bluuebunny/crossref_metadata_2025_split huggingface dataset:
Monocyte Anisocytosis Changes in Patients After Major Burn Injuries
Authors: Nazemidashtarjandi Saeed , Muldur Sinan , Supple Matthew D , Ryan Colleen M , Yonker Lael M , Karabacak Murat N , Goverman Jeremy , Yarmush Martin L , Irimia Daniel 
Published: May 2024

Abstract
The recovery of patients after severe burns is a long and complex process. Genomic analysis of white blood cells from burn and trauma patients revealed excessive and prolonged innate immune activation in patients with complicated outcomes. However, translating this knowledge into practical biomarkers has not been possible yet. Although several biomarkers for monitoring burn patients have been proposed, their ability to accurately distinguish between inflammation stemming from initial tissue destruction, infections, and organ failure complications is limited. Here, we focused on monocytes, critical innate immune cells in the response to burn injured tissues. We measured the monocyte anisocytosis (quantified as monocyte distribution width (MDW), a recently emerged marker of sepsis) throughout the recovery of patients from the time of burn injury until the end of the hospital stay. We observed that MDW increases in patients during the first week after major burns. Among the patients with major burns who survive, MDW starts decreasing in the second week and normalizes by the end of the hospital stay. The duration of hospital stay appears to be proportional to how fast MDW decreases during the second week after the injury. We also found that MDW decreases significantly in most patients after excision and debridement surgeries but not after allo- and auto-graft surgeries. Moreover, high MDW values correlated with a higher rate of positive microbiology blood culture samples and respiratory infections. These findings underscore the importance of monitoring MDW as a potential biomarker for the risk of complications during burn patient recovery.
#2837 Novel therapeutic for crescentic glomerulonephritis through targeting CLDN1 in parietal epithelial cells
Authors: Delbet Jean-Daniel , Anquetil Vincent , Saitoski Kevin , Toso Alberto , Baumert Thomas , Toovey Stephen , Manenti Luigi , Iacone Roberto , Ulinski Tim , Lenoir Olivia , Teixeira Geoffrey , Tharaux Pierre-Louis 
Published: May 2024

Abstract

Background and Aims
Crescentic glomerulonephritis (CrGN) is the final mode of kidney injury common to several immune-mediated kidney diseases. CrGN is characterized by extensive glomerular parietal epithelial cells (PECs) proliferation forming crescents. The destructive crescent is then progressively replaced by fibrosis. Currents therapies for CrGN do not directly target the deleterious response of resident kidney cells. In a pathological context, claudin-1 (CLDN1), a transmembrane protein involved in epithelial tight junctions, can be exposed outside the tight junctions and mediate pro-fibrotic pathways and extracellular matrix (ECM) remodelling. Lixudebart (formerly ALE.F02) is a first-in-class monoclonal antibody that specifically targets and blocks exposed CLDN1 in injured epithelial cells. A phase II clinical trial is under way for patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) with rapidly progressive glomerulonephritis which induces kidney fibrosis (RENAL-F02, NCT06047171). CLDN1 is highly expressed by glomerular PECs. This study investigated the functional role of CLDN1 in CrGN and the potential benefit to target CLDN1 in CrGN.

Method
CLDN1 expression in renal tissues of CrGN patients was analyzed using kidney multicolor immunofluorescence staining and spatial transcriptomics. Correlation between CLDN1 expression and clinical endpoints (eGFR, proteinuria), disease biomarkers and crescent evolution were studied. A spatially resolved molecular roadmap from CLDN1+ crescentic glomeruli was conducted. Proof-of-concept studies using anti-CLDN1 mAb were performed in preclinical models of CrGN.

Results
In tissues (n = 150) of patients with AAV and IgAN, multicolor immunofluorescence revealed up-regulated CLDN1 expression by cellular and fibrocellular crescents. At the time of diagnostic kidney biopsy, glomerular CLDN-1 expression was correlated with podocyte loss (as measured with P57 staining) and fibronectin area.
The extent of dual expression of CLDN1 and CD44 at the surface of active PECs was associated with poor renal outcome (eGFR &lt; 30 ml/min) in AAV and IgAN patients with a median follow-up of 2.5 and 3.7 years respectively. Spatial transcriptomics analysis highlighted the association between CLDN1+ crescentic glomeruli and ECM genes.
Treatment with anti-CLDN1 mAb reduced albuminuria, improved kidney function and decreased fibrosis biomarkers in nephrotoxic serum-induced CrGN in mice.

Conclusion
Our results suggest a functional role of CLDN1 in the pathogenesis of CrGN, providing preclinical proof-of-concept for anti-CLDN1 antibodies as a novel therapeutic approach in patients with CrGN.
#1308 Role of uremic compound, indoxyl sulfate, in the cardiac alterations lead by the acute kidney injury
Authors: Fogaça-Ruiz Fernanda , Carneiro-Ramos Marcela , Da Silva Jéssica Verônica , Falconi Carlos Alexandre 
Published: May 2024

Abstract

Background and Aims
Uremic toxins (UTs) have been largely discussed in the late years due to its deleterious effects in different tissues in the human body. In healthy people, UTs are excreted by the kidneys, however, if they are not filtered because of any imbalance of the organism, the state of uremia starts damaging not only the kidneys but also the heart and other organs. Indoxyl Sulfate (IS) is a protein-bound UT, that is not removed by the dialysis membrane, and has its mechanisms still unknown. The cross-talk between the heart and the kidneys is called cardiorenal syndrome (CRS) and is usually divided in 5 different types. The CRS 3 is described as an acute kidney injury (AKI) leading to posterior cardiac alterations. Therefore, the present work aims to investigate the effects of IS in a model of CRS 3 induced by AKI.

Method
All surgical procedures and protocols were approved by the Ethics Committee on Animal Use of the Federal University of ABC (no. 5250040123) in accordance with the National Council for Control of Animal Experimentation (CONCEA). Mice C57BL/6 (between 6 and 8 weeks of age) were submitted to the left kidney ischemia and reperfusion protocol as previously described by our group [1] for 60 minutes. After, they were divided in two groups: 1) Injected with IS (100 mg/kg/day) during 15 days intraperitoneally; 2) Control: treated with saline 0.9% for the same period. The Sham group went through the same procedures but didn't have the renal pedicle clipped. The animals were submitted to euthanasia and the blood, heart, kidneys and tibia were harvested to posterior analysis. Data are expressed as mean ± SEM. One-way ANOVA was used to statistically analyze all groups followed by Tukey's post hoc test; p &lt; 0.05 was considered statistically significant.

Results
The morphometric analysis demonstrated that there was no difference in the heart weight/body weight and heart weight/tibia length ratios in the different experimental groups. IR+IS promoted a significant increase in the right kidney weight/tibia length ratio (80.54 ± 2.919 sham vs 94.34 ± 2.698 IR+IS). Regarding the left kidney, IR promoted a decrease in the kidney weight/tibia length ratio, when compared to the sham group (35.88%), indicating success in the AKI induction protocol. The urea dosage was reduced in the group treated with IS in relation to IR (52.88 ± 1.767 Sham+IS vs 70.75 ± 3.004 IR), but it did not present statistical significance among the other groups. Creatinine levels remained unchanged regardless of the group.

Conclusion
Treatment with IS does not lead to morphometric changes in the heart, and in the kidneys, it does not intensify the effect of ischemia.
#2711 Cardiomyocytes exposed to medium conditioned by kidney cells treated with the uremic toxin p-cresyl sulfate undergo changes in cell viability
Authors: Bedin Beatriz Favero , de Souza Laura Francisca Leite Do Prado , Rodrigues Tiago , Ramos Marcela Sorelli Carneiro 
Published: May 2024

Abstract

Background and Aims
Cardiorenal Syndrome (CRS) is a condition involving the heart and the kidneys, where a disturbance in one of these organs can lead to alterations in the other. High levels of uremic toxins (UTs) such as p-Cresyl Sulfate (PCS) can induce renal injury. Furthermore, UTs play a crucial role in inflammatory status and cardiac function. Therefore, it is crucial that studies regarding the influence of uremic toxins in the context of cardiorenal syndrome be conducted. Nevertheless, few studies have been conducted in the context of Acute Kidney Injury (AKI) causing acute damage to the heart, and few mechanisms are still known. The objective of the study was to evaluate the role of PCS in cell viability and inflammatory genes in renal and cardiac cells, to simulate cardiorenal syndrome due to excessive PCS.

Method
The HEK293 (human epithelial renal cells) and H9c2 (murine cardiomyocyte cells) cell lines were used. HEK293 was treated with concentrations of 0.25 mM, 0.5 mM, 1 mM, and 1.5 mM PCS for 6, 24, and 48 hours. H9c2 was treated with PCS (1.5 mM) and conditioned media from PCS-treated renal cells (1.5 mM) for 6 and 24 hours. MTT assays, growth curve analysis, and Hoechst-PI staining were performed. Gene expression was evaluated by RT-qPCR. ANOVA followed by Bonferroni post-test was conducted, considering P &lt; 0.05 as significant.

Results
PCS treatment led to a time and dose-dependent decrease in cell viability. The cell growth curve indicated a negative impact across time on renal cell proliferation at all different PCS concentrations. Hoechst-PI assay revealed increased cell death in the treatment with PCS (1.5 mM) for 24 hours. There was no change in the gene expression of IL-6, IL-1β, Bax, and Bcl-2 in renal cells. Cardiac cell viability decreased both after direct PCS treatment (85.3%) and exposure to PCS-conditioned media from renal cells for 24 hours (87.3%).

Conclusion
PCS reduces renal cell viability and inhibits cell proliferation without affecting the inflammatory status and apoptosis signaling within the evaluated time frames. Cardiac cell viability decreased after PCS treatment, either directly or indirectly, suggesting a cardiotoxic effect of PCS, independent of changes in renal cells.
#2374 Long-term clinical outcomes in pediatric patients with primary nephrogenic insipidus
Authors: Ahn Yo Han , Lim Seon Hee , Kim Ji Hyun , Lee Seung Jae , Song Ji Yeon , Park Eujin , Park Se Jin , Park Min Ji , Cho Min Hyun , Kang Hee Gyung , Suh Jin Soon 
Published: May 2024

Abstract

Background and Aims
Nephrogenic diabetes insipidus (NDI) is a rare inherited disorder, and there is a paucity of studies assessing long-term clinical outcomes in affected individuals. This study aims to evaluate the long-term clinical outcomes, encompassing growth and kidney function, in pediatric patients with NDI.

Method
This multicenter retrospective study included forty-nine children diagnosed with NDI. The medical records of these patients were retrospectively reviewed, and a linear mixed model was employed to analyze variations in growth and kidney function with increasing age.

Results
Mutations in the AVPR2 and AQP2 genes were identified in 40 (81.6%) and 4 (8.2%) patients, retrospectively, while pathogenic variants were either not found or not tested in 5 (10.2%) patients. The median ages at diagnosis and the last follow-up were 0.41 (interquartile ranges (IQR) 0.12−0.64) years and 9.97 (IQR 2.42−18.66) years, respectively. Thiazide treatment was administered to all patients, with 43 (87.8%) and 14 (28.6%) patients also receiving amiloride and indomethacin, respectively, in conjunction with thiazide. Our analysis using linear mixed models revealed significant changes in growth including height, weight, and body mass index (BMI) with increasing age. The estimated marginal means (EMM) for height Z score decreased from −0.114 (95% confidence interval (CI) −0.507 to 0.279) at diagnosis to −1.464 (95% CI −1.880 to −1.048) at 2 years of age, subsequently increasing to −0.706 (95% CI −1.186 to −0.225) at 14 years of age (P &lt; 0.001). The height Z score at 19 year of age is −0.899 (95% CI −1.434 to −0.365), significantly lower than those at diagnosis (P = 0.038). The EMM for weight Z score increased from −1.580 (95% CI −2.009 to −1.149) at one year of age to 0.760 (95% CI 0.170 to 1.350) at 19 years of age, exhibiting a steady increase (P &lt; 0.001). The EMM for BMI Z score demonstrated a consistent increase after age of 2 years (P &lt; 0.001), which were −0.326 (95% CI −0.835 to 0.182) at 2 years of age and 1.210 (95% CI 0.602 to 1.817) at 19 years of age. The proportion of obesity increased from 3.2% at 3 years of age to 33.3% at 19 years of age. The EMM for estimated glomerular filtration rate (eGFR) consistently increased from 82.8 (95% CI 75.2 to 90.3) mL/min/m2 to 100.8 (95% CI 88.9 to 112.7) mL/min/m2. Although eGFR less than 60 mL/min/m2 is not present, the eGFR less than 90 mL/min/m2 is 47.5% at last follow up.

Conclusion
At the end of growth, the height Z score is low, and the proportion of obesity is high. To improve the growth pattern, clinicians need to monitor nutritional status and establish nutritional support during follow-up in patients with NDI. Since mild decreased kidney function developed in half, patients with NDI need long-term follow-up evaluation for kidney function.
#3127 Bedside cycling modulated the bone-resorption markers in patients with end-stage renal disease
Authors: Lu Kuo-Cheng , Hou Yi-Chou 
Published: May 2024

Abstract

Background and Aims
Exercise provided multifactorial benefits in improving the health of the CKD patients. The exercise itself improved the bone remodeling. For CKD patients, chronic kidney disease mineral bone disorder (CKD-MBD) is an important complication and the treatment for renal osteodystrophy is unsatisfactory. The aim of study is to validate the role of bedside cycling in bone remodeling markers for patients with end-stage renal disease (ESRD).

Method
Participants were grouped into 4 groups: health control, chronic kidney disease (GFR 15∼60 ml/min) and ESRD (GFR&lt;15 ml/min with maintenance dialysis). For ESRD patients, 12-week bedside cycling ((30 minutes per session; 3 times per week) were given for subjects. The pre-and post-exercise bone remodeling markers and clinical outcome were compared in ESRD with and without exercise in ESRD subjects.

Results
Bone formation markers (Bone specific alkaline phosphatase (15.57 ± 1.59 pg/dL) and Procollagen type 1 amino-terminal propeptide (1269.12 ± 116.34 pg/dL) were higher in ESRD patients with correlation with indoxyl sulfate and intact parathyroid hormone concentration(p &lt; 0.05) respectively. In ESRD patients, the post-exercise concentration of Tartrate-resistant acid phosphatase 5b (3.64 ± 0.25 pg/dL to 4.23 ± 0.31 pg/mL, p = 0.003) and N-terminal telopeptide-1 (113.67 ± 20.53 pg/mL to 260.61 ± 30.9 pg/mL, p = 0.001)increased after 12 weeks of bed-side cycling. The hospitalization and mortality were similar between ESRD with or without exercise.

Conclusion
The bone formation marker concentration increased along with the severity of CKD. Bedside cycling increased the concentration of the bone resorption markers in ESRD patients.
#1351 Assessment of safety and efficacy of expanded hemodialysis in comparison to HDF
Authors: Marcello Matteo , Simonini Marco , Virzì Grazia Maria , Lorenzin Anna , Brendolan Alessandra , Ronco Claudio , Zanella Monica 
Published: May 2024

Abstract

Background and Aims
In end-stage kidney disease, solutes with a wide spectrum of molecular weight, called uremic toxins, are retained due to impaired kidney cleansing capacity. Particularly, the retention of toxins in the middle molecular weight range 15–45 kDa might negatively affects multiple organ systems and metabolic pathways. The removal of such large uraemic toxins is still a challenge. HDF has produced some results although large convective volume, optimal vascular access to increase the blood flow rate and strict water quality management are required. Medium Cut-Off, high Retention Onset membrane have been recently developed introducing the concept therapy called “expanded haemodialysis” (HDx). Furthermore, vitamin E-coated membrane has potential beneficial effects on inflammation and oxidative stress.

Method
A prospective longitudinal single-center study was conducted for 3 months among 18 chronic haemodialysis patients. Patients were randomly assigned into either HDF with high flux membrane or HDx with Theranova or ViE-X membrane. The primary goal was to assess albumin loss among the three types of dialyzers. Secondary goals included assessment of depurative efficacy for uraemic toxins and clinical outcomes. Throughout the treatment, a proportional part of the dialysis fluid was collected to quantify albumin loss. Blood samples were taken before and after dialysis session in order to calculate the Removal Ratio and at two different intradialytic timepoints from arterial and venous line of the circuit in order to calculate instantaneous clearance.

Results
Mean albumin loss was significantly higher in patients undergoing HDx with Theranova membrane (ANOVA, p&lt;0.001) without any difference in serum albumin concentration among the three groups. Instantaneous clearance of small and middle molecules was significantly higher in patients undergoing HDF, but we didn't find differences in removal ratio. Reduction of Erythropoietin resistance index was observed in patients treated with ViE-X membrane but it was related to their lower dialysis vintage.

Conclusion
HDx with Theranova membrane was associated with higher albumin loss without any effect on pre-dialysis serum albumin. Moreover, patients treated Theranova membrane, in the presence lower Qb, lower convective dose and lower instantaneous clearance reached same dialysis efficacy compared to HDF.
#2158 Circulating kidney injury molecule-1 a valuable marker of mortality in hemodialysis patients?
Authors: Sircuta Alexandru , Bob Flaviu , Grosu Iulia Dana , Schiller Adalbert , Petrica Ligia , Schiller Oana-Marina , Ivan Viviana , Madalina Bodea Alexandra , Golet Ionut 
Published: May 2024

Abstract

Background and Aims
The importance of finding reliable biomarkers of mortality in CKD, and especially in patients treated with hemodialysis has become evident. Plasma KIM-1 has been mentioned as a marker of cardiovascular morbidity.. The aim of this study is to assess the level of plasma Kidney Injury Molecule- 1 (KIM-1) as a marker of mortality in patients treated with hemodialysis.

Method
We conducted a single-center study that included 63 CKD G5D patients (hemodialysis for 1-5 years) followed up for 48 months and a control group consisting of 52 patients diagnosed with CKD stages G1-G5, without HfrEF. All patients have been assessed at baseline, regarding cardiovascular disease (medical history, echocardiography and ECG). Circulating plasma KIM-1 levels were determined with single molecule counting immunoassay technology using the Enzyme-linked immunosorbent assay, we performed using standard methods blood biochemistry, and markers of inflammation (CRP, IL-6) and markers of anemia (complete blood count, serum ferritin, transferrin saturation- TSAT).

Results
Mean plasma KIM1 levels were 403.8 +/-546.8pg/ml) in the group of patients treated with hemodialysis, and was statistically significantly higher compared to the level in the control group (217.48 +/-267.10 pg/ml). In the group of patients treated with hemodialysis plasma KIM-1 levels showed a statistically significant correlation with inflammation (mean CRP- R=0.28, p=0.02 and IL6- R=0.36, p=0.005) and with anemia (hematocrit- R= -0.5, p=-0,0316; hemoglobin - R= -0.5, p=0.02 We found out using ANOVA that patients which presented left ventricular hypertrophy on echocardiography (37 out of 62) had significantly lower mean levels of plasma KIM-1 (155,51 vs 432,12 pg/ml; p=0,026). The group of patients with vascular calcifications on echocardiography (48 out of 62) had lower levels of serum KIM1 (210.01 vs 462.58 pg/ml, p=0.04).
After 24 months of follow up we found a mortality rate of 22.23%, while after 48 months the mortality rate was of 50.73%. Using a Cox proportion-hazards regression analysis of predicting factors of mortality we found that regarding the relationship between plasma levels of KIM-1 and mortality there is a significantly decreased survival in patients with low KIM-1&lt;81.98 pg/ml (p&lt;0.001), with a cut-off point for plasma KIM-1 levels= 81.98 pg/ml.

Conclusion
Plasma KIM-1 levels were significantly higher in patients treated with hemodialysis compared to the control group (ND CKD patients). However, surprisingly, low levels of plasma KIM1 were associated with some cardiovascular changes and also to an increased risk of mortality (at 4 years, not after few months).
#703 Usability of a mobile health app for peritoneal dialysis patients: a pilot study
Authors: Cely Javier , Sanabria Mauricio , Doria Cesar Mauricio , Dazzarola Maria Paz , del Castillo Alvaro , Martinez Anthony , Camargo David , Vesga Jasmin , Aldana Andrea , Sánchez Ricardo , Rivera Angela , Rutherford Peter 
Published: May 2024

Abstract

Background and Aims
Technology has changed how people interact with the world, so health apps may be useful for patients with long term conditions, facilitating adherence and enabling remote monitoring. Usability is a critical factor when evaluating the quality of a mobile health app, as it indicates the ease with which a user can use it to achieve specific clinically orientated goals with effectiveness, efficiency, and satisfaction.

Method
The mHealth App Usability Questionnaire (MAUQ), a reliable and validated tool, was used to evaluate the MyPD® mobile health app's usability for adult peritoneal dialysis (PD) patients. The arm using the My PD app in a pilot randomized clinical study in six renal clinics in Colombia from September 2022 to August 2023 was evaluated. The MAUQ questionnaire includes 18 items assessing 3 domains related to ease of use (5 items), interface and satisfaction (7 items) and usefulness (6 items). Patients rated each item on a seven-point Likert scale, with one (1) strongly disagreeing and seven (7) strongly agreeing. The overall rating is the mean of eighteen items (standalone version); closer to seven (7), higher usability. The socio-demographic and clinical characteristics of all patients were summarized descriptively.

Results
MyPD app allows patients to collect and view their clinical information and dialysis treatment. Figure 1 shows a general overview of the different navigation windows. A total of 65 patients were included in this analysis; the mean age was 52.2 years, 44.6% were in CAPD, and 21.5 % achieved elementary school education or were illiterate (Table 1).
The overall usability was 6.5 (SD 0.7), the maximum possible score is 7. The items related to satisfaction and interface have a mean of 6.8 (SD 0.5). Regarding ease of use, the mean was 6.6 (SD 0.8), a very high figure given the socio-cultural context of a middle-income country. In relation to usefulness, the mean was 6.1 (SD 1.5). Patients rated the overall satisfaction item with the app as 6.8 (SD 0.6). See details in Table 2. These results are better than those reported by other authors (Table 3).

Conclusion
The usability of the health app MyPD® was rated very high by patients, which will allow this application to be used widely as a tool that supports the outpatient care of PD patients.