Serum Phosphorus Management with Sucroferric Oxyhydroxide as a First-Line Phosphate Binder within the First Year of Hemodialysis.

INTRODUCTION: Sucroferric oxyhydroxide (SO), a non-calcium, chewable, iron-based phosphate binder (PB), effectively lowers serum phosphorus (sP) concentrations while reducing pill burden relative to other PBs. To date, SO studies have largely examined treatment-experienced, prevalent hemodialysis populations. We aimed to explore the role of first-line SO initiated during the first year of dialysis. METHODS: We retrospectively analyzed deidentified data from adults receiving in-center hemodialysis who were prescribed SO monotherapy within the first year of hemodialysis as part of routine clinical care. All patients continuing SO monotherapy for 12 months were included. Changes from baseline in sP, achievement of sP ≤5.5 and ≤4.5 mg/dL, and other laboratory parameters were analyzed quarterly for 1 year. RESULTS: The overall cohort included 596 patients, 286 of whom had a dialysis vintage ≤3 months. In the 3 months preceding SO initiation, sP rapidly increased (mean increases of 1.02 and 1.65 mg/dL in the overall cohort and incident cohort, respectively). SO treatment was associated with significant decreases in quarterly sP (mean decreases of 0.26-0.36; p < 0.0001 for each quarter and overall). While receiving SO, 55-60% of patients achieved sP ≤5.5 mg/dL and 21-24% achieved sP ≤4.5 mg/dL (p < 0.0001 for each quarter and overall vs. baseline). Daily PB pill burden was approximately 4 pills. Serum calcium concentrations increased and intact parathyroid hormone concentrations decreased during SO treatment (p < 0.0001 vs. baseline). CONCLUSIONS: Among patients on hemodialysis, initiating SO as a first-line PB resulted in significant reductions in sP while maintaining a relatively low PB pill burden.

Management of serum phosphorus over a 1-year follow-up in patients on peritoneal dialysis prescribed sucroferric oxyhydroxide as part of routine care: a retrospective analysis.

BACKGROUND: Hyperphosphatemia is associated with increased morbidity and mortality in patients with end-stage kidney disease (ESKD). Whereas clinical and observational studies have demonstrated the effectiveness of sucroferric oxyhydroxide (SO) in controlling serum phosphorus (sP) in ESKD, data on the real-world impact of switching to SO in patients on peritoneal dialysis (PD) are limited. In this retrospective database analysis, we examine the impact of SO on sP management over a 1-year period among PD patients prescribed SO as part of routine clinical care. METHODS: We analyzed de-identified data from adults on PD in Fresenius Kidney Care clinics who were prescribed SO monotherapy between May 2018 and December 2019 as part of routine clinical management. Changes from baseline in sP levels, phosphate binder (PB) pill burden, and laboratory parameters were evaluated during the four consecutive 91-day intervals of SO treatment. RESULTS: The mean age of the 402 patients who completed 1 year of SO was 55.2 years at baseline, and they had been on PD for an average of 19.9 months. SO was initiated with no baseline PB recorded in 36.1% of patients, whereas the remaining 257 patients were switched to SO from sevelamer (39.7%), calcium acetate (30.4%), lanthanum (1.2%), ferric citrate (14.0%), or more than one PB (14.8%). Mean sP at baseline was 6.26 mg/dL. After being prescribed SO, the percentage of patients achieving sP ≤ 5.5 mg/dL increased from 32.1% (baseline) to 46.5-54.0% during the 1-year follow-up, whereas the mean number of PB pills taken per day decreased from 7.7 at baseline (among patients on a baseline PB) to 4.6 to 5.4. Serum phosphorus and PB pill burden decreased regardless of changes in residual kidney function over the 12-month period. Similar results were observed for the full cohort (976 patients who either completed or discontinued SO during the 1-year follow-up). CONCLUSIONS: Patients on PD who were prescribed SO as part of routine care for phosphorus management experienced significant reductions in SP and PB pills per day and improvements in sP target achievement, suggesting the effectiveness of SO on SP management with a concurrent reduction in pill burden.

What is data stewardship? Towards a comprehensive understanding.

Data stewardship is a term that is understood in heterogenous ways. In recent organisational developments and efforts to build infrastructures and hire professional staff for research data management in various scientific fields in Europe, data stewardship is understood as mainly aiming at optimising data management in line with the FAIR principles (findability, accessibility, interoperability, reusability) forpurposes of reuse in the interests of the scientific community and the public. In addition, especially in the health and biomedical sciences some understandings of data stewardship mainly focus on the responsibility to respect the informational rights of data subjects. Following on from these different understandings and from recent developments to include ever more stakeholders in data stewardship, we propose a comprehensive understanding of data stewardship. According to this comprehensive understanding, data stewardship includes responsibilities towards all pertinent stakeholders and to equally consider and respect their legitimate rights and interests in order to build and maintain an efficient, trusted and fair data ecosystem. We also point out some of the practical challenges implied in such a comprehensive understanding.

Switching from high-flux dialysis to hemodiafiltration: Cost-consequences for patients, providers, and payers.

Hemodiafiltration (HDF) achieves a more efficient reduction of the uremic toxic load compared to standard high-flux hemodialysis (HF-HD) by virtue of the combined diffusive and convective clearances of a broad spectrum of uremic retention solutes. Clinical trials and registry data suggest that HDF improves patient outcomes. Despite the acknowledged need to improve survival rates of dialysis patients and the survival benefit HDF offers, there is little to no utilization in some countries (such as the US) in prescribing HDF to their patients. In this analysis, we present the healthcare value-based case for HDF (relative to HF-HD) from the patient, provider, and payor perspectives. The improved survival and reduced morbidity observed in studies conducted outside the US, as well as the reduced hospitalization, are attractive for each stakeholder. We also consider the potential barriers to greater utilization of HDF therapies, including unfounded concerns regarding additional costs of HDF, e.g., for the preparation and microbial testing of quality of substitution fluids. Ultrapure fluids are easily attainable and prepared from dialysis fluids using established "online" (OL) technologies. OL-HDF has matured to a level whereby little additional effort is required to safely implement it as all modern machine systems are today equipped with the OL-HDF functionality. Countries already convinced of the advantages of HF-HD are thus well positioned to make the transition to OL-HDF to achieve further clinical and associated economic benefits. Healthcare systems struggling to cope with the increasing demand for HD therapies would therefore, like patients, be beneficiaries in the long term with increased usage of OL-HDF for end stage kidney disease patients.

German funders' data sharing policies-A qualitative interview study.

BACKGROUND: Data sharing is commonly seen as beneficial for science but is not yet common practice. Research funding agencies are known to play a key role in promoting data sharing, but German funders' data sharing policies appear to lag behind in international comparison. This study aims to answer the question of how German data sharing experts inside and outside funding agencies perceive and evaluate German funders' data sharing policies and overall efforts to promote data sharing. METHODS: This study is based on sixteen guided expert interviews with representatives of German funders and German research data experts from stakeholder organisations, who shared their perceptions of German' funders efforts to promote data sharing. By applying the method of qualitative content analysis to our interview data, we categorise and describe noteworthy aspects of the German data sharing policy landscape and illustrate our findings with interview passages. RESULTS: We present our findings in five sections to distinguish our interviewees' perceptions on a) the status quo of German funders' data sharing policies, b) the role of funders in promoting data sharing, c) current and potential measures by funders to promote data sharing, d) general barriers to those measures, and e) the implementation of more binding data sharing requirements. DISCUSSION AND CONCLUSION: Although funders are perceived to be important promoters and facilitators of data sharing throughout our interviews, only few German funding agencies have data sharing policies in place. Several interviewees stated that funders could do more, for example by providing incentives for data sharing or by introducing more concrete policies. Our interviews suggest the academic freedom of grantees is widely perceived as an obstacle for German funders in introducing mandatory data sharing requirements. However, some interviewees stated that stricter data sharing requirements could be justified if data sharing is a part of good scientific practice.

Dose-response and efficacy of ferric citrate to treat hyperphosphatemia in hemodialysis patients: a short-term randomized trial.

BACKGROUND: Most dialysis patients require phosphate binders to control hyperphosphatemia. Ferric citrate has been tested in phase 2 trials as a phosphate binder. This trial was designed as a dose-response and efficacy trial. STUDY DESIGN: Prospective, phase 3, multicenter, open-label, randomized clinical trial. SETTING & PARTICIPANTS: 151 participants with hyperphosphatemia on maintenance hemodialysis therapy. INTERVENTION: Fixed dose of ferric citrate taken orally as a phosphate binder for up to 28 days (1, 6, or 8 g/d in 51, 52, and 48 participants, respectively). OUTCOMES: Primary outcome is dose-response of ferric citrate on serum phosphorus level; secondary outcomes are safety and tolerability. MEASUREMENTS: Serum chemistry tests including phosphorus, safety data. RESULTS: 151 participants received at least one dose of ferric citrate. Mean baseline phosphorus levels were 7.3 ± 1.7 (SD) mg/dL in the 1-g/d group, 7.6 ± 1.7 mg/dL in the 6-g/d group, and 7.5 ± 1.6 mg/dL in the 8-g/d group. Phosphorus levels decreased in a dose-dependent manner (mean change at end of treatment, -0.1 ± 1.3 mg/dL in the 1-g/d group, -1.9 ± 1.7 mg/dL in the 6-g/d group, and -2.1 ± 2.0 mg/dL in the 8-g/d group). The mean difference in reduction in phosphorus levels between the 6- and 1-g/d groups was 1.3 mg/dL (95% CI, 0.69 to 1.9; P < 0.001), between the 8- and 1-g/d groups was 1.5 mg/dL (95% CI, 0.86 to 2.1; P < 0.001), and between the 8- and 6-g/d groups was 0.21 mg/dL (95% CI, -0.39 to 0.81; P = 0.5). The most common adverse event was stool discoloration. LIMITATIONS: Sample size and duration confirm efficacy, but limit our ability to confirm safety. CONCLUSIONS: Ferric citrate is efficacious as a phosphate binder in a dose-dependent manner. A phase 3 trial is ongoing to confirm safety and efficacy.

A real-world analysis of the influence of age on maintenance hemodialysis patients: managing serum phosphorus with sucroferric oxyhydroxide as part of routine clinical care.

OBJECTIVE: Despite the growing number of elderly hemodialysis patients, the influence of age on nutritional parameters, serum phosphorus (sP), and use of phosphate-binder (PB) medications has not been well characterized. We aimed to describe age-related differences in patient characteristics in a large, real-world cohort of maintenance hemodialysis patients, and to examine the impact of age on sP management with sucroferric oxyhydroxide (SO). METHODS: We retrospectively analyzed de-identified data from 2017 adult, in-center hemodialysis patients who switched from another PB to SO monotherapy as part of routine clinical care. Changes in baseline PB pill burden, sP levels, and nutritional and dialytic clearance parameters were assessed across varying age groups through 6 months. RESULTS: At baseline, older patients had lower mean sP, serum albumin, and pre-dialysis weights compared with younger patients. Prescription of SO was associated with a 62% increase in the proportion of patients achieving sP ≤ 5.5 mg/dl and a 42% reduction in daily pill burden. The proportion of patients achieving sP ≤ 5.5 mg/dl after transitioning to SO increased by 113, 96, 68, 77, 61, 37 and 40% among those aged 19-29, 30-39, 40-49, 50-59, 60-69, 70-79, and ≥ 80 years, respectively. CONCLUSIONS: Older patients had worse nutritional parameters, lower pill burden, and lower sP at baseline versus younger counterparts. Prescription of SO was associated with improved sP control and reduced pill burden across all ages.

Neither carrots nor sticks? Challenges surrounding data sharing from the perspective of research funding agencies-A qualitative expert interview study.

BACKGROUND: Data Sharing is widely recognised as crucial for accelerating scientific research and improving its quality. However, data sharing is still not a common practice. Funding agencies tend to facilitate the sharing of research data by both providing incentives and requiring data sharing as part of their policies and conditions for awarding grants. The goal of our article is to answer the following question: What challenges do international funding agencies see when it comes to their own efforts to foster and implement data sharing through their policies? METHODS: We conducted a series of sixteen guideline-based expert interviews with representatives of leading international funding agencies. As contact persons for open science at their respective agencies, they offered their perspectives and experiences concerning their organisations' data sharing policies. We performed a qualitative content analysis of the interviews and categorised the challenges perceived by funding agencies. RESULTS: We identify and illustrate six challenges surrounding data sharing policies as perceived by leading funding agencies: The design of clear policies, monitoring of compliance, sanctions for non-compliance, incentives, support, and limitations for funders' own capabilities. However, our interviews also show how funders approach potential solutions to overcome these challenges, for example by coordinating with other agencies or adjusting grant evaluation metrics to incentivise data sharing. DISCUSSION AND CONCLUSION: Our interviews point to existing flaws in funders' data sharing policies, such as a lack of clarity, a lack of monitoring of funded researchers' data sharing behaviour, and a lack of incentives. A number of agencies could suggest potential solutions but often struggle with the overall complexity of data sharing and the implementation of these measures. Funders cannot solve each challenge by themselves, but they can play an active role and lead joint efforts towards a culture of data sharing.

Real-World Performance of High-Flux Dialyzers in Patients With Hypoalbuminemia.

There is little research on factors that influence the choice of dialyzer in patients undergoing hemodialysis. In patients at risk for poorer outcomes, including those with hypoalbuminemia, understanding how this choice impacts clinical parameters could inform patient management. The objective of this real-world analysis was to evaluate the use and performance of four single-use (i.e., nonreuse [NR]), high-flux Optiflux dialyzers with varying surface areas (F160NR [1.5 m2], F180NR [1.7 m2], F200NR [1.9 m2], and F250NR [2.5 m2]) in patients (N = 271) with baseline hypoalbuminemia (≤3.5 g/dl) receiving hemodialysis at a medium-sized dialysis organization. Thrice weekly, in-center dialysis was delivered for 6 months without adjustments to the hemodialysis prescription. Larger dialyzers were more frequently used in men, patients with higher body mass indices, and those with diabetes. Increases in serum albumin from baseline (month 1) to month 6 (p < 0.05) were observed with all dialyzer sizes. A mean increase in hemoglobin of 0.31 g/dl was also observed (p < 0.001). Among patients exhibiting increased serum albumin levels (n = 177), reductions in the neutrophil-to-lymphocyte ratio, a marker of inflammation, were observed (mean: 0.90; p < 0.001). These results support the use of high-flux dialyzers in patients with hypoalbuminemia.

Serum Phosphorus and Pill Burden Among Hemodialysis Patients Prescribed Sucroferric Oxyhydroxide: One-Year Follow-Up on a Contemporary Cohort.

Purpose: In prior analyses of real-world cohorts of hemodialysis patients switched from one phosphate binder (PB) to sucroferric oxyhydroxide (SO), SO therapy has been associated with improvements in serum phosphorus (sP) and reductions in daily PB pill burden. To characterize how SO initiation patterns have changed over time, we examined the long-term effectiveness of SO in a contemporary (2018-2019) cohort. Patients and Methods: Adult Fresenius Kidney Care hemodialysis patients first prescribed SO monotherapy as part of routine care between May 2018 and May 2019 (N = 1792) were followed for 1 year. All patients received a non-SO PB during a 91-day baseline period before SO prescription. Mean PB pills/day and laboratory parameters were compared before and during SO treatment. Results were divided into consecutive 91-day intervals (Q1-Q4) and analyzed using linear mixed-effects regression and Cochran's Q test. These results were contrasted with findings from a historical (2014-2015) cohort (N = 530). Results: The proportion of patients achieving sP ≤5.5 mg/dl increased after switching to SO (from 27.0% at baseline to 37.8%, 45.1%, 44.7%, and 44.0% at Q1, Q2, Q3, and Q4, respectively; P < 0.0001 for all). The mean daily PB pill burden decreased from a baseline of 7.7 to 4.4, 4.6, 4.8, and 4.9, respectively, across quarters (P < 0.0001 for all). Patients in the contemporary cohort had improved sP control (27.0% achieving sP ≤5.5 mg/dl vs 17.7%) and lower daily PB pill burden (mean 7.7 vs 8.5 pills/day) at baseline than those in the historical cohort. Overall use of active vitamin D was similar between cohorts, although higher use of oral active vitamin D (63.9% vs 15.7%) and lower use of IV active vitamin D lower (23.4% vs 74.2%) was observed in the contemporary cohort. Conclusion: Despite evolving treatment patterns, switching to SO resulted in improved sP control with fewer pills per day in this contemporary hemodialysis cohort.

The membrane perspective of uraemic toxins: which ones should, or can, be removed?

Informed decision-making is paramount to the improvement of dialysis therapies and patient outcomes. A cornerstone of delivery of optimal dialysis therapy is to delineate which substances (uraemic retention solutes or 'uraemic toxins') contribute to the condition of uraemia in terms of deleterious biochemical effects they may exert. Thereafter, decisions can be made as to which of the accumulated compounds need to be targeted for removal and by which strategies. For haemodialysis (HD), the non-selectivity of membranes is sometimes considered a limitation. Yet, considering that dozens of substances with potential toxicity need to be eliminated, and targeting removal of individual toxins explicitly is not recommended, current dialysis membranes enable elimination of several molecules of a broad size range within a single therapy session. However, because HD solute removal is based on size-exclusion principles, i.e. the size of the substances to be removed relative to the mean size of the 'pores' of the membrane, only a limited degree of selectivity of removal is possible. Removal of unwanted substances during HD needs to be weighed against the unavoidable loss of substances that are recognized to be necessary for bodily functions and physiology. In striving to improve the efficiency of HD by increasing the porosity of membranes, there is a greater potential for the loss of substances that are of benefit. Based on this elementary trade-off and availability of recent guidance on the relative toxicity of substances retained in uraemia, we propose a new evidence-linked uraemic toxin elimination (ELUTE) approach whereby only those clusters of substances for which there is a sufficient body of evidence linking them to deleterious biological effects need to be targeted for removal. Our approach involves correlating the physical properties of retention solutes (deemed to express toxicity) with key determinants of membranes and separation processes. Our analysis revealed that in attempting to remove the relatively small number of 'larger' substances graded as having only moderate toxicity, uncontrolled (and efficient) removal of several useful compounds would take place simultaneously and may compromise the well-being or outcomes of patients. The bulk of the uraemic toxin load comprises uraemic toxins below <30 000 Da and are adequately removed by standard membranes. Further, removal of a few difficult-to-remove-by-dialysis (protein-bound) compounds that express toxicity cannot be achieved by manipulation of pore size alone. The trade-off between the benefits of effective removal of the bulk of the uraemic toxin load and risks (increased loss of useful substances) associated with targeting the removal of a few larger substances in 'high-efficiency' HD treatment strategies needs to be recognized and better understood. The removability during HD of substances, be they toxic, inert or beneficial, needs be revised to establish the pros and cons of current dialytic elimination strategies. .

Slipping Through the Pores: Hypoalbuminemia and Albumin Loss During Hemodialysis.

Hypoalbuminemia results when compensatory mechanisms are unable to keep pace with derangements in catabolism/loss and/or decreased synthesis of albumin. Across many disease states, including chronic kidney disease (CKD), hypoalbuminemia is a well-established, independent risk factor for adverse outcomes, including mortality. In the setting of CKD, reduced serum albumin concentrations are often a manifestation of protein-energy wasting, a state of metabolic and nutritional alterations resulting in reduced protein and energy stores. The progression of CKD to kidney failure and the initiation of maintenance hemodialysis (HD) further predisposes an already at-risk population toward hypoalbuminemia such that approximately 60% of HD patients have albumin concentrations <4.0 g/dl. Albumin loss into the dialysate through the dialyzer appears to be a potentially modifiable cause of hypoalbuminemia in some patients. A group of newer dialyzers for maintenance HD-sometimes termed protein-leaking or medium cut-off membranes-aim to improve clearance of middle molecules (vs high flux dialyzers) but are associated with increased albumin losses. In this article, we will examine the impact of dialyzer selection on albumin losses during conventional HD, including the clinical relevance of such losses on serum albumin levels. Data on the clinical relevance of albumin losses during dialysis and current gaps in the evidence base are also discussed.

Effect of Citrate-Acidified Dialysate on Intact Parathyroid Hormone in Prevalent Hemodialysis Patients: A Matched Retrospective Cohort Study.

BACKGROUND: It has been proposed that substituting citrate-acidified dialysate (CAD) solutions for acetate-acidified dialysate (AAD) could improve hemodynamics and dialysis tolerance and reduce the requirement for systemic anticoagulation. Citrate chelates ionized calcium, but long-term effects of CAD use during maintenance hemodialysis have not been well studied. While many studies of the effects of CAD on serum calcium and intact parathyroid hormone (iPTH) have been short-term or have been limited by sample size, we aimed to determine if there are any long-term (i.e., 6-month) changes from pre-dialysis iPTH levels when patients are switched from AAD to CAD. METHODS: This retrospective cohort study compared various clinical parameters, including pre-dialysis iPTH and serum calcium as well as single pool Kt/V, from eligible patients who received in-center hemodialysis thrice-weekly in geographically matched CAD (n=3) or AAD clinics (n=12). CAD clinics were defined as clinics converting from AAD to CAD if >85% of the patients were prescribed CAD after implementation of CAD within the clinic. RESULTS: Pre-dialysis iPTH was not significantly different from baseline to 6-month follow-up within either CAD or AAD clinics. Moreover, the mean change from baseline to month 6 in iPTH between patients (n=142) in CAD clinics (-17 pg/mL) and patients (n=671) in AAD clinics (13 pg/mL) was similar (p = 0.24). Likewise, the differences in the mean change in serum calcium concentrations and dialysis adequacy (single pool Kt/V) were not significant between CAD and AAD clinics. For subgroups of patients who were never prescribed cinacalcet or calcium-based phosphate binders, there were no significantly different categorical shifts in iPTH between CAD and AAD clinics. CONCLUSION: Similar trends in single pool Kt/V, iPTH, and serum calcium levels were observed in clinics that switched from AAD to CAD versus the geographically matched AAD clinics. These results support CAD as a potential alternative to AAD in hemodialysis.