Renin–angiotensin–aldosterone system blockers effect in chronic kidney disease progression in hypertensive elderly patients without proteinuria: PROERCAN trial / Efecto de los bloqueantes del sistema renina-angiotensina-aldosterona en la progresión de enfermedad renal crónica en pacientes hipertensos añosos sin proteinuria: ensayo clínico Progresión de Enfermedad Renal Crónica en Ancianos

Introduction: Evidence about nefroprotective effect with RAAS blockers in elderly patients with chronic kidney disease (CKD) without proteinuria is lacking. The primary outcome of our study is to evaluate the impact of RAAS blockers in CKD progression in elderly patients without proteinuria. Materials and methods: Multicenter open-label, randomized controlled clinical trial including patients over 65 year-old with hypertension and CKD stages 3–4 without proteinuria. Patients were randomized in a 1:1 ratio to either receive RAAS blockers or other antihypertensive drugs and were followed up for three years. Primary outcome is estimated glomerular filtration rate (eGFR) decline at 3 years. Secondary outcome measures include BP control, renal and cardiovascular events and mortality. Results: 88 patients were included with a mean age of 77.9±6.1 years and a follow up period of 3 years: 40 were randomized to RAAS group and 48 to standard treatment. Ethiology of CKD was: 53 vascular, 16 interstitial and 19 of unknown ethiology. In the RAAS group eGFR slope during follow up was −4.3±1.1ml/min, whereas in the standard treatment group an increase on eGFR was observed after 3 years (+4.6±0.4ml/min), p=0.024. We found no differences in blood pressure control, number of antihypertensive drugs, albuminuria, potassium serum levels, incidence of cardiovascular events nor mortality during the follow up period. Conclusions: In elderly patients without diabetes nor cardiopathy and with non proteinuric CKD the use of RAAS blockers does not show a reduction in CKD progression. The PROERCAN (PROgresión de Enfermedad Renal Crónica en ANcianos) trial (trial registration: NCT03195023). (AU)

Introducción: Actualmente no existe suficiente evidencia sobre el efecto nefroprotector de los bloqueantes del sistema renina-angiotensina-aldosterona (BSRAA) en pacientes añosos con enfermedad renal crónica (ERC) sin proteinuria y sin cardiopatía. El objetivo es evaluar el efecto de los BSRAA en la progresión de la ERC en este grupo poblacional. Métodos: Se trata de un estudio prospectivo, aleatorizado, que compara la eficacia de los BSRAA vs. otros tratamientos antihipertensivos en la progresión renal en personas mayores de 65 años con ERC estadios 3 y 4 e índice albúmina/creatinina<30mg/g. Aleatorización 1:1 BSRAA o tratamiento antihipertensivo estándar. Se recogieron cifras tensionales y parámetros analíticos de un año previo a la aleatorización y durante el seguimiento. Resultados: Se incluyeron 88 pacientes seguidos durante tres años con edad media de 77,9±6,1 años. De estos, se aleatorizaron 40 al grupo BSRAA y 48 al estándar. La etiología de ERC fue: 53 vascular, 16 intersticial y 19 no filiada. En el primer grupo se observó una progresión de la ERC con una caída del filtrado glomerular estimado (FGe) de -4,3±1,1mL/min, mientras que en el grupo estándar un aumento del FGe durante el seguimiento de 4,6±0,4mL/min, p=0,024. No se apreciaron diferencias entre ambos en el control tensional, el número de antihipertensivos, la albuminuria, los niveles de potasio, la incidencia de eventos cardiovasculares ni la mortalidad durante el seguimiento. Conclusiones: En pacientes añosos no diabéticos con ERC no proteinúrica y sin cardiopatía el uso de BSRAA no añade beneficio en la progresión de la ERC. Ensayo clínico Progresión de Enfermedad Renal Crónica en Ancianos (PROERCAN) (NCT03195023). (AU)

Distribution of Traditional Chinese Medicine syndromes in diabetic kidney disease chronic kidney disease 1-5: a correlation study.

OBJECTIVE: To analyze the distribution of Traditional Chinese medicine (TCM) syndromes in patients with diabetic kidney disease (DKD) and its related factors. METHODS: We enrolled 435 patients with DKD, who were not undergoing dialysis, admitted to the Department of Nephrology, First Medical Center, Chinese PLA General Hospital from April 2020 to August 2021. Analysis of their TCM syndromes and related factors was carried out. RESULTS: The 435 patients included 109, 117, 86, and 123 chronic kidney disease (CKD) 1-2, CKD3, CKD4, and CKD5 cases, respectively. With the progression of CKD1-5, the proportion of Yin deficiency and dry heat syndrome, and that of Qi and Yin deficiency syndrome showed a downward trend, whereas the proportion of spleen-kidney Yang deficiency, blood deficiency, blood stasis, water stagnation, and phlegm turbidity syndromes showed an upward trend; the differences were statistically significant (P < 0.05). Multivariate logistic regression analysis showed that Yin deficiency and dry heat syndrome was positively correlated with hemoglobin [odds ratio (OR) = 1.022, P = 0.005], albumin (OR = 1.058, P = 0.006), and estimated glomerular filtration rate (eGFR) (OR = 1.020, P < 0.001) but negatively correlated with male sex (OR = 0.277, P = 0.004). Qi and Yin deficiency syndrome was positively correlated with albumin (OR = 1.056, P < 0.001) and eGFR (OR = 1.008, P = 0.022) but negatively correlated with age (OR = 0.977, P = 0.023). Liver-kidney Yin deficiency syndrome was positively correlated with age (OR = 1.028, P = 0.021) and glycosylated hemoglobin (OR = 1.223, P = 0.007) but negatively correlated with total cholesterol (OR = 0.792, P = 0.006). Spleen-kidney Yang deficiency syndrome was negatively correlated with hemoglobin (OR = 0.977, P < 0.001), albumin (OR = 0.891, P < 0.001), and eGFR (OR = 0.978, P < 0.001) but positively correlated with high density lipoprotein (OR = 3.376, P = 0.001). CONCLUSION: With CKD1-5 progression, TCM syndromes changed from Yin deficiency and dry heat syndrome to syndrome of deficiency of both Qi and Yin, liver-kidney Yin, and spleen-kidney Yang deficiency syndromes. TCM syndromes were correlated with laboratory test results.

Identification of ligand and receptor interactions in CKD and MASH through the integration of single cell and spatial transcriptomics.

BACKGROUND: Chronic Kidney Disease (CKD) and Metabolic dysfunction-associated steatohepatitis (MASH) are metabolic fibroinflammatory diseases. Combining single-cell (scRNAseq) and spatial transcriptomics (ST) could give unprecedented molecular disease understanding at single-cell resolution. A more comprehensive analysis of the cell-specific ligand-receptor (L-R) interactions could provide pivotal information about signaling pathways in CKD and MASH. To achieve this, we created an integrative analysis framework in CKD and MASH from two available human cohorts. RESULTS: The analytical framework identified L-R pairs involved in cellular crosstalk in CKD and MASH. Interactions between cell types identified using scRNAseq data were validated by checking the spatial co-presence using the ST data and the co-expression of the communicating targets. Multiple L-R protein pairs identified are known key players in CKD and MASH, while others are novel potential targets previously observed only in animal models. CONCLUSION: Our study highlights the importance of integrating different modalities of transcriptomic data for a better understanding of the molecular mechanisms. The combination of single-cell resolution from scRNAseq data, combined with tissue slide investigations and visualization of cell-cell interactions obtained through ST, paves the way for the identification of future potential therapeutic targets and developing effective therapies.

Mincle receptor in macrophage and neutrophil contributes to the unresolved inflammation during the transition from acute kidney injury to chronic kidney disease.

Background: Recent studies have demonstrated a strong association between acute kidney injury (AKI) and chronic kidney disease (CKD), while the unresolved inflammation is believed to be a driving force for this chronic transition process. As a transmembrane pattern recognition receptor, Mincle (macrophage-inducible C-type lectin, Clec4e) was identified to participate in the early immune response after AKI. However, the impact of Mincle on the chronic transition of AKI remains largely unclear. Methods: We performed single-cell RNA sequencing (scRNA-seq) with the unilateral ischemia-reperfusion (UIR) murine model of AKI at days 1, 3, 14 and 28 after injury. Potential effects and mechanism of Mincle on renal inflammation and fibrosis were further validated in vivo utilizing Mincle knockout mice. Results: The dynamic expression of Mincle in macrophages and neutrophils throughout the transition from AKI to CKD was observed. For both cell types, Mincle expression was significantly up-regulated on day 1 following AKI, with a second rise observed on day 14. Notably, we identified distinct subclusters of Minclehigh neutrophils and Minclehigh macrophages that exhibited time-dependent influx with dual peaks characterized with remarkable pro-inflammatory and pro-fibrotic functions. Moreover, we identified that Minclehigh neutrophils represented an "aged" mature neutrophil subset derived from the "fresh" mature neutrophil cluster in kidney. Additionally, we observed a synergistic mechanism whereby Mincle-expressing macrophages and neutrophils sustained renal inflammation by tumor necrosis factor (TNF) production. Mincle-deficient mice exhibited reduced renal injury and fibrosis following AKI. Conclusion: The present findings have unveiled combined persistence of Minclehigh neutrophils and macrophages during AKI-to-CKD transition, contributing to unresolved inflammation followed by fibrosis via TNF-α as a central pro-inflammatory cytokine. Targeting Mincle may offer a novel therapeutic strategy for preventing the transition from AKI to CKD.

The Intersection of Chronic Kidney Disease and Depression.

Chronic kidney disease (CKD) and depression often coexist, resulting in a complex interaction that can be detrimental to patient outcomes. This article examines the reciprocal association between CKD and depression, with a focus on the increased incidence of depression and the harmful effects of depressive symptoms among patients with CKD. Next, it investigates the role CKD plays as a risk factor for the onset and worsening of depression because symptoms of depression may interfere with the progression of CKD. In addition, it highlights the difficulties in making a suitable diagnosis between CKD progression and depression regarding overlapping symptoms. Finally, it emphasizes the impact of depression on CKD outcomes, and proposes routine screening and non-pharmacological and pharmaceutical therapies to ease this dual burden. It is critical to identify and treat depression in the context of CKD to maximize patient outcomes and promote a comprehensive treatment approach.

An Intervention to Reduce Sedentary Behavior in Adults with Chronic Kidney Disease: A Feasibility Study.

Adults with chronic kidney disease (CKD) tend to be extremely sedentary. We investigated the feasibility and acceptability of a sedentary-reducing intervention for adults with CKD. The intervention utilized telephone-delivered coaching and a consumer wearable device to support participants to reduce their sedentary time. The mean age of participants in the sample was 60.5 years; 72% were women, and 83% had CKD Stage 3. At baseline, participants spent 73% of their waking time sedentary. Inter vention phone call attendance was 100%, study retention was 82%, and the intervention was rated as enjoyable (9.1/10). A telephone-delivered, sedentary-reducing intervention is feasible and acceptable in adults with CKD. Future work is needed investigating the efficacy of sedentary-reducing interventions for adults with CKD.

Comparative mathematical modeling of causal association between metal exposure and development of chronic kidney disease.

Background: Previous studies have identified several genetic and environmental risk factors for chronic kidney disease (CKD). However, little is known about the relationship between serum metals and CKD risk. Methods: We investigated associations between serum metals levels and CKD risk among 100 medical examiners and 443 CKD patients in the medical center of the First Hospital Affiliated to China Medical University. Serum metal concentrations were measured using inductively coupled plasma mass spectrometry (ICP-MS). We analyzed factors influencing CKD, including abnormalities in Creatine and Cystatin C, using univariate and multiple analysis such as Lasso and Logistic regression. Metal levels among CKD patients at different stages were also explored. The study utilized machine learning and Bayesian Kernel Machine Regression (BKMR) to assess associations and predict CKD risk based on serum metals. A chained mediation model was applied to investigate how interventions with different heavy metals influence renal function indicators (creatinine and cystatin C) and their impact on diagnosing and treating renal impairment. Results: Serum potassium (K), sodium (Na), and calcium (Ca) showed positive trends with CKD, while selenium (Se) and molybdenum (Mo) showed negative trends. Metal mixtures had a significant negative effect on CKD when concentrations were all from 30th to 45th percentiles compared to the median, but the opposite was observed for the 55th to 60th percentiles. For example, a change in serum K concentration from the 25th to the 75th percentile was associated with a significant increase in CKD risk of 5.15(1.77,8.53), 13.62(8.91,18.33) and 31.81(14.03,49.58) when other metals were fixed at the 25th, 50th and 75th percentiles, respectively. Conclusions: Cumulative metal exposures, especially double-exposure to serum K and Se may impact CKD risk. Machine learning methods validated the external relevance of the metal factors. Our study highlights the importance of employing diverse methodologies to evaluate health effects of metal mixtures.

Risk factors associated with COVID-19 mortality in Mexico.

BACKGROUND: On December 31, 2019, one of the most serious pandemics in recent times made its appearance. Certain health conditions, such as obesity and diabetes mellitus, have been described to be related to COVID-19 unfavorable outcomes. OBJECTIVE: To identify factors associated with mortality in patients with COVID-19. MATERIAL AND METHODS: Retrospective cohort of 998,639 patients. Patient sociodemographic and clinical characteristics were analyzed, with survivors being compared with the deceased individuals. Cox proportional hazards model was used to identify variables predictive of COVID-19-associated mortality. RESULTS: Among the deceased patients, men accounted for 64.3%, and women, for 35.7%, with the difference being statistically significant. Subjects older than 80 years had a 13-fold higher risk of dying from COVID-19 (95% CI = 12,469, 13,586), while chronic kidney disease entailed a risk 1.5 times higher (95% CI = 1,341, 1,798), and diabetes mellitus involved a risk 1.25 times higher (95% CI = 1.238,1.276). CONCLUSIONS: Age, sex, diabetes mellitus and obesity were found to be predictors of COVID-19 mortality. Further research related to chronic obstructive pulmonary disease, cardiovascular diseases, smoking and pregnancy is suggested.

ANTECEDENTES: El 31 de diciembre de 2019, se inició una de las pandemias más graves de los últimos tiempos. Se ha descrito que ciertas condiciones de salud, como la obesidad y la diabetes mellitus, están relacionadas con desenlaces desfavorables por COVID-19. OBJETIVO: Identificar factores asociados a mortalidad en pacientes con COVID-19. MATERIAL Y MÉTODOS: Cohorte retrospectiva de 998 639 pacientes. Se analizaron las características sociodemográficas y clínicas de los pacientes, y se compararon supervivientes con fallecidos. Se utilizó el modelo de riesgos proporcionales de Cox para la identificación de variables predictivas de defunción por COVID-19. RESULTADOS: Entre los fallecidos, los hombres representaron 64.3 % y las mujeres 35.7 %, diferencia que resultó estadísticamente significativa. Las personas con más de 80 años presentaron un riesgo 13 veces mayor de morir por COVID-19 (IC 95 % = 12.469,13.586) y la enfermedad renal crónica, un riesgo de 1.5 (IC 95 % = 1.341, 1.798); la diabetes mellitus tuvo un riesgo de 1.25 (IC 95 % = 1.238,1.276). CONCLUSIONES: La edad, el sexo, la diabetes mellitus y la obesidad resultaron ser entidades predictivas de muerte por COVID-19. Se sugiere más investigación relacionada con enfermedad pulmonar obstructiva crónica, enfermedades cardiovasculares, tabaquismo y embarazo.

Puerariae lobatae Radix ameliorates chronic kidney disease by reshaping gut microbiota and downregulating Wnt/ß­catenin signaling.

Gut microbiota dysfunction is a key factor affecting chronic kidney disease (CKD) susceptibility. Puerariae lobatae Radix (PLR), a traditional Chinese medicine and food homologous herb, is known to promote the gut microbiota homeostasis; however, its role in renoprotection remains unknown. The present study aimed to investigate the efficacy and potential mechanism of PLR to alleviate CKD. An 8­week 2% NaCl­feeding murine model was applied to induce CKD and evaluate the therapeutic effect of PLR supplementary. After gavage for 8 weeks, The medium and high doses of PLR significantly alleviated CKD­associated creatinine, urine protein increasement and nephritic histopathological injury. Moreover, PLR protected kidney from fibrosis by reducing inflammatory response and downregulating the canonical Wnt/ß­catenin pathway. Furthermore, PLR rescued the gut microbiota dysbiosis and protected against high salt­induced gut barrier dysfunction. Enrichment of Akkermansia and Bifidobacterium was found after PLR intervention, the relative abundances of which were in positive correlation with normal maintenance of renal histology and function. Next, fecal microbiota transplantation experiment verified that the positive effect of PLR on CKD was, at least partially, exerted through gut microbiota reestablishment and downregulation of the Wnt/ß­catenin pathway. The present study provided evidence for a new function of PLR on kidney protection and put forward a potential therapeutic strategy target for CKD.

Integrin-linked kinase mRNA expression in circulating mononuclear cells as a biomarker of kidney and vascular damage in experimental chronic kidney disease.

BACKGROUND: Traditional biomarkers of chronic kidney disease (CKD) detect the disease in its late stages and hardly predict associated vascular damage. Integrin-linked kinase (ILK) is a scaffolding protein and a serine/threonine protein kinase that plays multiple roles in several pathophysiological processes during renal damage. However, the involvement of ILK as a biomarker of CKD and its associated vascular problems remains to be fully elucidated. METHODS: CKD was induced by an adenine-rich diet for 6 weeks in mice. We used an inducible ILK knockdown mice (cKD-ILK) model to decrease ILK expression. ILK content in mice's peripheral blood mononuclear cells (PBMCs) was determined and correlated with renal function parameters and with the expression of ILK and fibrosis and inflammation markers in renal and aortic tissues. Also, the expression of five miRNAs that target ILK was analyzed in whole blood of mice. RESULTS: The adenine diet increased ILK expression in PBMCs, renal cortex, and aortas, and creatinine and urea nitrogen concentrations in the plasma of WT mice, while these increases were not observed in cKD-ILK mice. Furthermore, ILK content in PBMCs directly correlated with renal function parameters and with the expression of renal and vascular ILK and fibrosis and inflammation markers. Finally, the expression of the five miRNAs increased in the whole blood of adenine-fed mice, although only four correlated with plasma urea nitrogen, and of those, three were downregulated in cKD-ILK mice. CONCLUSIONS: ILK, in circulating mononuclear cells, could be a potential biomarker of CKD and CKD-associated renal and vascular damage.

The association between circadian syndrome and chronic kidney disease in an aging population: a 4-year follow-up study.

Introduction: Circadian syndrome (CircS) is proposed as a novel risk cluster based on reduced sleep duration, abdominal obesity, depression, hypertension, dyslipidemia and hyperglycemia. However, the association between CircS and chronic kidney disease (CKD) remains unclear. To investigate the cross-sectional and longitudinal association between CircS and CKD, this study was performed. Methods: A national prospective cohort (China Health and Retirement Longitudinal Study, CHARLS) was used in this study. To define CKD, the estimated glomerular filtration rate (eGFR) was calculated based on the 2012 CKD-EPI creatinine-cystatin C equation. Participants with eGFR <60 mL.min-1/1.73/m2 were diagnosed with CKD. Multivariate binary logistic regression was used to assess the cross-sectional association between CircS and CKD. Subgroup and interactive analyses were performed to determine the interactive effects of covariates. In the sensitivity analysis, the obese population was excluded and another method for calculating the eGFR was used to verify the robustness of previous findings. In addition, participants without CKD at baseline were followed up for four years to investigate the longitudinal relationship between CircS and CKD. Results: A total of 6355 participants were included in this study. In the full model, CircS was positively associated with CKD (OR = 1.28, 95% CI = 1.04-1.59, P < 0.05). As per one increase of CircS components, there was a 1.11-fold (95% CI = 1.04-1.18, P < 0.05) risk of prevalent CKD in the full model. A significant interactive effect of hyperuricemia in the CircS-CKD association (P for interaction < 0.01) was observed. Sensitivity analyses excluding the obese population and using the 2009 CKD-EPI creatinine equation to diagnose CKD supported the positive correlation between CircS and CKD. In the 2011-2015 follow-up cohort, the CircS group had a 2.18-fold risk of incident CKD (95% CI = 1.33-3.58, P < 0.01) in the full model. The OR was 1.29 (95% CI = 1.10-1.51, P < 0.001) with per one increase of CircS components. Conclusion: CircS is a risk factor for CKD and may serve as a predictor of CKD for early identification and intervention.

Uncovering specific taxonomic and functional alteration of gut microbiota in chronic kidney disease through 16S rRNA data.

Introduction: Chronic kidney disease (CKD) is worldwide healthcare burden with growing incidence and death rate. Emerging evidence demonstrated the compositional and functional differences of gut microbiota in patients with CKD. As such, gut microbial features can be developed as diagnostic biomarkers and potential therapeutic target for CKD. Methods: To eliminate the outcome bias arising from factors such as geographical distribution, sequencing platform, and data analysis techniques, we conducted a comprehensive analysis of the microbial differences between patients with CKD and healthy individuals based on multiple samples worldwide. A total of 980 samples from six references across three nations were incorporated from the PubMed, Web of Science, and GMrepo databases. The obtained 16S rRNA microbiome data were subjected to DADA2 processing, QIIME2 and PICRUSt2 analyses. Results: The gut microbiota of patients with CKD differs significantly from that of healthy controls (HC), with a substantial decrease in the microbial diversity among the CKD group. Moreover, a significantly reduced abundance of bacteria Faecalibacterium prausnitzii (F. prausnitzii) was detected in the CKD group through linear discriminant analysis effect size (LEfSe) analysis, which may be associated with the alleviating effects against CKD. Notably, we identified CKD-depleted F. prausnitzii demonstrated a significant negative correlation with three pathways based on predictive functional analysis, suggesting its potential role in regulating systemic acidbase disturbance and pro-oxidant metabolism. Discussion: Our findings demonstrated notable alterations of gut microbiota in CKD patients. Specific gut-beneficial microbiota, especially F. prausnitzii, may be developed as a preventive and therapeutic tool for CKD clinical management.

Bone aluminum accumulation in the current era.

In the last few years, evidence from the Brazilian Registry of Bone Biopsy (REBRABO) has pointed out a high incidence of aluminum (Al) accumulation in the bones of patients with CKD under dialysis. This surprising finding does not appear to be merely a passive metal accumulation, as prospective data from REBRABO suggest that the presence of Al in bone may be independently associated with major adverse cardiovascular events. This information contrasts with the perception of epidemiologic control of this condition around the world. In this opinion paper, we discussed why the diagnosis of Al accumulation in bone is not reported in other parts of the world. We also discuss a range of possibilities to understand why bone Al accumulation still occurs, not as a classical syndrome with systemic signs of intoxication, as occurred it has in the past.

Measuring the perceived wellbeing of hemodialysis patients: A Mind Genomics cartography.

Chronic Kidney Disease patients under hemodialysis have high morbidity rate, which tends to considerably affect their health-related quality of life. Multiple studies that have made use of different questionnaries report the poor life quality of this patient group. The research in hand implemented the Mind Genomics Approach as a method to asses the health-related quality of life of hemodialysis patients, while relying on conjoint measurements to group individuals with similar patterns of responses to a certain mindset. The study is conducted in 3 clinics with 219 patients. It uncovers three clusters or mindsets: Mindset 1- Feels guardedly optimistic but worried about money, Mindset 2-Feels strongly positive because the state guarantees and the family supports, Mindset 3-Feels positive only about money. Based on the analysis of the collected data, the findings of this study suggest that the quality of life in hemodialysis patients is highly correlated to their financial status. The current study is one of the few first attempts to apply Mind Genomics in medical settings and the first, to our knowledge, in hemodialysis centers. This technology might enable healthcare proffesionals to provide personalized psychological treatment and additional social support to patients, which in turn could improve their clinical outcomes. The study is an example of using technology as a service.

Designing for Improved Patient Experiences in Home Dialysis: Usability and User Experience Findings From User-Based Evaluation Study With Patients With Chronic Conditions.

BACKGROUND: Chronic kidney disease affects 10% of the population worldwide, and the number of patients receiving treatment for end-stage kidney disease is forecasted to increase. Therefore, there is a pressing need for innovative digital solutions that increase the efficiency of care and improve patients' quality of life. The aim of the eHealth in Home Dialysis project is to create a novel eHealth solution, called eC4Me, to facilitate predialysis and home dialysis care for patients with chronic kidney disease. OBJECTIVE: Our study aimed to evaluate the usability, user experience (UX), and patient experience (PX) of the first version of the eC4Me solution. METHODS: We used a user-based evaluation approach involving usability testing, questionnaire, and interview methods. The test sessions were conducted remotely with 10 patients with chronic kidney disease, 5 of whom had used the solution in their home environment before the tests, while the rest were using it for the first time. Thematic analysis was used to analyze user test and questionnaire data, and descriptive statistics were calculated for the UMUX (Usability Metric for User Experience) scores. RESULTS: Most usability problems were related to navigation, the use of terminology, and the presentation of health-related data. Despite usability challenges, UMUX ratings of the solution were positive overall. The results showed noteworthy variation in the expected benefits and perceived effort of using the solution. From a PX perspective, it is important that the solution supports patients' own health-related goals and fits with the needs of their everyday lives with the disease. CONCLUSIONS: A user-based evaluation is a useful and necessary part of the eHealth solution development process. Our study findings can be used to improve the usability and UX of the evaluated eC4Me solution. Patients should be actively involved in the solution development process when specifying what information is relevant for them. Traditional usability tests complemented with questionnaire and interview methods can serve as a meaningful methodological approach for gaining insight not only into usability but also into UX- and PX-related aspects of digital health solutions.

Renal Dysfunction Increases Risk of Adverse Cardiovascular Events in 5-Year Follow-Up Study of Intermediate Coronary Artery Lesions.

BACKGROUND Progression of chronic coronary syndrome (CCS) is influenced by chronic kidney disease (CKD). This 5-year follow-up study aimed to assess 100 patients with 118 intermediate coronary artery lesions evaluated by fractional flow reserve (FFR) and intravascular imaging stratified according to renal function. MATERIAL AND METHODS This prospective study enrolled patients with intermediate coronary stenosis identified by coronary angiogram. Patients with severe renal dysfunction (estimated glomerular filtration rate (eGFR) <45 ml/min/1.73 m²) were excluded from the study. The remaining were divided into 2 groups according to eGFR: 45-60 ml/min/1.73 m² for mild-to-moderate renal dysfunction and >60 ml/min/1.73 m² for no renal dysfunction. We analyzed intermediate-grade stenoses (40-80% as assessed in coronary angiography) with the use of optical coherence tomography (OCT), FFR, and intravascular ultrasound (IVUS). RESULTS Renal dysfunction patients were older (67.7±8.1 vs 63.6±9.7 years, P=0.044). Lesion characteristics, including plaque type and minimal lumen area in OCT, showed no significant differences between the renal dysfunction and no renal dysfunction groups. Thin-cap fibroatheroma, calcific plaques, lipidic plaques, and fibrous plaques had similar prevalence. FFR values and IVUS parameters did not significantly differ between the groups. Over a 5-year follow-up, individuals with mild-to-moderate renal dysfunction had an elevated risk of all-cause mortality and major adverse cardiovascular events in multivariate analyses adjusted for age and sex. CONCLUSIONS Mild-to-moderate renal dysfunction was not associated with significant differences in OCT- and IVUS-derived plaque morphology nor with functional indices characterizing intermediate-grade coronary stenoses. Renal dysfunction was related to a higher risk of all-cause mortality and major adverse cardiovascular events prevalence in 5-year follow-up.

Prevotella copri promotes vascular calcification via lipopolysaccharide through activation of NF-κB signaling pathway.

Emerging evidence indicates that alteration of gut microbiota plays an important role in chronic kidney disease (CKD)-related vascular calcification (VC). We aimed to investigate the specific gut microbiota and the underlying mechanism involved in CKD-VC. We identified an increased abundance of Prevotella copri (P. copri) in the feces of CKD rats (induced by using 5/6 nephrectomy followed by a high calcium and phosphate diet) with aortic calcification via amplicon sequencing of 16S rRNA genes. In patients with CKD, we further confirmed a positive correlation between abundance of P. copri and aortic calcification scores. Moreover, oral administration of live P. copri aggravated CKD-related VC and osteogenic differentiation of vascular smooth muscle cells in vivo, accompanied by intestinal destruction, enhanced expression of Toll-like receptor-4 (TLR4), and elevated lipopolysaccharide (LPS) levels. In vitro and ex vivo experiments consistently demonstrated that P. copri-derived LPS (Pc-LPS) accelerated high phosphate-induced VC and VSMC osteogenic differentiation. Mechanistically, Pc-LPS bound to TLR4, then activated the nuclear factor κB (NF-κB) and nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome signals during VC. Inhibition of NF-κB reduced NLRP3 inflammasome and attenuated Pc-LPS-induced VSMC calcification. Our study clarifies a novel role of P. copri in CKD-related VC, by the mechanisms involving increased inflammation-regulating metabolites including Pc-LPS, and activation of the NF-κB/NLRP3 signaling pathway. These findings highlight P. copri and its-derived LPS as potential therapeutic targets for VC in CKD.

Why is health literacy an essential component of health of individuals with chronic kidney disease / Pourquoi la littératie en santé est une composante essentielle de la santé des individus ayant une maladie rénale chronique.

Health literacy (HL) is the ability of individuals to access, understand and use health information to improve their health. It is a multidimensional and contextual concept, whose definition has been enriched over time. Considered both as a health risk factor and a skill to be developed by individuals, HL also depends on the healthcare system in which patients have to navigate, and on healthcare professionals' awareness of this concept. In order to promote shared decision-making and thus individual empowerment in the healthcare, HL should be at the core of the concerns of nephrology care teams.

La littératie en santé (LS) est la capacité d'un individu à accéder à des informations en santé, à les comprendre et à les utiliser pour améliorer son état de santé. Il s'agit d'un concept pluridimensionnel et contextuel dont la définition s'est enrichie au fil du temps. Considérée à la fois comme un facteur de risque pour la santé et une aptitude à développer chez les individus, la LS dépend également du système de santé dans lequel les patients doivent naviguer et de la sensibilisation des professionnels de santé à ce concept. Afin de favoriser la décision partagée et ainsi l'émancipation des individus en matière de santé, la LS devrait être au cœur des préoccupations des équipes de néphrologie.

Handgrip strength is associated with cognitive function in older patients with stage 3-5 chronic kidney disease: results from the NHANES.

In this study, we aimed to investigate the association between handgrip strength (HGS) and cognitive performance in stage 3-5 chronic kidney disease (CKD) patients aged ≥ 60 years. This cross-sectional study analyzed data from National Health and Nutrition Examination Survey (NHANES) database 2011-2014. Three tests were used to assess the cognitive performance, including consortium to establish a registry for Alzheimer's disease (CERAD), animal fluency test (AFT), and digit symbol substitution test (DSST). The multivariate linear regression analyses adjusting for confounding factors were utilized to evaluate the association of HGS with cognitive performance. A total of 678 older stage 3-5 CKD patients were included in this study. After adjusting for multiple factors, a higher HGS was positively associated with a higher CERAD-delayed recall and DSST score. In addition, our analysis indicated that HGS probably correlated with better performance of immediate learning ability in male, while working memory, sustained attention, and processing speed in female. HGS may be an important indicator for cognitive deficits in stage 3-5 CKD patients, especially for learning ability and executive function. Further research to explore the sex-specific and domain-specific and possible mechanisms are required.