bluuebunny/crossref_metadata_2025_split huggingface dataset:
MO242: Intrarenal Single Cell Sequencing of Hepatitis B Virus Associated Membranous Nephropathy
Authors: Zhong Yong 
Published: May 2022

Abstract

BACKGROUND AND AIMS
The pathogenesis underlying hepatitis B virus (HBV)-associated membranous nephropathy (MN) remains incompletely understood.

METHOD
To decipher the etiopathogenesis of HBV-associated MN, intrarenal single-cell RNA sequencing (scRNA-seq) was applied to the kidney biopsy from a HBV-associated MN patient and a health control to define the transcriptomic landscape at single-cell resolution. Differentially expressed genes (DEGs) and enrichment analysis were compared between HBV-associated MN and anti-PLA2R positive idiopathic membranous nephropathy (IMN) using intrarenal scRNAseq.

RESULTS
We generated 4114 intrarenal single-cell transcriptomes from a HBV-associated MN patient by single-cell RNA-sequencing. We found that kidney podocytes cells in the HBV-associated MN patient displayed increased expression of several genes, including EDIL3, GPC6, HSPA5 and CTGF, which were closely related to extracellular matrix formation. Kidney endothelial cells of HBV-associated MN were mainly enriched in inflammatory pathways including TNF signaling, IL-17 signaling, NOD-like receptor signaling, NF-kappa B signaling pathway and Toll-like receptor signaling pathway. TNF signaling pathway and IL-17 signaling pathway activation were confirmed in proximal tubule cells from the HBV-associated MN patient. Moreover, ligand-receptor analysis highlighted the extensive communication of mesangial cells, which infers great importance in HBV-associated MN. Furthermore, gene ontology (GO) function enrichment analysis revealed that DEGs of endothelial cells from the HBV-associated MN patient were enriched in interleukin-6 secretion and interleukin-1 secretion when compared with anti-PLA2R positive IMN.

CONCLUSION
These results offer new insight into the pathogenesis of HBV-associated MN.
MO246: Belimumab Disrupts Memory B Cell Trafficking in Patients with Systemic Lupus Erythematosus
Authors: Arends Eline J , Zlei Mihaela , Tipton Christopher M , Osmani Zgjim , de Bie Fenna , Kamerling Sylvia W A , Rabelink Ton , Sanz Ignacio , Van Dongen Jacques J M , van Kooten Cees , Teng Yeo K O 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Belimumab (BEL), a recombinant human monoclonal antibody directed against B-cell activating factor (BAFF), is the first approved biological agent for patients with systemic lupus erythematosus (SLE) and a high level of disease activity or lupus nephritis (LN). BEL inhibits primary humoral immune responses by depleting naive B-cells that are dependent on BAFF for their survival while secondary humoral immune responses by memory B cells (MBCs) remain intact. Indeed, some studies reported an increase of circulating MBCs following neutralization of BAFF [1–3]. So far these effects of BEL on the MBC compartment in SLE patients have not been investigated. This study aimed to establish the dynamics of circulating MBCs in patients with SLE treated with BEL and to perform an in-depth analysis of the impact of BEL on the MBC compartment.

METHOD
First, extensive B cell subset phenotyping was performed prospectively by employing high-sensitivity flow cytometry (HSFC) based on EuroFlow protocols [4] in severe SLE/LN patients treated with BEL [5]. Additionally, in-depth characterisation of surging MBCs in circulation was performed by single-cell RNA sequencing (scRNA-seq).

RESULTS
HSFC established that the increase in MBCs was non-specific and observed in a broad range of MBC immunoglobulin subclasses peaking as early as 2 weeks after BEL initiation. Subsequent scRNA-seq analysis of the emerging MBCs revealed a non-proliferating phenotype with a prominent decrease in activation status. In these circulating MBCs, a large amount of migration and adhesion genes were downregulated suggesting that the accumulation of MBCs by BEL initiation was related to their impaired cell–cell adhesion disrupting cell-trafficking and preventing extravasation.

CONCLUSION
After initiation of BEL treatment, a substantial increase of circulating MBCs was firmly established in patients with SLE/LN. The surge of circulating MBCs appeared to be associated with disrupted lymphocyte trafficking of MBCs, thereby suggesting a new potential therapeutic mechanism of BEL on MBCs in SLE. These findings have important implications to our understanding and consequent improvement of B-cell targeted treatment strategies in patients with active SLE and LN as MBC accumulation in circulation might allow for more efficient targeting of the B-cell compartment.
MO248: A Renal Biopsy Might be a Mandatory Procedure in Patients with Hypertension and Decreased Renal Function Despite Normal Urinalysis Findings
Authors: Hee Cho Won , Cho Byoung-Soo , Min Jung Sung , Soon Lee Hyun 
Published: May 2022

Abstract

BACKGROUND AND AIMS
The most common cause of the end-stage renal disease is diabetes and hypertension. However, most centers do not try to find the cause of hypertension in patients with early-stage CKD but give antihypertensive medicine because most centers regard the cause as essential hypertension. Since blood pressure is regulated by the kidneys, we tried to find the cause of hypertension related to kidney disease.

METHOD
We carried out a single-center retrospective analysis of 1440 kidney biopsies performed for 8 years at a single center in Korea. All cases were done at the OPD level without admission, of which 367 cases (25.5%) showed hypertension/early-stage CKD with normal urinary findings at the time of renal biopsy.

RESULTS
The results are as follows in order of frequencies: IgA nephropathy (32.7%), mild focal nonspecific glomerulonephritis (GN) (17.7%), focal segmental glomerulosclerosis (FSGS) (15.3%), diffuse mesangial proliferative GN (12.8%), interstitial nephritis with tubular atrophy (7.6%), podocyte disease (3.3%) and membranous nephropathy (1.9%), and others include lupus nephritis, membranoproliferative GN, C1q nephropathy, C3GN, malignant hypertension (1.4%), etc. Most patients (95%) with hypertension/early-stage CKD were associated with chronic glomerulonephritis. Most patients with serious glomerular disease that may progress to ESRD, such as IgAN, FSGS and diffuse mesangial proliferative glomerulonephritis, have improved by aggressive immunotherapy.

CONCLUSION
In conclusion, before considering antihypertensive medicine in patients with early-stage CKD, a renal biopsy might be a mandatory procedure to save the kidney because more than 90% of cases are associated with glomerular disease.
MO258: Urinary Single-Cell Sequence Analyzes the Urinary Macrophage in Different Outcomes of Membranous Nephropathy
Authors: Liu XI , Zhao Yu , Niu Yangyang , Xie Qionghong , Zuo Wei , Yu Chen 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Great progresses have been made in the diagnosis and treatment of membranous nephropathy (MN), but some patients still do not respond to the treatment. We performed single-cell sequencing to analyze the urine cells of patients with and without complete remission of MN. Hope to provide some insights for understanding the different outcome of MN.

METHOD
Urine single-cell RNA sequencing was performed on 12 healthy controls (HC) and 15 patients with MN. The patients were divided into complete remission group (CR, n = 9) and no remission group (NR, n = 6), according to the response to at least 6 months of immunosuppressive treatment.

RESULTS
(i) Macrophages were the largest group in urine cells; they were 48.02%, 68.96% and 20.95% in the HC, CR and NR group, respectively. (ii) Detecting cell surface markers to tell their origins. The results showed that urinary macrophages expressing FIColin-1 and S100 calcium binding protein A8 were mainly in NC group and CR group, indicating that they were derived from bone marrow and peripheral blood, while the urinary macrophages expressing the regulator of G-protein signaling 1 and HLA-DPA1, mainly in the NR group, were differentiated from intrinsic kidney cells. (iii) There were different characteristics of urinary macrophage in the three groups. In healthy adults, urine macrophages expressed the metallothionein family, indicating that they can regulate anti-inflammatory and proinflammatory functions bidirectionally. In the CR group, the urine macrophages showed strong proinflammatory properties. In the NR group, the urinary macrophages mainly associated with the level of proteinuria and the impaired renal function with poor proinflammation.

CONCLUSION
Our study firstly delineated urinary cell maps of healthy individuals and the MN patients. Not only in origin but also in function of urine, macrophages were different in the NC, CR and NR group. This might be a significant help to our understanding of membranous nephropathy.
MO266: Deficiency of Urokinase-Type Plasminogen Activator Exacerbates CBSA-Induced Membranous Nephropathy in Mice
Authors: Jao Tzu-Ming , Guo Chian-Huei , Bai Chia-Yu , Chen Jin-Shuen 
Published: May 2022

Abstract

BACKGROUND AND AIMS
In nondiabetic population, primary membranous nephropathy (PMN) is the most common cause of idiopathic nephrotic syndrome in the world. Urokinase-type plasminogen activator (uPA) is one of the key members of fibrinolysis system, which functions as dissolving blood clots to prevent obstruction of blood vessels. Currently, the roles of uPA in PMN remain undefined.

METHOD
Six-week-old male mice with Plau wild-type and knockout in BALB/c strain were used to induce MN by cationic bovine serum albumin (cBSA). Biochemistry assays of blood and urine were measured by a Fuji Dri-Chem FDC NX 500 machine. Glomerular polyanions were determined by using Colloidal Iron Stain Kit. Reactive oxygen species (ROS) was detected by immunohistochemistry stained by 4-HNE antibody. TUNEL positivity in the kidneys of mice was determined using an ApopTag® Plus Peroxidase In Situ Apoptosis Kit. The deposition of immune complex in glomeruli was examined by a transmission electron microscope. Lymphocyte subsets were determined by flow cytometry. Serum concentrations of IgG1 and IgG2a were measured by ELISA.

RESULTS
It has been reported that BALB/c mice is an ideal strain for mimicking human PMN. Thus, we generated uPA deficient mice (Plau-/-) in BALB/c strain by backcrossing C.129S2-Plautm1Mlg/J mice with BALB/c wild-type mice to N10. Plau-/- mice exhibited severe urinary albumin-to-creatinine ratio significantly when compared with wild-type mice at 2 weeks post-cBSA administration. Consistently, cBSA-induced Plau-/- mice displayed higher serum creatinine, hypoalbuminemia and hypercholesterolemia than wild-type mice. Histologically, Plau-/- mice presented more severed glomerular basement thickening, IgG granular deposition, intensified podocyte effacement, irregular thickening of glomerular basement membrane and subepithelial deposits than wild-type mice. Attenuated colloidal iron stain was observed in Plau-/- mice when compared with wild-type mice. Moreover, elevated ROS and apoptosis in the kidneys of Plau-/- mice were observed. B lymphocyte subsets were enriched significantly in the Plau-/- mice with MN, suggesting that pathological aggravation of MN is associated with dominant B lymphocyte population. The enriched ratio of IgG1 to IgG2a further confirmed predominant Th2 subset in Plau-/- mice.

CONCLUSION
uPA deficiency enhances Th2 dominant immune response, leading to enhancement of ROS and apoptosis in the kidneys, which subsequently exacerbates the progression of MN. Maintenance of uPA homeostasis may be a promising therapeutic approach for MN management.
MO283: A Novel Hemoperfusion Adsorbent for Selective Removal of Circulating Histones in Septic Blood
Authors: LI Yupei , Song Tao , Jiang Luojia , Yu Qiao , Wang Liya , Xiong Yuqin , Chang Kaixi , Deng Ningyue , Geng Jiwen , Zhao Weifeng , Su Baihai 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Circulating histones play a crucial role in the development and progression of sepsis and is associated with high mortality. Hemadsorption with the CytoSorb® filter has been shown to non-specifically eliminate systemic circulating histones in plasma from injured patients ex vivo and in vitro. The aim of this study was to fabricate another novel hemoperfusion adsorbent for selective removal of histones in the blood of septic patients.

METHOD
Chitosan-cellulose composite hydrogels (CSCE) were first prepared using a liquid-liquid inversion method. Then, negatively charged heparin was grafted onto the surfaces of the CSCE hydrogels by EDC chemistry to obtain the histone sorbents (CSCEHEP hydrogels). The chemical structure of CSCEHEP hydrogels was characterized by Fourier transform infrared spectroscopy (FTIR) and its hemocompatibility was evaluated. The adsorption capacity and adsorption selectivity of CSCEHEP hydrogels for histone were then analysed by BCA protein quantitative method. Besides, the antagonistic effect of CSCEHEP hydrogels on histone-induced cytotoxicity was verified by in vitro cell experiments using HK-2 cell lines.

RESULTS
The obtained CSCEHEP hydrogels showed characteristic adsorption peaks of the sulfonic group at 1217 and 940 cm-1 in their FTIR spectrum, suggesting the successful immobilization of heparin onto the surface of the sorbent. The clotting time of plasma after a 30-min incubation with CSCEHEP hydrogels was significantly prolonged by 3 times while no obvious hemolysis, platelet activation, complement activation and other blood-material adverse reactions occurred during this incubation. With a heparin grafting, the adsorption capacity of CSCEHEP hydrogels towards histones (from calf thymus) increased significantly to 314.3 μg/g, with a clearance rate of 62.8%, compared to that of pristine CSCE, which is dependent on the initial histone concentrations in testing solutions. On the contrary, the adsorption capacity of bovine serum albumin by CSCEHEP hydrogels was significantly lower than that of histones, suggesting that the adsorption process of histone by CSCEHEP in plasma was selective. Meanwhile, CSCEHEP hydrogels significantly antagonized histone-induced cytotoxicity by binding histones, and the cell viability increased significantly from 47.1% (model group) to 72.0% (CSCEHEP-treat group).

CONCLUSION
CSCEHEP hydrogels are of good hemocompatibility and can effectively adsorb histones in PBS solution and antagonize histone-induced cytotoxicity. It is believed that the use of such a histone sorbent for extracorporeal blood purification may provide a novel insight into the modulation of aberrant immune responses in patients with sepsis.
MO288: Kidney Tubule Polyploidization Preserves Residual Kidney Function and Assures Survival During Acute Kidney Injury
Authors: De Chiara Letizia , Lazzeri Elena , Romagnani Paola 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Acute Kidney Injury (AKI) is characterized by a rapid deterioration of kidney function. Recently, we showed that tubular epithelial cells (TC) respond to AKI by triggering polyploidy, a condition in which a normally diploid cell acquires additional sets of chromosomes. Polyploidy offers several advantages, but in the kidney the biological significance of polyploidization remains unclear. In this study we hypothesized that polyploidy (i) is the predominant cellular response early during AKI and (ii) that is an adaptive stress response required to maintain a residual kidney function assuring survival.

METHOD
To address these hypotheses, we employed in vivo transgenic models based on the Fluorescence Ubiquitin Cell Cycle Indicator (FUCCI) technology in combination with YAP1 downregulation. In these models, mice were subjected to unilateral ischemia reperfusion injury (IRI) or glycerol-induced rhabdomyolysis to induce AKI. Polyploid cells have been then characterized by single cell-RNA sequencing analysis, cell sorting, FACS analysis, super-resolution and transmission electron microscopy.

RESULTS
After AKI, YAP1 is activated triggering TC polyploidization. Polyploid TC increase in parallel to massive cell death triggered by AKI suggesting that polyploidization could be a means to escape cell death. Indeed, we found that polyploid TC tends to accumulate genome instability and survive, while diploid TC do not. Of note, virtually all dying cells were cycling cells based on the Fucci2aR reporter suggesting that TC death occurred during the S or G2/M phase. As polyploid TC increase immediately following AKI, they may be required to survive injury and damage by sustaining renal function. In order to evaluate the functional role of polyploid cells during AKI, we generated mice where YAP1 is knocked-out specifically in TC (YAP1ko mice). Indeed, after AKI, YAP1ko mice showed a reduced number of polyploid cells, worsened kidney function and a dramatic reduction of mouse survival, proving that polyploidization is required to survive AKI.

CONCLUSION
We demonstrated that (i) after AKI TC accumulate genome instability and die or become polyploidy; (ii) TC polyploidy is essential to preserve residual kidney function immediately after AKI.
MO291: Comparison of Acute Kidney Failure in Patients With SARS-COV-2 Infection During the First and Second Waves in a Third-Level Hospital in Andalusia
Authors: Cintra Melissa , Burgos Martin Javier , Almenara Tejederas Marina , Valverde Ortiz Rocío , Galván Toribio Raquel , Salguiera Lazo Mercedes 
Published: May 2022

Abstract

BACKGROUND AND AIMS
The incidence of acute renal failure (ARF) is frequent and has an implication in the morbidity and mortality of SARS-CoV-2 infection.

METHOD
A retrospective descriptive study of patients admitted for SARS-CoV-2 infection during the first (G1) and second (G2) waves who presented with ARF. They correspond to the period from March to May 2020 (G1) and from August to December 2020 (G2). We compare populations, outcomes and treatments.

RESULTS
A total of 73 patients in the first wave (G1), with a cumulative incidence (CI) of 28.3% (G1), compared with 58 patients in the second wave (G2), with a CI of 8% (G2). The mean age was higher in G2 [65.8 ± 15 years (G1); 75.3 ± 14 (G2); P &lt;.05], with no difference regarding sex [63% (G1); 54% (G2)]. In G2, there was a higher proportion of patients with cardiovascular disease [23% (G1); 57% (G2)], hypertension [56% (G1); 83% (G2)]. The baseline glomerular filtration rate (GFR) being similar for both groups (CKD EPI: 69 mL/min/1.73² (G1); P = .27). In the first wave, the mean days from admission to ARF was 3.1 days ± 4.2, and 42% of the patients were diagnosed at admission (31 patients). In the second, it was 2.9 days ± 5.7, of which 60% at admission (35 patients). The most prevalent cause was prerenal in both. Higher proportion in G1 of KDIGO stage 3 (G1: 30% versus G2: 17%) and renal replacement therapy (RRT) (G1: 9 versusG2: 2 patients). Only 3 patients remained in RRT in G1 and 1 patient in G2. In G1, 64% recovered their GFR [mean time (MT): 7.5 ± 8 days], and the percentage of deaths was 34%. In G2, 72% recovered GFR (MT: 16 ± 25 days), and 19% of patients died.

CONCLUSION
Despite a lower age and comorbidity of the first wave patients, the severity and lethality was higher. There were no differences in the proportion of patients who recovered their baseline renal function, although the recovery time was longer in the second wave.
MO293: Evaluation of Uric Acid Concentration and Acute Renal Impairment in Patients on Admission for Hospital Treatment
Authors: Tasic Danijela , Dimitrijevic Zorica , Radenkovic Sonja , Kocic Gordana , Ignjatović Aleksandra , Djordjević Katarina 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Elevated uric acid (UA) is associated with comorbidities such as hypertension, diabetes, cardiovascular disease and chronic kidney disease. There are more studies that discuss the importance of uric acid (UA) for acute kidney failure. Anaemia is a common risk factor for the development of AKI in hospitalized patients. There is an association between elevated iron and urate production in healthy people. The aim of this study was to evaluate value of UA as a risk factor for the development of acute kidney damage on admission for hospital treatment. We also determined, risk factors related to UA value and its relationship with anaemia.

METHOD
The study included 86 hospitalized patients with acute renal impairment who were divided according to the stage of renal impairment at admission to hospital treatment into three groups. The assessment of acute renal impairment and the classification of disease stages were based on the diagnostic stages by the KDIGO group. All the examined patients were &gt;18 years of age. In the first stage of the disease, it was 12.79%, in the second stage, it was 15.12% and in the third, it was 72.09% of patients.

RESULTS
UA values were the lowest in the first stage 551.00 ± 225.64 μmol/L and highest in the third stage 670.02 ± 86.72 μmol/L, but without statistical significance. The lowest percentage with renal function was 12.9% in patients with stage 3 acute renal impairment. There was a statistically significant difference with patients with stage 1 and stage 2 (P &lt; .017) renal impairment. The ROC curve for the cut-off value of uric acid 903.00 μmol/L based on the Youden index method with a sensitivity of 91.70% and a predictive value of 17.00% as a marker of acute kidney damage in stage 2 disease is larger than in other stages acute kidney injury. Although there is a significant relationship with risk of UA with haemoglobin values according to the following results: OR 1.036 [95% confidence interval (95% CI) 1.003–1.071; P = .030] and haematocrit level based on predicted probability and OR 1.149 (95% CI 1.028–1.285; P = .015).

CONCLUSION
The study showed that high values of uric acid in patients with acute kidney damage at the beginning of hospital treatment did not show the same significance in different phases of kidney damage. We confirmed the link between anaemia and UA levles. Ineffective renal UA clearance means progression of the disease course to the next stage, and over time as a sign of progression of the renal continuum to chronic damage.