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Background: Non-traumatic lower extremity amputation (LEA) is a severe complication during dialysis. To inform decision-making for physicians, we developed a multivariable prediction model for LEA after starting dialysis., Methods: Data from the Swedish Renal Registry (SNR) between 2010 and 2020 were geographically split into a development and validation cohort. Data from Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD) between 1997 and 2009 were used for validation targeted at Dutch patients. Inclusion criteria were no previous LEA and kidney transplant and age ≥40 years at baseline. A Fine-Gray model was developed with LEA within 3 years after starting dialysis as the outcome of interest. Death and kidney transplant were treated as competing events. One coefficient, ordered by expected relevance, per 20 events was estimated. Performance was assessed with calibration and discrimination., Results: SNR was split into an urban development cohort with 4771 individuals experiencing 201 (4.8%) events and a rural validation cohort with 4.876 individuals experiencing 155 (3.2%) events. NECOSAD contained 1658 individuals experiencing 61 (3.7%) events. Ten predictors were included: female sex, age, diabetes mellitus, peripheral artery disease, cardiovascular disease, congestive heart failure, obesity, albumin, haemoglobin and diabetic retinopathy. In SNR, calibration intercept and slope were -0.003 and 0.912, respectively. The C-index was estimated as 0.813 (0.783-0.843). In NECOSAD, calibration intercept and slope were 0.001 and 1.142 respectively. The C-index was estimated as 0.760 (0.697-0.824). Calibration plots showed good calibration., Conclusion: A newly developed model to predict LEA after starting dialysis showed good discriminatory performance and calibration. By identifying high-risk individuals this model could help select patients for preventive measures., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Objective: Dietary restrictions are common in patients undergoing hemodialysis (HD). These restrictions result in a complex diet that becomes difficult for patients to understand and to follow. Therefore, we aimed to identify dietary needs, barriers, and facilitators that influence the adherence to dietary recommendations as perceived by patients on HD and their caregivers., Methods: Seventy-two Spanish patients on HD and 57 caregivers participated in this explorative study by replying a questionnaire consisting of 20 and 10 questions respectively. The responses were assessed using a Likert scale varying from 1 to 5 (strongly agree, agree, neither disagree or disagree, disagree, strongly disagree, respectively) to evaluate the perception of patients and caregivers regarding dietary needs, barriers, and facilitators to adhere to the recommended diet. For analysis purposes, the responses were grouped in 3 categories (agree, neither agree or disagree, disagree)., Results: Seventy percent of the patients agreed that knowing the food sources of potassium, protein and phosphate was a need for them to know to be able to adhere to the dietary recommendations. Moreover, patients stated that not being able to eat what they liked, and feeling thirsty, were important barriers. For caregivers, the support of a renal dietitian was mentioned as an important facilitator to assist those they cared for to adhere to the diet., Conclusions: Knowing food sources of potassium, phosphate, and protein, exploring foods patients like to eat and adjusting fluid intake to avoid feeling thirsty were identified as important by the patients. These findings can be used to develop strategies and educational material to improve the dietary adherence in patients undergoing HD. Moreover, the presence of a renal dietitian was identified as an important resource by the caregivers., (Copyright © 2024 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Mineral bone disease (MBD) is common in dialysis patients. Genetics and the hormonal environment influence the clinical picture and outcomes of women. This study aimed to determine how these factors affect mortality. In 234 female dialysis patients on Continuous Ambulatory (48%) or Automated (29%) Peritoneal Dialysis or Hemodialysis (23%), MBD biochemical variables, as well as bone density and genetic Bsm1 polymorphism of vitamin D receptor (VDR) were performed at baseline. The cohort was followed-up by 17 (IQ range 15-31) months. According to VDR polymorphism, the distribution of patients was bb: 64% and BB+Bb: 36%. Fifty-five patients died from all-cause mortality; the hs-C-reactive protein level was the most significant risk in multivariate Cox analysis. Nineteen died from cardiovascular mortality. None of the variables were significant for cardiovascular mortality. Patients with bb plus inflammation had the highest risk in the analysis; the significance persisted after adjustment for age, diabetes, and parathyroid hormone levels HR 2.33 (95% CI, 1.01-8.33) and after further adjustment for time on dialysis, albumin, and Osteoprotegerin levels HR 3.49 (95% CI, 1.20-10.9). The presence of the bb genotype from VDR and inflammation had the highest risk of death from all-cause mortality in females on CAPD, APD, and HD patient.

Objectives: Reduced handgrip strength (HGS) is associated with adverse clinical outcomes. We analyzed and compared associations of HGS with mortality risk in dialysis patients, using different normalization methods of HGS., Methods: HGS and clinical and laboratory parameters were measured in a cohort of 446 incident dialysis patients (median age 56 y, 62% men). The area under the receiver operating characteristic curve (AUROC) was used to compare different normalization methods of HGS as predictors of mortality: absolute HGS in kilograms; HGS normalized to height, weight, or body mass index; and HGS of a reference population of sex-matched controls (percentage of the mean HGS value [HGS%]). Multivariate linear regression analysis was used to assess HGS predictors. Competing risk regression analysis was used to evaluate 5-year all-cause mortality risk. Differences in survival time between HGS% tertiles were quantitated by analyzing the restricted mean survival time., Results: The AUROC for HGS% was higher than the AUROCs for absolute or normalized HGS values. Compared with the high HGS% tertile, low HGS% (subdistribution hazard ratio [sHR] = 2.36; 95% CI, 1.19-3.70) and middle HGS% (sHR = 1.79; 95% CI, 1.12-2.74) tertiles were independently associated with higher all-cause mortality and those with high HGS% tertile survived on average 7.95 mo (95% CI, 3.61-12.28) and 18.99 mo (95% CI, 14.42-23.57) longer compared with middle and low HGS% tertile, respectively., Conclusions: HGS% was a strong predictor of all-cause mortality risk in incident dialysis patients and a better discriminator of survival than absolute HGS or HGS normalized to body size dimensions., Competing Interests: Declaration of competing interest B. Lindholm reports financial support was provided by Baxter Healthcare Corporation and reports a relationship with Baxter Healthcare Corporation that includes employment, equity or stocks, funding grants, and travel reimbursement. P. Stenvinkel is or has been on scientific advisory boards of REATA, Baxter, GSK, AstraZeneca, Invizius, Behring, and Vifor and educational advisory boards for Astellas and FMC. The other authors do not declare any conflict of interest. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Plant-based diets (PBD) may induce hyperkalemia in chronic kidney disease (CKD) patients., Objectives: We explored the safety and feasibility of PBD in hyperkalemic CKD patients receiving the potassium binder sodium zirconium cyclosilicate (SZC)., Methods: In the current 6-wk trial, 26 hyperkalemic patients with CKD stage 4-5 not on dialysis received a low-protein low-potassium diet plus SZC for 3 wk and then a PBD with high potassium content delivered as a weekly food basket while continuing SZC for subsequent 3 wk. Plasma potassium was monitored weekly and SZC was titrated to achieve normokalemia. The 24-h urine excretion of potassium and sodium, 24-h food records, dietary quality, nutritional status, Bristol stool scale, Quality of life (QoL), and renal treatment satisfaction were assessed at baseline (week 0), week 3, and week 6., Results: Mean plasma potassium decreased from 5.5 to 4.4 mEq/L within 48-72 h after baseline, then rose to 4.7-5.0 mEq/L throughout the remaining study period following dose adjustments of SZC that matched the increased potassium intake of PBD from week 3 to week 6. Over the study period, 24-h urinary potassium excretion decreased from week 0 to week 3 and increased from week 3 to week 6. During the study, 58% of patients had fasting plasma potassium between 3.5 and 5.0 mEq/L and there was no episode of plasma potassium >6.5 mEq/L or <3.0 mEq/L during the study. P-carbon dioxide increased from baseline until week 6 (21 ± 2 to 23 ± 2 mEq/L; P = 0.002; mean ± SD), whereas remaining laboratory values remained unchanged. Fiber intake, dietary quality, the domain physical functioning from QoL, and 1 question of renal treatment satisfaction improved, whereas stool type and frequency did not change after starting PBD., Conclusions: PBD in hyperkalemia-prone CKD patients receiving SZC improved dietary quality and increased the intake of healthy foods, whereas plasma potassium concentration remained stable within normal values for most patients., Trial Registration Number: This trial was registered at the https://clinicaltrials.gov/study/NCT04207203 as NCT04207203., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Chronic kidney disease (CKD) poses a significant global health burden, with increasing prevalence and high morbidity and mortality rates, particularly in end-stage kidney disease (ESKD). While traditional risk factors contribute, the exact mechanisms remain elusive, with inflammation playing a pivotal role. Medium cutoff (MCO) membranes offer promise in improving dialysis outcomes by efficiently clearing uremic toxins without substantial albumin loss. We aimed to elucidate the impact of MCO and high-flux (HF) membranes on peripheral blood lymphocyte subpopulations in hemodialysis patients., Methods: Twenty-four ESKD patients underwent 36 sessions each with MCO and HF membranes. Immunophenotyping by flow cytometry was performed to analyze lymphocyte subsets., Results: NK cell percentages significantly increased with MCO, returning to baseline with HF. Th1 cells decreased post-HF, while Th2 and Tfh cells increased with MCO and persisted. Treg cells remained stable with MCO but decreased with HF., Conclusion: MCO dialysis induced an anti-inflammatory shift, evidenced by increased Th2 and Tfh cells and stable Treg cells. NK cells also responded favorably to MCO. These findings underscore MCO membranes' potential to modulate immune responses and improve patient outcomes in ESKD., (© 2024 S. Karger AG, Basel.)

Gait Speed Reserve (GSR) expresses a difference between fast and comfortable gait speed and may have an impact on everyday functioning. It was also hypothesized as a useful proxy measure of physiological reserve. However, height-normalizing values of GSR and its associated factors have not been evaluated in a general population of older adults. Therefore, we aimed to investigate the distribution of height-normalized GSR (HN-GSR) in an elderly population-based cohort from urban and rural areas (n = 4342) aged 60-93 years and evaluate associated physiological and lifestyle factors. Using linear mixed models, we identified gender and nine modifiable factors as significantly associated with HN-GSR across four age groups. Better handgrip strength, cognition and standing balance, higher physical activity level, larger calf circumference, and less smoking had positive associations with HN-GSR, while female gender, more leg pain, higher weight and, alcohol consumption had opposite effects. The Marginal R2 imply that this model explained 26% of the variance in HN-GSR. Physical activity and handgrip strength varied across age groups in impact on HN-GSR. The differences were however comparatively minor. In this large cohort study of older adults, we proposed for the first time that factors associated with HN-GSR represented multi-domain features that are in line with previous findings reported for GSR. Measuring HN-GSR/GSR may help clinicians identify early physiological impairments or unhealthy lifestyle habits, especially among older women, and may also have safety implications in daily life. Further work is needed to find out if measuring HN-GSR/GSR may be useful in identifying adverse health outcomes and overall physiological reserve., (© 2024. The Author(s).)

Background and Hypothesis: Remote monitoring (RM) of patients on automated peritoneal dialysis (APD) prevent complications and improve treatment quality. We analyzed the effect of RM-APD on mortality and complications related to cardiovascular disease (VD), fluid overload and insufficient dialysis efficiency., Methods: In a cluster-randomized, open-label, controlled trial, 21 hospitals with APD programs were assigned to use either RM-APD (10 hospitals; 403 patients) or conventional APD (11 hospitals; 398 patients) for the treatment of adult patients starting PD. Primary outcomes were time to first event of: 1) Composite Index-1 comprising all-cause mortality, first adverse events and hospitalizations of any cause, and 2) Composite Index-2 comprising cardiovascular mortality, first adverse event and hospitalizations related to CVD, fluid overload and insufficient dialysis efficiency. Secondary outcomes were time to first event of individual components of the two composite indices, and rates of adverse events, hospitalizations, unplanned visits, and transfer to hemodialysis. Patients were followed for a median of 9.5 months. Primary outcomes were evaluated by competing-risk analysis and restricted mean survival time (RMST) analysis., Results: While time to reach Composite Index-1 did not differ between the groups, Composite Index-2 was reached earlier (ΔRMST: -0.85 months; p=0.02), and all-cause mortality (55 vs. 33 deaths, p=0.01; sHR 1.69 (95%CI 1.39-2.05), p<0.001) and hospitalizations of any cause were higher in APD group than in RM-APD as were cardiovascular deaths (24 vs. 13 deaths, p=0.05; sHR 2.44 (95%CI 1.72 - 3.45), p<0.001) and rates of adverse events and hospitalizations related to CVD, fluid overload or insufficient dialysis efficiency. Dropouts were more common in the APD group (131 vs. 110, p=0.048)., Conclusions: This randomized controlled trial shows that remote monitoring may add significant advantages to APD, including improved survival and reduced rate of adverse events and hospitalizations, which can favorably impact the acceptance and adoption of the therapy., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Importance: Avoiding high protein intake in older adults with chronic kidney disease (CKD) may reduce the risk of kidney function decline, but whether it can be suboptimal for survival is not well known., Objective: To estimate the associations of total, animal, and plant protein intake with all-cause mortality in older adults with mild or moderate CKD and compare the results to those of older persons without CKD., Design, Setting, and Participants: Data from 3 cohorts (Study on Cardiovascular Health, Nutrition and Frailty in Older Adults in Spain 1 and 2 and the Swedish National Study on Aging and Care in Kungsholmen [in Sweden]) composed of community-dwelling adults 60 years or older were used. Participants were recruited between March 2001 and June 2017 and followed up for mortality from December 2021 to January 2024. Those with no information on diet or mortality, with CKD stages 4 or 5, or undergoing kidney replacement therapy and kidney transplant recipients were excluded. Data were originally analyzed from June 2023 to February 2024 and reanalyzed in May 2024., Exposures: Cumulative protein intake, estimated via validated dietary histories and food frequency questionnaires., Main Outcomes and Measures: The study outcome was 10-year all-cause mortality, ascertained with national death registers. Chronic kidney disease was ascertained according to estimated glomerular filtration rates, urine albumin excretion, and diagnoses from medical records., Results: The study sample consisted of 8543 participants and 14 399 observations. Of the 4789 observations with CKD stages 1 to 3, 2726 (56.9%) corresponded to female sex, and mean (SD) age was 78.0 (7.2) years. During the follow-up period, 1468 deaths were recorded. Higher total protein intake was associated with lower mortality among participants with CKD; adjusted hazard ratio (HR) for 1.00 vs 0.80 g/kg/d was 0.88 (95% CI, 0.79-0.98); for 1.20 vs 0.80 g/kg/d, 0.79 (95% CI, 0.66-0.95); and for 1.40 vs 0.80 g/kg/d, 0.73 (95% CI, 0.57-0.92). Associations with mortality were comparable for plant and animal protein (HRs, 0.80 [95% CI, 0.65-0.98] and 0.88 [95% CI, 0.81-0.95] per 0.20-g/kg/d increment, respectively) and for total protein intake in participants younger than 75 years vs 75 years or older (HRs, 0.94 [95% CI, 0.85-1.04] and 0.91 [95% CI, 0.85-0.98] per 0.20-g/kg/d increment in total protein intake, respectively). However, the hazards were lower among participants without CKD than in those with CKD (HRs, 0.85 [95% CI, 0.79-0.92] and 0.92 [95% CI, 0.86-0.98] per 0.20-g/kg/d increment, respectively; P = .02 for interaction)., Conclusions and Relevance: In this multicohort study of older adults, higher intake of total, animal, and plant protein was associated with lower mortality in participants with CKD. Associations were stronger in those without CKD, suggesting that the benefits of proteins may outweigh the downsides in older adults with mild or moderate CKD.

Background: Due to the slower dissipation of the osmotic gradient, icodextrin-based solutions, compared to glucose-based solutions, can improve water removal. We investigated scenarios where one icodextrin-based long dwell (Extraneal) replaced two glucose-based exchanges., Methods: The three-pore model with icodextrin hydrolysis was used for numerical simulations of a single exchange to investigate the impact of different peritoneal dialysis schedules on fluid and solute removal in patients with different peritoneal solute transfer rates (PSTRs). We evaluated water removal (ultrafiltration, UF), absorbed mass of glucose (AbsGluc) and carbohydrates (AbsCHO, for glucose and glucose polymers), ultrafiltration efficiency (UFE = UF/AbsCHO) per exchange, and specified dwell time, and removed solute mass for sodium (ReNa), urea (ReU), and creatinine (ReCr) for a single peritoneal exchange with 7.5% icodextrin (Extraneal ® ) and glucose-based solutions (1.36% and 2.27%) and various dwell durations in patients with fast and average PSTRs., Results: Introducing 7.5% icodextrin for the long dwell to replace one of three or four glucose-based exchanges per day leads to increased fluid and solute removal and higher UF efficiency for studied transport groups. Replacing two glucose-based exchanges with one icodextrin exchange provides higher or similar water removal and higher daily sodium removal but slightly lower daily removal of urea and creatinine, irrespective of the transport type present in the case of reference prescription with three and four daily exchanges., Conclusion: One 7.5% icodextrin can replace two glucose solutions. Unlike glucose-based solutions, it resulted only in minor differences between PSTR groups in terms of water and solute removal with UFE remaining stable up to 16 h., Competing Interests: Authors JY and QY were employed by Baxter Healthcare Corporation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Stachowska-Pietka, Waniewski, Olszowska, Garcia-Lopez, Yan, Yao, Wankowicz and Lindholm.)

Objective: A suboptimal dialysis initiation with insufficient or no planning before urgent start of dialysis remains a common problem associated with increased morbimortality. Whether nutritional markers differ between patients starting peritoneal dialysis (PD) in unplanned and planned modes has not yet been explored. Therefore, we aimed to evaluate whether the nutritional status at the start of dialysis differed between patients with unplanned and planned PD initiation., Methods: In this observational study comprising 47 adult patients starting PD (age 58 ± 15 years, 51% female), 29 patients had unplanned (starting dialysis up to 72 hours after peritoneal catheter implantation) and 18 planned (follow-up predialysis >90 days) dialysis initiation. Within 30 days of PD initiation, nutritional status was evaluated using anthropometric measurements, multifrequency bioelectrical impedance analysis, appetite assessment, handgrip strength, laboratory markers, and the malnutrition-inflammation score. Physical activity and performance were also evaluated., Results: Patients with an unplanned PD initiation had a higher frequency of diabetes, higher blood glucose, urea, and glycated hemoglobin levels, and lower hemoglobin and albumin levels. Furthermore, they had a lower calf circumference, slower gait speed, higher protein intake, and greater malnutrition-inflammation score, while their physical activity level and appetite did not differ., Conclusion: Patients with an unplanned PD had unfavorable clinical and nutritional markers compared with those with planned PD. These findings indicate that a lack of follow-up prior to dialysis initiation can influence the clinical and nutritional statuses of patients, reinforcing the importance of conservative treatment prior to dialysis initiation., (Copyright © 2024 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: General and abdominal obesity are prevalent, with established associations to frailty in the elderly. However, few studies have investigated these associations in patients with chronic kidney disease (CKD), yielding inconsistent results., Methods: This cross-sectional study analysed data from the National Health and Nutrition Examination Survey (NHANES 2003-2018). Frailty was evaluated by the 36-item frailty index. General obesity was defined as a body mass index (BMI) >30 kg/m 2 ; abdominal obesity was identified if waist circumference (WC) reached 102 cm in men and 88 cm in women. The associations of general and abdominal obesity with frailty were analysed using weighted multivariate logistic regression and restricted cubic splines. The interaction of general and abdominal obesity with frailty was examined., Results: A total of 5604 adult patients (median age 71 years, 42% men) with CKD were included in this analysis, with a median estimated glomerular filtration rate of 57.3 ml/min/1.73 m 2 . A total of 21% were frail with general obesity and 32% were frail with abdominal obesity. Neither general nor abdominal obesity alone was associated with frailty. There was an interaction between general and abdominal obesity with frailty. Compared with individuals with normal BMI and WC, those with both general and abdominal obesity, rather than either alone, exhibited significantly increased odds of frailty {odds ratio [OR] 1.53 [95% confidence interval (CI) 1.20-1.95]}. General obesity was associated with being frail only when CKD patients had abdominal obesity [OR 1.59 (95% CI 1.08-2.36)]., Conclusions: There may be an interaction between general and abdominal obesity with frailty in patients with CKD. Interventions aimed at preventing frailty should consider both aspects., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

The paracrine signaling pathways for the crosstalk between pericytes and endothelial cells are essential for the coordination of cell responses to challenges such as hypoxia in both healthy individuals and pathological conditions. Ischemia-reperfusion injury (IRI), one of the causes of cellular dysfunction and death, is associated with increased expression of genes involved in cellular adaptation to a hypoxic environment. Hypoxic inducible factors (HIFs) have a central role in the response to processes initiated by IRI not only linked to erythropoietin production but also because of their participation in inflammation, angiogenesis, metabolic adaptation, and fibrosis. While pericytes have an essential physiological function in erythropoietin production, a lesser-known role of HIF stabilization during IRI is that pericytes' HIF expression could influence vascular remodeling, cell loss and organ fibrosis. Better knowledge of mechanisms that control functions and consequences of HIF stabilization in pericytes beyond erythropoietin production is advisable for the development of therapeutic strategies to influence disease progression and improve treatments. Thus, in this review, we discuss the dual roles-for good or bad-of HIF stabilization during IRI, focusing on pericytes, and consequences in particular for the kidneys.

Objectives: Remote patient monitoring (RPM) of patients treated with automated peritoneal dialysis (APD) at home allows clinicians to supervise and adjust the dialysis process remotely. This study aimed to review recent scientific studies on the use of RPM in patients treated with APD and based on extracted relevant data assess possible clinical implications and potential economic value of introducing such a system into practice in Poland., Methods: A systematic literature review was performed in the MEDLINE, EMBASE, and Cochrane databases. The model of clinical effects and costs associated with APD was built as a cost-effectiveness analysis with a 10-year time horizon from the Polish National Health Fund perspective. Cost-effectiveness analysis compared 2 strategies: APD with RPM versus APD without RPM., Results: Thirteen publications assessing the clinical value of RPM among patients with APD were found. The statistical significance of APD with RPM compared with APD without RPM was identified for the main clinical outcomes: frequency and length of hospitalizations, APD technique failure, and death. An incremental cost-effectiveness ratio was equal to €27 387 per quality-adjusted life-year. The obtained incremental cost-effectiveness ratio is below the willingness-to-pay threshold for the use of medical technologies in Poland (€36 510 per quality-adjusted life-year), which means that APD with RPM was a cost-effective technology., Conclusions: RPM in patients starting APD is a clinical option that is worth considering in Polish practice because it has the potential to decrease the frequency of APD technique failure and shorten the length of hospitalization., (Copyright © 2023 International Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Background: Malnutrition, sedentary lifestyle, cognitive dysfunction and poor psychological well-being are often reported in patients on haemodialysis (HD)., Aims: We aimed to explore needs, barriers and facilitators-as perceived by patients, their carers, and healthcare professionals (HCPs) for increasing the adherence to the diet, to physical activity and cognition and psychological well-being., Methods: This is an observational cross-sectional study following the STROBE statement. This study is part of an ERASMUS+ project, GoodRENal-aiming to develop digital tools as an educational approach to patients on HD. For that, the GoodRENal comprises HD centers located in four Belgium, Greece, Spain and Sweden. Exploratory questionnaires were developed regarding the perceived needs, barriers and facilitators regarding the diet, physical activity, cognition and psychological well-being from the perspective of patients, their carers and HCPs., Results: In total, 38 patients, 34 carers and 38 HCPs were included. Nutrition: For patients and carers, the main needs to adhere to the diet included learning more about nutrients and minerals. For patients, the main barrier was not being able to eat what they like. Physical activity: As needs it was reported information about type of appropriate physical activity, while fatigue was listed as the main barrier. For Cognitive and emotional state, it was perceived as positive for patients and carers perception but not for HCPs. The HCPs identified as needs working as a team, having access to specialised HCP and being able to talk to patients in private., Conclusions: Patients and their carers listed as needs guidance regarding nutrition and physical activity but were positive with their cognitive and emotional state. The HCPs corroborated these needs and emphasised the importance of teamwork and expert support., (© 2023 The Authors. Journal of Clinical Nursing published by John Wiley & Sons Ltd.)

Muscle wasting and low muscle mass are prominent features of protein energy wasting (PEW), sarcopenia and sarcopenic obesity in patients with chronic kidney disease (CKD). In addition, muscle wasting is associated with low muscle strength, impaired muscle function and adverse clinical outcomes such as low quality of life, hospitalizations and increased mortality. While assessment of muscle mass is well justified, the assessment of skeletal muscle should go beyond quantity. Imaging techniques provide the means for non-invasive, comprehensive, in-depth assessment of the quality of the muscle such as the infiltration of ectopic fat. These techniques include computed tomography (CT), magnetic resonance imaging (MRI) and ultrasound. Dual energy X-ray absorptiometry is also an imaging technique, but one that only provides quantitative and not qualitative data on muscle. The main advantage of imaging techniques compared with other methods such as bioelectrical impedance analysis and anthropometry is that they offer higher precision and accuracy. On the other hand, the higher cost for acquiring and maintaining the imaging equipment, especially CT and MRI, makes these less-used options and available mostly for research purposes. In the field of CKD and end-stage kidney disease (ESKD), imaging techniques are gaining attention for evaluating muscle quantity and more recently muscle fat infiltration. This review describes the potential of these techniques in CKD and ESKD settings for muscle assessment beyond that of muscle quantity., Competing Interests: AS has previously received honoraria and/or paid consultancy from Fresenius Kabi, Dr Schär and Baxter. CMA has previously received honoraria and/or paid consultancy from Fresenius Kabi, Astra-Zeneca and Baxter. BL was supported by a grant from Baxter Healthcare Corporation to Karolinska Institutet. PS has been on scientific advisory boards for Invizius, CSL, Vifor, GSK, Astra Zeneca, Baxter, and Fresenius. PS has lectured at meetings sponsored by Novo Nordisk, Astra Zeneca, Baxter, Astellas, Fresenius and Pfizer. Non of the authors have conflict of interest with the current study., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Aim:  Frailty is common and is reported to be associated with adverse outcomes in patients with chronic diseases in Western countries. However, the prevalence of frailty remains unclear in individuals with chronic kidney disease (CKD) in China. We examined the prevalence of frailty and factors associated with frailty in patients with CKD., Methods:  This was a cross-sectional analysis of 177 adult patients (mean age 54 ± 15 years, 52% men) with CKD from the open cohort entitled Physical Evaluation and Adverse outcomes for patients with chronic Kidney disease IN Guangdong (PEAKING). Frailty at baseline were assessed by FRAIL scale which included five items: fatigue, resistance, ambulation, illnesses, and loss of weight. Potential risk factors of frailty including age, sex, body mass index, and daily step counts recorded by ActiGraph GT3X + accelerometer were analyzed by multivariate logistic regression analysis., Results: The prevalence of prefrailty and frailty was 50.0% and 11.9% in patients with stages 4-5 CKD, 29.6% and 9.3% in stage 3, and 32.1% and 0 in stages 1-2. In the multivariate logistic regression analysis, an increase of 100 steps per day (OR = 0.95, 95% CI 0.91-0.99, P = 0.01) and an increase of 5 units eGFR (OR = 0.82, 95% CI 0.68-0.99, P = 0.045) were inversely associated with being frail; higher BMI was associated with a higher likelihood of being frail (OR = 1.52, 95% CI 1.11-2.06, P = 0.008) and prefrail (OR = 1.25, 95% CI 1.10-1.42, P = 0.001)., Conclusion:  Frailty and prefrailty were common in patients with advanced CKD. A lower number of steps per day, lower eGFR, and a higher BMI were associated with frailty in this population., (© 2023. The Author(s).)

Irisin is a hormone that is produced mainly by skeletal muscles in response to exercise. It has been found to have a close correlation with obesity and diabetes mellitus for its energy expenditure and metabolic properties. Recent research has revealed that irisin also possesses anti-inflammatory, anti-oxidative and anti-apoptotic properties, which make it associated with major chronic diseases, such as chronic kidney disease (CKD), liver diseases, osteoporosis, atherosclerosis and Alzheimer s disease. The identification of irisin has not only opened up new possibilities for monitoring metabolic and non-metabolic diseases but also presents a promising therapeutic target due to its multiple biological functions. Studies have shown that circulating irisin levels are lower in CKD patients than in non-CKD patients and decrease with increasing CKD stage. Furthermore, irisin also plays a role in many CKD-related complications like protein energy wasting (PEW), cardiovascular disease (CVD) and chronic kidney disease-mineral and bone disorder (CKD-MBD). In this review, we present the current knowledge on the role of irisin in kidney diseases and their complications., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Peripheral neuropathy (PN) becomes more common with increasing life expectancy, but general population prevalence estimates are lacking. We investigated an epidemiological distribution of signs of PN among 2,996 community-dwelling participants in Good Aging in Skåne Study, age 60-97, and their impact on physical and autonomic function., Methods: Signs of PN were measured with Utah Early Neuropathy Scale (UENS). Associations between UENS and physical tests, pain, and dysautonomic phenomena were calculated for each sex, adjusted for age, with estimated marginal means (EMM) and odds ratios (ORs) in four UENS quantiles (Q1-Q4)., Results: Participants in Q4 had worse EMM for: time to complete Timed Up and Go test (Q4-Q1: male 10.8-9.6 s; female 11.7-10.2 s), 15 m Walk test (Q4-Q1: male 11.1-9.9 s; female 11.2-10.4 s), and fewer repetitions in Step test (Q4-Q1: male 15.2-17.0 steps; female 14.5-15.8 steps). Higher OR of failing one-leg balance 60 s test {male 2.5 (confidence interval [CI] 95%: 1.7-3.8); female 2.1 (1.1-3.2)}, Foam Pad Balance test (male 4.6 [CI 95%: 3.2-6.7]; female 1.8 [1.3-2.6]), and lower physical quality of life were seen in Q4 compared to Q1. Participants in Q4 had higher OR for walking aid usage, falls, fear of falling, pain, and urinary incontinence, while in males, higher OR for orthostatic intolerance, fecal incontinence, and constipation., Conclusions: In a general population, 20-25% of older adults who have highest UENS scores, a sensitive measure of early PN, express slower gait, worse balance, lower quality of life, pain, falls and fear of falling, and autonomic symptoms., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Background: Several oral drugs are recommended to be taken with large amounts of water for reasons such as peptic ulcer prophylaxis. On the other hand, there are many patients with diseases that restrict water intake, and the actual frequency of patients receiving prescriptions in these conflicting situations is not clear., Objective: Using a large claims database in Japan, this study aimed to determine the proportion of patients aged ≥ 75 years on fluid restriction who received drugs whose drug package insert mentioned "a large amount of water intake is needed when taking the drug"., Methods: We performed a prescription survey of older patients over 75 years of age using the Japan Medical Data Centre (JMDC) claims database. Out of approximately 8800 oral drugs used in Japan, we defined 29 drugs for which package inserts noted that a large amount of water intake is recommended during drug administration. We defined diagnosis codes for some common diseases for which restricted water intake is likely recommended: heart failure (NYHA class III or IV), liver cirrhosis with ascites, and chronic kidney disease stage 5, including dialysis patients., Results: Of 5968 patients aged ≥ 75 years (men 47.7%), 320 (5.4%) patients with heart failure (2.8%, n = 170), liver cirrhosis (0.7%, n = 40), or chronic kidney disease (1.9%, n = 113), diagnoses likely associated with the need for fluid restriction, were prescribed drugs for which abundant fluid at intake was recommended. Among 29 identified drugs, 15 drugs were administered to older patients over 75 years with fluid restriction due to said diseases., Conclusions: Of patients 75 years and older with disease likely requiring water restriction, 5.4% faced the dilemma of following advice to restrict fluid intake due to their diagnoses or to adhere to instructions in drug package inserts to have abundant fluid intake when taking the drug. Our study raises awareness regarding the dilemma of water restriction and intake in clinical settings, highlighting the importance of considering individual patient needs. These real-world findings emphasize the need for information and guidelines to assist healthcare professionals in navigating this dilemma and making informed decisions for the benefit of their patients., (© 2023. The Author(s).)

Background: The first year of dialysis is critical given the significant risk for complications following dialysis initiation. We analysed complications during the first year among incident peritoneal dialysis (PD) patients., Methods: This retrospective cohort study comprised adult kidney failure patients starting PD in Baxter Renal Care Services in Colombia, receiving their first PD catheter between 1 January 2017 and 31 December 2020 and were followed up for up to 1 year. We analysed incidence, causes and factors associated with complications using logistic regression and transfer to haemodialysis (HD) using the Fine-Gray regression model., Results: Among 4743 patients receiving their first PD catheter: 4628 (97.6%) of catheter implantations were successful; 377 (7.9%) patients experienced early complications. The incidence rate of complications during the year was 0.51 events per patient-year (95% CI: 0.48-0.54). Age, obesity and urgent start were associated with higher probability of complications after catheter implantation. The cumulative incidence of transfer to HD within 1 year of PD initiation was 10.1% [95% CI: 9.2-11.1%]. The hazard function for transfer to HD showed an accelerating pattern during the first month followed by progressive decrease during the first year., Conclusions: In this large population of incident PD patients, there is a high primary catheter placement success rate. Urgent start, age ≥65 years, obesity, centre size ≥150 PD patients and diabetes were risk factors associated with early complications. The follow-up of the cohort from day 1 of PD treatment showed that the risk for transfer to HD was higher during the first month., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: ASR is full-time employee of Baxter Healthcare Corporation, Deerfield, IL, USA; JIV and LEN are full-time employee of Baxter Renal Care Services Bucaramanga, Colombia; SP is an employee of Department of Statistics, Science Faculty, National University of Colombia, Bogota DC, Colombia, and he has received honorarium for consultancy and statistical analysis from Baxter Renal Care Services-Colombia; KA, AA, YA and JCC are full-time employee of Baxter Renal Care Services, Bogota DC, Colombia; BL is an employee of Division of Baxter Novum and Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden; MS is full-time employee of Baxter Renal Care Services-Latin America, Bogota DC, Colombia and PR is an employee of Baxter Healthcare Corporation, Zürich, Switzerland.

The increasing consumption of ultra-processed food (UPF) and the global chain of food production have a negative impact on human health and planetary health. These foods have been replacing the consumption of nonprocessed healthy foods. This shift has not only worsened human health by increasing the risk of the development of noncommunicable diseases, but also resulted in environmental perturbations. This review aims to bring awareness of the problems caused by the industrialized food production chain, addressing the negative effects it has on the environment and human health, with special reference to chronic kidney disease (CKD). We discuss possible solutions focusing on the benefits of adopting plant-based diets with low UPF content to promote a sustainable and healthy food production and diet for patients with CKD. For a sustainable future we need to "connect the dots" of planetary health, food production, and nutrition in the context of CKD., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Patients on kidney replacement therapy (KRT) have been identified as a vulnerable group during the coronavirus disease 2019 (COVID-19) pandemic. This study reports the outcomes of COVID-19 in KRT patients in Sweden, a country where patients on KRT were prioritized early in the vaccination campaign., Methods: Patients on KRT between January 2019 and December 2021 in the Swedish Renal Registry were included. Data were linked to national healthcare registries. The primary outcome was monthly all-cause mortality over 3 years of follow-up. The secondary outcomes were monthly COVID-19-related deaths and hospitalizations. The results were compared with the general population using standardized mortality ratios. The difference in risk for COVID-19-related outcomes between dialysis and kidney transplant recipients (KTRs) was assessed in multivariable logistic regression models before and after vaccinations started., Results: On 1 January 2020, there were 4097 patients on dialysis (median age 70 years) and 5905 KTRs (median age 58 years). Between March 2020 and February 2021, mean all-cause mortality rates increased by 10% (from 720 to 804 deaths) and 22% (from 158 to 206 deaths) in dialysis and KTRs, respectively, compared with the same period in 2019. After vaccinations started, all-cause mortality rates during the third wave (April 2021) returned to pre-COVID-19 mortality rates among dialysis patients, while mortality rates remained increased among transplant recipients. Dialysis patients had a higher risk for COVID-19 hospitalizations and death before vaccinations started {adjusted odds ratio [aOR] 2.1 [95% confidence interval (CI) 1.7-2.5]} but a lower risk after vaccination [aOR 0.5 (95% CI 0.4-0.7)] compared with KTRs., Conclusions: The COVID-19 pandemic in Sweden resulted in increased mortality and hospitalization rates among KRT patients. After vaccinations started, a distinct reduction in hospitalization and mortality rates was observed among dialysis patients, but not in KTRs. Early and prioritized vaccinations of KRT patients in Sweden probably saved many lives., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

The lack of consensus on diagnostic criteria for malnutrition has hampered developments in research and clinical practice pertaining to nutrition. This opinion paper describes the applicability and other aspects of using the Global Leadership Initiative on Malnutrition (GLIM) criteria for diagnosing malnutrition in patients with chronic kidney disease (CKD). We examine the purpose of GLIM, the particularities of CKD that can affect the nutritional and metabolic status and the diagnosis of malnutrition. In addition, we make an appraisal of previous studies that used GLIM in the context of CKD and discuss the value and relevance of using the GLIM criteria in patients with CKD., Competing Interests: Conflict of Interest BL has been affiliated with Baxter Healthcare. The other authors do not declare any conflict of interest., (Copyright © 2023 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

High energy intake combined with low physical activity generates positive energy balance, which, when maintained, favours obesity, a highly prevalent morbidity linked to development of non-communicable chronic diseases, including chronic kidney disease (CKD). Among many factors contributing to disproportionately high energy intakes, and thereby to the obesity epidemic, the type and degree of food processing play an important role. Ultraprocessed foods (UPFs) are industrialized and quite often high-energy-dense products with added sugar, salt, unhealthy fats and food additives formulated to be palatable or hyperpalatable. UPFs can trigger an addictive eating behaviour and is typically characterized by an increase in energy intake. Furthermore, high consumption of UPFs, a hallmark of a Western diet, results in diets with poor quality. A high UPF intake is associated with higher risk for CKD. In addition, UPF consumption by patients with CKD is likely to predispose and/or to exacerbate uraemic metabolic derangements, such as insulin resistance, metabolic acidosis, hypertension, dysbiosis, hyperkalaemia and hyperphosphatemia. Global sales of UPFs per capita increased in all continents in recent decades. This is an important factor responsible for the nutrition transition, with home-made meals being replaced by ready-to-eat products. In this review we discuss the potential risk of UPFs in activating hedonic eating and their main implications for health, especially for kidney health and metabolic complications of CKD. We also present various aspects of consequences of UPFs on planetary health and discuss future directions for research to bring awareness of the harms of UPFs within the CKD scenario., Competing Interests: The authors declare no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

In peritoneal dialysis, ultrafiltration is achieved by adding an osmotic agent into the dialysis fluid. During an exchange with icodextrin-based solution, polysaccharide chains are degraded by α-amylase activity in dialysate, influencing its osmotic properties. We modelled water and solute removal taking into account degradation by α-amylase and absorption of icodextrin from the peritoneal cavity. Data from 16 h dwells with icodextrin-based solution in 11 patients (3 icodextrin-exposed, 8 icodextrin-naïve at the start of the study) on dialysate volume, dialysate concentrations of glucose, urea, creatinine and α-amylase, and dialysate and blood concentrations of seven molecular weight fractions of icodextrin were analysed. The three-pore model was extended to describe hydrolysis of icodextrin by α-amylase. The extended model accurately predicted kinetics of ultrafiltration, small solutes and icodextrin fractions in dialysate, indicating differences in degradation kinetics between icodextrin-naïve and icodextrin-exposed patients. In addition, the model provided information on the patterns of icodextrin degradation caused by α-amylase. Modelling of icodextrin kinetics using an extended three-pore model that takes into account absorption of icodextrin and changes in α-amylase activity in the dialysate provided accurate description of peritoneal transport and information on patterns of icodextrin hydrolysis during long icodextrin dwells., (© 2023. The Author(s).)

Background: Diabetes is associated with systemic complications. Prevalence of diabetic nephropathy, and retinopathy, in type 1 diabetes mellitus (T1DM) is declining, but it is not known if this is true also for diabetic neuropathy., Aim: To investigate the relationship between large fibre diabetic neuropathy and other diabetic complications., Materials and Methods: Neuropathy, defined here as large fibre neuropathy, was assessed by measuring vibration perception thresholds at four different frequencies on the sole of the foot, using a standard VibroSense Meter and/or neuropathic symptoms, in 599 individuals with T1DM. Retinopathy status was graded using the International Clinical Disease Severity Scale. Grade of albuminuria and previous history of any macrovascular complications were registered., Results: Diabetic individuals without retinopathy had similar vibration thresholds as age- and gender-matched control participants without diabetes, whereas those without microalbuminuria had higher thresholds than controls. Two individuals out of 599 (0.3%) had microalbuminuria, but not retinopathy or neuropathy, and 12/134 (9%) without retinopathy had signs of neuropathy. Totally 119/536 (22%) of the patients without microalbuminuria had neuropathy. Vibration thresholds increased with the rising severity of retinopathy and grade of albuminuria. In a multinomial logistic regression analysis, neuropathy was associated with retinopathy (OR 2.96 [1.35-6.49], p=0.007), nephropathy (OR 6.25 [3.21-12.15]; p=6.7×10-8) and macrovascular disease (OR 2.72 [1.50-4.93], p=0.001)., Conclusions: Despite recent changes in the incidence of diabetic complications, the onset of large fibre neuropathy follows that of retinopathy but precedes the onset of nephropathy in T1DM., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Muscle fat infiltration (MFI) also known as myosteatosis refers to any deposit of lipids found in the skeletal muscle. MFI is preferably assessed by image-based methods like computed tomography (CT), magnetic resonance image (MRI) and ultrasound, normally from muscle groups located in the legs, arms and in the trunk. MFI is understood as a marker of muscle quality, where a muscle with higher fat deposition has lower contraction power and capacity to produce force per unit of muscle mass. This concept supports the hypothesis that a decrease in muscle strength is not always explained by a decrease in muscle mass, but also by other factors, including lipid deposition in the muscle. In the general population, MFI is associated with older age, physical inactivity and with insulin resistance and inflammation. In chronic kidney disease (CKD), MFI has been associated with a decrease in muscle strength and impaired muscle quality as well as with metabolic abnormalities, cardiovascular disease and increased mortality. Interventions aimed at reducing MFI in CKD are incipient, but it seems that guided exercise can ameliorate muscle quality in patients on hemodialysis. The aim of this narrative review about MFI in CKD is to draw attention to a still not often addressed complication in CKD. We conclude that more studies are warranted to investigate mechanisms and factors promoting MFI in CKD. Thus, clinical trials aimed at understanding the type, frequency and intensity of exercise that can diminish MFI and improve the clinical condition of the patients are needed., (© 2023. The Author(s).)

Protein-energy wasting (PEW) is common in patients with chronic kidney disease (CKD) and is associated with increased morbidity and mortality, and lower quality of life. It is a complex syndrome, in which inflammation and retention of uremic toxins are two main factors. Causes of inflammation and uremic toxin retention in CKD are multiple; however, gut dysbiosis plays an important role, serving as a link between those entities and PEW. Besides, there are several pathways by which microbiota may influence PEW, e.g., through effects on appetite mediated by microbiota-derived proteins and hormonal changes, or by impacting skeletal muscle via a gut-muscle axis. Hence, microbiota disturbances may influence PEW independently of its relationship with local and systemic inflammation. A better understanding of the complex interrelationships between microbiota and the host may help to explain how changes in the gut affect distant organs and systems of the body and could potentially lead to the development of new strategies targeting the microbiota to improve nutrition and clinical outcomes in CKD patients. In this review, we describe possible interactions of gut microbiota with nutrient metabolism, energy balance, hunger/satiety signals and muscle depletion, all of which are strongly related to PEW in CKD patients., (© 2023. The Author(s).)

Background: Anthropometric indices of central obesity, waist circumference (WC), conicity index (CI), and a-body shape index (ABSI), are prognostic indicators of cardiovascular (CV) risk. The association of CI and ABSI with other CV risk indices, markers of nutritional status and inflammation, and clinical outcomes in chronic kidney disease (CKD) stage 5 (CKD5) patients was investigated., Methods: In a cross-sectional study with longitudinal follow up of 203 clinically stable patients with CKD5 (median age 56 years; 68% males, 17% diabetics, 22% with CV disease, and 39% malnourished), we investigated CI and ABSI and their associations with atherogenic index of plasma (AIP), Framingham CV risk score (FRS), Agatston scoring of coronary artery calcium (CAC) and aortic valve calcium (AVC), handgrip strength (HGS), high sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6). CV events (CVE) and all-cause mortality during up to 10-years follow up were analyzed by multivariate survival analysis of restricted mean survival time (RMST)., Results: Chronic kidney disease patients with middle and highest CI and ABSI tertiles (indicating greater abdominal fat deposition), compared to those with the lowest CI and ABSI tertiles, tended to be older, more often men and diabetic, had significantly higher levels of hsCRP, IL-6, AIP, FRS, CAC and AVC scores. CI and ABSI were positively correlated with CAC, FRS, AIP, hsCRP and IL-6. Both CI and ABSI were negatively correlated with HGS. In age-weighted survival analysis, higher CI and ABSI were associated with higher risk of CVE (Wald test = 4.92, p  = 0.027; Wald test = 4.95, p  = 0.026, respectively) and all-cause mortality (Wald test = 5.24, p  = 0.022; Wald test = 5.19, p  = 0.023, respectively). In RMST analysis, low vs. high and middle tertiles of CI and ABSI associated with prolonged CVE-free time and death-free time, and these differences between groups increased over time., Conclusion: Abdominal fat deposit indices, CI and ABSI, predicted CV outcomes and all-cause mortality, and were significantly associated with the inflammatory status in CKD patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ryu, Suliman, Qureshi, Chen, Avesani, Brismar, Ripsweden, Barany, Heimbürger, Stenvinkel and Lindholm.)

Objectives: Chronic kidney disease (CKD) leads to metabolic and nutritional abnormalities including resistance to insulin-like growth factor-1 (IGF-1) action, and reduced muscle mass and strength. Low IGF-1 as well as low hand-grip muscle strength (HGS) are independent predictors of increased mortality in CKD patients., Methods: In 685 patients (CKD Stage 3-5, median age 58 years; 62% men), baseline measurements of IGF-1, HGS, subjective global assessment (SGA), lean body mass index (LBMI), and metabolic and inflammatory biomarkers potentially linked to IGF-1 were analyzed in relation to mortality during 5 years of follow-up. We compared survival in 4 groups with high or low (cut-offs defined by receiver operating characteristic curve analysis) levels of IGF-1 and HGS., Results: Patients with low IGF-1 were older; had lower BMI, HGS, and LBMI, were more likely to have diabetes, cardiovascular disease (CVD), and malnutrition (SGA >1); and had high-sensitivity C-reactive protein levels. During 5 years of follow-up, 208 patients died. The mortality rate was highest among patients with Low IGF-1 + Low HGS. In competing-risk regression analysis, Low IGF-1 + Low HGS was independently associated with 2.8 times higher all-cause mortality risk than Low IGF-1 + High HGS, after adjusting for Framingham's CVD risk score, presence of CVD, SGA, dialysis status, high-sensitivity C-reactive protein, albumin, LBMI, and sample time in freezer., Conclusion: Low IGF-1 was associated with increased all-cause mortality in patients who also had low HGS but not in those with high HGS, suggesting that the association of IGF-1 with survival in CKD patients depends on nutritional status., (Copyright © 2022 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Preclinical evidence shows that activation of the cholinergic anti-inflammatory pathway (CAP) may have direct and indirect beneficial effects on the kidney. Cholinesterase inhibitors (ChEIs) are specific Alzheimer's dementia (AD) therapies that block the action of cholinesterases and activate CAP. Here, we explored a plausible effect of ChEIs on slowing kidney function decline by comparing the risk of CKD progression among patients with newly diagnosed AD that initiated ChEI or not within 90 days. Using complete information of routine serum creatinine tests, we evaluated changes in estimated glomerular filtration rate (eGFR) and defined the outcome of chronic kidney disease (CKD) progression as the composite of an eGFR decline of over 30%, initiation of dialysis/transplant or death attributed to CKD. A secondary outcome was death. Inverse probability of treatment-weighted Cox regression was used to estimate hazard ratios. Among 11, 898 patients, 6,803 started on ChEIs and 5,095 did not. Mean age was 80 years (64% women) and the mean eGFR was 68 ml/min/1.73m 2 . During a median 3.0 years of follow-up, and compared to non-use, ChEI use was associated with 18% lower risk of CKD progression (1,231 events, adjusted hazard ratio 0.82; 95% confidence interval 0.71-0.96) and a 21% lower risk of death (0.79; 0.72-0.86). Results were consistent across subgroups, ChEI subclasses and after accounting for competing risks. Thus, in patients with AD undergoing routine care, use of ChEI (vs no-use) was associated with lower risk of CKD progression., (Copyright © 2022 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Introduction: In patients with chronic kidney disease (CKD), high interleukin-6 (IL-6) and low albumin circulating concentrations are associated with worse outcomes. We examined the IL-6-to-albumin ratio (IAR) as a predictor of risk of death in incident dialysis patients., Methods: In 428 incident dialysis patients (median age 56 years, 62% men, 31% diabetes mellitus, 38% cardiovascular disease [CVD]), plasma IL-6 and albumin were measured at baseline to calculate IAR. We compared the discrimination of IAR with other risk factors for predicting 60-month mortality using receiver operating characteristic curve (ROC) and analyzed the association of IAR with mortality using Cox regression analysis. We divided patients into IAR tertiles and analyzed: (1) cumulative incidence of mortality and the association of IAR with mortality risk in Fine-Gray analysis, taking kidney transplantation as competing risk and (2) the restricted mean survival time (RMST) to 60-month mortality and differences of RMST (∆RMST) between IAR tertiles to describe quantitative differences of survival time., Results: For all-cause mortality, the area under the ROC curve (AUC) for IAR was 0.700, which was greater than for IL-6 and albumin separately, while for CV mortality, the AUC for IAR (0.658) showed negligible improvement over IL-6 and albumin separately. In Cox regression analysis, IAR was significantly associated with all-cause mortality but not with CV mortality. Both high versus low and middle versus low tertiles of IAR associated with higher risk of all-cause mortality, subdistribution hazard ratio of 2.22 (95% CI 1.40-3.52) and 1.85 (95% CI 1.16-2.95), respectively, after adjusting for age, sex, diabetes mellitus, CVD, smoking, and estimated glomerular filtration rate. ∆RMST at 60 months showed significantly shorter survival time in middle and high IAR tertiles compared with low IAR tertile for all-cause mortality., Conclusions: Higher IAR was independently associated with significantly higher all-cause mortality risk in incident dialysis patients. These results suggest that IAR may provide useful prognostic information in patients with CKD., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Increased muscle protein catabolism leading to muscle wasting is a prominent feature of the syndrome of protein-energy wasting (PEW) in patients with chronic kidney disease (CKD). PEW and muscle wasting are induced by factors such as inflammation, oxidative stress and metabolic acidosis that activate the ubiquitin-proteasome system, the main regulatory mechanism of skeletal muscle degradation. Whether deficiency of nuclear factor erythroid 2-related factor 2 (NRF2), which regulates expression of antioxidant proteins protecting against oxidative damage triggered by inflammation, may exacerbate PEW has yet to be examined in aging patients with CKD. This review focuses on the hypothesis that NRF2 is involved in the maintenance of muscle mass and explores whether sustained activation of NRF2 by non-pharmacological interventions using nutraceutical activators to improve redox homeostasis could be a plausible strategy to prevent skeletal muscle disorders, including muscle wasting, sarcopenia and frailty associated with PEW in aging CKD patients., (© 2022. The Author(s).)

In non-anuric patients undergoing peritoneal dialysis (PD), residual kidney function (RKF) is a main contributor to fluid and solute removal and an independent predictor of survival. We investigated if urine volume could be used to estimate renal clearances and removal of urea, creatinine, and phosphorus in PD patients. The observational, cross-sectional study included 93 non-anuric prevalent PD patients undergoing continuous ambulatory PD (CAPD; n = 34) or automated PD (APD; n = 59). Concentrations of urea, creatinine and phosphorus in serum and in 24-h collections of urine volume were measured to calculate weekly residual renal clearance (L/week) and removed solute mass (g/week). Median [interquartile range], 24-h urine output was 560 [330-950] mL and measured GFR (the mean of creatinine and urea clearances) was 3.24 [1.47-5.67] mL/min. For urea, creatinine and phosphorus, residual renal clearance was 20.60 [11.49-35.79], 43.02 [19.13-75.48] and 17.50 [8.34-33.58] L/week, respectively, with no significant differences between CAPD and APD. Urine volume correlated positively with removed solute masses (rho = 0.82, 0.67 and 0.74) and with weekly residual renal clearances (rho = 0.77, 0.62 and 0.72 for urea, creatinine, and phosphorus, respectively, all p < 0.001). Residual renal clearances and urinary mass removal rates for urea, creatinine, and phosphorus correlate strongly with 24-h urine volume suggesting that urine volume could serve as an estimator of typical values of residual solute removal indices in PD patients., (© 2022. The Author(s).)

Dysbiosis is recognized as a new cardiovascular disease (CVD) risk factor in hemodialysis (HD) patients because it is linked to increased generation in the gut of uremic toxins such as trimethylamine N-Oxide (TMAO) from dietary precursors (choline, betaine, or L-carnitine). Nutritional strategies have been proposed to modulate the gut microbiota and reduce the production of these toxins. This study aimed to evaluate the effect of amylose-resistant starch (RS) supplementation on TMAO plasma levels in HD patients., We conducted a randomized, double-blind, placebo-controlled trial (NCT02706808) with patients undergoing HD enrolled in a previous pilot study. The participants were allocated to RS or placebo groups to receive 16 g/d of RS or placebo for 4 weeks. Plasma TMAO, choline, and betaine levels were measured with LC-MS/MS. Fecal microbiome composition was evaluated by 16S ribosomal RNA sequencing, followed by a search for TMA-associated taxa. Anthropometric, routine biochemical parameters, and food intake were evaluated., Twenty-five participants finished the study, 13 in the RS group, and 12 in the placebo group. RS supplementation did not reduce TMAO plasma levels. Moreover, no significant alterations were observed in choline, betaine, anthropometric, biochemical parameters, or food intake in both groups. Likewise, RS was not found to exert any influence on the proportion of potential TMA-producing bacterial taxa in fecal matter., RS supplementation did not influence plasma TMAO, choline, betaine, or fecal taxa potentially linked to TMAO. Thus, RS does not seem to modify the TMA-associated bacterial taxa, precursors of TMAO., Supplemental data for this article is available online at https://doi.org/10.1080/07315724.2021.1967814 .

Aim: Half of heart failure (HF) patients have chronic kidney disease (CKD) complicating their pharmacological management. We evaluated physicians' and patients' patterns of use of evidence-based medical therapies in HF across CKD stages., Methods and Results: We studied HF patients with reduced (HFrEF) and mildly reduced (HFmrEF) ejection fraction enrolled in the Swedish Heart Failure Registry in 2009-2018. We investigated the likelihood of physicians to prescribe guideline-recommended therapies to patients with CKD, and of patients to fill the prescriptions within 90 days of incident HF (initiating therapy), to adhere (proportion of days covered ≥80%) and persist (continued use) on these treatments during the first year of therapy. We identified 31 668 patients with HFrEF (median age 74 years, 46% CKD). The proportions receiving a prescription for angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor-neprilysin inhibitors (ACEi/ARB/ARNi) were 96%, 92%, 86%, and 68%, for estimated glomerular filtration rate (eGFR) ≥60, 45-59, 30-44, and <30 ml/min/1.73 m 2 , respectively; for beta-blockers 94%, 93%, 92%, and 92%, for mineralocorticoid receptor antagonists (MRAs) 45%, 44%, 37%, 24%; and for triple therapy (combination of ACEi/ARB/ARNi + beta-blockers + MRA) 38%, 35%, 28%, and 15%. Patients with CKD were less likely to initiate these medications, and less likely to adhere to and persist on ACEi/ARB/ARNi, MRA, and triple therapy. Among stoppers, CKD patients were less likely to restart these medications. Results were consistent after multivariable adjustment and in patients with HFmrEF (n = 15 114)., Conclusions: Patients with HF and CKD are less likely to be prescribed and to fill prescriptions for evidence-based therapies, showing lower adherence and persistence, even at eGFR categories where these therapies are recommended and have shown efficacy in clinical trials., (© 2022 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Refilling of the vascular space through absorption of interstitial fluid by micro vessels is a crucial mechanism for maintaining hemodynamic stability during hemodialysis (HD) and allowing excess fluid to be removed from body tissues. The rate of vascular refilling depends on the imbalance between the Starling forces acting across the capillary walls as well as on their hydraulic conductivity and total surface area. Various approaches have been proposed to assess the vascular refilling process during HD, including the so-called refilling coefficient (Kr) that describes the rate of vascular refilling per changes in plasma oncotic pressure, assuming that other Starling forces and the flow of lymph remain constant during HD. Several studies have shown that Kr decreases exponentially during HD, which was attributed to a dialysis-induced decrease in the whole-body capillary hydraulic conductivity (L p S). Here, we employ a lumped-parameter mathematical model of the cardiovascular system and water and solute transport between the main body fluid compartments to assess the impact of all Starling forces and the flow of lymph on vascular refilling during HD in order to explain the reasons behind the observed intradialytic decrease in Kr. We simulated several HD sessions in a virtual patient with different blood priming procedures, ultrafiltration rates, session durations, and constant or variable levels of L p S. We show that the intradialytic decrease in Kr is not associated with a possible reduction of L p S but results from the inherent assumption that plasma oncotic pressure is the only variable Starling force during HD, whereas in fact other Starling forces, in particular the oncotic pressure of the interstitial fluid, have an important impact on the transcapillary fluid exchange during HD. We conclude that Kr is not a good marker of L p S and should not be used to guide fluid removal during HD or to assess the fluid status of dialysis patients., (© 2022. The Author(s).)

Background and Purpose: Although distal radius fracture (DRF) is the most common fracture type in children, research on its seasonality across different age groups is limited. We investigated secular trends in incidence and seasonal variation of pediatric DRF based on Swedish nationwide population database., Patients and Methods: In this observational study, data for all children aged <18 years in Sweden with DRF defined by ICD-codes were analyzed for each month and each year during 2002-2016 using the Swedish National Patient Register. The general population counts for each age and sex-category were acquired to evaluate population at risk for each period. We calculated the age standardized and sex specific annual incidence rates, seasonal incidence rates, and monthly incidence rates and analyzed the seasonal variation in the mechanisms of injury., Results: A total of 155,891 DRF cases were identified. The age standardized and sex specific incidence rate was 531 (95%CI 528-533) per 100,000 patient years at risk. Fracture risk was highest during summer and lowest in the winter. The highest seasonal variation was observed among boys 2- < 5 years. The crude incidence rate and the age-standardized incidence rates in winter significantly decreased between 2002 and 2016 (annual percentage change, -2 %)., Interpretation: We found significant seasonal variation in DRF among all age groups in Swedish children. The findings can help in developing strategies to prevent fractures as well as in allocating medical and social resources., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Remote patient monitoring (RPM) of patients undergoing automated peritoneal dialysis (APD-RPM) may potentially enhance time on therapy due to possible improvements in technique and patient survival., Objective: To evaluate the effect of APD-RPM as compared to APD without RPM on time on therapy., Methods: Adult incident APD patients undergo APD for 90 days or more in the Baxter Renal Care Services (BRCS) Colombia network between January 1, 2017, and June 30, 2019, with the study follow-up ending June 30, 2021. The exposure variable was APD-RPM vs. APD-without RPM. The outcomes of time on therapy and mortality rate over two years of follow-up were estimated in the full sample and in a matched population according to the exposure variable. A propensity score matching (PSM) 1:1 without replacement utilizing the nearest neighbor within caliper (0.035) was used and created a pseudopopulation in which the baseline covariates were well balanced. Fine & Gray multivariate analysis was performed to assess the effect of demographic, clinical, and laboratory variables on the risk of death, adjusting for the competing risks of technique failure and kidney transplantation., Results: In the matched sample, the time on APD therapy was significantly longer in the RPM group than in the non-RPM group, 18.95 vs. 15.75 months, p < 0.001. The mortality rate did not differ between the two groups: 0.10 events per patient-year in the RPM group and 0.12 in the non-RPM group, p =0.325., Conclusion: Over two years of follow-up, the use of RPM vs. no RPM in APD patients was associated with a significant increase in time on therapy, by 3.2 months. This result indicates that RPM-supported APD therapy may improve the clinical effectiveness and the overall quality of APD., Competing Interests: Dr Sanabria is a full-time employee of Baxter Renal Care Services-Latin-America, Bogotá, Colombia. Ms. Vesga is a full-time employee of Baxter Renal Care Services-Colombia, Bucaramanga, Colombia. Dr. Lindholm is an employee of Baxter Healthcare Corporation and Karolinska Institutet, Stockholm, Sweden. Dr. Rivera is an employee of Baxter Healthcare Corporation, Deerfield, Illinois, USA. Dr. Rutherford is an employee of Baxter Healthcare Corporation, Zurich, Switzerland., (Copyright © 2022 Mauricio Sanabria et al.)

Background: The knowledge about striatal hand deformities (SHD) in Parkinson's disease (PD), has recently increased but need more attention due to their early impact on dexterity. The focus of clinical studies has been on the staging of SHD severity and neurological features. However, a hand surgical perspective has not been considered., Objectives: Our purpose was to examine SHD in patients with PD using hand surgical assessment methods and the recommended staging of SHD., Methods: In this observational study, a specialist in neurological physiotherapy examined 100 consecutive PD patients and identified 35 with suspected SHD, who were then examined by two hand surgeons. Their hands were clinically evaluated for severity of SHD, according to a previous proposed staging, focusing on metacarpophalangeal (MCP) joint flexion, presence of intrinsic and extrinsic tightness, as well as other hand deformities., Results: Three kinds of deformities were identified among 35 included patients: surgical diagnoses unrelated to PD (n = 5), SHD (n = 23), and PD related hand deformities with increased extrinsic tightness (n = 10); three of these 10 patients had also contralateral SHD, thus are included in SHD group. In addition to previously described MCP joint flexion, swan neck deformity and z-thumb deformity, we found in most hands finger "clefting," abduction of the little finger and/or an increased intrinsic tightness, indicating pathology of intrinsic muscles of the hand involved in SHD., Conclusions: SHD diagnosed with a modified staging method, including features of intrinsic and extrinsic hand deformities, should be considered in PD to implement early and more accurate treatment., Competing Interests: Elisabeth Brogren: no specific funding; Lars B. Dahlin: Lund University and Skåne University Hospital, Region Skåne; Beata Lindholm: The Stoltz foundation, Skåne County Council's research and development foundation, The Erik Hardebos foundation, Kockska foundation, Neuro foundation and Norrbacka‐Eugenia foundation. The authors declare that there are no conflicts of interest relevant to this work., (© 2022 International Parkinson and Movement Disorder Society.)

Objective: Malnutrition is a prevalent condition in maintenance hemodialysis (MHD) patients. This study aimed to evaluate the performance of the recently developed GLIM (Global Leadership Initiative on Malnutrition) in MHD by assessing the agreement, accuracy, sensitivity, specificity, and survival prediction of GLIM when compared to 7-point subjective global assessment (7p-SGA) and malnutrition inflammation score (MIS)., Design and Methods: We investigated 2 cohorts: MHD ltaly (121 adults from Italy; 67 ± 16 years, 65% men, body mass index 25 ± 5 kg/m 2 ) and MHD Brazil (169 elderly [age > 60 years] from Brazil; 71 ± 7 years, 66% men, body mass index 25 ± 4 kg/m 2 ), followed for all-cause mortality for median 40 and 17 months, respectively. We applied the 2-step approach from GLIM: (1) screening and (2) confirming malnutrition by phenotypic and etiologic criteria. For 7p-SGA and MIS, a score ≤5 and ≥8, respectively, defined malnutrition., Results: Malnutrition was present in 38.8% by GLIM, 25.6% by 7p-SGA, and 29.7% by MIS in the MHD Italy cohort, and in 47.9% by GLIM, 59.8% by 7p-SGA, and 49.7% by MIS in the MHD Brazil cohort. Cohen's kappa coefficient (κ) showed only "fair" agreement between GLIM and SGA (MHD Italy : κ = 0.26, P = .003; MHD Brazil : κ = 0.22, P = .003) and between GLIM and MIS (MHD Italy : κ = 0.33, P < .001; MHD Brazil : κ = 0.25, P = .001). Cox regression analysis showed that all 3 methods were able to predict mortality in crude analysis; however in the adjusted model, the association seemed more consistent and stronger in magnitude for 7p-SGA and MIS., Conclusion: In MHD patients, GLIM showed low agreement, sensitivity, and accuracy in identifying malnourished subjects by either 7p-SGA or MIS. Considering the specific wasting characteristics that predominate in MHD, the well-established 7p-SGA and MIS methods may be more useful in this clinical setting., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Controversy surrounds which factors are important for predicting early mortality after dialysis initiation (DI). We investigated associations of predialysis course and circumstances affecting planning and execution of DI with mortality following DI., Methods: Among 1580 patients participating in the Peridialysis study, a study of causes and timing of DI, we registered features of predialysis course, clinical and biochemical data at DI, incidence of unplanned suboptimal DI, contraindications to peritoneal dialysis (PD) or hemodialysis (HD), and modality preference, actual choice, and cause of modality choice. Patients were followed for 12 months or until transplantation. A flexible parametric model was used to identify independent factors associated with all-cause mortality., Results: First-year mortality was 19.33%. Independent factors predicting death were high age, comorbidity, clinical contraindications to PD or HD, suboptimal DI, high eGFR, low serum albumin, hyperphosphatemia, high C-reactive protein, signs of overhydration and cerebral symptoms at DI. Among 1061 (67.2%) patients who could select dialysis modality based on personal choice, 654 (61.6%) chose PD, 368 (34.7%) center HD and 39 (3.7%) home HD. The 12-months survival did not differ significantly between patients receiving PD and in-center HD., Conclusions: First-year mortality in incident dialysis patients was in addition to high age and comorbidity, associated with clinical contraindications to PD or HD, clinical symptoms, hyperphosphatemia, inflammation, and suboptimal DI. In patients with a "free" choice of dialysis modality based on their personal preferences, PD and in-center HD led to broadly similar short-term outcomes., (© 2022. The Author(s).)

Background/Aims: Some previous observations have noted that after six months of peritoneal dialysis (PD) treatment with icodextrin solutions, blood pressure (BP) and NT-proBNP tend to return to baseline values. This may be due to accumulation of icodextrin products that exert a colloid osmotic effect, which drives water into the bloodstream, causing the rise in blood pressure. Since icodextrin is metabolized by α-Amylase and its gene copies are lower in females than in males, we hypothesized icodextrin metabolites reach higher concentrations in females and that cardiovascular effects of icodextrin are influenced by sex. Methods: Secondary analysis of a RCT comparing factors influencing fluid balance control in diabetic PD patients with high or high average peritoneal transport receiving icodextrin ( n = 30) or glucose ( n = 29) PD solutions. Serum icodextrin metabolites, osmolality, body composition and Inferior Vena Cava (IVC) diameter were measured at baseline, and at 6 and 12 months of follow-up. Results: After six months of treatment, icodextrin metabolites showed higher levels in females than in males, particularly G5-7 and >G7, serum osmolality was lower in females. In spite of reduction in total and extracellular body water, ultrafiltration (UF) was lower and IVC diameter and BP increased in females, suggesting increment of blood volume. Conclusion: Females undergoing PD present with higher levels of icodextrin metabolites in serum that may exert an increased colloid-osmotic pressure followed by less UF volumes and increment in blood volume and blood pressure. Whether this could be due to the lesser number of α-Amylase gene copies described in diabetic females deserves further investigation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Paniagua, García-López, Ávila-Díaz, Ventura, Orihuela, Prado-Uribe, Gallardo-Montoya and Lindholm.)

Background: Remote patient monitoring (RPM) programs in automated peritoneal dialysis (APD) allow clinical teams to be aware of many aspects and events of the therapy that occur in the home. The present study evaluated the association between RPM use and APD technique failure., Methods: A retrospective, multicentre, observational cohort study of 558 prevalent adult APD patients included between 1 October 2016 and 30 June 2017 with follow-up until 30 June 2018 at Renal Therapy Services network in Colombia. Patients were divided into two cohorts based on the RPM use: APD-RPM ( n = 148) and APD-without RPM ( n = 410). Sociodemographic and clinical characteristics of all patients were summarized descriptively. A propensity score was used to create a pseudo-population in which the baseline covariates were well balanced. The association of RPM with technique failure was estimated adjusting for the competing events death and kidney transplant., Results: Five hundred fifty-eight patients were analyzed. 26.5% had APD-RPM. In the matched sample comprising 148 APD-RPM and 148 APD-without RPM patients, we observed a lower technique failure rate of 0.08 [0.05-0.15] episodes per patient-year in APD-RPM versus 0.18 [0.12-0.26] in APD-without RPM cohort; incidence rate ratio = 0.45 95% confidence interval: [0.22-0.91], p -value = 0.03., Conclusions: The use of an RPM program in APD patients may be associated with a lower technique failure rate. More extensive and interventional studies are needed to confirm its potential benefits and to measure other patient-centered outcomes.

Background: To investigate the comparative effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP1-RA) on cardiovascular outcomes in routine clinical practice, which have never been directly compared in head-to-head outcome trials., Methods: We compared outcomes of adults who newly started SGLT2i or GLP1-RA therapy in Stockholm, Sweden, during 2013-2019. The primary outcome was major adverse cardiovascular events (MACE), a composite of cardiovascular (CV) death, myocardial infarction and stroke. Secondary outcomes included the individual MACE components and hospitalization for heart failure. Cox regression with propensity score overlap weighting was used to estimate hazard ratios (HRs) with 95% confidence intervals and adjust for 57 covariates., Results: We included 12,375 individuals, of which 5489 initiated SGLT2i and 6886 GLP1-RA therapy, followed for median 1.6 years. Mean age was 61 years and 37.6% were women. Compared with GLP1-RA, SGLT2i new users had similar risk of MACE risk (adjusted HR 1.04; 95% CI 0.83-1.31). The adjusted HRs (95% CI) for SGLT2i vs. GLP1-RA were 0.80 (0.59-1.09) for heart failure hospitalization, 0.95 (0.58-1.55) for cardiovascular death, 0.91 (0.67-1.24) for myocardial infarction and 1.71 (1.14-2.59) for ischemic stroke (5-year absolute risk difference for stroke 1.9% [95% CI 0.8-3.0])., Conclusions: In a largely primary-prevention population of people undergoing routine care, no differences were observed in MACE risk among initiators of SGLT2i and GLP1-RA. However, compared with GLP1RA, the use of SGLT2i was associated with an increased risk of ischemic stroke that was small in absolute magnitude., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: The risk-benefit ratio of continuing with renin-angiotensin system inhibitors (RASi) after an episode of acute kidney injury (AKI) is unclear. While stopping RASi may prevent recurrent AKI or hyperkalaemia, it may deprive patients of the cardiovascular benefits of using RASi., Methods: We analysed outcomes of long-term RASi users experiencing AKI (stage 2 or 3, or clinically coded) during hospitalization in Stockholm and Sweden during 2007-18. We compared stopping RASi within 3 months after discharge with continuing RASi. The primary study outcome was the composite of all-cause mortality, myocardial infarction (MI) and stroke. Recurrent AKI was our secondary outcome and we considered hyperkalaemia as a positive control outcome. Propensity score overlap weighted Cox models were used to estimate hazard ratios (HRs), balancing 75 confounders. Weighted absolute risk differences (ARDs) were also determined., Results: We included 10 165 individuals, of whom 4429 stopped and 5736 continued RASi, with a median follow-up of 2.3 years. The median age was 78 years; 45% were women and median kidney function before the index episode of AKI was 55 mL/min/1.73 m 2 . After weighting, those who stopped had an increased risk [HR, 95% confidence interval (CI)] of the composite of death, MI and stroke [1.13, 1.07-1.19; ARD 3.7, 95% CI 2.6-4.8] compared with those who continued, a similar risk of recurrent AKI (0.94, 0.84-1.05) and a decreased risk of hyperkalaemia (0.79, 0.71-0.88)., Discussion: Stopping RASi use among survivors of moderate-to-severe AKI was associated with a similar risk of recurrent AKI, but higher risk of the composite of death, MI and stroke., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)