bluuebunny/crossref_metadata_2025_split huggingface dataset:
#3802 ROLE OF NEUTROPHIL EXTRACELLULAR TRAPS IN DIABETIC KIDNEY DISEASE: DATA FROM INTEGRATION OF BULK RNA AND SINGLE-NUCLEUS RNA SEQUENCING ANALYSES
Authors: Xie Ruiyan , Zhu Litong , Jason Sher Ka Ho , Yap Desmond 
Published: June 2023

Abstract

Background and Aims
Neutrophil extracellular traps (NETs) is an important immune response against infections that is implicated in various immune-mediated conditions. Growing evidence shows that inflammation has key pathogenic contributions in diabetic kidney disease (DKD) but the role of NETs remains unclear.

Method
We evaluated the differentially expressed genes (DEGs) of NETs in human DKD using the bulk RNA sequencing datasets of kidney biopsy from DKD patients (GSE30528 and GSE30529). The candidate genes were further selected based on the machine learning algorithms (LASSO and SVM-RFE). The single-nucleus RNA sequencing (GSE195460 and GSE131882) and DKD bulk RNA sequencing (GSE30122) were used to validate the results. Receiver Operating Characteristics (ROC) curve were constructed to assess the diagnostic performance of the identified genes for DKD. Candidate drugs were further screened from the DSigDB database.

Results
Three characteristic genes (ITGAM, ITGB2 and TLR7) were selected using machine learning approach, which were all upregulated in human DKD glomerular and tubulointerstitial portion compared to healthy controls (all P &lt;0.05). Single-cell analysis further demonstrated that ITGAM, ITGB2 and TLR7 were mainly overexpressed in leucocytes. ITGAM, ITGB2 and TLR7 expression in tubulointerstitial compartment also showed good diagnostic performance for DKD (ROC AUC 0.983, 0.975 and 0.958 respectively). Candidate drugs that target ITGAM, ITGB2 or TLR7 genes in DKD include ropivacaine, lidocaine and sulfasalazine.

Conclusion
ITGAM, ITGB2 and TLR7 may serve as biomarkers for DKD and drugs that target these genes may have therapeutic potential for DKD.
#3804 ASSOCIATION BETWEEN PLASMA XOR AND OUTCOMES IN CKD PATIENTS
Authors: Makino Shuzo , Okushima Hiroki , Kani Nao , Hashimoto Nobuhiro , Iio Rei , Ueda Yoshiyasu , Hayashi Terumasa 
Published: June 2023

Abstract

Background and Aims
Plasma xanthine oxidoreductase (pXOR) is an enzyme plays a key role in uric acid (UA) production and produces reactive oxygen species (ROS), and it has been reported that pXOR activity is related with cardiovascular events in the general population. However, the relationship between pXOR activity and prognosis in patients with chronic kidney disease (CKD) remains unclear.

Method
We measured pXOR activity by Liquid chromatography tandem quadruple mass spectrometer (LC-TQMS method) in 415 outpatients with CKD, and compared demographic and laboratory data between two groups based on the median pXOR activity. Furthermore, we examined the association between pXOR activity and outcomes; renal replacement therapy (RRT), major adverse cardiovascular events (MACE), and all-cause mortality, using multivariate Cox proportional hazards model.

Results
Median age and eGFR were 71 years old and 21.6 ml/min/1.73 m2, respectively. Median pXOR activity is 3.33 pmol/h/ml and 26.3 pmol/h/ml in the lower and higher pXOR activity groups, respectively. eGFR was significantly lower and UA was significantly higher in the lower pXOR activity group compared with the higher pXOR group (eGFR, 18.9 vs 27.4, P, &lt;0.001; UA, 5.7 vs 6.1, P, &lt;0.001). During the follow-up period of 38 months, the incidence of each outcome including RRT, MACE, or all-cause mortality were significantly higher in the lower pXOR group (log rank test, P&lt;0.001). Multivariate Cox proportional hazards analysis including eGFR and UA levels showed that lower pXOR activity was significantly associated with poor renal? outcome (HR, 1.4; 95% CI, 1.0-2.1; P, 0.038). Furthermore, in subgroup analysis with or without antihyperuricemic use, univariate Cox analysis showed similar association between pXOR and each outcome.

Conclusion
In patients with CKD, lower pXOR activity has a significantly higher risk of all outcome (RRT, MACE, and all-cause mortality).
#3812 ARE KIDNEY CYSTS MORE COMMON IN PEOPLE WITH COL4A3/COL4A4 PATHOGENIC VARIANTS?
Authors: Teran Melissa Pilco , Furlano Monica , Pybus Marc , Jiménez Víctor Martínez , Peris Asunción Rius , Gomez Maria Vanessa Perez , Redondo Gerson Berna , De Arizon Leonor Fayos , Ars Elisabet , Torra Roser 
Published: June 2023

Abstract

Background and Aims
Individuals with pathogenic heterozygous variants in the COL4A3/COL4A4 genes are usually asymptomatic or present only with microhaematuria, although some may develop proteinuria and chronic kidney disease (CKD). Simple renal cysts are common in healthy individuals, with an increasing incidence with age and CKD grade. A possible association between pathogenic variants of collagen type IV and renal cysts has been described. This study investigates the presence of renal cysts in a large cohort of individuals with heterozygous pathogenic variants in COL4A3/COL4A4.

Method
We evaluated the presence of kidney cysts, kidney size and lithiasis by ultrasound in 162 individuals with pathogenic variants in COL4A3/COL4A4 without kidney replacement therapy. The correlation between kidney cysts and age, proteinuria, eGFR, causing gene and type of variant, was analysed. Genetic testing had been performed in index cases by next generation sequencing (NGS) of a kidney-disease gene panel containing more than 400 genes including COL4A3, COL4A4 and COL4A5 genes.

Results
153 patients with a heterozygous disease-causing variant in COL4A3 or COL4A4 and 9 patients with digenic/complex inheritance were included. The mean age at renal ultrasound was 46.19 years (SD 14.93) and the mean eGFR was 75 ml/min/1.73 m2 (SD 35 ml/min/1.73 m2). Renal cysts were present in 50% of patients (81/162) and were bilateral in 30.25%. The mean age of patients with renal cysts was 53.26 years vs. 39.12 years for those without, and the mean eGFR was 60ml/min/1.73 m2 vs. 89ml/min/1.73 m2 for patients with and without renal cysts. Only 2.5% (4/162) of patients had renal lithiasis. The mean kidney size was 104.05 mm (SD 13.86 mm) for the right kidney and 104.98 mm (SD 13.94 mm) for the left kidney. Cystic nephromegaly was observed in 3.7% (6/162). No correlation was found between renal cysts and gender (p = 0.632). Age and CKD stage had a positive correlation with the development of renal cysts (p = &lt;0.001) (Tables 1 and 2). Proteinuria was more common in individuals with renal cysts 61% vs 39% (p = 0.012), but was related to age and CKD stage. The presence of a kidney cyst did not correlate with the mutated gene or the type of variant.

Conclusion
Individuals with COL4A3/COL4A4 pathogenic variants develop kidney cysts at a higher rate than age-matched healthy individuals, and their presence is also related to ageing, as in the general population. Gender is not relevant for the development of renal cysts, in contrast to the general population cohorts. Proteinuria and CKD grade correlate with the development of renal cysts but nephromegaly is rare. Renal cysts in heterozygous carriers of COL43 or COL4A4 pathogenic variants are common but have no clinical consequences.
#3823 CAN HLA MOLECULAR MISMATCH GUIDE CLINICAL DECISION IN PAEDIATRIC KIDNEY TRANSPLANT RECIPIENTS: A RETROSPECTIVE STUDY
Authors: Gramkow Ann-Maria , Baatrup Johanne , Thiesson Helle Charlotte , Koefoed-Nielsen Pernille 
Published: June 2023

Abstract

Background and Aims
Optimizing graft survival and diminishing anti-HLA sensitization are essential in paediatric kidney transplant recipients (KTRs) facing multiple retransplantations. Improved pretransplant risk stratification and donor selection using in silico molecular HLA matching could enhance personalized immunosuppression and improve outcomes. HLA EMMA is a new in silico method to predict B cell epitope mismatches, and its clinical applicability needs confirmation in paediatric transplantation. We investigated the association of HLA B cell epitope (HLA EMMA) and predicted HLA T cell epitope (PIRCHE) mismatches with de novo donor specific antibodies (dnDSA), anti-HLA antibodies, rejection, and graft survival.

Method
We retrospectively analysed 49 consecutive paediatric KTRs aged 1 to 16 transplanted from 2009-2020 at a single Danish centre. The centre has a long tradition of steroid-free kidney transplantations in immunologically uncomplicated recipients, and 80% of the KTRs did not receive steroids. Donors and recipients were all high-resolution HLA typed, and HLA EMMA (v 1.00) and PIRCHE (v 3.3.60) predicted the molecular mismatches. KTRs were screened with mixed and single bead antigen kits after the transplantation. Logistic regression analyses were performed to explore the association of molecular mismatches and dnDSA, sensitization, graft loss, and rejection.

Results
The median age of the KTRs was 11 years (IQR 8), with a median follow-up time of 5 years (IQR 5). 11.36% developed dnDSA (60% class II, 40% class I and II) within a median of 3.91 years (IQR 2.28; range: 2.22-9.20). 57.45% had detectable anti-HLA antibodies during follow-up. Six KTRs lost their graft. None of the graft losses were related to alloimmunity, and 5-year death censored (one KTR died) graft survival was 88%. The cumulative incidence of rejection was 4% (95% CI: -1.5; 5.5) after one year and 10% (95% CI: 1.6; 18.7) after five years. The mean PIRCHE score was 368.47 (95% CI: 316.79; 420.15), the mean HLA EMMA class I mismatch was 20.33 (95% CI: 17.56; 23.09), and the mean HLA EMMA class II mismatch was 30.02 (95% CI: 24.99; 35.05). We found no association between PIRCHE or HLA EMMA with dnDSA, sensitization, graft loss, or rejection in the logistic regression models. We did see a tendency towards an increased odds ratio in PIRCHE predicting dnDSA (odds ratio: 1.31 (95% CI: 0.96; 1.80)) (Figure 1).

Conclusion
We did not find evidence to support the inclusion of the prediction of molecular mismatches in our clinical practice. The role of molecular mismatches in a clinical setting has yet to be established.
#3839 THERAPEUTIC TARGETS OF ARSENIC TRIOXIDE IN LUPUS NEPHRITIS – DATA FROM BIOINFORMATICS ANALYSIS AND IN VITRO STUDIES
Authors: Xie Ruiyan , Zhu Litong , Jason Sher Ka Ho , Yap Desmond 
Published: June 2023

Abstract

Background and Aims
Patients with systemic lupus erythematosus (SLE) are at an increased risk of developing lupus nephritis (LN), which results in high morbidity and mortality. There is preliminary data showing the efficacy of low dose of Arsenic Trioxide (ATO) in reducing renal flares amongst LN patients, but the underlying mechanism for such benefit remains unclear.

Method
We performed bioinformatic analysis and network pharmacology to elucidate the potential targets from differentially expressed genes (DEGs) of human SLE and LN peripheral blood mononuclear cells (PBMCs) datasets and pharmacological databases. The relationship between the potential targets and immune cells was further analyzed.

Results
Twelve intersection genes of DEGs in SLE, predicting targets of ATO and immune related genes were identified. KEGG pathway analysis suggested that the mechanisms of ATO in SLE were associated with IL-17 signalling pathway (p = 1.67E-18), TNF signalling pathway (p = 5.77E-11) and
NOD-like receptor signalling pathway (p = 1.93E-09). Ten types of immune cells showed significant difference with intersection genes expression in SLE using ssGSEA approach. MMP9 was the most significantly associated with immune cells and showed positive correlations with macrophages and neutrophils. A significant TF-MMP9-miRNA regulatory network was constructed using cytoscape software. Pilot data from our in vitro studies suggested that ATO might downregulate MMP9 expression in PBMCs obtained from LN patients during disease remission (n = 3).

Conclusion
ATO interacts with immune cells in LN patients via different inflammatory pathways and may downregulate MMP9 expression in PBMCs.
#3841 ASSOCIATION BETWEEN BODY MASS INDEX, WAIST CIRCUMFERENCE AND CLINICAL OUTCOMES IN KOREAN ADVANCED CHRONIC KIDNEY DISEASE PATIENTS
Authors: Kim Ji Hye , Im Dha Woon , Park Yeongwon , Kim Minsang , Kang Eunjeong , Jeong Yujin , Lee Hyanglim , Oh Kook-Hwan 
Published: June 2023

Abstract

Background and Aims
This study analysed the association between body mass index (BMI) and waist circumference (WC) with all-cause death, 3-point major cardiovascular event (MACE), end-stage kidney disease (ESKD) and total composite events in nation-wide cohort of Korean advanced chronic kidney disease (CKD) patients.

Method
This nationwide cohort study, using the National Health Insurance Database, included adult health examinees who received two or more check-ups from 2009 to 2012. Among them, CKD patients (N = 325,657, stage G3a, G3b and 4) were identified. Patients were classified into three groups for BMI (&lt;18.5, 18.5-25 [reference] and ≥25) and four groups for WC (female; &lt;75 cm or male; &lt;85 cm [WC1], female; 75 cm≤WC&lt;85 cm or male; 85 cm≤WC&lt;95 cm [reference], female; 85 cm≤WC&lt;95 cm, male; 95 cm≤WC&lt;105 cm [WC2] and female; ≥95 cm, male; ≥105 cm [WC3]). Risks were evaluated using Cox proportional hazard analysis.

Results
Patients (58.6±7.7 years) had mean eGFR of 54.32±5.83ml/min/1.73 m2. The underweight (BMI&lt;18.5) group had increased risks of death [HR 1.757, 95% CI (1.573-1.964)] and total events [HR 1.244, (1.144-1.353)]. Overweight (BMI≥25) group showed lower risks of death [HR 0.888, (0.86-0.917)], ESKD [HR 0.855, (0.788-0.927)] and total events [HR 0.975, (0.956-0.995)]. However, the risk was increased for 3-point MACE [HR 1.056, (1.031-1.081)]. For the association between WC and clinical outcomes, the low WC group (WC1) had increased risk of death [HR 1.129, (1.089-1.17)] and reduced risk for 3-point MACE [HR 0.92, (0.894-0.947)]. In higher WC groups, increased risks were observed for death [WC2: HR 1.052, (1.008-1.098), WC3: HR 1.32, (1.213-1.437)], 3-point MACE [WC2: HR 1.071, (1.038-1.104), WC3: HR 1.104, (1.036-1.176)] and total events [WC2: HR 1.049, (1.022-1.077), WC3: HR 1.12, (1.062-1.181)].

Conclusion
In CKD patients, both lower BMI and WC were risk factors for mortality and ESKD. However, compared to the reference group, higher BMI group exhibited better outcomes while higher WC groups exhibited poorer outcomes. As increased WC is more specifically related to central obesity, we need different approaches to interpreting clinical risks associated with different BMI and WC criteria.
#3849 PERITONEAL DIALYSIS CATHETER LOCK: PREVENTING RELAPSES
Authors: Marin Jorge , Huete M Jose Espigares , Escolano Francisco Javier Ruiz , Pérez Elisa Pereira , Galindo Pilar 
Published: June 2023

Abstract

Background and Aims
The incidence of peritonitis has markedly decreased in the last decades, nevertheless it remains one of the main causes of catheter removal and subsequent dialysis modality change. In the long-term severe peritonitis and relapses can lead to peritoneal membrane failure. Some bacteria can form biofilms in the peritoneal catheter lumen granting them resistance against antibiotics and thus being one of the causes for infection recurrences. To find a viable way to avoid or/and eradicate the bacterial biofilm in the peritoneal catheters given the importance of infections.

Method
We present the experience in our peritoneal dialysis unit in the coadjuvant treatment of peritoneal dialysis-associated peritonitis with peritoneal catheter locks in the past few years. We used two kinds of peritoneal catheter lock depending on the isolated germ and divided them in two groups. Group I for the gram-positive staphylococcus group and Group II for gram-negative germs, specifically pseudomona. We reported 12 cases from which 10 were the first episode of gram-positive staphylococcus (epidermidis and Aureus) peritonitis. For the treatment we locked the catheter with 350mg of daptomycin in 7ml of saline solution once a week without using the catheter for 12 hours. For the other 2 cases of pseudomona peritonitis we locked the catheter with taurolidine/urokinase during the exchange with icodextrin twice a week with a 12 hours dwell time until 9 locks were archived.

Results
We treated 12 patients (Table 1). Peritonitis was resolved without recurrences in 9 of 10 patients in group I. In one case were a Methicillin-resistant Staphylococcus aureus was involved there was no response to the treatment and the peritoneal catheter was removed. In Group II both patients resolved their peritoneal infection without recurrences.

Conclusion
In our study peritoneal catheter locking seems to avoid the biofilm and reduce the peritoneal infection recurrences.
#3882 THE PREVALENCE AND EVOLUTIONARY EFFECTS OF FRAILTY IN PERITONEAL DIALYSIS PATIENTS
Authors: Tingchen Yi , Lai Tai-Shuan , Lin Shuei-Liong , Chen Yung-Ming 
Published: June 2023

Abstract

Background and Aims
Frailty is an age-related condition that predicts adverse outcomes. The clinical effect of frailty in peritoneal dialysis (PD) patients is unmet. The study was aimed to investigate the clinical implications of frailty in PD patients.

Method
In this prospective study, PD patients completed frailty assessment at entry and 6 months by a semiautomated frailty index of 80 risk factors (FI80) which also contained the 5 components of Fried frailty phenotype. A score ≥13/80 (FI80 ≥0.16) or ≥3/5 (frailty phenotype) was designated to define frailty.

Results
A total of 337 PD patients were recruited (new-onset 23.4%, prevalent 76.6%). Two hundred (59.3%) and 163 (48.4%) patients were frail by FI80 and frailty phenotype, respectively. Predictors for frailty were old age, dialysis, diabetes mellitus, gout and sleep disorder. New-onset patients aged &lt;55 years displayed the best evolution of frailty over 6 months (stable or improved, n = 29/47, 61.7% by FI80, p = 0.0293), compared with other groups. Survival analysis found that frail patients exhibited the worse outcomes (overall death and hospitalization) than their robust and prefrail counterparts. Poisson regression showed frailty was associated with increased utilizations of outpatient and ER visit; however multivariate Cox models identified only diabetes, gout history and low body mass index (&lt;19kg/m2), but not frailty, predicted overall death and hospitalizations.

Conclusion
Our data indicate that frailty is a common medical condition in PD patients, and the status of which can be stabilized or improved in new-onset, young patients at least over the short term. Compared with frailty, certain comorbidities (diabetes and gout history) and undernutrition appeared to be more robust in the prediction of adverse outcomes.
#3922 CLINICOPATHOLOGICAL CHARACTERISTICS OF LIGHT AND HEAVY CHAIN DEPOSITION DISEASE: A CASE SERIES FROM A SINGLE CENTER
Authors: Wang Yujie , Liang Shaoshan , Liang Dandan , Xu Feng , Zhang Xiaodong , Chen Dacheng , Lin Yao , Zeng Caihong 
Published: June 2023

Abstract

Background and Aims
Light and heavy chain deposition disease (LHCDD) is the rarest form of monoclonal immunoglobulin deposition disease (MIDD) characterized by the deposition of the monoclonal light chain and heavy chain. At present, the large-scale clinical research data of LHCDD is limited. We explore the clinical-pathologic characteristics and outcome of LHCDD in a single center of China, to obtain a better understanding of this disease.

Method
We reviewed 65291 native kidney biopsies from January 2008 to December 2022. Ten patients with biopsy-proven LHCDD diagnosed were studies retrospectively.

Results
4 males and 6 females, with an average age of 52.5 ± 8.9 years were enrolled. The patients were presented with hypertension (80%), anemia (90%), elevated serum creatinine (70%), proteinuria (100%), nephrotic syndrome (30%) and microscopic hematuria (90%). Serum immunofixation electrophoresis showed that 8 (80%) patients were positive for monoclonal immunoglobulin (IgG-κ/IgG-λ/IgA-λ: 3/2/3). Serum free light chain (FLC) ratio was abnormal in 9 (90%) patients. Among them, 5 patients had an Elevated FLC ratio (κ:λ &gt; 1.65), and an FLC ratio &lt; 0.26 was observed in 4 patients. Two patients were diagnosed with multiple myeloma. Histologically, nodular mesangial sclerosis was identified in 9 (90%) patients. Immunofluorescence showed that 6 patientshad depositions of heavy chain IgG (γ1-κ/γ1-λ/γ2-κ/γ2-λ/γ3-κ:2/1/1/1/1), and 4 patients of heavy chain IgA (α-κ/α-λ:1/3). During a median of 28 months of follow-up (range, 6–104 months) in 9 patients, 8 patients received chemotherapy. Three (33%) patients had complete hematologic remission (CR), 2 (22%) had very good partial hematologic response (VGPR) or partial hematologic response (PR), and 4 (44%) had no response (NR). One (11%) had stable/improved renal function, 6 (67%) had worsening renal function, and 3 (33%) progressed to ESRD. All 9 patients survived.

Conclusion
In this case series of LHCDD in a single center in China, light and heavy chain deposition in renal tissues was most frequent with IgG-κ, followed by IgA-λ, IgG-λ and IgA-κ. More than half patients had hematologic response but poor renal prognosis.
#3934 SAFETY AND EFFICACY OF EVOLOCUMAB AMONG KIDNEY TRANSPLANT PATIENTS AT HIGH CARDIOVASCULAR RISK
Authors: Alotaibi Torki , Nagib Ayman Maher , Aboatya Hasaneen Hasaneen Ahmed Aboatya , Abdulhalim Medhat , Said Tarek , Emam Mohamed , Elsayed Zakaria , Nair Prasad , Gheith Osama Ashry Ahmed 
Published: June 2023

Abstract

Background and Aims
Proprotein convertase subtilisin/Kexin type A(PCSK-9) inhibitors have not been evaluated among kidney transplant recipients (KTR) despite its favorable cardiovascular profile. We aimed to evaluate the safety and efficacy of evolocumab in reducing lipids and cardiovascular events among risky KTR.

Method
One hundred ninety-five KTR - who were followed up in Hamed Al-Essa organ transplant center with high cardiovascular risk score (&gt;20)-were enrolled in this prospective randomized controlled study between June 2017 and June 2018. Patients who received statin and evolocumab (140 mg/ 2 weeks, group1, n = 97) while those maintained on statin alone comprised group 2(n = 98). After 24 months, they were followed up clinically and by laboratory investigations.

Results
The two groups had comparable demographics. Before enrollment in the study, we observed a higher prevalence of NODAT in group 2 and more smokers in group 1(p &lt; 0.05). Basal graft function was significantly higher in group 1, while the type of immunosuppression was equivalent in both groups(p &gt; 0.05). We found no significant differences between the two groups concerning cardiovascular events, and both graft and patient outcomes (p &gt; 0.05). Despite the comparable triglycerides levels, we found significantly higher basal cholesterol in group 1(5.5 vs. 4.7, p &lt; 0.001), which came down significantly in the same group after three months and thereafter (p = 0.031) compared to group 2 and basal values (p &lt; 0.001). We reported 2 cases of acute MI and one atrial fibrillation in group2.

Conclusion
Evolocumab is a promising lipid-lowering agent among risky KTR. Earlier cholesterol reduction was observed in group 1 without significant positive cardiovascular impact.