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.

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.

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.

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.

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.

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.

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.

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.

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.

Evolution of body composition and wasting indicators by time of day of haemodialysis.

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.

Practice Patterns and Outcomes of Online Hemodiafiltration: A Real-World Evidence Study in a Russian Dialysis Network.

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.

Sodium, volume and pressure control in haemodialysis patients for improved cardiovascular outcomes.

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.

Long-term mortality risk associated with citric acid- and acetic acid-based bicarbonate haemodialysis: a historical cohort propensity score-matched study in a large, multicentre, population-based study.

BACKGROUND: Citric 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. METHODS: In 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. RESULTS: We 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. CONCLUSIONS: We 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.

Clinical target achievement is associated with better quality of life among dialysis patients: results from a continuous quality improvement program in a Portuguese healthcare network.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Using Bioimpedance Spectroscopy to Assess Volume Status in Dialysis Patients.

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.

The real-world effectiveness of sucroferric oxyhydroxide in European hemodialysis patients: a 1-year retrospective database analysis.

BACKGROUND: The 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. METHODS: De-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). RESULTS: 1096 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). CONCLUSION: In 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.

Increased Mortality Associated with Higher Pre-Dialysis Serum Sodium Variability: Results of the International MONitoring Dialysis Outcome Initiative.

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.

Is high-volume post-dilution haemodiafiltration associated with risk of fluid volume imbalance? A national multicentre cross-sectional cohort study.

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.

Detecting high-risk chronic kidney disease-mineral bone disorder phenotypes among patients on dialysis: a historical cohort study.

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® 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 35 721 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 < 0.001). There were 15 795 deaths [126.7 deaths/1000 person-years; 95% confidence interval (CI) 124.7-128.7]; 18 014 had at least one hospitalization (203.9 hospitalizations/1000 person-years; 95% CI 201.0-206.9); the incidence of the composite endpoint was 280.0 events/1000 person-years (95% CI 276.6-283.5). In the fully adjusted model, relative mortality risk ranged from hazard ratio (HR) = 1.07 (PTH/Ca/P: TLT) to HR = 1.59 (PTH/Ca/P: LTL), whereas the relative composite endpoint risk ranged from HR = 1.07 (PTH/Ca/P: TTH) to HR = 1.36 (PTH/Ca/P: LTL). CONCLUSION: We identified several CKD-MBD phenotypes associated with reduced hospitalization-free survival and increased mortality. Ranking of relative risk estimates or excess events concurs in informing healthcare priority setting.