A stepped wedge cluster randomized trial of graphical surveillance of kidney function data to reduce late presentation for kidney replacement therapy.

Late presentation for kidney replacement therapy (KRT) is an important cause of avoidable morbidity and mortality. Here, we evaluated the effect of a complex intervention of graphical estimated glomerular filtration rate (eGFR) surveillance across 15% of the United Kingdom population on the rate of late presentation using data routinely collected by the United Kingdom Renal Registry. A stepped wedge cluster randomized trial was established across 19 sites with eGFR graphs generated from all routine blood tests (community and hospital) across the population served by each site. Graphs were reviewed by trained laboratory or clinical staff and high-risk graphs reported to family doctors. Due to delays outside the control of clinicians and researchers few laboratories activated the intervention in their randomly assigned time period, so the trial was converted to a quasi-experimental design. We studied 6,100 kidney failure events at 20 laboratories served by 17 main kidney units. A total of 63,981 graphs were sent out. After adjustment for calendar time there was no significant reduction in the rate of presentation during the intervention period. Therefore, implementation of eGFR graph surveillance did not reduce the rate of late presentation for KRT after adjustment for secular trends. Thus, graphical surveillance is an intervention aimed at reducing late presentation, but more evidence is required before adoption of this strategy can be recommended.

Organization and Structures for Detection and Monitoring of CKD Across World Countries and Regions: Observational Data From a Global Survey.

RATIONALE & OBJECTIVE: Established therapeutic interventions effectively mitigate the risk and progression of chronic kidney disease (CKD). Countries and regions have a compelling need for organizational structures that enable early identification of people with CKD who can benefit from these proven interventions. We aimed to report the current global status of CKD detection programs. STUDY DESIGN: A multinational cross-sectional survey. SETTING & PARTICIPANTS: Stakeholders, including nephrologist leaders, policymakers, and patient advocates from 167 countries, participating in the International Society of Nephrology (ISN) survey from June to September 2022. OUTCOMES: Structures for the detection and monitoring of CKD, including CKD surveillance systems in the form of registries, community-based detection programs, case-finding practices, and availability of measurement tools for risk identification. ANALYTICAL APPROACH: Descriptive statistics. RESULTS: Of all participating countries, 19% (n=31) reported CKD registries and 25% (n=40) reported implementing CKD detection programs as part of their national policies. There were variations in CKD detection program, with 50% (n=20) using a reactive approach (managing cases as identified) and 50% (n=20) actively pursuing case-finding in at-risk populations. Routine case-finding for CKD in high-risk populations was widespread, particularly for diabetes (n=152; 91%) and hypertension (n=148; 89%). Access to diagnostic tools, estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR), was limited, especially in low-income (LICs) and lower-middle-income (LMICs) countries, at primary (eGFR: LICs 22%, LMICs 39%, UACR: LICs 28%, LMICs 39%) and secondary/tertiary healthcare levels (eGFR: LICs 39%, LMICs 73%, UACR: LICs 44%, LMICs 70%), potentially hindering CKD detection. LIMITATIONS: A lack of detailed data prevented an in-depth analysis. CONCLUSION: This comprehensive survey highlights a global heterogeneity in the organization and structures (surveillance systems, detection programs and tools) for early identification of CKD. Ongoing efforts should be geared toward bridging such disparities to optimally prevent the onset and progression of CKD and its complications.

The safety of a low protein diet in older adults with advanced chronic kidney disease.

BACKGROUND: A low protein diet (LPD) is recommended to patients with advanced chronic kidney disease (CKD), whereas geriatric guidelines recommend a higher amount of protein. The aim of this study was to evaluate the safety of LPD treatment in older adults with advanced CKD. METHODS: The EQUAL study is a prospective, observational study, including patients ≥65 years, incident estimated glomerular filtration rate <20 ml/min/1.73m², in six European countries with follow-up up till six years. Nutritional status was assessed by 7-point subjective global assessment (SGA) every 3-6 months. Prescribed diet (gram protein/kilogram/bodyweight) was recorded on every study visit; measured protein intake was available in three countries. Time to death and decline in nutritional status (SGA decrease by ≥2 points) were analysed using marginal structural models with dynamic inverse probability of treatment and censoring weights. RESULTS: Out of 1738 adults (631 prescribed LPD at any point during follow-up) there were 1319 with repeated SGA measurements of which 267 (20%) declined in SGA ≥ 2 points and 565 (32.5%) died. There was no difference in survival or decline in nutritional status for patients prescribed LPD ≤0.8 g/kg ideal bodyweight (Odds Ratio (OR) for mortality 1.15 (95% Confidence interval (CI) 0.86-1.55) and OR for decline in SGA 1.11 (95% CI 0.74-1.66) in the adjusted models. In patients prescribed LPD <0.6 g/kg ideal bodyweight, the results were similar. There was a significant interaction with LPD and higher age >75 years, lower SGA, and higher comorbidity burden for both mortality and nutritional status decline. CONCLUSIONS: In older adults with CKD approaching end-stage kidney disease, a traditional LPD prescribed and monitored according to routine clinical practice in Europe appears to be safe.

Global variability of vascular and peritoneal access for chronic dialysis.

AIM: Vascular and peritoneal access are essential elements for sustainability of chronic dialysis programs. Data on availability, patterns of use, funding models, and workforce for vascular and peritoneal accesses for dialysis at a global scale is limited. METHODS: An electronic survey of national leaders of nephrology societies, consumer representative organizations, and policymakers was conducted from July to September 2018. Questions focused on types of accesses used to initiate dialysis, funding for services, and availability of providers for access creation. RESULTS: Data from 167 countries were available. In 31 countries (25% of surveyed countries), >75% of patients initiated haemodialysis (HD) with a temporary catheter. Seven countries (5% of surveyed countries) had >75% of patients initiating HD with arteriovenous fistulas or grafts. Seven countries (5% of surveyed countries) had >75% of their patients starting HD with tunnelled dialysis catheters. 57% of low-income countries (LICs) had >75% of their patients initiating HD with a temporary catheter compared to 5% of high-income countries (HICs). Shortages of surgeons to create vascular access were reported in 91% of LIC compared to 46% in HIC. Approximately 95% of participating countries in the LIC category reported shortages of surgeons for peritoneal dialysis (PD) access compared to 26% in HIC. Public funding was available for central venous catheters, fistula/graft creation, and PD catheter surgery in 57%, 54% and 54% of countries, respectively. CONCLUSION: There is a substantial variation in the availability, funding, workforce, and utilization of vascular and peritoneal access for dialysis across countries regions, with major gaps in low-income countries.

Global variations in funding and use of hemodialysis accesses: an international report using the ISN Global Kidney Health Atlas.

BACKGROUND: There is a lack of contemporary data describing global variations in vascular access for hemodialysis (HD). We used the third iteration of the International Society of Nephrology Global Kidney Health Atlas (ISN-GKHA) to highlight differences in funding and availability of hemodialysis accesses used for initiating HD across world regions. METHODS: Survey questions were directed at understanding the funding modules for obtaining vascular access and types of accesses used to initiate dialysis. An electronic survey was sent to national and regional key stakeholders affiliated with the ISN between June and September 2022. Countries that participated in the survey were categorized based on World Bank Income Classification (low-, lower-middle, upper-middle, and high-income) and by their regional affiliation with the ISN. RESULTS: Data on types of vascular access were available from 160 countries. Respondents from 35 countries (22% of surveyed countries) reported that > 50% of patients started HD with an arteriovenous fistula or graft (AVF or AVG). These rates were higher in Western Europe (n = 14; 64%), North & East Asia (n = 4; 67%), and among high-income countries (n = 24; 38%). The rates of > 50% of patients starting HD with a tunneled dialysis catheter were highest in North America & Caribbean region (n = 7; 58%) and lowest in South Asia and Newly Independent States and Russia (n = 0 in both regions). Respondents from 50% (n = 9) of low-income countries reported that > 75% of patients started HD using a temporary catheter, with the highest rates in Africa (n = 30; 75%) and Latin America (n = 14; 67%). Funding for the creation of vascular access was often through public funding and free at the point of delivery in high-income countries (n = 42; 67% for AVF/AVG, n = 44; 70% for central venous catheters). In low-income countries, private and out of pocket funding was reported as being more common (n = 8; 40% for AVF/AVG, n = 5; 25% for central venous catheters). CONCLUSIONS: High income countries exhibit variation in the use of AVF/AVG and tunneled catheters. In low-income countries, there is a higher use of temporary dialysis catheters and private funding models for access creation.

Exploring Patients' Perceptions About Chronic Kidney Disease and Their Treatment: A Qualitative Study.

BACKGROUND: Unhelpful illness perceptions can be changed by means of interventions and can lead to improved outcomes. However, little is known about illness perceptions in patients with chronic kidney disease (CKD) prior to kidney failure, and no tools exist in nephrology care to identify and support patients with unhelpful illness perceptions. Therefore, this study aims to: (1) identify meaningful and modifiable illness perceptions in patients with CKD prior to kidney failure; and (2) explore needs and requirements for identifying and supporting patients with unhelpful illness perceptions in nephrology care from patients' and healthcare professionals' perspectives. METHODS: Individual semi-structured interviews were conducted with purposive heterogeneous samples of Dutch patients with CKD (n = 17) and professionals (n = 10). Transcripts were analysed using a hybrid inductive and deductive approach: identified themes from the thematic analysis were hereafter organized according to Common-Sense Model of Self-Regulation principles. RESULTS: Illness perceptions considered most meaningful are related to the seriousness (illness identity, consequences, emotional response and illness concern) and manageability (illness coherence, personal control and treatment control) of CKD. Over time, patients developed more unhelpful seriousness-related illness perceptions and more helpful manageability-related illness perceptions, caused by: CKD diagnosis, disease progression, healthcare support and approaching kidney replacement therapy. Implementing tools to identify and discuss patients' illness perceptions was considered important, after which support for patients with unhelpful illness perceptions should be offered. Special attention should be paid towards structurally embedding psychosocial educational support for patients and caregivers to deal with CKD-related symptoms, consequences, emotions and concerns about the future. CONCLUSIONS: Several meaningful and modifiable illness perceptions do not change for the better by means of nephrology care. This underlines the need to identify and openly discuss illness perceptions and to support patients with unhelpful illness perceptions. Future studies should investigate whether implementing illness perception-based tools will indeed improve outcomes in CKD.

International Society of Nephrology first consensus guidance for preclinical animal studies in translational nephrology.

Preclinical tests in animal models are key steps in early drug development. Consequently, the International Society of Nephrology held a consensus meeting that connected experts in the global kidney community in order to provide guidance on optimal management of translational animal studies for the development of new drugs to treat kidney disease, entitled "TRANSFORM; TRAnslational Nephrology Science FOR new Medications." The meeting covered various themes, including the following: (i) selection of disease model; (ii) pharmacokinetics; (iii) interventions in late preclinical models; (iv) choice of animal; (v) statistical power; (vi) organoids and organ-on-a-chip models; and (vii) reporting of results. This guidance is the first to be provided on the optimal conduct of translational animal studies for the development of new drugs to treat kidney disease. These recommendations are designed to accelerate development of new drugs for efficacious treatment of kidney diseases, and to improve the prognosis and quality of life of patients with a variety of kidney diseases.

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.

Defining myocardial infarction in trials of people receiving hemodialysis: consensus report from the SONG-HD MI Expert Working group.

Cardiovascular disease is the leading cause of death in patients receiving hemodialysis. Currently, there is no standardized definition of myocardial infarction (MI) for patients receiving hemodialysis. Through an international consensus process MI was established as the core CVD measure for this population in clinical trials. The Standardised Outcomes in Nephrology Group-Hemodialysis (SONG-HD) initiative convened a multidisciplinary, international working group to address the definition of MI in this population. On the basis of current evidence, the working group recommends using the Fourth Universal Definition of Myocardial Infarction with specific caveats with regard to the interpretation of "ischemic symptoms" and performing a baseline 12-lead electrocardiogram to facilitate interpretation of acute changes on subsequent tracings. The working group does not recommend obtaining baseline cardiac troponin values, though does recommend obtaining serial cardiac biomarkers in settings where ischemia is suspected. The application of an evidence-based uniform definition should increase the reliability and accuracy of trial results.

Serum Potassium and Risk of Death or Kidney Replacement Therapy in Older People With CKD Stages 4-5: Eight-Year Follow-up.

RATIONALE & OBJECTIVE: Hypokalemia may accelerate kidney function decline. Both hypo- and hyperkalemia can cause sudden cardiac death. However, little is known about the relationship between serum potassium and death or the occurrence of kidney failure requiring replacement therapy (KRT). We investigated this relationship in older people with chronic kidney disease (CKD) stage 4-5. STUDY DESIGN: Prospective observational cohort study. SETTING & PARTICIPANTS: We followed 1,714 patients (≥65 years old) from the European Quality (EQUAL) study for 8 years from their first estimated glomerular filtration rate (eGFR)<20mL/min/1.73m2 measurement. EXPOSURE: Serum potassium was measured every 3 to 6 months and categorized as≤3.5,>3.5-≤4.0,>4.0-≤4.5,>4.5-≤5.0 (reference),>5.0-≤5.5, >5.5-≤6.0, and>6.0mmol/L. OUTCOME: The combined outcome death before KRT or start of KRT. ANALYTICAL APPROACH: The association between categorical and continuous time-varying potassium and death or KRT start was examined using Cox proportional hazards and restricted cubic spline analyses, adjusted for age, sex, diabetes, cardiovascular disease, renin-angiotensin-aldosterone system (RAAS) inhibition, eGFR, and subjective global assessment (SGA). RESULTS: At baseline, 66% of participants were men, 42% had diabetes, 47% cardiovascular disease, and 54% used RAAS inhibitors. Their mean age was 76±7 (SD) years, mean eGFR was 17±5 (SD) mL/min/1.73m2, and mean SGA was 6.0±1.0 (SD). Over 8 years, 414 (24%) died before starting KRT, and 595 (35%) started KRT. Adjusted hazard ratios for death or KRT according to the potassium categories were 1.6 (95% CI, 1.1-2.3), 1.4 (95% CI, 1.1-1.7), 1.1 (95% CI, 1.0-1.4), 1 (reference), 1.1 (95% CI, 0.9-1.4), 1.8 (95% CI, 1.4-2.3), and 2.2 (95% CI, 1.5-3.3). Hazard ratios were lowest at a potassium of about 4.9mmol/L. LIMITATIONS: Shorter intervals between potassium measurements would have allowed for more precise estimations. CONCLUSIONS: We observed a U-shaped relationship between serum potassium and death or KRT start among patients with incident CKD 4-5, with a nadir risk at a potassium level of 4.9mmol/L. These findings underscore the potential importance of preventing both high and low potassium in patients with CKD 4-5. PLAIN-LANGUAGE SUMMARY: Abnormal potassium blood levels may increase the risk of death or kidney function decline, especially in older people with chronic kidney disease (CKD). We studied 1,714 patients aged≥65 years with advanced CKD from the European Quality (EQUAL) study and followed them for 8 years. We found that both low and high levels of potassium were associated with an increased risk of death or start of kidney replacement therapy, with the lowest risk observed at a potassium level of 4.9 mmol/L. In patients with CKD, the focus is often on preventing high blood potassium. However, this relatively high optimum potassium level stresses the potential importance of also preventing low potassium levels in older patients with advanced CKD.

Comparative Effectiveness of Dynamic Treatment Strategies for Medication Use and Dosage: Emulating a Target Trial Using Observational Data.

BACKGROUND: Availability of detailed data from electronic health records (EHRs) has increased the potential to examine the comparative effectiveness of dynamic treatment strategies using observational data. Inverse probability (IP) weighting of dynamic marginal structural models can control for time-varying confounders. However, IP weights for continuous treatments may be sensitive to model choice. METHODS: We describe a target trial comparing strategies for treating anemia with darbepoetin in hemodialysis patients using EHR data from the UK Renal Registry 2004 to 2016. Patients received a specified dose (microgram/week) or did not receive darbepoetin. We compared 4 methods for modeling time-varying treatment: (A) logistic regression for zero dose, standard linear regression for log dose; (B) logistic regression for zero dose, heteroscedastic linear regression for log dose; (C) logistic regression for zero dose, heteroscedastic linear regression for log dose, multinomial regression for patients who recently received very low or high doses; and (D) ordinal logistic regression. RESULTS: For this dataset, method (C) was the only approach that provided a robust estimate of the mortality hazard ratio (HR), with less-extreme weights in a fully weighted analysis and no substantial change of the HR point estimate after weight truncation. After truncating IP weights at the 95th percentile, estimates were similar across the methods. CONCLUSIONS: EHR data can be used to emulate target trials estimating the comparative effectiveness of dynamic strategies adjusting treatment to evolving patient characteristics. However, model checking, monitoring of large weights, and adaptation of model strategies to account for these is essential if an aspect of treatment is continuous.

Clinical and patient-reported trajectories at end-of-life in older patients with advanced CKD.

BACKGROUND: We explore longitudinal trajectories of clinical indicators, patient-reported outcomes, and hospitalizations, in the years preceding death in a population of older patients with advanced chronic kidney disease (CKD). METHODS: The EQUAL study is a European observational prospective cohort study with an incident eGFR <20 ml/min per 1.73 m2 and ≥65 years of age. The evolution of each clinical indicator was explored using generalized additive models during the 4 years preceding death. RESULTS: We included 661 decedents with a median time to death of 2.0 years (IQR 0.9-3.2). During the years preceding death, eGFR, Subjective Global Assessment score, and blood pressure declined, with accelerations seen at 6 months preceding death. Serum hemoglobin, hematocrit, cholesterol, calcium, albumin, and sodium values declined slowly during follow-up, with accelerations observed between 6 and 12 months preceding death. Physical and mental quality of life declined linearly throughout follow-up. The number of reported symptoms was stable up to 2 years prior to death, with an acceleration observed at 1 year prior to death. The rate of hospitalization was stable at around one hospitalization per person year, increasing exponentially at 6 months preceding death. CONCLUSIONS: We identified clinically relevant physiological accelerations in patient trajectories that began ∼6 to 12 months prior to death, which are likely multifactorial in nature, but correlate with a surge in hospitalizations. Further research should focus on how to effectively use this knowledge to inform patient and family expectations, to benefit the planning of (end-of-life) care, and to establish clinical alert systems.

Association between CKD-MBD and mortality in older patients with advanced CKD-results from the EQUAL study.

BACKGROUND: Chronic kidney disease-mineral and bone disorder (CKD-MBD) is a common complication of CKD; it is associated with higher mortality in dialysis patients, while its impact in non-dialysis patients remains mostly unknown. We investigated the associations between parathyroid hormone (PTH), phosphate and calcium (and their interactions), and all-cause, cardiovascular (CV) and non-CV mortality in older non-dialysis patients with advanced CKD. METHODS: We used data from the European Quality study, which includes patients aged ≥65 years with estimated glomerular filtration rate ≤20 mL/min/1.73 m2 from six European countries. Sequentially adjusted Cox models were used to assess the association between baseline and time-dependent CKD-MBD biomarkers and all-cause, CV and non-CV mortality. Effect modification between biomarkers was also assessed. RESULTS: In 1294 patients, the prevalence of CKD-MBD at baseline was 94%. Both PTH [adjusted hazard ratio (aHR) 1.12, 95% confidence interval (CI) 1.03-1.23, P = .01] and phosphate (aHR 1.35, 95% CI 1.00-1.84, P = .05), but not calcium (aHR 1.11, 95% CI 0.57-2.17, P = .76), were associated with all-cause mortality. Calcium was not independently associated with mortality, but modified the effect of phosphate, with the highest mortality risk found in patients with both hypercalcemia and hyperphosphatemia. PTH level was associated with CV mortality, but not with non-CV mortality, whereas phosphate was associated with both CV and non-CV mortality in most models. CONCLUSIONS: CKD-MBD is very common in older non-dialysis patients with advanced CKD. PTH and phosphate are independently associated with all-cause mortality in this population. While PTH level is only associated with CV mortality, phosphate seems to be associated with both CV and non-CV mortality.

Management and outcomes of myocardial infarction in people with impaired kidney function in England.

BACKGROUND: Acute myocardial infarction (AMI) causes significant mortality and morbidity in people with impaired kidney function. Previous observational research has demonstrated reduced use of invasive management strategies and inferior outcomes in this population. Studies from the USA have suggested that disparities in care have reduced over time. It is unclear whether these findings extend to Europe and the UK. METHODS: Linked data from four national healthcare datasets were used to investigate management and outcomes of AMI by estimated glomerular filtration rate (eGFR) category in England. Multivariable logistic and Cox regression models compared management strategies and outcomes by eGFR category among people with kidney impairment hospitalised for AMI between 2015-2017. RESULTS: In a cohort of 5 835 people, we found reduced odds of invasive management in people with eGFR < 60mls/min/1.73m2 compared with people with eGFR ≥ 60 when hospitalised for non-ST segment elevation MI (NSTEMI). The association between eGFR and odds of invasive management for ST-elevation MI (STEMI) varied depending on the availability of percutaneous coronary intervention. A graded association between mortality and eGFR category was demonstrated both in-hospital and after discharge for all people. CONCLUSIONS: In England, patients with reduced eGFR are less likely to receive invasive management compared to those with preserved eGFR. Disparities in care may however be decreasing over time, with the least difference seen in patients with STEMI managed via the primary percutaneous coronary intervention pathway. Reduced eGFR continues to be associated with worse outcomes after AMI.

Mixed-methods research in nephrology.

Mixed-methods research involves the mixing of at least 1 qualitative and 1 quantitative method in the same research project or set of related projects. Combined use of qualitative and quantitative research methods in nephrology has increased over the last 10 years. In this review, we aim to advance the understanding of mixed-methods research within the kidney community. Qualitative and quantitative techniques provide different but noncompeting representations of what exists in the world; findings from qualitative research do not generalize to a large population, whereas those from quantitative research may not apply to individuals within the diverse and heterogeneous larger population. Mixed-methods research combines these complementary representations, allowing the strengths of each method to be combined and the strengths of 1 method to address the limitations of the other. Mixed-methods approaches can be used to: (i) gain a more complete understanding of a research problem, (ii) explain initial results from one method with results from another, (iii) generate instruments, for example, survey tools and interventions, (iv) evaluate services, and (v) optimize clinical trial design and delivery. There are 3 core mixed-methods designs: explanatory sequential, exploratory sequential, and convergent parallel, which can be combined. We discuss each design in turn before discussing analysis and integration of findings from the different methods. We provide case studies that illustrate the application of these study designs to kidney research questions. We briefly discuss mixed-methods systematic reviews and evidence synthesis before finally highlighting guidance on how to appraise published mixed-methods research.

Using datasets to ascertain the generalizability of clinical cohorts: the example of the European QUALity study on the treatment of advanced chronic kidney disease.

BACKGROUND: Cohort studies are among the most robust of observational studies but have issues with external validity. This study assesses threats to external validity (generalizability) in the European QUALity (EQUAL) study, a cohort study of people >65 years of age with Stage 4/5 chronic kidney disease. METHODS: Patients meeting the EQUAL inclusion criteria were identified in The Health Improvement Network database and stratified into those attending renal units, a secondary care cohort (SCC) and a not primary care cohort (PCC). Survival, progression to renal replacement therapy (RRT) and hospitalization were compared. RESULTS: The analysis included 250, 633 and 2464 patients in EQUAL, PCC and SCC. EQUAL had a higher proportion of men compared with PCC and SCC (60.0% versus 34.8% versus 51.4%). Increasing age ≥85 years {odds ratio [OR] 0.25 [95% confidence interval (CI) 0.15-0.40]} and comorbidity [Charlson Comorbidity Index ≥4, OR 0.69 (95% CI 0.52-0.91)] were associated with non-participation in EQUAL. EQUAL had a higher proportion of patients starting RRT at 1 year compared with SCC (8.1% versus 2.1%; P < 0.001). Patients in the PCC and SCC had increased risk of hospitalization [incidence rate ratio 1.76 (95% CI 1.27-2.47) and 2.13 (95% CI 1.59-2.86)] and mortality at 1 year [hazard ratio 3.48 (95% CI 2.1-5.7) and 1.7 (95% CI 1.1-2.7)] compared with EQUAL. CONCLUSIONS: This study provides evidence of how participants in a cohort study can differ from the broader population of patients, which is essential when considering external validity and application to local practice.

Converting from face-to-face to postal follow-up and its effects on participant retention, response rates and errors: lessons from the EQUAL study in the UK.

BACKGROUND: Prospective cohort studies are challenging to deliver, with one of the main difficulties lying in retention of participants. The need to socially distance during the COVID-19 pandemic has added to this challenge. The pre-COVID-19 adaptation of the European Quality (EQUAL) study in the UK to a remote form of follow-up for efficiency provides lessons for those who are considering changing their study design. METHODS: The EQUAL study is an international prospective cohort study of patients ≥65 years of age with advanced chronic kidney disease. Initially, patients were invited to complete a questionnaire (SF-36, Dialysis Symptom Index and Renal Treatment Satisfaction Questionnaire) at research clinics every 3-6 months, known as "traditional follow-up" (TFU). In 2018, all living patients were invited to switch to "efficient follow-up" (EFU), which used an abbreviated questionnaire consisting of SF-12 and Dialysis Symptom Index. These were administered centrally by post. Response rates were calculated using returned questionnaires as a proportion of surviving invitees, and error rates presented as the average percentage of unanswered questions or unclear answers, of total questions in returned questionnaires. Response and error rates were calculated 6-monthly in TFU to allow comparisons with EFU. RESULTS: Of the 504 patients initially recruited, 236 were still alive at the time of conversion to EFU; 111 of these (47%) consented to the change in follow-up. In those who consented, median TFU was 34 months, ranging from 0 to 42 months. Their response rates fell steadily from 88% (98/111) at month 0 of TFU, to 20% (3/15) at month 42. The response rate for the first EFU questionnaire was 60% (59/99) of those alive from TFU. With this improvement in response rates, the first EFU also lowered errors to baseline levels seen in early follow-up, after having almost trebled throughout traditional follow-up. CONCLUSIONS: Overall, this study demonstrates that administration of shorter follow-up questionnaires by post rather than in person does not negatively impact patient response or error rates. These results may be reassuring for researchers who are trying to limit face-to-face contact with patients during the COVID-19 pandemic.

Patient-Reported Outcomes as Endpoints in Clinical Trials of Kidney Transplantation Interventions.

Patient-reported outcomes (PROs) that assess individuals' perceptions of life participation, medication adherence, disease symptoms, and therapy side effects are extremely relevant in the context of kidney transplantation. All PROs are potentially suitable as primary or secondary endpoints in interventional trials that aim to improve outcomes for transplant recipients. Using PRO measures (PROMs) in clinical trials facilitates assessment of the patient's perspective of their health, but few measures have been developed and evaluated in kidney transplant recipients; robust methodologies, which use validated instruments and established frameworks for reporting, are essential. Establishing a core PROM for life participation in kidney transplant recipients is a critically important need, which is being developed and validated by the Standardized Outcomes in Nephrology (SONG)-Tx Initiative. Measures involving electronic medication packaging and smart technologies are gaining traction for monitoring adherence, and could provide more robust information than questionnaires, interviews, and scales. This article summarizes information on PROs and PROMs that was included in a Broad Scientific Advice request on clinical trial design and endpoints in kidney transplantation. This request was submitted to the European Medicines Agency (EMA) by the European Society for Organ Transplantation in 2016. Following modifications, the EMA provided its recommendations in late 2020.

Expectations of a new opt-out system of consent for deceased organ donation in England: A qualitative interview study.

INTRODUCTION: In 2020 England moved to an opt-out deceased donation law. We aimed to investigate the views of a mixed stakeholder group comprising people with kidney disease, family members and healthcare practitioners towards the change in legislation. We investigated the expected impacts of the new legislation on deceased-donor and living-donor transplantation, and views on media campaigns regarding the law change. METHODS: We undertook in-depth qualitative interviews with people with kidney disease (n = 13), their family members (n = 4) and healthcare practitioners (n = 15). Purposive sampling was used to ensure diversity for patients and healthcare practitioners. Family members were recruited through snowball sampling and posters. Interviews were audio-recorded and transcribed verbatim. Transcripts were analysed using thematic analysis. RESULTS: Three themes with six subthemes were identified: (i) Expectations of impact (Hopeful patients; Cautious healthcare professionals), (ii) Living-donor transplantation (Divergent views; Unchanged clinical recommendations), (iii) Media campaigns (Single message; Highlighting recipient benefits). Patients expected the law change would result in more deceased-donor transplant opportunities. CONCLUSIONS: Clinicians should ensure patients and families are aware of the current evidence regarding the impact of opt-out consent: expectations of an increased likelihood of receiving a deceased-donor transplant are not currently supported by the evidence. This may help to prevent a decline in living-donor transplantation seen in other countries with similar legislation. Media campaigns should include a focus on the impact of organ receipt. PATIENT OR PUBLIC CONTRIBUTION: Two patient representatives from the Kidney Disease Health Integration Team, Primrose Granville and Soumeya Bouacida, contributed to the content and design of the study documents.

Patient-Reported Measures and Lifestyle Are Associated With Deterioration in Nutritional Status in CKD Stage 4-5: The EQUAL Cohort Study.

OBJECTIVE: The aim of this study was to explore the changes in nutritional status before dialysis initiation and to identify modifiable risk factors of nutritional status decline in older adults with advanced renal disease. DESIGN AND METHODS: The European Quality Study on treatment in advanced chronic kidney disease (EQUAL) is a prospective, observational cohort study involving six European countries. We included 1,103 adults >65 years with incident estimated glomerular filtration rate <20 mL/min/1.73 m2 not on dialysis, attending nephrology care. Nutritional status was assessed with the 7-point Subjective Global Assessment tool (7-p SGA), patient-reported outcomes with RAND-36 and the Dialysis Symptom Index. Logistic regression was used to estimate the associations between potential risk factors and SGA decline. RESULTS: The majority of the patients had a normal nutritional status at baseline, 28% were moderately malnourished (SGA ≤5). Overall, mean SGA decreased by -0.18 points/year, (95% confidence interval -0.21; -0.14). More than one-third of the study participants (34.9%) deteriorated in nutritional status (1 point decline in SGA) and 10.9% had a severe decline in SGA (≥2 points). The proportion of patients with low SGA (≤5) increased every 6 months. Those who dropped in SGA also declined in estimated glomerular filtration rate and mental health score. Every 10 points decrease in physical function score increased the odds of decline in SGA by 23%. Lower physical function score at baseline, gastrointestinal symptoms, and smoking were risk factors for impaired nutritional status. There was an interaction between diabetes and physical function on SGA decline. CONCLUSIONS: Nutritional status deteriorated in more than one-third of the study participants during the first year of follow-up. Lower patient-reported physical function, more gastrointestinal symptoms, and current smoking were associated with decline in nutritional status.