bluuebunny/crossref_metadata_2025_split huggingface dataset:
#6547 ON104, A NOVEL BIOENGINEERED ANTIBODY TARGETING OXIDIZED MACROPHAGE MIGRATION INHIBITORY FACTOR (OXMIF) AMELIORATES EXPERIMENTAL GLOMERULONEPHRITIS
Authors: Ferhat Maroua , Kerschbaumer Randolf , Tam Frederick , Prendecki Maria , Costa Lyndon , Thiele Michael , Landlinger Christine 
Published: June 2023

Abstract

Background and Aims
Macrophage Migration Inhibitory Factor (MIF) is a pleiotropic inflammatory cytokine and a primary counter-regulator of glucocorticoids (GCs) that emerged as a pivotal regulator of immune-mediated disorders including glomerulonephritis (GN). MIF occurs in two immunologically distinct, conformational isoforms: reduced MIF, ubiquitously present in various tissues and the circulation of healthy subjects, and oxidized MIF (oxMIF), described as the pathogenic and druggable isoform of MIF [1]. We previously reported a positive correlation between disease severity and urinary oxMIF levels in patients with acute lupus nephritis, suggesting oxMIF contribution to kidney damage [2]. In this study we evaluated the anti-inflammatory effects of oxMIF neutralization using ON104 antibody during crescentic GN.

Method
By advanced antibody engineering we generated the fully human antibody ON104 that is specific and highly affine for human oxMIF and its orthologs. ON104 was tested for its therapeutic potential in a rodent model of GN. Nephritis was induced in male WKY rats by a single intravenous (i.v.) injection of rabbit anti-rat GBM (glomerular basement membrane) serum. On day 4 and day 6 after GN induction, ON104 was administrated intraperitoneally (i.p.). Body weight, proteinuria, and hematuria were assessed to evaluate GN severity. On day 8, kidneys were harvested for immuno-histological examinations by HE, PAS-staining and IHC staining.

Results
Treatment with ON104 substantially attenuated clinical signs of GN by preserving kidney function demonstrated by reduced proteinuria, and reduced hematuria. Furthermore, ON104 significantly reduced tissue injury, reduced crescentic glomerulus formation, and increased the percentage of normal glomeruli. On the cellular level, oxMIF neutralization by ON104 reduced CD68+ macrophage accumulation within the inflamed kidneys compared to untreated and isotype Ig-treated rats.

Conclusion
Our findings substantiate the role of oxMIF in the pathogenesis of experimental GN. Thus, targeting oxMIF may represent a new and promising treatment option for kidney diseases.
#6562 ITGAM PROMOTES MACROPHAGE ALTERNATIVE ACTIVATION IN HYPERURICEMIA-RELATED CHRONIC KIDNEY DISEASE
Authors: Liu Jing , Guo Fan , MA Liang , Fu Ping 
Published: June 2023

Abstract

Background and Aims
Hyperuricemia is an essential risk factor in chronic kidney disease (CKD), while urate-lowering therapy to prevent or delay CKD progression is controversial. Alternatively activated macrophages in response to local microenvironment play diverse roles in kidney injury, repair, and fibrosis. Here, we aim to investigate whether and how macrophage ITGAM contributes to hyperuricemia-related CKD.

Method
In vivo, we explored dynamic characteristics of renal tissue in hyperuricemia-related CKD. By incorporating mRNA and protein sequencing data, we analyzed gene expression profile, hub genes and potential pathways responsible for disease development, which was further confirmed using qPCR, western blotting, and immunofluorescent stainings. In vitro, we validated bioinformatic findings under different conditions of macrophages with interventions corresponding to core nodes in pathway.

Results
Hyperuricemia-related CKD was characterized by the rise in serum uric acid, decline in renal function, macrophage alternative (M2) polarization, and kidney fibrosis. Integrated bioinformatic analyses revealed ITGAM as the potential core gene mediating disease progression which was associated with FAK/Akt1/β-catenin signaling. Notably, we confirmed the upregulated macrophage ITGAM, activated pathway, and macrophage M2 polarization in injured kidneys and Raw 264.7 macrophages. In vitro, we verified ITGAM/FAK/Akt1/β-catenin pathway participated in promoting macrophage M2 polarization through silencing Itgam and inhibiting FAK or Akt1 phosphorylation, where the expression of M2 phenotype macrophage markers and downstream molecules in pathway were down-regulated.

Conclusion
In hyperuricemia-related CKD, ITGAM promotes macrophage M2 polarization contributing to renal fibrosis through FAK/Akt1/β-catenin signaling pathway. Targeting macrophage ITGAM might be a promising therapeutic approach for preventing or delaying CKD.
#6648 LONG TERM EFFECT OF MEDIUM CUT-OFF DIALYZER ON MIDDLE UREMIC TOXINS
Authors: Bushljetik Irena Rambabova- , Markovska Zhaklina Shterjova- , Taneska Aleksandra Canevska , Janevski Zoran , Filipovski Stefan , Nikolov Igor , Andreevska Galina Severova- , Bushljetikj Oliver , Gjorgjievski Nikola , Pushevski Vladimir , Spasovski Goce , Trajcheska Lada 
Published: June 2023

Abstract

Background and Aims
Better removal capacities for middle and large middle molecules in hemodialysis was achieved in (HD) treatment with the new medium cut-off (MCO) membranes. The aim of this study was to evaluate the long term removal efficacy of Theranova® in standard HD in comparison with standard high-flux HD.

Method
11 patients were assigned to high flux and 11 to MCO membranes in 12-months observational study. Each patient was assessed every three months from T0 with high-flux dialyzers, T1 to T5 with MCO at first, third, sixth, nineth and twelfth month by measuring pre- and post-HD samples of β2-microglobilin (β2M), myoglobin, albumin, free light chains kappa (FLC-k), and free light chains lambda (FLC-λ). The cumulative change from as RR from T0 to T5 was defined as long term outcome.

Results
The data showed a higher average removal rate (RR) for all the uremic toxins with Theranova® dialyzers for β2M, myoglobin, FLC-k, and FLC-λ (66.1, 53.2, 59.2.5, and 60.9%, respectively) compared to high flux (57.1, 10.8, 29.9 and 37.4%, respectively). The analyses on the cumulative RR from T0 to T5 found significant decrement of β2M, myoglobin, FLC-λ in MCO vs high flux group where those values significantly raised (14.9 vs −6.1, p = 0.043; 27.7 vs −7.8, p = 0.001; 21.9 vs −4.2, p = 0.017, respectively). The FLC-k showed borderline significantly better removal with MCO (17.8 vs 8.4. p = 0.067). The distribution of patients with 12 month middle molecules reduction was much better in the MCO group. Albumin retention was better in MCO group and did not change between T0 and T5 (p = 0.824).

Conclusion
Compared to high-flux membranes, MCO membranes show greater permeability for middle molecules and albumin stability in long-term report. Their use in HD standard setting is effective and safe.
#6681 MT-TL1 M.3243A&gt;G MITOCHONDRIAL DNA VARIANT DETECTED FROM WHOLE EXOME SEQUENCING CAN EXPLAIN CASES OF ADULT UNKNOWN NEPHROPATHIES
Authors: Bensouna Ilias , Dancer Marine , Lebre Anne-Sophie , Raymond Laure , Doreille Alice , Lauteri-Badin Florence , Mesnard Laurent 
Published: June 2023

Abstract

Background and Aims
In a population-based study, mainly constituted of unknown nephropathies (cohort Sorbonne University, Paris, France N = 1197 patients), beyond reporting the diagnostic yield of nuclear genes, we also investigated the incidence of the mtDNA pathogenic variant MT-TL1 m.3243A&gt;G. This variation was systematically searched from whole exome sequencing (WES) data. In retrospect, we described the renal phenotype and studied the heteroplasmy level of the mtDNA variation in urine or kidney tissues compared to its blood fraction. The prevalence of m.3243A&gt;G has been estimated ranging from 0.08% to up to 0.25%.

Method
From September 2018, to February 2023, WES has been prospectively performed, as a first exploration of adult's nephropathies of unknown origin or when a genetic renal disease was clinically suggested. As off-target result, we retrieved m.3243A&gt;G variation in blood DNA and then determined the mtDNA heteroplasmic level respective from urine sample or kidney tissue when available with an orthogonal method.

Results
We report a molecular diagnosis in 294 over 1197 adult patients sequenced (diagnostic yield: 24%, Age 43 y/o in average). Among these 294 patients with molecular diagnoses, 48 were distinct monogenic disorders, out of which 8 accounted for 52% of the genetic diagnoses. MT-TL1 m.3243A&gt;G pathogenic variant was detected in 1,7% of the patients (20 patients over 1197 patients). An orthogonal method confirmed the presence of m.3243A&gt;G variant in 10 patients supporting the possibility to diagnose from blood DNA analysed by WES. In all cases, the presence of m.3243A&gt;G had major clinical implications for the patients and their families: living related donor aborted for two patients, a molecular diagnosis in three patients with unknown nephropathies and in three patients with histological diagnosis of focal segmental glomerulosclerosis. Other mitochondrial diseases appeared less likely involved in our adult cohort (only one patient with COQ2 pathogenic variants).

Conclusion
This population-based study reinforces the place of WES as first-tier exploration for adult patients with chronic kidney disease in whom phenotypes are often poor and/or atypical. The mitochondrial genome analysis with the same assay allowed the detection of yet unsuspected MT-TL1 m.3243A&gt;G variant in 1,7% of patients suggesting enrichment compared to current prevalence observed in other population. Our data suggest that the entity “mitochondrial nephropathy” can represent a significant part of adult unknown nephropathies.
#6698 THROMBOPROPHYLAXIS IN PEDIATRIC KIDNEY TRANSPLANTATION: A META-ANALYSIS
Authors: Azharuddin MD , Sharma Manju 
Published: June 2023

Abstract

Background and Aims
Kidney transplant patients are at higher risk for developing renal graft thrombosis, especially in pediatric patients. Renal graft thrombosis mainly causes graft failure leading to high morbidity, mortality, and a significant impact on quality of life. To minimize the risk of renal graft thrombosis, antithrombotic prophylaxis is widely used. However, the effect of antithrombotic prophylaxis for kidney transplantation is still a matter of discussion. Therefore, we carried out a meta-analytic synthesis to determine the effect of antithrombotic prophylaxis in pediatric kidney transplantation patients.

Method
We systematically searched MEDLINE, CENTRAL (Cochrane Central Register of Controlled Trials), and Web of Science. The eligible studies were identifying the incidence of renal graft thrombosis, hemorrhagic complication (bleeding and bleeding severity), and adverse outcomes related to antithrombotic prophylaxis compared with control group (placebo, active treatment, and no antithrombotic prophylaxis). Meta-analysis was carried out using Review Manager 5.3. The random-effects model was used to compute the pooled estimates of risk ratio (RR) and 95% confidence intervals (CI).

Results
A total of seven studies with 10,51 patients were included in the meta-analytic synthesis. Heparin was used across all the studies as the preferred antithrombotic prophylaxis. Results from the pooled meta-analysis reported that the overall risk for developing renal graft thrombosis was significantly lower in the antithrombotic prophylaxis group compared with the control group (RR = 0.81, 95% CI = 0.06-0.56, p = 0.003). There is no significant difference was found in incidence of hemorrhagic complications between antithrombotic prophylaxis and control group (RR = 0.81, 95% CI = 0.43-1.54). Similarly, there were no significant deaths were found in antithrombotic prophylaxis group compared with the control group (RR = 0.33, 95% CI = 0.01-22.45)

Conclusion
The results showed that antithrombotic prophylaxis significantly reduced the risk of renal graft thrombosis in pediatric kidney transplantation. However, due to limited outcomes, further real-world studies with long-term follow-up are required to generate sufficient data on the use of antithrombotic prophylaxis in pediatric kidney transplantation patients.
#6706 ACUTE KIDNEY DISEASE FOLLOWING COVID-19 VACCINATION: A RETROSPECTIVE, SINGLE- CENTER STUDY
Authors: Chen Chien-Chou , Yang Sung-Sen , Hsu Yu-Juei , Sung Chih-Chien , Chu Pauling , Wu Chia-Chao , Hsu Shun-Neng , Wang Han-En , Lin Shih-Hua 
Published: June 2023

Abstract

Background and Aims
The rare de novo or relapsed kidney diseases associated with coronavirus disease 2019 (COVID-19) vaccination have been increasingly reported. The aim of the study was to investigate the incidence, characteristics, and outcome of acute kidney disease (AKD) following COVID-19 vaccination.

Method
This retrospective study scrutinized the data from renal registry in a single academic medical center from Jan. 1st, 2020, to Apr. 30th, 2022. Patients who developed AKD within 90 days after COVID-19 vaccination were first included. Naranjo score as a causality assessment tool for adverse vaccination reaction and charts review by peer nephrologists were utilized for the exclusion of other causes. The etiologies of AKD, their characteristics, treatment, and outcome attributing to the COVID-19 vaccines were examined (Fig. 1).

Results
Twenty-seven aged 23 to 80 patients with AKD were identified from 1897 patients (incidence of 6.3 per 1000 patient-years). Their Naranjo score was 7.7± 1.5, and 14 of 27 patients (51.9%) had definite diagnosis (Naranjo score ≥ 9). They incorporated both glomerular disease (n = 16) including IgA nephropathy (n = 7), anti-neutrophil cytoplasmic antibodies-associated glomerulonephritis (AAN) (n = 4), membranous glomerulonephritis (n = 3), minimal change disease (MCD) (n = 2), and chronic kidney disease (CKD) with acute deterioration (n = 11). The majority (21 of 27, 77.8%) of COVID-19 vaccination was messenger RNA (mRNA)-based regimen. Four patients (14.8%) rapidly progressed to end stage kidney disease (ESKD) requiring dialysis despite aggressive management. Extra-renal features such as pulmonary hemorrhage, myopericarditis and hepatitis/pancreatitis were observed in 4 patients.

Conclusion
In summary, AKD after COVID-19 vaccination may occur with more alarm in this renal registry. In addition to GN, patients with pre-existing moderate to severe CKD should also receive more intensive evaluation before vaccination despite the established benefits of vaccination in this vulnerable population likely outweigh the risk.
#6732 EPICARDIAL ADIPOSE TISSUE AND REVERSE EPIDEMIOLOGY IN DIALYSIS PATIENTS
Authors: D'marco Luis , Checa-Ros Ana , Karohl Cristina , Soto Carlos , Bermudez Valmore , Raggi Paolo 
Published: June 2023

Abstract

Background and Aims
Conventional risk factors of cardiovascular disease and mortality in the general population such as body mass is relate to adverse outcome in dialysis patients, but often in an opposite direction (reverse epidemiology). On the contrary, epicardial adipose tissue (EAT) has reported to have a local inflammatory and proatherogenic effect. Thus, the association of EAT as direct measures of region specific adipose tissue in chronic kidney disease (CKD) has been studied.

Method
The study evaluated 37 CKD-5 patients in hemodialysis (mean dialysis duration 26±30 months, 70% males, 57% African-American, 48% diabetic) that underwent MSCT to measure EAT and coronary artery calcium (CAC) score. CAC distribution in quartiles of EAT was assessed. Finally, we measured patients’ body mass index (BMI) and categorized them as normal (BMI 18.5-25 kg/m2) and abnormal BMI (BMI &gt;25 kg/m2).

Results
The mean BMI was 28.6±5.7 kg/m2, and the mean EAT volume was 66±29 ml and 102±69 ml for normal and abnormal BMI groups. There was a direct correlation between dialysis vintage and EAT while BMI showed an inverse relationship with dialysis vintage (p = 0.05). In this small sample size, the association of CAC and EAT was only marginally significant (p = 0.7). EAT was significantly correlated with age (p = 0.02), history of cardiovascular disease (p = 0.03) and diabetes (p = 0.001).

Conclusion
The direct association of EAT with dialysis vintage in the face of an inverse association of BMI with dialysis duration appear to support the notion that chronic hemodialysis is a state of chronic inflammation and malnutrition.
#6733 THE PREDICTORS OF CARDIO-RENAL SYNDROME AMONG PATIENTS WITH COVID-19 INFECTION
Authors: Attallaha Aber , Mansour Hazem , Khouly Ahmed Tareq El , Farrag Osama , Tanagho Bishoy Abd El Maseeh 
Published: June 2023

Abstract

Background and Aims
Several reports showed that some Covid-19 patients tend to have serious and fatal complications related to the kidney and heart. Rationale and mechanisms inducing this pathogenesis is unclear, but it's more common to happen in patients with hemodynamic instability and refractory severe hypotension related to cytokine storm. It represents an irreversible stage of a sepsis-like illness that induces simultaneous damage to various organs as the myocardium and renal tubules alike the cardio-renal syndrome. The predictors for this injurious effect of COVID-19 on both myocardium and renal tissues might be related to the co-morbidities, late presentation and other factors which need further evaluation.The aim of this article is to study the predictors of cardio-renal syndrome in COVID-19 patients

Method
Our study is a prospective observational study conducted upon confirmed 160 COVID-19 ICU patients admitted from 15th March till 20th May 2020. All patients were subjected to clinical assessment, full laboratory evaluation including PCR for COVID-19 from nasopharyngeal swab and full radiological evaluation

Results
As regards the predictors for cardio-renal syndrome [15-17]; Age showed high statistically significance (P &lt;0.0004). Furthermore, serum creatinine and serum K were statistically significant in patients with cardio-renal affection (P= 0.015, 0.021) whereas GFR, D-dimer, need for mechanical ventilation and vasopressors were highly statistically significant with cardio-renal affected patients (P &lt;0.001).

Conclusion
Cardio-renal syndrome was common in COVID-19 ICU patients. Hypokalemia, lower GFR on admission, mechanical ventilation, vasopressors, age and D-dimer were significant independent predictors for CRS. Moreover,CRS during hospitalization was associated with an increased risk of in-hospital death.
#6760 EFFICACY OF HEMOSORPTION IN REMOVAL OF HIGH MOLECULAR WEIGHT UREMIC TOXINS IN CHRONIC HEMODIALYSIS PATIENTS
Authors: Karpov Pavel , Vishnevskii Konstantin , Gerasimchuk Roman 
Published: June 2023

Abstract

Background and Aims
Symptoms associated with the accumulation of large uremic toxins (the development of chronic inflammation, accelerated progression of cardiovascular diseases and an increase in the incidence of protein-energy malnutrition) are common for patients who get chronic hemodialysis (HD) for a long time. HD effectively removes small and medium molecules (up to 15 kDa), while convection techniques, which are not always available, are used to remove substances of higher molecular weight. An alternative strategy for removing uremic toxins, especially large medium molecules, is the use of sorption techniques. The aim of the study was to compare the removal efficiency of substances with a molecular weight from 11.8 to 45 kDa using HD on a high-flux membrane and a combination of a high-flux membrane with hemosorption.

Method
The study included patients with a duration of hemodialysis therapy for more than 5 years. Blood sampling was carried out before and after the procedures, in the average RRT session per week. The following indicators were determined: β-2-microglobulin, leptin, free light chains (FLC) κ and λ, Il-6. The first HD session was performed on a Fresenius Fx-80 high-flux membrane. The second procedure (one week after) was carried out using the same filter, but with the connection of a Jafron HA130 sorption column (HD+HP). The duration of the both procedures was 4 hours. Blood flow did not exceed 300 ml/min.

Results
Total 10 patients were included in the study. Mean duration of renal replacement therapy was 12±5 years. The ratio of men and women was equal. Mean age 54±12 years. All patients used AV fistulas as vascular access. When determining and comparing the concentrations of β-2-microglobulin, leptin, Il-6, a comparable significant decrease in concentrations was noted after both procedures without significant statistical differences between the methods. At the same time, the efficiency of FLC removal on HD and HD+GP was convincingly different:
- average kappa-FLC concentration change after HD was +1.8±9.1 mcg/ml, after HD+GP:
-9.4±7.5 mcg/ml, p = 0.04.
- average lambda -FLC concentration change after HD/HD+GP was +3.2±16.3 and -12.9±4.4 mcg/ml, respectively. p = 0.02.

Conclusion
The use of sorption techniques as an adjunct to standard HD therapy can increase the excretion of medium-large molecular substances, such as FLC kappa/lambda, which may help reduce the severity of symptoms associated with the accumulation of these uremic toxins. Additional studies are required to evaluate the clinical effectiveness of the new sorption method in chronic HD.
#6768 TIO2/TI3C2 NANOCOMPOSITES FOR BILIRUBIN CLEARANCE FROM BLOOD
Authors: Chang Kaixi , Su Baihai 
Published: June 2023

Abstract

Background and Aims
The artificial liver treatment based on blood purification is an important and commonly used treatment for liver failure. Aggressive management of hyperbilirubinemia is one of the key steps to reduce mortality in patients with liver failure. Herein, targeting bilirubin in nano-sized, we synthesized a TiO2/Ti3C2 nanocomposite from Ti3C2 MXenes via hydrothermal oxidation for bilirubin clearance from whole blood.

Method
Firstly, Ti3C2 MXene was prepared by hydrofluoric acid etching method reported in our previous work [1]. Then, it was transferred into Teflon-lined stainless-steel autoclaves (2 mg/ml, 30 ml) and was undergone the hydrothermal process at 180 °C for 6 h and 12 h. TiO2/Ti3C2 nanocomposites were obtained after lyophilization. Hemocompatibility evaluation assays include hemolysis ratio test, complement activation (human complement fragment 5a (C5a)), contact activation (Thrombin–anti-thrombin (TAT) complex) and platelet activation (platelet factor 4 (PF 4)) were systemically conducted in vitro to evaluate the feasibility of the novel nanocomposites (0.5 mg/ml) in contact with blood. We evaluated the bilirubin adsorption capacity of original Ti3C2 (0 h) and TiO2/Ti3C2 (6 h and 12 h) at the concentration of 0.5 mg/ml, respectively, in bilirubin solution (250 mg/l, 10 ml) for 2 h at 37 °C in an air bath away from light. The sphere-forming properties of TiO2/Ti3C2 with polyethersulfone (PES), a commonly used blood purification material, were first verified using a liquid-liquid inversion method.

Results
TiO2/Ti3C2 (6 h and 12 h) showed better hemocompatibility than the original Ti3C2 (0 h) (Figure 1). The bilirubin adsorption capacities by the original Ti3C2 (0 h) and TiO2/Ti3C2 (6 h and 12 h) were 354.11 mg/g, 492.83 mg/g and 492.52 mg/g, respectively. From the original Ti3C2 (0 h) to TiO2/Ti3C2 (6 h), the clearance rate of bilirubin improved from 70.82% to 98.57%. Therefore, we chose TiO2/Ti3C2 (6 h) to verify the sphere-forming properties of TiO2/Ti3C2 with PES. TiO2/Ti3C2-PES spheres were constructed successfully by a liquid-liquid inversion method. More 3D porous structure on the surface and uniform distribution of TiO2/Ti3C2 (Ti element) in the substrate were observed via a scanning electron microscope (SEM) images and energy dispersive spectroscopy (EDS) mapping images (Figure 2).

Conclusion
The TiO2/Ti3C2 nanocomposite showed excellent bilirubin clearance capability, superior hemocompatibility, and the great application potential in the form of spheres for hemoperfusion, which may provide a promising choice in the performance enhancement of artificial liver characterized by bilirubin clearance. Importantly, the above properties are adjustable by the heating temperature and the time period, other application forms and strategies of the TiO2/Ti3C2 nanocomposite to target bilirubin in nano-sized are worth being explored and expected.