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Purpose of review: International definitions exist for chronic kidney disease (CKD) progression and kidney failure but despite evidence that kidney function may improve, there are no agreed definitions for regression and remission of CKD. In the light of recent novel kidney protective therapies and the promise of regenerative medicine to reverse kidney damage, it is time to critically examine these neglected aspects of CKD epidemiology.Recent findings: We propose that CKD regression is viewed as a process of improvement defined as a sustained increase in glomerular filtration rate (GFR) by ?25% and an improvement in GFR category or increase in GFR of 1?ml/min/year, whereas remission is considered a category of improvement defined as GFR ?60 ml/min/1.73m2 and urine albumin to creatinine ratio

Background/Aims: People receiving in-centre haemodialysis (ICHD) during the COVID-19 pandemic had to adjust to more challenging treatment conditions. This article aims to explore people's experiences of adjustment to ICHD during the pandemic. Methods: Thematic analysis of in-depth, semi-structured interviews with 14 adult UK ICHD patients. Findings: A total of four themes were identified: perceptions of the threat, impacts on treatment, impaired communication and coping and positive adjustment. These themes described participants' experiences of vulnerability to COVID-19; the ways the pandemic affected dialysis and clinical care; the impact that measures to reduce viral transmission had on communication and interaction within dialysis units; and ways that participants coped and made positive adjustments to the adversities imposed by the pandemic. Conclusions: The findings give insights into adjustment during extreme adversity. They also help to identify how support for ICHD patients could be improved as pandemic conditions recede and ways that dialysis units could prepare for future outbreaks of infectious illness.

Background: Many people with end-stage chronic kidney disease continued attending clinical centres for dialysis despite the risk of contracting COVID-19 and developing severe disease. Aims: To assess the impact of COVID-19 on patients' adjustment and wellbeing. Methods: Some 40 people (18 female, 22 male) receiving in-centre haemodialysis reported COVID-19-related adverse impacts on treatment and rated their COVID-19-related concerns, then completed the Depression, Anxiety and Stress Scale-21 and four scales of the Kidney Disease Quality of Life Short Form. Findings: The most common adverse impacts were staff shortages/changes and impaired interaction with staff/patients. Of the sample, 32.4% were severely depressed, 14.7% severely anxious and 18.9% severely stressed. Participants who had tested positive for COVID-19 were more depressed and reported more adverse impacts. Older and married/cohabiting participants had better adjustment and wellbeing. Conclusions: The results help to identify patients with the greatest needs and suggest ways to maintain patient wellbeing during outbreaks of infectious disease.

BackgroundDecline in kidney function can result in adverse health outcomes. The Oxford Renal Cohort Study has detailed baseline assessments from 884 participants ≥60 years of age.AimTo determine the proportion of participants with a decline in estimated glomerular filtration rate (eGFR), identify determinants of decline, and determine proportions with chronic kidney disease (CKD) remission.Design and settingObservational cohort study in UK primary care.MethodData were used from baseline and annual follow-up assessments to monitor change in kidney function. Rapid eGFR decline was defined as eGFR decrease >5 ml/min/1.73 m2/year, improvement as eGFR increase >5 ml/min/1.73 m2/year, and remission in those with CKD at baseline and eGFR >60 ml/min/1.73 m2 during follow-up. Cox proportional hazard models were used to identify factors associated with eGFR decline.ResultsThere was a net decline in eGFR in the 884 participants over 5 years of follow-up. In 686 participants with >2 eGFR tests with a median follow-up of 2.1 years, 164 (24%) evidenced rapid GFR decline, 185 (27%) experienced eGFR improvement, and 82 of 394 (21%) meeting CKD stage 1–4 at baseline experienced remission. In the multivariable analysis, smoking status, higher systolic blood pressure, and being known to have CKD at cohort entry were associated with rapid GFR decline. Those with CKD stage 3 at baseline were less likely to exhibit GFR decline compared with normal kidney function.ConclusionThis study established that 24% of people evidenced rapid GFR decline whereas 21% evidenced remission of CKD. People at risk of rapid GFR decline may benefit from closer monitoring and appropriate treatment to minimise risks of adverse outcomes, although only a small proportion meet the National Institute for Health and Care Excellence criteria for referral to secondary care.

Cardiovascular events are the leading cause of death in chronic kidney disease. A recent analysis from the High-Sensitivity Troponin in the Evaluation of Patients With Suspected Acute Coronary Syndrome trial focused on results in those with reduced estimated glomerular filtration rate. This commentary discusses aspects of acute coronary syndrome diagnosis in this group and the differential approach to acute coronary syndrome management that was observed between those with normal and reduced kidney function.

Objective To develop and validate a prognostic model for LEF discontinuation with abnormal blood test results. Methods Data from the Clinical Practice Research Datalink Gold and Aurum were used for model development and external validation, respectively. Participants prescribed LEF between 1 January 2007 and 31 December 2019 were followed up from 6 months after the first general practitioner prescription to the earliest of date of outcome, death, 5 year follow-up or 31 December 2019. Candidate prognostic factors were ascertained using theory and data-driven approaches. Penalized Cox regression was performed to develop the risk equation, followed by internal validation using 500 bootstraps to correct for optimism. Multiple imputation was applied to handle missing data. Model performance was assessed in terms of calibration and discrimination. Results Data for 1487 and 2329 participants contributing 3140 and 5246 person-years follow-up were included in the development and validation cohorts, respectively. Thirteen candidate predictors were included in the model. Epilepsy and either cytopenia or elevated liver enzymes during the first 6 months of shared-care LEF prescription were strong predictors of drug discontinuation with a hazard ratio of 4.39 (95% CI 1.74, 11.06) and 3.06 (2.15, 4.35), respectively. The unadjusted and optimism-adjusted calibration slope in development data was 1.00 (95% CI 0.75, 1.25) and 0.72 (95% CI 0.47, 0.97), respectively. The calibration slope in validation data was 0.91 (95% CI 0.74, 1.07). The model showed prognostic separation with an optimism-adjusted Royston D statistic of 0.73 (95% CI 0.44, 1.02). Conclusion We have developed and externally validated an easy-to-use prognostic model that may be used to risk stratify monitoring for LEF toxicity and to make informed choices about risks when choosing treatments.

Introduction Whether clinically implementable exercise interventions in people receiving hemodialysis (HD) therapy improve health-related quality of life (HRQoL) remains unknown. The PrEscription of intraDialytic exercise to improve quAlity of Life (PEDAL) study evaluated the clinical benefit and cost-effectiveness of a 6-month intradialytic exercise program. Methods In a multicenter, single-blinded, randomized, controlled trial, people receiving HD were randomly assigned to (i) intradialytic exercise training (exercise intervention group [EX]) and (ii) usual care (control group [CON]). Primary outcome was change in Kidney Disease Quality of Life Short-Form Physical Component Summary (KDQOL-SF 1.3 PCS) from baseline to 6 months. Cost-effectiveness was determined using health economic analysis; physiological impairment was evaluated by peak oxygen uptake; and harms were recorded. Results We randomized 379 participants; 335 and 243 patients (EX n = 127; CON n = 116) completed baseline and 6-month assessments, respectively. Mean difference in change PCS from baseline to 6 months between EX and CON was 2.4 (95% confidence interval [CI]: −0.1 to 4.8) arbitrary units (P = 0.055); no improvements were observed in peak oxygen uptake or secondary outcome measures. Participants in the intervention group had poor compliance (47%) and poor adherence (18%) to the exercise prescription. Cost of delivering intervention ranged from US$598 to US$1092 per participant per year. The number of participants with harms was similar between EX (n = 69) and CON (n = 56). A primary limitation was the lack of an attention CON. Many patients also withdrew from the study or were too unwell to complete all physiological outcome assessments. Conclusions A 6-month intradialytic aerobic exercise program was not clinically beneficial in improving HRQoL as delivered to this cohort of deconditioned patients on HD., Graphical abstract

IntroductionThe quantitative measurement of circulating gut bacteria-derived metabolites has increased in recent years due to their associations with health and disease. While much of the previous attention has been placed on metabolites considered as deleterious to health, a shift to the investigation of short-chain fatty acids (SCFAs) as potential health promotors has been observed.ObjectivesTo develop a simple, high-throughput and quantitative assay to measure gut-derived SCFAs in clinically relevant biofluids using gas chromatography-mass spectrometry (GC–MS).MethodsA short (7.5 min) GC–MS assay was optimized for measurement of seven straight- and branched-chain SCFAs and their deuterated isotopes using a wax-based column for analysis without prior derivatization. The assay was validated using routine criteria to assess precision, accuracy, matrix effects, recovery, and extraction reproducibility. Assay applicability was tested in cohorts of healthy individuals and kidney disease patients.ResultsThe assay was demonstrated to be precise, accurate and reproducible with acceptable levels of matrix effect and analyte recovery. Lower limits of detection and quantitation were in the low ng/mL range. An investigation into different blood collection tube chemistries demonstrated that lithium heparin plasma and serum clotting activator tubes are recommended for use in future cross-study comparisons. Kidney disease patient analyses demonstrated variable differences across SCFAs when comparing hemodialysis to earlier stages of chronic kidney disease, demonstrating the suitability of the assay for translation to clinical analyses.ConclusionThe assay has been validated and identified as reliable for use in larger-scale studies for the analysis of SCFAs in human plasma and serum.

Health-related quality of life (HRQoL) is severely impaired in persons receiving dialysis. Malnutrition has been associated with some measures of poor HRQoL in cross-sectional analyses in dialysis populations, but no studies have assessed the impact of malnutrition and dietary intake on change in multiple measures of HRQoL over time. We investigated the most important determinants of poor HRQoL and the predictors of change in HRQoL over time using several measures of HRQoL. We enrolled 119 haemodialysis and thirty-one peritoneal dialysis patients in this prospective study. Nutritional assessments (Subjective Global Assessment (SGA), anthropometry and 24-h dietary recalls) and HRQoL questionnaires (Short Form-36 (SF-36) mental (MCS) and physical component scores (PCS) and European QoL-5 Dimensions (EQ5D) health state (HSS) and visual analogue scores (VAS)) were performed at baseline, 6 and 12 months. Mean age was 64 (14) years. Malnutrition was present in 37 % of the population. At baseline, malnutrition assessed by SGA was the only factor independently (and negatively) associated with all four measures of HRQoL. No single factor was independently associated with decrease in all measures of HRQoL over 1 year. However, prevalence/development of malnutrition over 1 year was an independent predictor of 1-year decrease in EQ5D HSS, and 1-year decrease in fat intake independently predicted the 1-year decline in SF-36 MCS and PCS, and EQ5D VAS. These findings strengthen the importance of monitoring for malnutrition and providing nutritional advice to all persons on dialysis. Future studies are needed to evaluate the impact of nutritional interventions on HRQoL and other long-term outcomes.

Objective Advanced glycation end-products (AGEs) are uremic toxins that result from oxidative stress and food consumption. It has been reported that markers of malnutrition are more important determinants of increased skin autofluorescence (SAF), a measure of AGE accumulation and risk factor for mortality, than high dietary AGE intake in a hemodialysis (HD) population, suggesting that correcting malnutrition may decrease SAF. Design and methods We investigated this hypothesis in a single-center, nonrandomized proof-of-principle study. We enrolled 27 patients on HD and one on peritoneal dialysis with malnutrition who received individualized nutritional advice and support over 6 months. SAF was measured at baseline, 3 months, and 6 months. Dietary intake and nutritional status were assessed at baseline and 6 months. Results were compared with a control group of malnourished patients on dialysis (n = 41 HD and 8 peritoneal dialysis) from a previous observational study. Results The intervention group showed a significant increase in dietary intake, including AGEs, Subjective Global Assessment score, and serum albumin, while SAF levels remained stable for over 6 months (3.8 ± 0.7 arbitrary units [AU] vs. 3.7 ± 0.7 AU; P = .3). Conversely, in the control group, SAF increased significantly during the observation period (3.5 ± 0.9 AU vs. 3.8 ± 1.2 AU; P = .03) during which there was no improvement in nutritional intake and other markers of nutrition, although dietary AGE intake and Subjective Global Assessment score did increase. Conclusion Dietetic support was associated with stable SAF levels in this proof-of-principal study despite an increase in dietary AGE intake, suggesting that interventions to improve nutrition may be important in preventing the rise in SAF observed in malnourished dialysis populations. Further long-term studies are needed to test this hypothesis and evaluate the impact on survival.

Purpose of review: Malnutrition is a frequent complication and risk factor for adverse outcomes in the dialysis population that is often underrecognized and neglected. This article reviews published literature on the associations between malnutrition, mortality, quality of life and hospitalisations in persons on dialysis in order to raise awareness of the importance of preventing and treating it. Recent findings: All methods of nutritional assessment namely serum biochemistry, body composition, dietary intake, handgrip strength and nutritional scoring tools are independently associated with increased mortality in dialysis populations. Malnutrition severely affects physical and mental measures of quality of life and increases the number and length of hospitalisations in persons receiving dialysis, resulting in increased healthcare costs. Worsening of nutritional status is also associated with poor survival and higher rates of hospitalisations in this patient population. Summary: Malnutrition is an unacceptably common complication in dialysis patients that is substantially associated with adverse outcomes and higher hospital costs. Further interventional studies assessing the impact of preventing and treating malnutrition on clinical outcomes are warranted and should be considered a priority.

Background Exercise interventions designed to improve physical function and reduce sedentary behaviour in haemodialysis (HD) patients might improve exercise capacity, reduce fatigue and lead to improved quality of life (QOL). The PrEscription of intraDialytic exercise to improve quAlity of Life study aimed to evaluate the effectiveness of a 6-month intradialytic exercise programme on QOL and physical function, compared with usual care for patients on HD in the UK. Methods We conducted a prospective, pragmatic multicentre randomized controlled trial in 335 HD patients and randomly (1:1) assigned them to either (i) intradialytic exercise training plus usual care maintenance HD or (ii) usual care maintenance HD. The primary outcome of the study was the change in Kidney Disease Quality of Life Short Form (KDQOL-SF 1.3) Physical Component Score between baseline and 6 months. Additional secondary outcomes included changes in peak aerobic capacity, physical fitness, habitual physical activity levels and falls (International Physical Activity Questionnaire, Duke’s Activity Status Index and Tinetti Falls Efficacy Scale), QOL and symptom burden assessments (EQ5D), arterial stiffness (pulse wave velocity), anthropometric measures, resting blood pressure, clinical chemistry, safety and harms associated with the intervention, hospitalizations and cost-effectiveness. A nested qualitative study investigated the experience and acceptability of the intervention for both participants and members of the renal health care team. Results At baseline assessment, 62.4% of the randomized cohort were male, the median age was 59.3 years and 50.4% were white. Prior cerebrovascular events and myocardial infarction were present in 8 and 12% of the cohort, respectively, 77.9% of patients had hypertension and 39.4% had diabetes. Baseline clinical characteristics and laboratory data for the randomized cohort were generally concordant with data from the UK Renal Registry. Conclusion The results from this study will address a significant knowledge gap in the prescription of exercise interventions for patients receiving maintenance HD therapy and inform the development of intradialytic exercise programmes both nationally and internationally. Trial Registration ISRCTN N83508514; registered on 17 December 2014.

Data from three completed cardiovascular outcome trials (CVOTs), EMPA-REG OUTCOME, CANVAS Program and DECLARE-TIMI 58, add to the evidence supporting the potential renoprotective effects of sodium-glucose linked transporter-2 (SGLT2) inhibitors in patients with type 2 diabetes. Despite recommendations in recent guidelines, it is difficult to support a view that definitive evidence for renoprotection exists from these SGLT2 inhibitor CVOT results. To date, the only dedicated trial to report definitive data on the renal impact of SGLT2 inhibition is CREDENCE. Notably, the total number of patient-relevant renal endpoint events (dialysis, transplant or renal death) observed in CREDENCE was significantly higher than the total for all three CVOTs collectively (183 events/4401 patients vs. 69 events/34 322 patients, respectively), which shows the increased statistical power of CREDENCE for these renal endpoints. Treatment with canagliflozin was associated with a 30% relative risk reduction (RRR) in the primary composite endpoint of end-stage kidney disease, doubling of serum creatinine, or death from renal or cardiovascular causes and a 34% RRR for the renal-specific elements of this primary endpoint (P

Objective The aim was to examine the incidence and pattern of MMF discontinuation associated with abnormal monitoring blood-test results. Methods Data from people prescribed MMF for common inflammatory conditions in the Clinical Practice Research Datalink were used. Participants were followed from the first MMF prescription. The primary outcome was drug discontinuation with an associated abnormal blood-test result within 60 days. Secondary outcomes were drug discontinuation for any reason and discontinuation associated with severely abnormal blood-test results within 60 days. Multivariable Cox regression was used to examine factors associated with the primary outcome. Results The cohort included 992 participants (68.9% female, mean age 51.95 years, 47.1% with SLE) contributing 1885 person-years of follow-up. The incidence of MMF discontinuation associated with any (severely) abnormal blood-test results was 153.46 (21.07) per 1000 person-years in the first year of prescription and 32.39 (7.91) per 1000 person-years in later years. Of those patients prescribed MMF, 11.5% (1.7%) discontinued treatment with any (severely) abnormal blood-test results in the first year of prescription. After this period, a mean of 2.6% (0.7%) of patients discontinued treatment with any (severely) abnormal blood-test results per year. Increased serum creatinine and cytopenia were more commonly associated with MMF discontinuation than elevated liver enzymes. Chronic kidney disease stage 3 or higher was significantly associated with MMF discontinuation with any blood-test abnormalities [adjusted hazard ratio (95% CI) 2.22 (1.47, 3.37)]. Conclusion MMF is uncommonly discontinued for blood-test abnormalities and even less often discontinued for severe blood-test abnormalities after the first year of prescription. Consideration can be given to less frequent monitoring after 1 year of treatment, especially in those without chronic kidney disease stage 3 or higher.

Background Theory-based intervention materials must be carefully adapted to meet the needs of users with specific physical conditions. Acceptance and Commitment Therapy (ACT) has been adapted successfully for cancer, chronic pain, diabetes, irritable bowel syndrome, multiple sclerosis, and a range of other conditions, but not so far for people receiving renal haemodialysis. This paper presents findings from a study to adapt ACT-based intervention materials specifically for renal dialysis. Methods Draft written materials consisting of four stories depicting fictitious individuals who used ACT-related techniques to help overcome different challenges and difficulties related to dialysis were adapted using a systematic patient consultation process. The participants were 18 people aged 19–80 years, with chronic kidney disease and receiving renal dialysis. Individual, semi-structured interviews were conducted to elicit participants’ views about how the content of the draft materials should be adapted to make them more realistic and relevant for people receiving renal dialysis and about how the materials should be presented and delivered to people receiving renal dialysis. The interview transcripts were analysed using a qualitative adaptation of the Delphi method in which themes are used as a framework for translating feedback into proposals for modifications. Results The analysis of patient feedback supported the use of patient stories but suggested they should be presented by video and narrated by real dialysis patients. They also indicated specific adaptations to make the stories more credible and realistic. Participant feedback was translated into proposals for change that were considered along with clinical, ethical and theoretical factors. The outcome was a design for a video-based intervention that separated the stories about individuals from the explanations of the specific ACT techniques and provided greater structure, with material organised into smaller chunks. This intervention is adapted specifically for people receiving renal dialysis while retaining the distinctive theoretical principles of ACT. Conclusions The study shows the value of consulting patients in the development of intervention materials and illustrates a process for integrating patient feedback with theoretical, clinical and practical considerations in intervention design.

Contains fulltext : 215593.pdf (Publisher’s version ) (Closed access) Although blood pressure control is a major goal in chronic kidney disease, no worldwide overview of either its achievement or antihypertensive prescriptions is currently available. To evaluate this we compared crude prevalence of uncontrolled blood pressure among 17 cohort studies, including 34 602 individuals with estimated glomerular filtration rate under 60 ml/min/1.73 m(2) and treated hypertension across four continents, and estimated observed to expected prevalence ratios, adjusted for potential confounders. Crude prevalence of blood pressure of 140/90 mm Hg or more varied from 28% to 61% and of blood pressure of 130/80 or more from 54% to 84%. Adjusted prevalence ratios indicated poorer hypertension control than expected in cohorts from European countries, India, and Uruguay, and better control in patients from North American and high-income Asian countries. Four antihypertensive drug classes or more were prescribed to more than 30% of participants in North American and some European cohorts, but this practice was less common elsewhere. Renin angiotensin-aldosterone system inhibitors were the most common antihypertensive drugs, prescribed for 54% to 91% of cohort participants. Differences for other drug classes were much stronger, ranging from 11% to 79% for diuretics, 22% to 70% for beta-blockers, and 27% to 75% for calcium-channel blockers. The confounders studied explain only a part of the international variation in blood pressure control among individuals with chronic kidney disease. Thus, considerable heterogeneity in prescription patterns worldwide calls for further investigation into the impact of different approaches on patient outcomes.

Item does not contain fulltext Current criteria for the diagnosis of CKD in adults include persistent signs of kidney damage, such as increased urine albumin-to-creatinine ratio or a GFR below the threshold of 60 ml/min per 1.73 m(2) This threshold has important caveats because it does not separate kidney disease from kidney aging, and therefore does not hold for all ages. In an extensive review of the literature, we found that GFR declines with healthy aging without any overt signs of compensation (such as elevated single-nephron GFR) or kidney damage. Older living kidney donors, who are carefully selected based on good health, have a lower predonation GFR compared with younger donors. Furthermore, the results from the large meta-analyses conducted by the CKD Prognosis Consortium and from numerous other studies indicate that the GFR threshold above which the risk of mortality is increased is not consistent across all ages. Among younger persons, mortality is increased at GFR

Peritoneal ultrafiltration (PuF) has been employed for severe heart failure (HF), but evidence for its benefit is lacking. The Peritoneal Dialysis for Heart Failure (PDHF) study was a multicenter prospective randomized controlled trial which aimed to investigate this issue. The trial stopped early due to inadequate recruitment. We describe methods, trial activity, and lessons learned. The trial aimed to recruit 130 participants with severe diuretic-resistant HF (New York Heart Association [NYHA] 3/4) and chronic kidney disease (CKD) stage 3/4 on optimal medical treatment for ≥ 4 weeks from 6 UK centers. Participants were randomized to either continuation of conventional HF treatment or to additionally receiving PuF (1 overnight exchange using Icodextrin dialysate). Primary outcome was change in 6-minute walk test (6MWT) between baseline and 28 weeks (end of trial). Secondary outcomes were changes in patient reported quality of life as assessed by the Kansas City Cardiomyopathy Questionnaire, short form 36 (SF 36) health survey results, hospitalization, and mortality. Over a 2-year period, 290 patients were screened from which only 20 met inclusion criteria and 10 were recruited. Reasons for ineligibility were fluctuating estimated glomerular filtration rate (eGFR), suboptimal HF treatment, frailty, and patients being too unwell for randomization. Barriers to recruitment included patient frailty, with some participants considered only when they were at end of life, unwillingness to engage in an invasive therapy, and suboptimal coordination between cardiology and renal services. This is a challenging patient group in which to perform research, and lessons learned from the peritoneal dialysis (PD)-HF trial will be helpful in the planning of future studies in this area.

Background Multi-parametric magnetic resonance imaging (MRI) provides the potential for a more comprehensive non-invasive assessment of organ structure and function than individual MRI measures, but has not previously been comprehensively evaluated in chronic kidney disease (CKD). Methods We performed multi-parametric renal MRI in persons with CKD (n = 22, 61 ± 24 years) who had a renal biopsy and measured glomerular filtration rate (mGFR), and matched healthy volunteers (HV) (n = 22, 61 ± 25 years). Longitudinal relaxation time (T1), diffusion-weighted imaging, renal blood flow (phase contrast MRI), cortical perfusion (arterial spin labelling) and blood-oxygen-level-dependent relaxation rate (R2*) were evaluated. Results MRI evidenced excellent reproducibility in CKD (coefficient of variation Conclusion Comprehensive multi-parametric MRI is reproducible and correlates well with available measures of renal function and pathology. Larger longitudinal studies are warranted to evaluate its potential to stratify prognosis and response to therapy in CKD.

Objective: Advanced glycation end-products (AGEs) are uremic toxins that result from hyperglycemia, oxidative stress and systemic inflammation. AGEs are also formed in food during cooking. On the other hand, malnutrition may contribute to AGE formation through its association with oxidative stress and inflammation. AGE accumulation can be measured by skin autofluorescence (SAF) and elevated SAF is independently associated with higher mortality on hemodialysis (HD). We aimed to investigate associations between SAF, dietary AGE intake and markers of malnutrition in persons receiving HD. Design and setting: single center cross-sectional study. Subjects: 120 participants on HD dialyzing at least three times per week for 3-4 hours. Main outcome measures: SAF was measured using an Autofluorescence Reader. Dietary AGE, energy, protein and fat intake, handgrip strength (HGS), anthropometric measurements and biochemistry were also assessed. Subjective Global Assessment was performed to evaluate nutritional status. Results: SAF was higher in malnourished participants and correlated negatively with serum albumin and cholesterol, HGS and energy, protein and fat intake and positively with C reactive protein and chronological age; SAF did not correlate with dietary AGE intake. Multivariable linear regression analysis showed that diabetes, smoking, serum albumin, HGS, protein intake and dialysis vintage were independent predictors of increased SAF. Conclusions: Markers of malnutrition were more important determinants of increased SAF than high dietary AGE intake in this HD population. Nutritional interventions aiming to reduce SAF by correcting malnutrition should therefore be investigated. The observed association between higher SAF and malnutrition may in part explain the previously reported association between higher SAF and mortality on HD.

INTRODUCTION End-stage kidney disease (ESKD) is characterised by several complications, leading to reduced functional ability and quality of life during transition to dialysis. This study aimed to establish the feasibility and effectiveness of a patient-centred programme of exercise, nutritional intervention and multidisciplinary education for persons approaching dialysis. METHODS Patients with eGFR

Background: Higher beat-to-beat blood pressure (BP) variation during haemodialysis (HD) has been shown to be associated with elevated cardiac damage markers and white matter ischaemic changes in the brain suggesting relevance to end-organ perfusion. We aimed to characterize individual patterns of BP variation and associated haemodynamic responses to HD. Methods: Fifty participants underwent continuous non-invasive haemodynamic monitoring during HD and BP variation were assessed using extrema point (EP) frequency analysis. Participants were divided into those with a greater proportion of low frequency (LF, n = 21) and high frequency (HF, n = 22) of BP variation. Clinical and haemodynamic data were compared between groups. Results: Median EP frequencies for mean arterial pressure (MAP) of mid-week HD sessions were 0.54 Hz (interquartile range 0.18) and correlated with dialysis vintage (r = 0.32, p = 0.039), NT pro-BNP levels (r = 0.32, p = 0.038), and average real variability (ARV) of systolic BP (r = 0.33, p = 0.029), ARV of diastolic BP (r = 0.46, p = 0.002), and ARV of MAP (r = 0.57, p < 0.001). In the LF group, MAP positively correlated with cardiac power index (CPI) in each hour of dialysis, but not with total peripheral resistance index (TPRI). In contrast, in the HF group, MAP correlated with TPRI in each hour of dialysis but only with CPI in the first hour. Conclusions: EP frequency analysis of continuous BP monitoring during dialysis allows assessment of BP variation and categorization of individuals into low- or high-frequency groups, which were characterized by different haemodynamic responses to dialysis. This may assist in improved individualization of dialysis therapy.

Objective: Intradialytic haemodynamic instability is a significant clinical problem, leading to end-organ ischaemia and contributing to morbidity and mortality in haemodialysis patients. Non-invasive continuous blood pressure monitoring is not currently part of routine practice but may aid detection and prevention of significant falls in blood pressure during dialysis. Brachial blood pressure is currently recorded intermittently during haemodialysis via a sphygmomanometer. Current methods of continuous non-invasive blood pressure monitoring tend to restrict movement, can be sensitive to external disturbances and patient movement, and can be uncomfortable for the wearer. Additionally, poor patient blood circulation can lead to unreliable measurements. In this feasibility study we performed an initial validation of a novel method and associated technology to continuously estimate blood pressure using pressure sensors in the extra-corporeal dialysis circuit, which does not require any direct contact with the person receiving dialysis treatment. Method: The paper describes the development of the measurement system and subsequent in vivo patient feasibility study with concurrent measurement validation by Finapres Nova physiological measurement device. Real-time physiological data is collected over the entire period of (typically 4-hour) dialysis treatment. Results: We identify a quasi-linear mathematical function to describe the relationship between arterial line pressure and brachial artery BP, which is confirmed in a patient study. The results from this observational study suggest that it is feasible to derive a continuous measurement of brachial pressure from continuous measurements of arterial and venous line pressures via an empirically based and updated mathematical model. Conclusion: The methodology presented requires no interfacing to proprietary dialysis machine systems, no sensors to be attached to the patient directly, and is robust to patient movement during treatment and also to the effects of the cyclical pressure waveforms induced by the hemodialysis peristaltic blood pump. This represents a key enabling factor to the development of a practical continuous blood pressure monitoring device for dialysis patients.

Chronic kidney disease (CKD) causes substantial global morbidity and increases cardiovascular and all-cause mortality. Unlike other chronic diseases with established strategies for screening, there has been no consensus on whether health systems and governments should prioritize early identification and intervention for CKD. Guidelines on evaluating and managing early CKD are available but have not been universally adopted in the absence of incentives or quality measures for prioritizing CKD care. The burden of CKD falls disproportionately upon persons with lower socioeconomic status, who have a higher prevalence of CKD, limited access to treatment, and poorer outcomes. Therefore, identifying and treating CKD at the earliest stages is an equity imperative. In 2019, Kidney Disease: Improving Global Outcomes (KDIGO) held a controversies conference entitled "Early Identification and Intervention in CKD." Participants identified strategies for screening, risk stratification, and treatment for early CKD and the key health system and economic factors for implementing these processes. A consensus emerged that CKD screening coupled with risk stratification and treatment should be implemented immediately for high-risk persons and that this should ideally occur in primary or community care settings with tailoring to the local context.

ObjectiveChronic kidney disease (CKD) is often a multimorbid condition and progression to more severe disease is commonly associated with increased management requirements, including lifestyle change, more medication and greater clinician involvement. This study explored patients’ and kidney care team’s perspectives of the nature and extent of this workload (treatment burden) and factors that support capacity (the ability to manage health) for older individuals with CKD.DesignQualitative semistructured interview and focus group study.Setting and participantsAdults (aged 60+) with predialysis CKD stages G3–5 (identified in two general practitioner surgeries and two renal clinics) and a multiprofessional secondary kidney care team in the UK.Results29 individuals and 10 kidney team members were recruited. Treatment burden themes were: (1) understanding CKD, its treatment and consequences, (2) adhering to treatments and management and (3) interacting with others (eg, clinicians) in the management of CKD. Capacity themes were: (1) personal attributes (eg, optimism, pragmatism), (2) support network (family/friends, service providers), (3) financial capacity, environment (eg, geographical distance to unit) and life responsibilities (eg, caring for others). Patients reported poor provision of CKD information and lack of choice in treatment, whereas kidney care team members discussed health literacy issues. Patients reported having to withdraw from social activities and loss of employment due to CKD, which further impacted their capacity.ConclusionImproved understanding of and measures to reduce the treatment burden (eg, clear information, simplified medication, joined up care, free parking) associated with CKD in individuals as well as assessment of their capacity and interventions to improve capacity (social care, psychological support) will likely improve patient experience and their engagement with kidney care services.

Biomarker discovery in the field of risk prediction in chronic kidney disease (CKD) embraces the prospect of improving our ability to risk stratify future adverse outcomes and thereby guide patient care in a new era of personalised medicine. However, many studies that report biomarkers predictive of CKD progression share a key methodological limitation: failure to characterise patients’ renal progression precisely. This weakens any observable association between a biomarker and an outcome poorly defined by a patient’s change in renal function over time. In this commentary, we discuss the need for a better approach in this research arena and describe a compelling strategy that has the advantage of offering robust and meaningful biomarker exploration relevant to CKD progression.

An amendment to this paper has been published and can be accessed via the original article.

Hemodialysis has saved many lives, albeit with significant residual mortality. Although poor outcomes may reflect advanced age and comorbid conditions, hemodialysis per se may harm patients, contributing to morbidity and perhaps mortality. Systemic circulatory “stress” resulting from hemodialysis treatment schedule may act as a disease modifier, resulting in a multiorgan injury superimposed on preexistent comorbidities. New functional intradialytic imaging (i.e., echocardiography, cardiac magnetic resonance imaging [MRI]) and kinetic of specific cardiac biomarkers (i.e., Troponin I) have clearly documented this additional source of end-organ damage. In this context, several factors resulting from patient-hemodialysis interaction and/or patient management have been identified. Intradialytic hypovolemia, hypotensive episodes, hypoxemia, solutes, and electrolyte fluxes as well as cardiac arrhythmias are among the contributing factors to systemic circulatory stress that are induced by hemodialysis. Additionally, these factors contribute to patients’ symptom burden, impair cognitive function, and finally have a negative impact on patients’ perception and quality of life. In this review, we summarize the adverse systemic effects of current intermittent hemodialysis therapy, their pathophysiologic consequences, review the evidence for interventions that are cardioprotective, and explore new approaches that may further reduce the systemic burden of hemodialysis. These include improved biocompatible materials, smart dialysis machines that automatically may control the fluxes of solutes and electrolytes, volume and hemodynamic control, health trackers, and potentially disruptive technologies facilitating a more personalized medicine approach.

Background Initial reports indicate a high incidence of acute kidney injury (AKI) in Coronavirus Disease 2019 (COVID-19), but more data are required to clarify if COVID-19 is an independent risk factor for AKI and how COVID-19–associated AKI may differ from AKI due to other causes. We therefore sought to study the relationship between COVID-19, AKI, and outcomes in a retrospective cohort of patients admitted to 2 acute hospitals in Derby, United Kingdom. Methods and findings We extracted electronic data from 4,759 hospitalised patients who were tested for COVID-19 between 5 March 2020 and 12 May 2020. The data were linked to electronic patient records and laboratory information management systems. The primary outcome was AKI, and secondary outcomes included in-hospital mortality, need for ventilatory support, intensive care unit (ICU) admission, and length of stay. As compared to the COVID-19–negative group (n = 3,374), COVID-19 patients (n = 1,161) were older (72.1 ± 16.1 versus 65.3 ± 20.4 years, p < 0.001), had a greater proportion of men (56.6% versus 44.9%, p < 0.001), greater proportion of Asian ethnicity (8.3% versus 4.0%, p < 0.001), and lower proportion of white ethnicity (75.5% versus 82.5%, p < 0.001). AKI developed in 304 (26.2%) COVID-19–positive patients (COVID-19 AKI) and 420 (12.4%) COVID-19–negative patients (AKI controls). COVID-19 patients aged 65 to 84 years (odds ratio [OR] 1.67, 95% confidence interval [CI] 1.11 to 2.50), needing mechanical ventilation (OR 8.74, 95% CI 5.27 to 14.77), having congestive cardiac failure (OR 1.72, 95% CI 1.18 to 2.50), chronic liver disease (OR 3.43, 95% CI 1.17 to 10.00), and chronic kidney disease (CKD) (OR 2.81, 95% CI 1.97 to 4.01) had higher odds for developing AKI. Mortality was higher in COVID-19 AKI versus COVID-19 patients without AKI (60.5% versus 27.4%, p < 0.001), and AKI was an independent predictor of mortality (OR 3.27, 95% CI 2.39 to 4.48). Compared with AKI controls, COVID-19 AKI was observed in a higher proportion of men (58.9% versus 51%, p = 0.04) and lower proportion with white ethnicity (74.7% versus 86.9%, p = 0.003); was more frequently associated with cerebrovascular disease (11.8% versus 6.0%, p = 0.006), chronic lung disease (28.0% versus 19.3%, p = 0.007), diabetes (24.7% versus 17.9%, p = 0.03), and CKD (34.2% versus 20.0%, p < 0.001); and was more likely to be hospital acquired (61.2% versus 46.4%, p < 0.001). Mortality was higher in the COVID-19 AKI as compared to the control AKI group (60.5% versus 27.6%, p < 0.001). In multivariable analysis, AKI patients aged 65 to 84 years, (OR 3.08, 95% CI 1.77 to 5.35) and ≥85 years of age (OR 3.54, 95% CI 1.87 to 6.70), peak AKI stage 2 (OR 1.74, 95% CI 1.05 to 2.90), AKI stage 3 (OR 2.01, 95% CI 1.13 to 3.57), and COVID-19 (OR 3.80, 95% CI 2.62 to 5.51) had higher odds of death. Limitations of the study include retrospective design, lack of urinalysis data, and low ethnic diversity of the region. Conclusions We observed a high incidence of AKI in patients with COVID-19 that was associated with a 3-fold higher odds of death than COVID-19 without AKI and a 4-fold higher odds of death than AKI due to other causes. These data indicate that patients with COVID-19 should be monitored for the development of AKI and measures taken to prevent this. Trial registration ClinicalTrials.gov NCT04407156, Author summary Why was this study done? Recent reports have suggested that some patients with Coronavirus Disease 2019 (COVID-19) develop acute kidney injury (AKI). There is a need to better understand risk factors for AKI in patients with COVID-19. It is also unclear if AKI in patients with COVID-19 differs from AKI due to other causes. What did the researchers do and find? In this study, we examined risk factors for AKI in patients with COVID-19 and also compared AKI in COVID-19 with AKI due to other causes. We found that males and patients of nonwhite ethnicity as well as those with comorbidities were at increased risk of developing AKI in COVID-19. AKI was associated with a 3-fold increase in mortality in COVID-19 patients. Patients with COVID-19 and AKI had higher mortality (60.5% versus 27.6%) than patients with AKI due to other causes, and COVID-19 was an independent predictor of mortality associated with an almost 4-fold odds of death. What do these findings mean? COVID-19 frequently causes AKI, and when it does, it is associated with a higher mortality than COVID-19 without AKI or AKI due to other causes. Patients with COVID-19 should be monitored for early evidence of AKI so that preventive measures can be taken to avoid AKI.

Kidney failure is an important outcome for patients, clinicians, researchers, healthcare systems, payers, and regulators. However, no harmonized international consensus definitions of kidney failure and key surrogates of progression to kidney failure exist specifically for clinical trials. The International Society of Nephrology convened an international multi-stakeholder meeting to develop consensus on this topic. A core group, experienced in design, conduct, and outcome adjudication of clinical trials, developed a database of 64 randomized trials and the 163 included definitions relevant to kidney failure. Using an iterative process, a set of proposed consensus definitions were developed and subsequently vetted by the larger multi-stakeholder group of 83 participants representing 18 different countries. The consensus of the meeting participants was that clinical trial kidney failure outcomes should be comprised of a composite that includes receipt of a kidney transplant, initiation of maintenance dialysis, and death from kidney failure; it may also include outcomes based solely on laboratory measurements of glomerular filtration rate: a sustained low glomerular filtration rate and a sustained percent decline in glomerular filtration rate. Discussion included important considerations, such as (i) recognition of existing nomenclature for kidney failure; (ii) applicability across resource settings; (iii) ease of understanding for all stakeholders; and (iv) avoidance of inappropriate complexity so that the definitions can be used across ranges of populations and trial methodologies. The final definitions reflect the consensus for use in clinical trials.