bluuebunny/crossref_metadata_2025_split huggingface dataset:
MO578: UBE-1099, A Novel Non-Covalent Keap1-NRF2 Inhibitor, Protects Against Renal Ischemia-Reperfusion Injury
Authors: Ogi Sayaka , Sunamoto Hidetoshi , Fukiya Hirohiko , Nara Futoshi , Onuma Kazuhiro 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Bardoxolone methyl is a covalent Kelch-like ECH-associated protein 1 (Keap1) inhibitor that induces nuclear factor erythroid 2-related factor 2 (Nrf2) activation. Bardoxolone methyl improved glomerular filtration rate (GFR) in clinical trials for chronic kidney disease (CKD), although the mechanism remains unclear. Bardoxolone imidazole, an analog of Bardoxolone methyl suppressed tubular damage in a mouse acute kidney injury (AKI)-to-CKD model of unilateral ischemic reperfusion without contralateral nephrectomy (U-IR). Here, we evaluated the renal protective effect and the mechanism of a novel non-covalent Keap1 inhibitor, UBE-1099 in the U-IR mice.

METHOD
A fluorescence polarization-based (FP) assay and NQO1 activity-induction assay were performed to evaluate an inhibitory activity of Keap1 inhibitors. An U-IR mice were orally administered either the inhibitor (30 mg/kg, 10 mL/kg, once a day) or vehicle for 14 days and efficacy was evaluated. The whole transcriptome analysis with RNA-seq was conducted with whole kidney of the U-IR mice after 14 days treatment. A pathway analysis of the significantly differentially expressed genes detected was performed using Ingenuity Pathway Analysis (IPA) software.

RESULTS
UBE-1099 directly inhibited the interaction of Nrf2-Keap1 and induced NQO1 activity. The oral administration of UBE-1099 to the U-IR mice upregulated NQO1 expression in the kidney. UBE-1099 inhibited the decline in GFR and renal weight and significantly improved tubular damage and atrophic lesions in the U-IR model as effective as CDDO-Im without body weight loss. In addition, UBE-1099 significantly decreased the number of macrophages in the kidney.

CONCLUSION
A novel non-covalent Keap1 inhibitor, UBE-1099 improved the atrophic pathology, reduced tubular damage and inflammation resulting from Nrf2 activation in the U-IR mice. The compound has been suggested to be a promising drug for the renal diseases. Currently, the mechanism of action in improving renal function is being analyzed through RNA-seq analysis.
Figure:
MO592: Evolution of Body Composition During a Intradialysis Exercise Program Using Virtual Reality
Authors: Cana Poyatos Alicia , Segura-Ortí Eva , Vercher Narbona Verónica , Antonio Gil-Gómez José , José Martínez-Olmos Francisco , Valtueña-Gimeno Noemi , Benavent Caballer Vicente , Toquero Correa Marina , Garcia-Maset Rafael , Royo-Maicas Pilar , Garcia-Testal Alicia 
Published: May 2022

Abstract

BACKGROUND AND AIMS
There are few follow-up studies on the composition body by bioimpedance in exercise programs in different population. It is necessary to know if the body composition measured by bioimpedance change during a intradialysis exercise program using virtual reality. The aim is to determine evolution of body composition of patients on intradialysis exercise program using virtual reality.

METHOD
This is a subanalysis in a clinical trial with intradialysis exercise intervention. Intradialysis exercise consists in a video game adapted to dialysis: Treasure hunting. It is a nonimmersive virtual reality game in which the patient must catch some objectives avoiding obstacles by moving the lower limbs. The exercise lasts from 20 to 40 min. Intensity was checked through the rate of perceived exertion. The body composition is determined by multi-frequency stereoscopic bioimpedance . The study started in September 2019 (Baseline) but due to the COVID-19 pandemic it was paused for 1 year and started again in March 2021 (Restart). Body composition was determined basal, at 3th and 6th month in program. This study is funding from Programa Estatal de I + D + i Orientada a los Retos de la Sociedad, del Plan Estatal de Investigación Científica y Técnica y de Innovación 2017–2020 del Gobierno de España.

RESULTS
This is an open recruitment study, 49 patients have been recruited as of September 2021, mean (SD) age 72 (13) years, females 18. About 17 patients dropped out (16 of them don’t return after the pandemic start). To date, 32 patients are in exercise program.
Paired data analysis showed no difference in normohydrated weight, lean tissue index, or overhydration. The fat tissue index increased significantly (P 0.04) during the pause period in the first year of the pandemic. At the time of this communication, only 12 patients have completed 6 months of the program. We await the evolution of all included patients to report results at 6 months.

CONCLUSION
The evolution of body composition measured by bioimpedance during an intradialysis exercise program by virtual reality did not show relevant changes. Considering our results and those of previous studies, it’s possible that bioimpedance is not a very sensitive test to evaluate an intradialysis exercise program in the short to medium term. Longer and larger studies are needed.
MO596: Intradialysis Exercise at the Beginning Versus end of the Dialysis Session: Effect on the Dialysis Dose
Authors: Ortiz Sáez Natalia , Segura-Ortí Eva , Antonio Gil-Gómez José , Cana Poyatos Alicia , Garcia-Maset Rafael , Rico-Salvador Inmaculada , José Martínez-Olmos Francisco , Valtueña-Gimeno Noemi , Benavent Caballer Vicente , Toquero Correa Marina , Jose Cañada Martínez Antonio , Garcia-Testal Alicia 
Published: May 2022

Abstract

BACKGROUND AND AIMS
There is controversy over whether intradialysis exercise has an effect on the dialysis dose. Moreover, theoretical models indicate that intradialytic exercise performed at the end of session may have a beneficial effect in postdialysis rebound. Perhaps this effect of exercise at the end of dialysis can improve the dialysis dose. The aim in this study is to determine the effect of intradialysis exercise on dialysis dose, as well as its effect on dialysis dose when performed during the first two or the last two hours of dialysis session.

METHOD
This study is a randomized clinical trial. Patients were randomized to exercise in the first (Start group) or last two hours (End group) of dialysis session. Intradialysis exercise consists of a video game adapted to dialysis: Treasure hunting. It is a non-immersive virtual-reality game in which the patient must catch some objectives avoiding obstacles by moving the lower limbs. The exercise session lasts from 20 to 40 min. Intensity was checked through the rate of perceived exertion. Dialysis dose was measured through Kt/V single pool (Kt/V sp), urea reduction percentage (URP), KT and dialisance Kt/V (Kt/Vds) in the short period between dialysis, midweek. These was determined in two different weeks, in one week patients were at rest and in the other week patients did intradialysis exercise. The lean tissue mass (LTM) was determined by multi-frequency stereoscopic bioimpedance. This study is funding from Programa Estatal de I + D + i Orientada a los Retos de la Sociedad, del Plan Estatal de Investigación Científica y Técnica y de Innovación 2017–2020 del Gobierno de España.

RESULTS
This is an open recruitment study, at the time of this communication 29 patients are active, 14 in Start group and 15 in End group. Age mean (SD) 74 (12) years, males 17, Charlson's Index 8.1 (2.24), time on hemodialysys treatment 55.72 (57.67) months, central venous catheter 8, HDFOL 8. A mixed analysis of repeated measures has been developed with each measure of dialysis dose as the dependent variable (Kt/Vsp, URP, KT and Kt/V ds) and independent variables: group (Start versus End), duration of exercise session and LTM. There were no differences in dialysis dose between Start and End groups. Duration of exercise session significantly increased the dialysis dose (Kt/Vsp + 0.015, P = 0.007, URP + 0.23 P = 0.01 and Kt/V ds + 0.015, P = 0.01).

CONCLUSION
The time of the dialysis session in which physical exercise is performed does not influence the dialysis dose. Longer duration of the intradialysis exercise session increases the dialysis dose.
MO624: The Relationship Between Renal Tubular Epithelial Cell Necroptosis and The Severity of Diabetic Nephropathy
Authors: Yu Qi , Chen Ying , Qu Lei , Wu Wenyan , Huang Shuo , Wang Hui , Wang Suxia , Liu Gang , Yang L I 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Diabetic nephropathy (DN), a common complication of diabetic patients, usually contributes to end-stage renal failure. Accidental cell death (ACD) and regulated cell death (RCD) cause renal cell loss and deteriorate renal function during the progression of DN. MLKL is the executor of necroptosis, a major form of RCD. The multimer of phosphorylated MLKL (p-MLKL) gather at the cell membrane and form the leaking pores, performing the last step of necroptosis. This study aims to study the relationship of p-MLKL expression and the disease severity in DN patients, providing promising treatment target.

METHOD
A total of 30 patients who diagnosed with DN clinical-pathologically in the Peking University First Hospital from January 1998 to August 2018 were enrolled (excluding DN with primary or secondary glomerular diseases, DN combined with thrombotic microangiopathies and small vasculitis). p-MLKL were stained on renal biopsy kidney sections by immunohistochemistry. Image-Pro Plus 6.0 software (IPP) was used to analyze the expression of p-MLKL on 10 randomly taken images for each patient. The relationship between p-MLKL expression and clinical-pathological parameters was explored. Clinical parameters of plasma creatinine, peak plasma creatinine during renal biopsy period, estimated glomerular filtration rate (eGFR) were used. DN pathological changes contained: (i) glomerular lesions, (ii) arteriole lesions (iii) tubular lesions and (iv) tubules chronic interstitial lesions.

RESULTS
Compared with normal control, the positive expression of p-MLKL could be detected in the renal tubular interstitium of patients with DN. However, no p-MLKL positive signal was seen in the glomeruli. Patients with p-MLKL positive signals accounted for 73.33% (22/30) of the enrolled patients. Among the 30 patients, the value of p-MLKL kidney tissue IOD (integrated optical density) was positively correlated with peak serum creatinine (r = 0.373, P = 0.042), the pathological score of spherical sclerosis (r = 0.364, P = 0.048) and tubular brush border (TBB) loss (r = 0.363, P = 0.049).

CONCLUSION
The expression of necroptosis marker p-MLKL was significantly correlated with the clinical-pathological changes of DN patients. Its role in the progression of DN deserves further exploration.
MO628: A Clinical Score for Identifying Non-Diabetic Nephropathy in Patients with Diabetes and Kidney Disease
Authors: Bermejo Garcia Sheila , Agraz Irene , Vergara Ander , Jose Soler Romeo Maria 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Between 50% and 60% of diabetics with renal involvement have nondiabetic nephropathy (NDN). Renal biopsy is crucial for renal diagnosis that includes diabetic nephropathy (DN), NDN or mixed form. The objective of the current study is to provide a tool in the daily clinical practice through a predictive model of NDN that is clue for the indication of renal biopsy.

METHOD
Observational, retrospective and multicenter study was undertaken of the pathological results of kidney biopsies in patients with diabetes from 2002 to 2014. A logistic regression analysis and the probability of presenting NDN was calculated using a punctuation score.

RESULTS
The cohort of 832 patients includes 621 men (74.6%), median age 61.7 ± 12.8 years, creatinine 2.8 ± 2.2 mg/dL and proteinuria 2.7 (1.2–5.4)g/24 h. Time of evolution of diabetes was 10.8 ± 8.6 years. 26.6% (n = 221) of patients presented diabetic retinopathy, 18.8% (n = 156) peripheral vasculopathy and 17.7% (n = 147) ischemic heart disease. A total of 288 patients (34.6%) presented microhematuria. A total of 39.5% (n = 329) presented DN, 49.6% (n = 413) NDN and 10.8% (n = 90) mixed forms.
In the multivariate analysis, age (OR: 1.03; 1.01–1.04; P &lt; 0.001), absence of microhematuria (OR: 0.6; 0.4–0.86; P = 0.005), absence of diabetic retinopathy (OR: 3.97; 2.7–5.82; P &lt; 0.001) and absence of peripheral vasculopathy (OR: 1.61, 1.03–2.52, P = 0.038) were identified as independent risk factors for NDN. A ROC curve with an area under the curve of 0.724 was obtained. A predictive model obtaining a score (see Figure 1) for each variable and finally a NDN prediction score was performed. In our new score, the number increased as increased the probability of NDN.

CONCLUSION
In our study, ∼66% of biopsied patients with diabetes presented NDN. Microhematuria, absence of diabetic retinopathy, absence of peripheral vascular disease and older age were identified as independent risk factors for NDN. We obtained a score that increased as increased the probability of NDN. This could be in a next future a useful tool for renal biopsy indication in patients with diabetes and kidney disease.
MO635: Early Diabetic Kidney Disease in Type 2 Diabetes Mellitus Patients is Associated with A Particular Ganglioside Profile, Identified by High-Resolution Tandem Mass Spectrometry:A Pilot Study
Authors: Suteanu-Simulescu Anca , Ica Raluca , Sarbu Mirela , Munteanu Cristian , Gadalean Florica , Vlad Adrian , Velciov Silvia , Anca Gluhovschi Cristina , Bob Flaviu , Jianu Catalin , Cretu Octavian , Oana Milas Livia , Mogos Maria , Patruica Mihaela , Lavinia Balint , Silvia Ienciu , Diana Zamfir Alina , Petrica Ligia 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Metabolic biomarkers are of high importance for the identification of early renal involvement in the course of type 2 diabetes mellitus (DM). Gangliosides, which are complex cell type-specific glycosphingolipids, consist of a sialylated oligosaccharide chain attached to a ceramide of different composition with respect to the sphingoid base and fatty acid residues [1]. Gangliosides play a major role in the pathogenesis of diabetic kidney disease (DKD). The aim of the study was to assess the pattern of urinary gangliosides in patients with type 2 DM.

METHOD
The urine gangliosidome of 30 type 2 DM patients (10 normo-, 10 micro-, and 10 macroalbuminuric) has been investigated in a cross-sectional pilot study, by a comparative assay with 10 healthy controls. Following the optimization of urine ganglioside extraction procedure [2, 3], we have determined the composition of native ganglioside mixtures from the 24-h collected urine samples using a modern bioanalytical platform based on nanoelectrospray ionization (nanoESI) high-resolution mass spectrometry (HR MS) on an Orbitrap instrument.

RESULTS
HR MS screening and fragmentation analysis by tandem MS revealed that: (i) the urinary gangliosidome of type 2 DM patients contains a significantly higher number of distinct species differing in either their glycan or ceramide structure than the controls; (ii) the ganglioside urinary level was significantly increased in normoalbuminuric patients compared with healthy control subjects; (iii) the gangliosidome of macroalbuminuric patients is characterized by an elevated overall sialic acid content than normo- and microalbuminuric diabetics and more complex structures, including fucosylated, O-GalNAc- and CH3COO--modified compounds; (iv) the degree of sialylation of species presented correlations with the level of albuminuria and renal function; (v) further detailed structural analysis of a type GQ1(d18:1/18:0) species (identified only in macroalbuminuric patients) demonstrated that the present isomer is of type D (all four syalic acids are linked to the inner galactose).

CONCLUSION
HR MS by tandem MS methods, using an Orbitrap instrument, are a reliable tool for the identification of a particular ganglioside profile in the urine of type 2 DM patients. The sialylated species and those altered by peripheral attachments to the glycan core might be considered useful indicators of early DKD.
MO638: Direct Oral Anticoagulants in Patients with Atrial Fibrillation and Obesity, Type Two Diabetes, CKD
Authors: Abdullaev Sherzod , Igamberdieva Ranokhon 
Published: May 2022

Abstract

BACKGROUND AND AIMS
We aimed to estimate the clinical characteristics and outcomes of rivaroxaban and warfarin in patients with nonvalvular atrial fibrillation (NVAF) and concurrent obesity, type two diabetes (T2D) and chronic kidney disease (CKD).

METHOD
A multicenter prospective cohort study, where consecutive eligible rivaroxaban or warfarin treated patients with NVAF concurrent obesity, T2D and CKD, were registered. Patients were also required to be ≥18 years of age, and have obesity, which was defined as BMI ≥30 kg/m2 diabetes and CKD. Patients were followed-up for clinical events over a mean period of 1 year. Primary outcome was a composite of 1-year mortality, stroke or systemic embolism, major bleeding and myocardial infarction, end-stage kidney disease, while secondary outcomes included those components separated. Treatment cohorts were matched using propensity scores and were compared for stroke/systemic embolism (SE) and major bleeding using Cox proportional hazards models.

RESULTS
A total of 194 (n = 103, rivaroxaban; n = 91, warfarin) matched pairs of NVAF patients with obesity, T2D and CKD who initiated treatment with rivaroxaban or warfarin were included. Prior to matching, rivaroxaban patients were younger than warfarin patients (mean age, 67.9 versus 69.2 years) and had lower mean scores for the QCI, CHA2DS2-VASc and HAS-BLED. In the intent-to-treat analysis, patients receiving rivaroxaban had a significant 19% reduction in the composite risk of stroke or SE compared with those receiving warfarin [HR 0.85 (95% CI 0.77–0.90)]. The risk of each component of the composite outcome was lower in the rivaroxaban cohort versus the warfarin cohort with significant differences for ischemic stroke and hemorrhagic stroke. The difference in SE was not statistically significant. Outcome rates were lower in the as-treated sensitivity analysis, with significant reductions in the composite outcome of stroke/SE risk observed for rivaroxaban versus warfarin [HR 0.70 (95% CI 0.61–0.80)]. Ischemic stroke and hemorrhagic stroke risks were also significantly lower with rivaroxaban versus warfarin in the as-treated sensitivity analysis. The risk of major bleeding was similar between the rivaroxaban cohort and the warfarin cohort [HR 0.91 (95% CI 0.79–1.06)].

CONCLUSION
In NVAF patients with comorbidities of obesity, T2D and CKD, who initiated rivaroxaban had a significantly lower risk of stroke/SE compared with patients initiating warfarin. The risk of major bleeding was not significantly different between treatment groups. Patients receiving rivaroxaban had a significantly higher rate of adherence to treatment, supporting the use of rivaroxaban as an alternative to warfarin in NVAF patients with comorbidities of obesity, T2D and CKD.
MO650: In Vitro Performance Evaluation of a Filter Used for Hemodiafiltration by Using Β-Lactoglobulin
Authors: Sekiguchi Masaya , Kurihara Yoshitaka , Shigeta Yoshimi , Kobayashi Kozue , Kokubo Kenichi , Kubota Masaru 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Filters currently used for hemodiafiltration (HF) can remove sufficiently low to middle molecular weight solutes, like urea to β2 microglobulin (molecular weight: 11.800). Therefore, the removal rate of α1 microglobulin (α1-MG; molecular weight: 33.000) and albumin leakage are used as a guide to select a filter and to set appropriate operating conditions. Since α1-MG is very expensive, in vitro performance evaluation of the filters using α1-MG is not practical. In the present study, we aimed to investigate whether β-lactoglobulin (β-LG), which has a molecular weight of 18.400 and forms dimer (molecular weight: 36.800) under physiological conditions, can be used as a marker solute in the 30.000 molecular weight region.

METHOD
HF experiments were performed using 1.8 L of porcine whole blood (hematocrit: 30 ± 3%, total protein concentration: 6.5 ± 0.5 g/dL). The sieving coefficients of β-LG, separated from milk by membrane separation (untreated), made whey containing β-LG by acid treatment of milk and pH adjusted (acid-treated) and powdered reagent, were measured in porcine blood. In addition, HF experiments with permeate recycle were performed using three filters with different pore sizes (MFX-S, MFX-E and MFX-M; Nipro) at a blood flow rate of 250 mL/min and filtration flow rate of 42 mL/min for 240 min. The concentration of β-LG was measured by an enzyme-linked immunosorbent assay.

RESULTS
The sieving coefficient of acid-treated or powdered reagent β-LG added to the blood was almost equal to that of untreated β-LG. When the powdered reagent β-LG was treated with mercaptoethanol, the sieving coefficient became larger, meaning that the β-LG is tightly bound by disulfide bonds to form a stable dimer. In HF experiments using three filters with different pore sizes, the filter with a larger pore size resulted in lower transmembrane pressure. The sieving coefficients of β-LG decreased with time and were 0.15 ± 0.024, 0.39 ± 0.023, 0.75 ± 0.064 (mean ± SD, n = 3) at 60 min for MFX-M, MFX-E and MFX-S, respectively, indicating that the difference in filter performance was able to classify in the sieving coefficient of β-LG.

CONCLUSION
β-lactoglobulin existed stably as a dimer and was able to classify the performance of filters used for hemodiafiltration as a marker solute in the 30.000 molecular weight region.
MO666: Telemonitoring in Automated Peritoneal Dialysis. Analysis of the First 3 Months of the RM-APD Multicenter Study
Authors: Javier Centellas Pérez Francisco , Devesa Such Ramon , García Isabel , Vera Manel , Flores Carmen , Muñoz de Bustillo Eduardo , Manzano Diana , Alonso Valente Rafael , Prats Mercedes , Pedro Morais Jose , Luis Quirós Ganga Pedro , Díez Ojea Beatriz , Pérez Martínez Juan , Ortega Cerrato Agustin 
Published: May 2022

Abstract

BACKGROUND AND AIMS
The use of remote monitoring programs in peritoneal dialysis (RMAPD) has been related to favorable clinical events, as well as possible reductions in healthcare costs, although the medical literature is scarce.

METHOD
Prospective, multicenter, longitudinal 2-year study of cohorts to evaluate the number of significant interventions: face-to-face consultations and unscheduled teleconsultations, number of kilometers (km) saved, as well as clinical consequences (hospitalizations, peritonitis) in a cohort of patients in automated peritoneal dialysis with and without exposure to RMAPD. The data are presented in terms of mean, standard deviation and percentage.

RESULTS
The results of the first 3 months of analysis are shown, in descriptive terms, of incident patients in RMAPD versus No RMAPD, corresponding to 10 Spanish centers participating in the study. The data are shown in the Tables 1 and 2.

CONCLUSION
In this first quarterly exploratory analysis, despite its limitations, it is evident:
Although these results are promising, they still need to be confirmed during the follow-up of the patients over time and checked whether they are also related to other clinical and therapy parameters: time in therapy, technique abandonment rate, dialysis dose, peritonitis rate, hospitalizations and quality of life of the patient.