Outcomes for clinical trials involving adults with chronic kidney disease: a multinational Delphi survey involving patients, caregivers and health professionals.

BACKGROUND: Many outcomes of high priority to patients and clinicians are infrequently and inconsistently reported across trials in chronic kidney disease (CKD), which generates research waste and limits evidence-informed decision making. We aimed to generate consensus among patients/caregivers and health professionals on critically important outcomes for trials in CKD prior to kidney failure and the need for kidney replacement therapy, and to describe the reasons for their choices. METHODS: This was an online two-round international Delphi survey. Adult patients with CKD (all stages and diagnoses), caregivers and health professionals who could read English, Spanish or French were eligible. Participants rated the importance of outcomes using a Likert scale (7-9 indicating critical importance) and a Best-Worst Scale. The scores for the two groups were assessed to determine absolute and relative importance. Comments were analysed thematically. RESULTS: In total, 1399 participants from 73 countries completed Round 1 of the Delphi survey, including 628 (45%) patients/caregivers and 771 (55%) health professionals. In Round 2, 790 participants (56% response rate) from 63 countries completed the survey including 383 (48%) patients/caregivers and 407 (52%) health professionals. The overall top five outcomes were: kidney function, need for dialysis/transplant, life participation, cardiovascular disease and death. In the final round, patients/caregivers indicated higher scores for most outcomes (17/22 outcomes), and health professionals gave higher priority to mortality, hospitalization and cardiovascular disease (mean difference >0.3). Consensus was based upon the two groups yielding median scores of ≥7 and mean scores >7, and the proportions of both groups rating the outcome as 'critically important' being >50%. Four themes reflected the reasons for their priorities: imminent threat of a health catastrophe, signifying diminishing capacities, ability to self-manage and cope, and tangible and direct consequences. CONCLUSION: Across trials in CKD, the outcomes of highest priority to patients, caregivers and health professionals were kidney function, need for dialysis/transplant, life participation, cardiovascular disease and death.

Home dialysis: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.

Home dialysis modalities (home hemodialysis [HD] and peritoneal dialysis [PD]) are associated with greater patient autonomy and treatment satisfaction compared with in-center modalities, yet the level of home-dialysis use worldwide is low. Reasons for limited utilization are context-dependent, informed by local resources, dialysis costs, access to healthcare, health system policies, provider bias or preferences, cultural beliefs, individual lifestyle concerns, potential care-partner time, and financial burdens. In May 2021, KDIGO (Kidney Disease: Improving Global Outcomes) convened a controversies conference on home dialysis, focusing on how modality choice and distribution are determined and strategies to expand home-dialysis use. Participants recognized that expanding use of home dialysis within a given health system requires alignment of policy, fiscal resources, organizational structure, provider incentives, and accountability. Clinical outcomes across all dialysis modalities are largely similar, but for specific clinical measures, one modality may have advantages over another. Therefore, choice among available modalities is preference-sensitive, with consideration of quality of life, life goals, clinical characteristics, family or care-partner support, and living environment. Ideally, individuals, their care-partners, and their healthcare teams will employ shared decision-making in assessing initial and subsequent kidney failure treatment options. To meet this goal, iterative, high-quality education and support for healthcare professionals, patients, and care-partners are priorities. Everyone who faces dialysis should have access to home therapy. Facilitating universal access to home dialysis and expanding utilization requires alignment of policy considerations and resources at the dialysis-center level, with clear leadership from informed and motivated clinical teams.

Bio-impedance spectroscopy added to a fluid management protocol does not improve preservation of residual kidney function in incident hemodialysis patients in a randomized controlled trial.

Avoiding excessive dialysis-associated volume depletion may help preserve residual kidney function (RKF). To establish whether knowledge of the estimated normally hydrated weight from bioimpedance measurements (BI-NHW) when setting the post-hemodialysis target weight (TW) might mitigate rate of loss of RKF, we undertook an open label, randomized controlled trial in incident patients receiving HD, with clinicians and patients blinded to bioimpedance readings in controls. A total of 439 patients with over 500 ml urine/day or residual GFR exceeding 3 ml/min/1.73m2 were recruited from 34 United Kingdom centers and randomized 1:1, stratified by center. Fluid assessments were made for up to 24 months using a standardized proforma in both groups, supplemented by availability of BI-NHW in the intervention group. Primary outcome was time to anuria, analyzed using competing-risk survival models adjusted for baseline characteristics, by intention to treat. Secondary outcomes included rate of RKF decline (mean urea and creatinine clearance), blood pressure and patient-reported outcomes. There were no group differences in cause-specific hazard rates of anuria (0.751; 95% confidence interval (0.459, 1.229)) or sub-distribution hazard rates (0.742 (0.453, 1.215)). RKF decline was markedly slower than anticipated, pooled linear rates in year 1: -0.178 (-0.196, -0.159)), year 2: -0.061 (-0.086, -0.036)) ml/min/1.73m2/month. Blood pressure and patient-reported outcomes did not differ by group. The mean difference agreement between TW and BI-NHW was similar for both groups, Bioimpedance: -0.04 kg; Control: -0.25 kg. Thus, use of a standardized clinical protocol for fluid assessment when setting TW is associated with excellent preservation of RKF. Hence, bioimpedance measurements are not necessary to achieve this.

Association of single and serial measures of serum phosphorus with adverse outcomes in patients on peritoneal dialysis: results from the international PDOPPS.

BACKGROUND: While high serum phosphorus levels have been related to adverse outcomes in hemodialysis patients, further investigation is warranted in persons receiving peritoneal dialysis (PD). METHODS: Longitudinal data (2014-17) from the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS), a prospective cohort study, were used to examine associations of serum phosphorus with all-cause mortality and major adverse cardiovascular events via Cox regression adjusted for confounders. Serum phosphorus levels were parameterized by four methods: (i) baseline serum phosphorus; (ii) mean 6-month serum phosphorus; (iii) number of months with serum phosphorus >4.5 mg/dL; and (iv) mean area-under-the-curve of 6-month serum phosphorus control. RESULTS: The study included 5847 PD patients from seven countries; 9% of patients had baseline serum phosphorus <3.5 mg/dL, 24% had serum phosphorus ≥3.5 to ≤4.5 mg/dL, 30% had serum phosphorus >4.5 to <5.5 mg/dL, 20% had serum phosphorus ≥5.5 to <6.5 mg/dL, and 17% had serum phosphorus ≥6.5 mg/dL. Compared with patients with baseline serum phosphorus ≥3.5 to ≤4.5 mg/dL, the adjusted all-cause mortality hazard ratio (HR) was 1.19 (0.92,1.53) for patients with baseline serum phosphorus ≥5.5 to <6.5 mg/dL and HR was 1.53 (1.14,2.05) for serum phosphorus ≥6.5 mg/dL. Associations between serum phosphorus measurements over 6 months and clinical outcomes were even stronger than for a single measurement. CONCLUSIONS: Serum phosphorus >5.5 mg/dL was highly prevalent (37%) in PD patients, and higher serum phosphorus levels were a strong predictor of morbidity and death, particularly when considering serial phosphorus measurements. This highlights the need for improved treatment strategies in this population. Serial serum phosphorus measurements should be considered when assessing patients' risks of adverse outcomes.

Catheter insertion techniques for improving catheter function and clinical outcomes in peritoneal dialysis patients.

BACKGROUND: Peritoneal dialysis (PD) relies on the optimal functionality of the flexible plastic PD catheter present within the peritoneal cavity to enable effective treatment. As a result of limited evidence, it is uncertain if the PD catheter's insertion method influences the rate of catheter dysfunction and, thus, the quality of dialysis therapy. Numerous variations of four basic techniques have been adopted in an attempt to improve and maintain PD catheter function. This review evaluates the association between PD catheter insertion technique and associated differences in  PD catheter function and post-PD catheter insertion complications OBJECTIVES: Our aims were to 1) evaluate if a specific technique used for PD catheter insertion has lower rates of PD catheter dysfunction (early and late) and technique failure; and 2) examine if any of the available techniques results in a reduction in post-procedure complication rates including postoperative haemorrhage, exit-site infection and peritonitis. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 24 November 2022 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: We included randomised controlled trials (RCTs) examining adults and children undergoing PD catheter insertion. The studies examined any two PD catheter insertion techniques, including laparoscopic, open-surgical, percutaneous and peritoneoscopic insertion. Primary outcomes of interest were PD catheter function and technique survival.  DATA COLLECTION AND ANALYSIS: Two authors independently performed data extraction and assessed the risk of bias for all included studies. Main outcomes in the Summary of Findings tables include primary outcomes - early PD catheter function, long-term PD catheter function, technique failure and postoperative complications. A random effects model was used to perform meta-analyses; risk ratios (RRs) were calculated for dichotomous outcomes, and mean differences (MD) were calculated for continuous outcomes, using 95% confidence intervals (CIs) for effect estimates. The certainty of the evidence was evaluated using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach.  MAIN RESULTS: Seventeen studies were included in this review. Nine studies were suitable for inclusion in quantitative meta-analysis (670 randomised participants). Five studies compared laparoscopic with open PD catheter insertion, and four studies compared a 'medical' insertion technique with open surgical PD catheter insertion: percutaneous (2) and peritoneoscopic (2). Random sequence generation was judged to be at low risk of bias in eight studies. Allocation concealment was reported poorly, with only five studies judged to be at low risk of selection bias. Performance bias was judged to be high risk in 10 studies. Attrition bias and reporting bias were judged to be low in 14 and 12 studies, respectively. Six studies compared laparoscopic PD catheter insertion with open surgical insertion. Five studies could be meta-analysed (394 participants). For our primary outcomes, data were either not reported in a format that could be meta-analysed (early PD catheter function, long-term catheter function) or not reported at all (technique failure). One death was reported in the laparoscopic group and none in the open surgical group. In low certainty evidence, laparoscopic PD catheter insertion may make little or no difference to the risk of peritonitis (4 studies, 288 participants: RR 0.97, 95% CI 0.63 to 1.48; I² = 7%), PD catheter removal (4 studies, 257 participants: RR 1.15, 95% CI 0.80 to 1.64; I² = 0%), and dialysate leakage (4 studies, 330 participants: RR 1.40, 95% CI 0.49 to 4.02; I² = 0%), but may reduce the risk of haemorrhage (2 studies, 167 participants: RR 1.68, 95% CI 0.28 to 10.31; I² = 33%) and catheter tip migration (4 studies, 333 participants: RR 0.43, 95% CI 0.20 to 0.92; I² = 12%). Four studies compared a medical insertion technique with open surgical insertion (276 participants). Technique failure was not reported, and no deaths were reported (2 studies, 64 participants). In low certainty evidence, medical insertion may make little or no difference to early PD catheter function (3 studies, 212 participants: RR 0.73, 95% CI 0.29 to 1.83; I² = 0%), while one study reported long-term PD function may improve with peritoneoscopic insertion (116 participants: RR 0.59, 95% CI 0.38 to 0.92). Peritoneoscopic catheter insertion may reduce the episodes of early peritonitis (2 studies, 177 participants: RR 0.21, 95% CI 0.06 to 0.71; I² = 0%) and dialysate leakage (2 studies, 177 participants: RR 0.13, 95% CI 0.02 to 0.71; I² = 0%). Medical insertion had uncertain effects on catheter tip migration (2 studies, 90 participants: RR 0.74, 95% CI 0.15 to 3.73; I² = 0%). Most of the studies examined were small and of poor quality, increasing the risk of imprecision. There was also a significant risk of bias therefore cautious interpretation of results is advised. AUTHORS' CONCLUSIONS: The available studies show that the evidence needed to guide clinicians in developing their PD catheter insertion service is lacking. No PD catheter insertion technique had lower rates of PD catheter dysfunction. High-quality, evidence-based data are urgently required, utilising multi-centre RCTs or large cohort studies, in order to provide definitive guidance relating to PD catheter insertion modality.

The trajectory of a range of commonly captured symptoms with standard care in people with kidney failure receiving haemodialysis: consideration for clinical trial design.

BACKGROUND: Despite the recognized high symptom prevalence in haemodialysis population, how these symptoms change over time and its implications for clinical practice and research is poorly understood. METHODS: Prevalent haemodialysis patients in the SHAREHD trial reported 17 POS-S Renal symptoms (none, mild, moderate, severe and overwhelming) at baseline, 6, 12 and 18 months. To assess the prevalence change at population level in people reporting moderate or worse symptoms at baseline, the absolute change in prevalence was estimated using multi-level mixed effects probit regression adjusting for age, sex, time on haemodialysis and Charlson Comorbidity Score. To assess changes at individual level, the proportion of people changing their symptom score every 6 months was estimated. RESULTS: Five hundred fifty-two participants completed 1725 questionnaires at four timepoints. Across all 17 symptoms with moderate or worse symptom severity at baseline, the majority of the change in symptom prevalence at population level occurred in the 'severe' category. The absolute improvement in prevalence of the 'severe' category was ≤ 20% over 18 months in eleven of the seventeen symptoms despite a large degree of relatively balanced movement of individuals in and out of severe category every six months. Examples include depression, skin changes and drowsiness, which had larger proportion (75-80%) moving in and out of severe category each 6 months period but < 5% difference between movement in and out of severe category resulting in relatively static prevalence over time. Meanwhile, larger changes in prevalence of > 20% were observed in six symptoms, driven by a 9 to 18% difference between movement in and movement out of severe category. All symptoms had > 50% of people in severe group changing severity within 6 months. CONCLUSIONS: Changes in the severity of existing symptoms under standard care were frequent, often occurring within six months. Certain symptoms exhibited clinically meaningful shifts at both the population and individual levels. This highlighted the need to consider improvements in symptom severity when determining sample size and statistical power for trials. By accounting for potential symptom improvements with routine care, researchers can design trials capable of robustly detecting genuine treatment effects, distinguishing them from spontaneous changes associated with standard haemodialysis.

Study protocol for Vascular Access outcome measure for function: a vaLidation study In hemoDialysis (VALID) : A multi-center, multinational validation study to assess the accuracy and feasibility of measuring vascular access function in clinical practice.

BACKGROUND: A functioning vascular access (VA) is crucial to providing adequate hemodialysis (HD) and considered a critically important outcome by patients and healthcare professionals. A validated, patient-important outcome measure for VA function that can be easily measured in research and practice to harvest reliable and relevant evidence for informing patient-centered HD care is lacking. Vascular Access outcome measure for function: a vaLidation study In hemoDialysis (VALID) aims to assess the accuracy and feasibility of measuring a core outcome for VA function established by the international Standardized Outcomes in Nephrology (SONG) initiative. METHODS: VALID is a prospective, multi-center, multinational validation study that will assess the accuracy and feasibility of measuring VA function, defined as the need for interventions to enable and maintain the use of a VA for HD. The primary objective is to determine whether VA function can be measured accurately by clinical staff as part of routine clinical practice (Assessor 1) compared to the reference standard of documented VA procedures collected by a VA expert (Assessor 2) during a 6-month follow-up period. Secondary outcomes include feasibility and acceptability of measuring VA function and the time to, rate of, and type of VA interventions. An estimated 612 participants will be recruited from approximately 10 dialysis units of different size, type (home-, in-center and satellite), governance (private versus public), and location (rural versus urban) across Australia, Canada, Europe, and Malaysia. Validity will be measured by the sensitivity and specificity of the data acquisition process. The sensitivity corresponds to the proportion of correctly identified interventions by Assessor 1, among the interventions identified by Assessor 2 (reference standard). The feasibility of measuring VA function will be assessed by the average data collection time, data completeness, feasibility questionnaires and semi-structured interviews on key feasibility aspects with the assessors. DISCUSSION: Accuracy, acceptability, and feasibility of measuring VA function as part of routine clinical practice are required to facilitate global implementation of this core outcome across all HD trials. Global use of a standardized, patient-centered outcome measure for VA function in HD research will enhance the consistency and relevance of trial evidence to guide patient-centered care. TRIAL REGISTRATION: Clinicaltrials.gov: NCT03969225. Registered on 31st May 2019.

Patient-reported outcome measures for life participation in peritoneal dialysis: a systematic review.

BACKGROUND: Patients receiving peritoneal dialysis (PD) endure an ongoing regimen of daily fluid exchanges and are at risk of potentially life-threatening complications and debilitating symptoms that can limit their ability to participate in life activities. The aim of the study was to identify the characteristics, content and psychometric properties of measures for life participation used in research in PD. METHODS: We searched MEDLINE, Embase, PsychInfo, the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and the Cochrane Central Register of Controlled Trials from inception to May 2020 for all studies that reported life participation in patients on PD. The characteristics, dimensions of life participation and psychometric properties of these measures were extracted and analyzed. RESULTS: Of the 301 studies included, 17 (6%) were randomized studies and 284 (94%) were nonrandomized studies. Forty-two different measures were used to assess life participation. Of these, 23 (55%) were used in only one study. Fifteen (36%) measures were specifically designed to assess life participation, while 27 (64%) measures assessed broader constructs, such as quality of life, but included questions on life participation. The 36-Item Short Form Health Survey and Kidney Disease Quality of Life Short Form were the most frequently used measures [122 (41%) and 86 (29%) studies, respectively]. Eight (19%) measures had validation data to support their use in patients on PD. CONCLUSIONS: The many measures currently used to assess life participation in patients receiving PD vary in their characteristics, content and validation. Further work to pilot and validate potential measures is required to establish a core patient-reported outcome measure to assess life participation in patients receiving PD.

Establishing a Core Outcome Set for Peritoneal Dialysis: Report of the SONG-PD (Standardized Outcomes in Nephrology-Peritoneal Dialysis) Consensus Workshop.

Outcomes reported in randomized controlled trials in peritoneal dialysis (PD) are diverse, are measured inconsistently, and may not be important to patients, families, and clinicians. The Standardized Outcomes in Nephrology-Peritoneal Dialysis (SONG-PD) initiative aims to establish a core outcome set for trials in PD based on the shared priorities of all stakeholders. We convened an international SONG-PD stakeholder consensus workshop in May 2018 in Vancouver, Canada. Nineteen patients/caregivers and 51 health professionals attended. Participants discussed core outcome domains and implementation in trials in PD. Four themes relating to the formation of core outcome domains were identified: life participation as a main goal of PD, impact of fatigue, empowerment for preparation and planning, and separation of contributing factors from core factors. Considerations for implementation were identified: standardizing patient-reported outcomes, requiring a validated and feasible measure, simplicity of binary outcomes, responsiveness to interventions, and using positive terminology. All stakeholders supported inclusion of PD-related infection, cardiovascular disease, mortality, technique survival, and life participation as the core outcome domains for PD.

Patient and Caregiver Priorities for Outcomes in CKD: A Multinational Nominal Group Technique Study.

RATIONALE & OBJECTIVE: Patients with chronic kidney disease (CKD) are at an increased risk for premature death, cardiovascular disease, and burdensome symptoms that impair quality of life. We aimed to identify patient and caregiver priorities for outcomes in CKD. STUDY DESIGN: Focus groups with nominal group technique. SETTING & PARTICIPANTS: Adult patients with CKD (all stages) and caregivers in the United States, Australia, and United Kingdom. ANALYTICAL APPROACH: Participants identified, ranked, and discussed outcomes that were important during the stages of CKD before kidney replacement therapy. For each outcome, we calculated a mean importance score (scale, 0-1). Qualitative data were analyzed using thematic analysis. RESULTS: 67 (54 patients, 13 caregivers) participated in 10 groups and identified 36 outcomes. The 5 top-ranked outcomes for patients were kidney function (importance score, 0.42), end-stage kidney disease (0.29), fatigue (0.26), mortality (0.25), and life participation (0.20); and for caregivers, the top 5 outcomes were life participation (importance score, 0.38), kidney function (0.37), mortality (0.23), fatigue (0.21), and anxiety (0.20). Blood pressure, cognition, and depression were consistently ranked in the top 10 outcomes across role (patient/caregiver), country, and treatment stage. Five themes were identified: re-evaluating and reframing life, intensified kidney consciousness, battling unrelenting and debilitating burdens, dreading upheaval and constraints, and taboo and unspoken concerns. LIMITATIONS: Only English-speaking participants were included. CONCLUSIONS: Patients and caregivers gave highest priority to kidney function, mortality, fatigue, life participation, anxiety, and depression. Consistent reporting of these outcomes in research may inform shared decision making based on patient and caregiver priorities in CKD.

Meaning of empowerment in peritoneal dialysis: focus groups with patients and caregivers.

BACKGROUND: While peritoneal dialysis (PD) can offer patients more independence and flexibility compared with in-center hemodialysis, managing the ongoing and technically demanding regimen can impose a burden on patients and caregivers. Patient empowerment can strengthen capacity for self-management and improve treatment outcomes. We aimed to describe patients' and caregivers' perspectives on the meaning and role of patient empowerment in PD. METHODS: Adult patients receiving PD (n = 81) and their caregivers (n = 45), purposively sampled from nine dialysis units in Australia, Hong Kong and the USA, participated in 14 focus groups. Transcripts were thematically analyzed. RESULTS: We identified six themes: lacking clarity for self-management (limited understanding of rationale behind necessary restrictions, muddled by conflicting information); PD regimen restricting flexibility and freedom (burden in budgeting time, confined to be close to home); strength with supportive relationships (gaining reassurance with practical assistance, comforted by considerate health professionals, supported by family and friends); defying constraints (reclaiming the day, undeterred by treatment, refusing to be defined by illness); regaining lost vitality (enabling physical functioning, restoring energy for life participation); and personal growth through adjustment (building resilience and enabling positive outlook, accepting the dialysis regimen). CONCLUSIONS: Understanding the rationale behind lifestyle restrictions, practical assistance and family support in managing PD promoted patient empowerment, whereas being constrained in time and capacity for life participation outside the home undermined it. Education, counseling and strategies to minimize the disruption and burden of PD may enhance satisfaction and outcomes in patients requiring PD.

An international Delphi survey helped develop consensus-based core outcome domains for trials in peritoneal dialysis.

Shared decision-making about clinical care options in end-stage kidney disease is limited by inconsistencies in the reporting of outcomes and the omission of patient-important outcomes in trials. Here we generated a consensus-based prioritized list of outcomes to be reported during trials in peritoneal dialysis (PD). In an international, online, three-round Delphi survey, patients/caregivers and health professionals rated the importance of outcomes using a 9-point Likert scale (with 7-9 indicating critical importance) and provided comments. Using a Best-Worst Scale (BWS), the relative importance of outcomes was estimated. Comments were analyzed thematically. In total, 873 participants (207 patients/caregivers and 666 health professionals) from 68 countries completed round one, 629 completed round two and 530 completed round three. The top outcomes were PD-related infection, membrane function, peritoneal dialysis failure, cardiovascular disease, death, catheter complications, and the ability to do usual activities. Compared with health professionals, patients/caregivers gave higher priority to six outcomes: blood pressure (mean difference, 0.4), fatigue (0.3), membrane function (0.3), impact on family/friends (0.1), peritoneal thickening (0.1) and usual activities (0.1). Four themes were identified that underpinned the reasons for ratings: contributing to treatment longevity, preserving quality of life, escalating morbidity, and irrelevant and futile information and treatment. Patients/caregivers and health professionals gave highest priority to clinical outcomes. In contrast to health professionals, patients/caregivers gave higher priority to lifestyle-related outcomes including the impact on family/friends and usual activities. Thus, prioritization will inform a core outcome set to improve the consistency and relevance of outcomes for trials in PD.

International Variations in Peritoneal Dialysis Utilization and Implications for Practice.

In many countries, the use of peritoneal dialysis (PD) remains low despite arguments that support its greater use, including dialysis treatment away from hospital settings, avoidance of central venous catheters, and potential health economic advantages. Training patients to manage aspects of their own care has the potential to enhance health literacy and increase patient involvement, independence, quality of life, and cost-effectiveness of care. Complex reasons underlie the variable use of PD across the world, acting at the level of the patient, the health care team that is responsible for them, and the health care system that they find themselves in. Important among these is the availability of competitively priced dialysis fluid. A number of key interventions can affect the uptake of PD. These include high-quality patient education around dialysis modality choice, timely and successful catheter placement, satisfactory patient training, and continued support that is tailored for specific needs, for example, when people present late requiring dialysis. Several health system changes have been shown to increase PD use, such as targeted funding, PD First initiatives, or physician-inserted PD catheters. This review explores the factors that explain the considerable international variation in the use of PD and presents interventions that can potentially affect them.

Estimating risk of encapsulating peritoneal sclerosis accounting for the competing risk of death.

BACKGROUND: Risk of encapsulating peritoneal sclerosis (EPS) is strongly associated with the duration of peritoneal dialysis (PD), such that patients who have been on PD for some time may consider elective transfer to haemodialysis to mitigate the risk of EPS. There is a need to determine this risk to better inform clinical decision making, but previous studies have not allowed for the competing risk of death. METHODS: This study included new adult PD patients in Australia and New Zealand (ANZ; 1990-2010) or Scotland (2000-08) followed until 2012. Age, time on PD, primary renal disease, gender, data set and diabetic status were evaluated as predictors at the start of PD, then at 3 and 5 years after starting PD using flexible parametric competing risks models. RESULTS: In 17 396 patients (16 162 ANZ, 1234 Scotland), EPS was observed in 99 (0.57%) patients, less frequently in ANZ patients (n = 65; 0.4%) than in Scottish patients (n = 34; 2.8%). The estimated risk of EPS was much lower when the competing risk of death was taken into account (1 Kaplan-Meier = 0.0126, cumulative incidence function = 0.0054). Strong predictors of EPS included age, primary renal disease and time on PD. The risk of EPS was reasonably discriminated at the start of PD (C-statistic = 0.74-0.79) and this improved at 3 and 5 years after starting PD (C-statistic = 0.81-0.92). CONCLUSIONS: EPS risk estimates are lower when calculated using competing risk of death analyses. A patient's estimated risk of EPS is country-specific and can be predicted using age, primary renal disease and duration of PD.

The association between longer haemodialysis treatment times and hospitalization and mortality after the two-day break in individuals receiving three times a week haemodialysis.

BACKGROUND: On the first haemodialysis (HD) day after the 2-day break in three times a week (3×W) in-centre HD, mortality and hospitalization are higher. If longer HD sessions prescribed 3×W is associated with a reduction in these events is unknown. METHODS: HD session length in 19 557 prevalent European in-centre 3×W HD patients participating in the Dialysis Outcomes and Practice Patterns Study (1998-2011) were categorized into <200, 200-225, 226-250 or >250 min. Standardized event rates on the first (HD1) versus the second (HD2) HD day after the 2-day break, with supporting Cox proportional hazards models adjusted for patient and dialysis characteristics, were generated for all-cause mortality, all-cause hospitalization, out-of-hospital death and fluid overload hospitalization. RESULTS: By comparing HD1 with HD2, increased rates of all endpoints were observed (all P < 0.002). As HD session lengthened across the four groups, all-cause mortality per 100 patient-years on the HD1 (23.0, 20.4, 16.4 and 14.6) and HD2 (26.1, 13.3, 13.4 and 12.1) reduced. Similar improvements were observed for out-of-hospital death but were less marked for hospitalization endpoints. However, even patients dialysing >250 min were at significantly greater risk on HD1 when compared with their HD2 for out-of-hospital death [hazard ratio (HR) = 2.1, 95% CI 1.0-4.3], all-cause hospitalization (HR = 1.3, 95% CI 1.2-1.4) and fluid overload hospitalization (HR = 3.2, 95% CI 1.8-6.0). CONCLUSIONS: Despite the association between reduced mortality across all dialysis days in patients performing longer sessions, elevated risk on the first dialysis day relative to the second persists even in patients dialysing 4.5 h 3×W.

Renal Association Clinical Practice Guideline on Haemodialysis.

This guideline is written primarily for doctors and nurses working in dialysis units and related areas of medicine in the UK, and is an update of a previous version written in 2009. It aims to provide guidance on how to look after patients and how to run dialysis units, and provides standards which units should in general aim to achieve. We would not advise patients to interpret the guideline as a rulebook, but perhaps to answer the question: "what does good quality haemodialysis look like?"The guideline is split into sections: each begins with a few statements which are graded by strength (1 is a firm recommendation, 2 is more like a sensible suggestion), and the type of research available to back up the statement, ranging from A (good quality trials so we are pretty sure this is right) to D (more like the opinion of experts than known for sure). After the statements there is a short summary explaining why we think this, often including a discussion of some of the most helpful research. There is then a list of the most important medical articles so that you can read further if you want to - most of this is freely available online, at least in summary form.A few notes on the individual sections: 1. This section is about how much dialysis a patient should have. The effectiveness of dialysis varies between patients because of differences in body size and age etc., so different people need different amounts, and this section gives guidance on what defines "enough" dialysis and how to make sure each person is getting that. Quite a bit of this section is very technical, for example, the term "eKt/V" is often used: this is a calculation based on blood tests before and after dialysis, which measures the effectiveness of a single dialysis session in a particular patient. 2. This section deals with "non-standard" dialysis, which basically means anything other than 3 times per week. For example, a few people need 4 or more sessions per week to keep healthy, and some people are fine with only 2 sessions per week - this is usually people who are older, or those who have only just started dialysis. Special considerations for children and pregnant patients are also covered here. 3. This section deals with membranes (the type of "filter" used in the dialysis machine) and "HDF" (haemodiafiltration) which is a more complex kind of dialysis which some doctors think is better. Studies are still being done, but at the moment we think it's as good as but not better than regular dialysis. 4. This section deals with fluid removal during dialysis sessions: how to remove enough fluid without causing cramps and low blood pressure. Amongst other recommendations we advise close collaboration with patients over this. 5. This section deals with dialysate, which is the fluid used to "pull" toxins out of the blood (it is sometimes called the "bath"). The level of things like potassium in the dialysate is important, otherwise too much or too little may be removed. There is a section on dialysate buffer (bicarbonate) and also a section on phosphate, which occasionally needs to be added into the dialysate. 6. This section is about anticoagulation (blood thinning) which is needed to stop the circuit from clotting, but sometimes causes side effects. 7. This section is about certain safety aspects of dialysis, not seeking to replace well-established local protocols, but focussing on just a few where we thought some national-level guidance would be useful. 8. This section draws together a few aspects of dialysis which don't easily fit elsewhere, and which impact on how dialysis feels to patients, rather than the medical outcome, though of course these are linked. This is where home haemodialysis and exercise are covered. There is an appendix at the end which covers a few aspects in more detail, especially the mathematical ideas. Several aspects of dialysis are not included in this guideline since they are covered elsewhere, often because they are aspects which affect non-dialysis patients too. This includes: anaemia, calcium and bone health, high blood pressure, nutrition, infection control, vascular access, transplant planning, and when dialysis should be started.

Does alanyl-glutamine supplementation offer potential to improve peritoneal dialysate biocompatibility?

Peritoneal dialysis technique survival remains challenging due to peritonitis and long-term alterations to peritoneal membrane function and integrity. Up to now, the development of less bio-incompatible dialysis solutions have not had a major impact on these aspects of the therapy. A novel approach, supplementing dialysis solutions with a cytoprotective additive, alanyl-glutamine, has shown benefits to surrogate biomarkers of cell function in a randomized controlled study.

A prospective, proteomics study identified potential biomarkers of encapsulating peritoneal sclerosis in peritoneal effluent.

Encapsulating peritoneal sclerosis (EPS) is a potentially devastating complication of peritoneal dialysis (PD). Diagnosis is often delayed due to the lack of effective and accurate diagnostic tools. We therefore examined peritoneal effluent for potential biomarkers that could predict or confirm the diagnosis of EPS and would be valuable in stratifying at-risk patients and driving appropriate interventions. Using prospectively collected samples from the Global Fluid Study and a cohort of Greek PD patients, we utilized 2D SDSPAGE/ MS and iTRAQ to identify changes in the peritoneal effluent proteome from patients diagnosed with EPS and controls matched for treatment exposure. We employed a combinatorial peptide ligand library to compress the dynamic range of protein concentrations to aid identification of low-abundance proteins. In patients with stable membrane function, fibrinogen γ-chain and heparan sulphate proteoglycan core protein progressively increased over time on PD. In patients who developed EPS, collagen-α1(I), γ-actin and Complement factors B and I were elevated up to five years prior to diagnosis. Orosomucoid-1 and a2-HS-glycoprotein chain-B were elevated about one year before diagnosis, while apolipoprotein A-IV and α1-antitrypsin were decreased compared to controls. Dynamic range compression resulted in an increased number of proteins detected with improved resolution of protein spots, compared to the full fluid proteome. Intelectin-1, dermatopontin, gelsolin, and retinol binding protein-4 were elevated in proteome-mined samples from patients with EPS compared to patients that had just commenced peritoneal dialysis. Thus, prospective analysis of peritoneal effluent uncovered proteins indicative of inflammatory and pro-fibrotic injury worthy of further evaluation as diagnostic/prognostic markers.

Rationale and design for SHAREHD: a quality improvement collaborative to scale up Shared Haemodialysis Care for patients on centre based haemodialysis.

BACKGROUND: The study objective is to assess the effectiveness and economic impact of a structured programme to support patient involvement in centre-based haemodialysis and to understand what works for whom in what circumstances and why. It implements a program of Shared Haemodialysis Care (SHC) that aims to improve experience and outcomes for those who are treated with centre-based haemodialysis, and give more patients the confidence to dialyse independently both at centres and at home. METHODS/DESIGN: The 24 month mixed methods cohort evaluation of 600 prevalent centre based HD patients is nested within a 30 month quality improvement program that aims to scale up SHC at 12 dialysis centres across England. SHC describes an intervention where patients who receive centre-based haemodialysis are given the opportunity to learn, engage with and undertake tasks associated with their treatment. Following a 6-month set up period, a phased implementation programme is initiated across 12 dialysis units using a randomised stepped wedge design with 6 centres participating in each of 2 steps, each lasting 6 months. The intervention utilises quality improvement methodologies involving rapid tests of change to determine the most appropriate mechanisms for implementation in the context of a learning collaborative. Running parallel with the stepped wedge intervention is a mixed methods cohort evaluation that employs patient questionnaires and interviews, and will link with routinely collected data at the end of the study period. The primary outcome measure is the number of patients performing at least 5 dialysis-related tasks collected using 3 monthly questionnaires. Secondary outcomes measures include: the number of people choosing to perform home haemodialysis or dialyse independently in-centre by the end of the study period; end-user recommendation; home dialysis establishment delay; staff impact and confidence; hospitalisation; infection and health economics. DISCUSSION: The results from this study will provide evidence of impact of SHC, barriers to patient and centre level adoption and inform development of future interventions to support its implementation. TRIAL REGISTRATION: ISRCTN Number: 93999549 , (retrospectively registered 1st May 2017); NIHR Research Portfolio: 31566.

Rationale and design of BISTRO: a randomized controlled trial to determine whether bioimpedance spectroscopy-guided fluid management maintains residual kidney function in incident haemodialysis patients.

BACKGROUND: Preserved residual kidney function (RKF) and normal fluid status are associated with better patient outcomes in incident haemodialysis patients. The objective of this trial is to determine whether using bioimpedance technology in prescribing the optimal post-dialysis weight can reduce the rate of decline of RKF and potentially improve patient outcomes. METHODS/DESIGN: 516 pateints commencing haemodialysis, aged >18 with RKF of > 3 ml/min/1.73 m2 or a urine volume >500 ml per day or per the shorter inter-dialytic period will be consented and enrolled into a pragmatic, open-label, randomized controlled trial. The intervention is incorporation of bioimpedance spectroscopy (BI) determination of normally hydrated weight to set a post-dialysis target weight that limits volume depletion, compared to current standard practice. Clinicians and participants will be blinded to BI measures in the control group and a standardized record capturing management of fluid status will be used in all participants. Primary outcome is preservation of residual kidney function assessed as time to anuria (≤100 ml/day or ≤200 ml urine volume in the short inter-dialytic period). A sample size of 516 was based upon a cumulative incidence of 30% anuria in the control group and 20% in the treatment group and 11% competing risks (death, transplantation) over 10 months, with up to 2 years follow-up. Secondary outcomes include rate of decline in small solute clearance, significant adverse events, hospitalization, loss of vascular access, cardiovascular events and interventions, dialysis efficacy and safety, dialysis-related symptoms and quality of life. Economic evaluation will be carried out to determine the cost-effectiveness of the intervention. Analyses will be adjusted for patient characteristics and dialysis unit practice patterns relevant to fluid management. DISCUSSION: This trial will establish the added value of undertaking BI measures to support clinical management of fluid status and establish the relationship between fluid status and preservation of residual kidney function in incident haemodialysis patients. TRIAL REGISTRATION: ISCCTN Number: 11342007 , completed 26/04/2016; NIHR Portfolio number: CPMS31766; Sponsor: Keele University.