD), studies in patients undergoing dialysis are conflicting. It has been postulated that low SUA simply reflects poor nutritional status in dialysis patients. We here characterize the association between SUA and the risk of death in a large dialysis cohort and explore effect modification by underlying nutritional status as reflected by body composition. Methods In this retrospective cohort study, we included 16,057 hemodialysis (HD) patients treated during 2007 to 2016 in NephroCare centers as recorded in the European Clinical Database (EuCliD). The association between SUA, all-cause, and cardiovascular (CV)−related mortality was evaluated with competing risk models and characterized with splines. Effect modification was explored by lean tissue index (LTI) and fat tissue index (FTI). Results During a mean of 1.8 years of follow-up, 2791 patients (17.4%) died. We found a multivariable-adjusted U-shaped pattern between SUA and all-cause mortality. Patients with SUA levels of 6.5 mg/dl (387 μmol/l) were at the lowest risk of death (subdistribution hazard ratio = 0.94 [confidence interval {CI} 0.91; 0.96]). The form of association was not meaningfully affected by underlying LTI and FTI. Conclusion We found a U-shaped pattern between SUA levels and all-cause mortality among HD patients, which was independent of the patients’ body composition., Graphical abstract

Cardiovascular (CV) events are increased 36-fold in patients with end-stage renal disease. However, randomized controlled trials to lower LDL cholesterol (LDL-C) and serum total cholesterol (TC) have not shown significant mortality improvements. An inverse association of TC and LDL-C with all-cause and CV mortality has been observed in patients on chronic dialysis. Lipoproteins also may protect against infectious diseases. We used data from 37,250 patients in the international Monitoring Dialysis Outcomes (MONDO) database to evaluate the association between lipids and infection-related or CV mortality. The study began on the first day of lipid measurement and continued for up to 4 years. We applied Cox proportional models with time-varying covariates to study associations of LDL-C, HDL cholesterol (HDL-C), and triglycerides (TGs) with all-cause, CV, infectious, and other causes of death. Overall, 6,147 patients died (19.2% from CV, 13.2% from infection, and 67.6% from other causes). After multivariable adjustment, higher LDL-C, HDL-C, and TGs were independently associated with lower all-cause death risk. Neither LDL-C nor TGs were associated with CV death, and HDL-C was associated with lower CV risk. Higher LDL-C and HDL-C were associated with a lower risk of death from infection or other non-CV causes. LDL-C was associated with reduced all-cause and infectious, but not CV mortality, which resulted in the inverse association with all-cause mortality.

Background Fluid overload and interdialytic weight gain (IDWG) are discrete components of the dynamic fluid balance in haemodialysis patients. We aimed to disentangle their relationship, and the prognostic importance of two clinically distinct, bioimpedance spectroscopy (BIS)-derived measures, pre-dialysis and post-dialysis fluid overload (FOpre and FOpost) versus IDWG. Methods We conducted a retrospective cohort study on 38 614 incident patients with one or more BIS measurement within 90 days of haemodialysis initiation (1 October 2010 through 28 February 2015). We used fractional polynomial regression to determine the association pattern between FOpre, FOpost and IDWG, and multivariate adjusted Cox models with FO and/or IDWG as longitudinal and time-varying predictors to determine all-cause mortality risk. Results In analyses using 1-month averages, patients in quartiles 3 and 4 (Q3 and Q4) of FO had an incrementally higher adjusted mortality risk compared with reference Q2, and patients in Q1 of IDWG had higher adjusted mortality compared with Q2. The highest adjusted mortality risk was observed for patients in Q4 of FOpre combined with Q1 of IDWG [hazard ratio (HR) = 2.66 (95% confidence interval 2.21–3.20), compared with FOpre-Q2/IDWG-Q2 (reference)]. Using longitudinal means of FO and IDWG only slightly altered all HRs. IDWG associated positively with FOpre, but negatively with FOpost, suggesting a link with post-dialysis extracellular volume depletion. Conclusions FOpre and FOpost were consistently positive risk factors for mortality. Low IDWG was associated with short-term mortality, suggesting perhaps an effect of protein-energy wasting. FOpost reflected the volume status without IDWG, which implies that this fluid marker is clinically most intuitive and may be best suited to guide volume management in haemodialysis patients.

INTRODUCTION: Long-term inappropriate proton pump inhibitors use (PPIs) is a matter of concern because of the risks associated with their long-term use in older patients with chronic conditions. The risk of PPI treatment in hemodialysis patients remains unexplored. METHODS: We assessed the relationship between the use of PPIs and the risk of death in hemodialysis patients throughout a retrospective multicenter propensity score-matched study. Information about demographic, hemodialysis treatment, laboratory data, and concomitant medication was obtained from the EuCliD database (Fresenius Medical Care). We studied 1776 hemodialysis patients on PPI therapy compared to 466 patients not receiving PPIs. The resulting population comprising 2 groups of 410 matched patients was studied. RESULTS: PPI use was associated with hypomagnesemia (Mg

Introduction Although several studies suggest that the prognosis of hypertensive dialysis patients can be improved by using antihypertensive drug therapy, it is unknown whether the prescription of a particular class or combination of antihypertensive drugs is beneficial during hemodialysis. Methods We performed a propensity score matching study to compare the effectiveness of various classes of antihypertensive drugs on cardiovascular (CV) mortality in 2518 incident hemodialysis patients in Spain. The patients had initially received antihypertensive therapy with a renin-angiotensin system (RAS) blocker (728 patients), a s-blocker (679 patients), antihypertensive drugs other than a RAS blocker or a s-blocker (787 patients), or the combination of a s-blocker and a RAS inhibitor (324 patients). These patients were followed for a maximum of 5 years (median: 2.21 yr; range: 1.04–3.34 yr). Results After adjustment for baseline CV risk covariates, no significant differences were observed in the risk of CV mortality between patients taking a RAS blocker and patients treated with s-blocker–based antihypertensive therapy. The combination of a RAS blocker with a s-blocker was associated with better CV survival than either agent alone (RAS blocker: hazard ratio [HR]: 1.68; 95% confidence interval [CI] 1.05–2.69; s-blocker: HR: 1.59; 95% CI: 1.01–2.50; antihypertensive medication other than a RAS blocker or s-blocker: HR: 1.67; 95% CI: 1.08–2.58). Discussion Our data suggested that the combination of a RAS blocker and a s-blocker could improve survival in hemodialysis patients. Further prospective randomized controlled trials are necessary to confirm the beneficial effects of this combination of antihypertensive drugs in patients undergoing hemodialysis.

Improved responsiveness to erythropoiesis stimulating agents (ESAs) in patients on on-line post-dilution hemodiafiltration (Post-HDF) compared with conventional hemodialysis (HD) was reported by some authors but challenged by others. This prospective, cross-over randomized study tested the hypothesis that an alternative infusion modality of HDF, mixed-dilution HDF (Mixed HDF), could further reduce ESAs requirement in dialysis patients compared to the traditional Post-HDF. One-hundred-twenty prevalent patients from 6 Dialysis Centers were randomly assigned to two six-months treatment sequences: A–B and B–A (A, Mixed HDF; B, Post-HDF). Primary outcome was comparative evaluation of ESA (darbepoetin alfa) requirement and ESA resistance. Treatments efficiency, iron and vitamins status, inflammation and nutrition parameters were monitored. In sequence A, darbepoetin requirement decreased during Mixed HDF from 29.5 to 23.7 µg/month and increased significantly during Post-HDF (32.3 µg/month at 6th month) while, in sequence B, it increased during Post-HDF from 38.2 to 43.7 µg/month and decreased during Mixed HDF (23.9 µg/month at 6th month). Overall, EPO doses at 6 months on Mixed and Post-HDF were 23.8 and 38.4 µg/month, respectively, P

International audience; Bioimpedance spectroscopy (BIS) is an easily applicable tool to assess body composition. The three compartment model BIS (3C BIS) conventionally expresses body composition as lean tissue index (LTI) (lean tissue mass [LTM]/height in meters squared) and fat tissue index (FTI) (adipose tissue mass/height in meters squared), and a virtual compartment reflecting fluid overload (FO). It has been studied extensively in relation to diagnosis and treatment guidance of fluid status disorders in patients with advanced-stage or end-stage renal disease. It is the aim of this article to provide a narrative review on the relevance of 3C BIS in the nutritional assessment in this population. At a population level, LTI decreases after the start of hemodialysis, whereas FTI increases. LTI below the 10th percentile is a consistent predictor of outcome whereas a low FTI is predominantly associated with outcome when combined with a low LTI. Recent research also showed the connection between low LTI, inflammation, and FO, which are cumulatively associated with an increased mortality risk. However, studies toward nutritional interventions based on BIS data are still lacking in this population. In conclusion, 3C BIS, by disentangling the components of body mass index, has contributed to our understanding of the relevance of abnormalities in different body compartments in chronic kidney disease patients, and appears to be a valuable prognostic tool, at least at a population level. Studies assessing the effect of BIS guided nutritional intervention could further support its use in the daily clinical care for renal patients.

BackgroundAnemia is a major comorbidity of patients with end-stage renal disease and poses an enormous economic burden to health-care systems. High dose erythropoiesis-stimulating agents (ESAs) have been associated with unfavorable clinical outcomes. We explored whether mixed-dilution hemodiafiltration (Mixed-HDF), based on its innovative substitution modality, may improve anemia outcomes compared to the traditional post-dilution hemodiafiltration (Post-HDF).MethodsWe included 174 adult prevalent dialysis patients (87 on Mixed-HDF, 87 on Post-HDF) treated in 24 NephroCare dialysis centers between January 2010 and August 2016 into this retrospective cohort study. All patients were dialyzed three times per week and had fistula/graft as vascular access. Patients were matched at baseline and followed over a one-year period. The courses of hemoglobin levels (Hb) and monthly ESA consumption were compared between the two groups with linear mixed models.ResultsMean baseline Hb was 11.9±1.3 and 11.8±1.1g/dl in patients on Mixed- and Post-HDF, respectively. While Hb remained stable in patients on Mixed-HDF, it decreased slightly in patients on Post-HDF (at month 12: 11.8±1.2 vs 11.1±1.2g/dl). This tendency was confirmed by our linear mixed model (p = 0.0514 for treatment x time interaction). Baseline median ESA consumption was 6000 [Q1:0;Q3:16000] IU/4 weeks in both groups. Throughout the observation period ESA doses tended to be lower in the Mixed-HDF group (4000 [Q1:0;Q3:16000] vs 8000 [Q1:0;Q3:20000] IU/4 weeks at month 12; p = 0.0791 for treatment x time interaction). Sensitivity analyses, adjusting for differences not covered by matching at baseline, strengthened our results (Hb: p = 0.0124; ESA: p = 0.0687).ConclusionsResults of our explorative study suggest that patients on Mixed-HDF may have clinical benefits in terms of anemia management. This may also have a beneficial economic impact. Future studies are needed to confirm our hypothesis-generating results and to provide additional evidence on the potential beneficial effects of Mixed-HDF.

Background The clinical management of chronic kidney disease-mineral bone disorder (CKD-MBD) remains extremely challenging, partially due to difficulties in defining high-risk phenotypes based on serum biomarkers. We evaluated the prevalence and outcomes of 27 mutually exclusive CKD-MBD phenotypes in a large, multi-national cohort of chronic dialysis patients over a 5-year follow-up study. Methods In this historical cohort study, we enrolled all haemodialysis patients registered in EuCliD((R)) on 1 July 2011 across 28 Europe, the Middle East and Africa (EMEA) and South American countries. We created 27 mutually exclusive phenotypes based on combinations of serum parathyroid hormone (PTH), phosphorus (P) and calcium (Ca) 6-month averages (L, low ; T, target ; H, high). We tested the association between CKD- MBD phenotypes and 5-year mortality and hospitalization risk by outcome risk score- adjusted proportional hazard regression. Results We enrolled 35721 eligible patients. Eastern European and South American countries generally achieved poorer CKD-MBD control when compared with Western European countries (prevalence ratio: 0.79 ; P

There are an estimated 14,000 randomized trials published in chronic kidney disease. The most frequently reported outcomes are biochemical endpoints, rather than clinical and patient-reported outcomes including cardiovascular disease, mortality, and quality of life. While many trials have focused on optimizing kidney health, the heterogeneity and uncertain relevance of outcomes reported across trials may limit their policy and practice impact. The international Standardized Outcomes in Nephrology (SONG) Initiative was formed to identify core outcomes that are critically important to patients and health professionals, to be reported consistently across trials. We convened a SONG Implementation Workshop to discuss the implementation of core outcomes. Eighty-two patients/caregivers and health professionals participated in plenary and breakout discussions. In this report, we summarize the findings of the workshop in two main themes: socializing the concept of core outcomes, and demonstrating feasibility and usability. We outline implementation strategies and pathways to be established through partnership with stakeholders, which may bolster acceptance and reporting of core outcomes in trials, and encourage their use by end-users such as guideline producers and policymakers to help improve patient-important outcomes. ispartof: pages:1053-1068 ispartof: Kidney Int vol:94 issue:6 pages:1053-1068 ispartof: location:United States status: published

Background. Pre-dialysis fluid overload (FO) associates with mortality and causes elevated pre-dialysis systolic blood pressure (pre-SBP). However, low pre-SBP is associated with increased mortality in haemodialysis patients. The objective of this study was to investigate the interaction between pre-dialysis fluid status (FS) and pre-SBP in association withmortality. Methods. We included all patients from the international Monitoring Dialysis Outcome Initiative (MONDO) database with a pre-dialysis multifrequency bioimpedance spectroscopy measurement in the year 2011. We used all parameters available during a 90-day baseline period. All-cause mortality was recorded during 1-year follow-up. Associations with outcome were assessed with Cox models and a smoothing spline Cox analysis. Results. We included 8883 patients. In patients with predialysis FO (> thorn1.1 tothorn2.5 L), pre-SBP < 110 mmHg was associated with an increased risk of death {hazard ratio (HR) 1.52 [95% confidence interval (CI) 1.06-2.17]}. An increased risk of death was also associated with pre-dialysis fluid depletion (FD

International audience; Managing anemia in hemodialysis patients can be challenging because of competing therapeutic targets and individual variability. Because therapy recommendations provided by a decision support system can benefit both patients and doctors, we evaluated the impact of an artificial intelligence decision support system, the Anemia Control Model (ACM), on anemia outcomes. Based on patient profiles, the ACM was built to recommend suitable erythropoietic-stimulating agent doses. Our retrospective study consisted of a 12-month control phase (standard anemia care), followed by a 12-month observation phase (ACM-guided care) encompassing 752 patients undergoing hemodialysis therapy in 3 NephroCare clinics located in separate countries. The percentage of hemoglobin values on target, the median darbepoetin dose, and individual hemoglobin fluctuation (estimated from the intrapatient hemoglobin standard deviation) were deemed primary outcomes. In the observation phase, median darbepoetin consumption significantly decreased from 0.63 to 0.46 μg/kg/month, whereas on-target hemoglobin values significantly increased from 70.6% to 76.6%, reaching 83.2% when the ACM suggestions were implemented. Moreover, ACM introduction led to a significant decrease in hemoglobin fluctuation (intrapatient standard deviation decreased from 0.95 g/dl to 0.83 g/dl). Thus, ACM support helped improve anemia outcomes of hemodialysis patients, minimizing erythropoietic-stimulating agent use with the potential to reduce the cost of treatment.

Hyporesponsiveness to erythropoiesis-stimulating agent therapy in dialysis patients is poorly understood. Some studies report an improvement in the erythropoiesis-stimulating agent resistance index (ERI) with hemodiafiltration (HDF) versus high-flux hemodialysis (HD). We explored ERI dynamics in 38,340 incident HDF and HD patients treated in 22 countries over a 7-year period. Groups were matched by propensity score at baseline (6 months after dialysis initiation). The follow-up period (mean of 1.31 years) was stratified into 1 month intervals with delta analyses performed for key ERI-related parameters. Dialysis modality, time interval, and polycystic kidney disease were included in a linear mixed model with the outcome ERI. Baseline ERI was nonsignificantly higher in HDF versus HD treatment. ERI decreased significantly faster in HDF-treated patients than in HD-treated patients, was decreased in both HD and HDF when patients were treated with intravenous darbepoetin alfa, but only in HDF when treated with intravenous recombinant human erythropoietin (rHuEPO). A clear difference between HD- and HDF-treated patients could only be found for patients with high baseline ERI and assigned to intravenous rHuEPO treatment. A significant advantage in terms of lower ERI for patients treated by HDF was found. Sensitivity analysis limited this advantage for HDF to those patients treated with intravenous rHuEPO (not darbepoetin alfa or subcutaneous rHuEPO) and to patients with a high baseline ERI. Thus, our results allow more accurate planning for future clinical trials addressing anemia management in dialysis patients.

Background: Stroke prevention in dialysis-dependent patients with atrial fibrillation (AF) is an unresolved clinical dilemma. Indeed, no randomized controlled trial evaluating the efficacy and safety of oral anticoagulants in this population, has been conducted so far. Observational research on the use of warfarin in patients on dialysis has shown conflicting results. This uncertainty is mirrored by the wide variations in warfarin prescription patterns across centers. We sought to evaluate the association between the use of vitamin K antagonists (VKAs) and mortality among hemodialysis patient with AF and to assess potential factors affecting the risk-benefit profile of warfarin in this population. Methods: A total of 91,987 patients registered in the European Clinical Dialysis Database® system from January 2004 to January 2015. Of which, 9,238 patients were identified with a diagnosis of AF. After excluding ineligible patients, a 1:1 propensity score matched cohort of 1,324 warfarin users and non-users were assembled. Results: VKA use was associated with both increased 90-day survival (hazard ratio, HR 0.47, p < 0.01) and 6-year survival (HR 0.76, p < 0.01); however, a trend indicated a stronger early benefit (p for time-interaction Conclusion: VKA may provide an early survival benefit; however, this is partially offset later during the follow-up. In addition, heterogeneous risk-benefit profiles were observed among subgroups of dialysis-dependent patients with AF, further emphasizing the complexities of tailoring stroke prevention strategies in this population.

Background/Aim: Calcium acetate/magnesium carbonate (CaMg) is a recent phosphate binder that has been shown to have protective cardiovascular (CV) effects in animal models. The aim of this study was to evaluate the relationship between CaMg therapy and CV risk markers like pulse pressure (PP), left ventricular mass index (LVMI) and valvular calcifications compared to sevelamer or no phosphate binder (NPB) therapy in chronic hemodialysis (HD) patients. Methods: We performed a 48-month prospective study in 138 HD patients under hemodiafiltration with a dialysate Mg concentration of 0.5 mmol/l. Patients underwent treatment with CaMg or sevelamer for at least 36 months or NPB therapy. Demographic, clinical, biochemical and echocardiographic parameters were evaluated at baseline and after a 48-month period. Results: At the end of the study, patients who had taken CaMg showed a significant reduction in PP (p < 0.001), LVMI (p = 0.003), aortic (p = 0.004) and mitral valve calcifications (p = 0.03) compared with NPB patients. Patients under CaMg showed a significant reduction of PP (p < 0.001), LVMI (p = 0.01) and aortic valve calcifications (p = 0.02) compared to sevelamer patients. In a multivariable analysis, CaMg therapy was negatively associated with progression of LVMI (p = 0.02) and aortic valve calcifications (p = 0.01). Patients under CaMg showed higher serum Mg levels (0.93 ± 0.14 mmol/l) compared to patients under sevelamer (0.87 ± 0.13) or NPB patients (0.82 ± 0.12; p < 0.001). Conclusions: In prevalent HD patients, the use of CaMg over 48 months was associated with a reduction of PP and LVMI and with a stabilization of aortic valve calcifications. These protective and promising results of this new phosphate binder need to be confirmed in randomized controlled studies.