P1062expanded Dialysis (Hdx): Is There an Impact on Patient Reported Symptom?

Abstract

Background and Aims High flux dialysis membranes sufficiently remove smaller sized uremic toxins however, the accumulation and retention of larger middle molecular weight toxins, which are associated with chronic inflammation, cardiovascular disease and suboptimal outcomes are poorly cleared. The recent advent of medium-cut-off dialysis membranes, labelled “expanded dialysis” (HDx) are permeable to molecules of larger size responsible for poor clinical outcomes. However, it remains unclear if HDx can directly impact the symptoms associated with hemodialysis (HD). Symptom burden plays a significant role in quality of life (QOL) and mortality rates in the HD population. The London Evaluation of Illness (LEVIL), an application-based platform has been developed to measure patient reported outcomes (PROM). In comparison to cross-sectional PROM’s, LEVIL more accurately represents the fluctuations in daily symptoms and the impact of intervention. LEVIL evaluates general well-being, energy, sleep, appetite, pain and breathing, all of which are outcomes of interest on symptom burden in chronic kidney disease. Our aim was to determine if HDx therapy had any effect on symtoms/QOL domains using LEVIL. Method 28 patients from two dialysis centers in London Ontario were consented to participate. Patients were required to be over 18 years of age and on conventional thrice weekly maintenance HD for at least three months. 23 participants completed study and analyzed (five lost for various reasons). Baseline (BL) symptom characteristics were obtained while using high flux membrane for two weeks. Symptoms continued to be measured throughout the 12 weeks of HDx therapy two-three times weekly using LEVIL. Laboratory biomarkers including beta-2 microglobulin and free-light chains were collected at baseline and after 12 weeks of HDx therapy. Results Patients were stratified into tertiles (high/middle/low) using mean values of BL symptoms scores in each domain (wellbeing, energy, sleep, appetite, pain, breathing). Those in the high BL group were labeled as “control”. Low and middle BL measures were further stratified into responders vs. non-responders (responders were considered to have a 50% increase in any symptom domain by ≥50%). Of those domains which responded to HDx, 76% also had low BL scores with 27% having middle BL scores. General wellbeing, energy and sleep were domains with the greatest response reaching statistical significance after eight weeks of therapy. HDx had limited effect on appetite, pain and breathing. Although stratification was per domain, overall, 74% of the population studied did respond in at least one domain, with some responding in as many as five. Conclusion HDx using Theranova (Baxter) shows the most benefit in domains with low BL measures. Additionally, not everyone who had low BL scores responded after 12 weeks of therapy, leaving us to question whether HDx may have a latent effect in some individuals/populations. Those who had no response to therapy in certain domains also had greater baseline quality of life respectively. This information may assist in decision making/rationale for the utilization and implementation of such therapy. Although more work is required to further stratify symptoms in relation to demographic/biochemical finding and clinical outcomes. It is evident that HDx improves patient reported symptoms and QOL.

Effects of Medium Cut-Off Versus High-Flux Hemodialysis Membranes on Biomarkers: A Systematic Review and Meta-Analysis

“…We included 26 studies in this review of biomarkers, 15-40 excluding 5 reports of exclusively clinical outcomes. 41-45 Groupings of related citations are in Appendix D.…”

Clinical Outcomes With Medium Cut-Off Versus High-Flux Hemodialysis Membranes: A Systematic Review and Meta-Analysis

“… 23 - 26 Among the nonrandomized studies, 2 were cohort studies 27 , 28 and the remainder used before-after 16 - 18 , 29 - 37 or crossover designs. 38 Six were abstracts, 29 , 30 , 32 , 34 , 37 and the remaining 16 were full texts, one of which was a manuscript under review. 31 Theranova was the only MCO membrane identified in our search.…”

“…For studies reporting PROs, we considered the risk of bias due to a lack of blinding as low risk of bias (see discussion). Factors contributing to risk of bias included attrition, 16 - 18 , 28 , 32 , 37 lack of risk adjustment, 27 and selection bias. 17 We found no evidence of selective reporting or publication bias.…”

“…Such effects are important not only as direct measures of quality of life but also for their prognostic importance given their strong associations with survival and hospitalization. 55 The study by Penny et al 37 used a novel quality of life instrument (LEVIL) administered at consecutive dialysis sessions with a large effect in patients with baseline scores below 70/100, highlighting the utility of separating potential responders from non-responders who might otherwise exhibit ceiling effects. The presence of ceiling effects might explain the apparent lack of effect with MCO dialysis on the KDQOL Symptoms domain for which baseline scores ranged between 70 and 90 across studies.…”

“… 61 Moreover, one study found a linear increase in quality of life scores over time on MCO dialysis, with a return to baseline after washout, supporting a potential causal effect rather than satisficing or manipulating of scores. 37 Importantly, as all randomized and nonrandomized studies in this review were open label, downgrading one additional level for this factor would not have helped us to differentiate levels of certainty between these bodies of evidence. Nevertheless, users of this review can at their discretion rate down an additional level if it aids their decision-making.…”