bluuebunny/crossref_metadata_2025_split huggingface dataset:
#4383 WHEN SHOULD WE TRY TREATMENT FOR PERITONEAL SCLEROSIS?
Authors: Martika Antigoni , Lampropoulou Ioanna , Ntemka Alexandra , Tsamelasvili Maria , Pozoukidou Kalliopi , Georgilas Nikolaos , Spaia Sofia 
Published: June 2023

Abstract

Background and Aims
Although it is very important to detect patients at increased risk of developing encapsulating peritonitis (EPS), there are not established predictors which would promote early diagnosis and treatment of EPS ensuring sustainability of peritoneal dialysis (PD). D-Dimers are considered a significant test in evaluation of peritoneal fibrinolysis activity and Ca 125 is used as an alternative marker for the integrity of peritoneal membrane.[1] We examined prospectively a combination of these surrogate markers both in serum and effluent to discern early peritoneal sclerosis.

Method
In a cohort of 39 PD patients D-Dimers, Ca 125, CRP along with a complete biochemical profile were tested both in serum and overnight effluent dialysate at the beginning of the study. In 9 patients, who presented with recurrent gastrointestinal symptoms, such as mild nausea, incidence of gastric discomfort or sense of bloating, CT imaging was performed for evaluation of potent EPS and thickening of the bowel wall was measured. The latter group of nine patients received tamoxifene for a period of approximately one year and both serum/effluent biomarkers and CT imaging were repeated at the end of this period.

Results
In Table 1 characteristics of patients are shown. At the beginning of the study CRP was the only biomarker that was different between the group with or without gastrointestinal symptoms (4±6mg/dl vs 0.8±1.1mg/dl, p = 0.04). In patients, who received tamoxifene gastrointestinal symptoms improved. In these patients follow up with CT imaging demonstrated amelioration of bowel wall thickening compared to the beginning (3±1.2mm vs 2.1±0.4mm), which was not statistically significant. Moreover, Ca 125 in dialysate decreased (60.4±74 U/ml vs 27±27 U/ml, p = 0.04). No side effects were recorded. Five patients are still on PD, 3 patients died from unrelated causes and 1 was transferred to hemodialysis.

Conclusion
In this study neither D-Dimers, a test for the assessment of the peritoneal fibrinolysis activity, nor Ca 125 an alternative marker for assessing the integrity of peritoneal membrane helped us to distinguish patients at risk for EPS. In fact Ca 125 levels in the effluent were higher in the treated group just before initiation of treatment, although in some references it is proposed that it is minimized.[1,2] Clinical evaluation along with radiologic findings led us to the decision to treat patients with tamoxifene, which exerts a protective effect on the peritoneal membrane during both early and late stages of fibrotic disorders.[3] Despite the small number of patients in this study, bowel wall thickening showed a tendency to decrease and symptoms improved.
#4387 LIQUID BIOPSY IN PATIENTS TREATED WITH BIOCOMPATIBLE PERITONEAL DIALYSIS FLUIDS – ITS RELATIONSHIP WITH CYTOLOGICAL AND HISTOLOGICAL FINDINGS
Authors: Gilsanz Gloria del Peso , Albar Patricia , Heffernan Jose Jiménez- , Osorio Marta , Machado Lina Maria Leon , Perdomo Yanieli Hernandez , Botella Mario , López-Cabrera Manuel , Rubio María Auxiliadora Bajo 
Published: June 2023

Abstract

Background and Aims
Peritoneal fibrosis can limit long term peritoneal membrane function in peritoneal dialysis (PD) patients. It has been related to bioincompatible PD fluids and peritoneal infections. There are no prospective studies regarding correlation between effluent biomarkers and peritoneal biopsy findings. Our aim was to study the possible relation of peritoneal effluent biomarkers and peritoneal morphology alterations.

Method
Multicenter prospective study in a cohort of stable PD patients treated with biocompatible PD fluids who received a kidney transplant. We collected in each patient peritoneal biopsy samples and peritoneal effluent fluid. We analyzed the relation between effluent biomarkers, phenotype of mesothelial cells (MC) cultured ex vivo, and peritoneal biopsy parameters (mesothelial integrity, fibrosis and hyalinizing vasculopathy). We compared them with patient characteristics, including peritoneal transport parameters. The biomarkers tested were Collagen-1 (COL-1), Fibronectin (FN), Collagen-13 (COL-13), Interleukin-6 (IL-6), Trombospondin-1, Cadherin 13 (CDH-13), CA-125, Gremlin-1 (GREM-1), Matrix metalloproteinase 2 (MMP-2), CC chemokine ligand 18 (CCL18), Plasminogen activator inhibitor 1 (PAI-1) and Vascular endothelial growth factor A (VEGF-A).

Results
Forty patients were included (mean age 54.5±15 years, 64% male, 24.1% diabetics). Mean time on PD was 25.5±27 months, 62.1% were on automated PD (APD) and 17.2% had prior peritonitis episodes. A normal MC culture phenotype was observed in 78% of patients. In peritoneal biopsies samples we found partial or total mesothelium preservation in 39%, submesothelial thickness in 42% and vasculopathy in 14% of cases. Effluent PAI-1 levels were significantly lower in patients with mesothelial cell loss than in those with mesothelial preservation (21.62 vs. 38.59 pg/ml respectively; p = 0.031). Patients with peritoneal fibrosis showed significantly higher effluent CDH-13 levels (3.51 vs. 2.32 pg/ml; p = 0.048) and supernatant PAI-1 levels (1183 vs. 72.73; p = 0.000) than those without fibrosis. No other statistical differences were found in other biomarkers analysed.

Conclusion
Most patients treated with biocompatible peritoneal dialysis fluids showed normal mesothelial cell phenotype in peritoneal effluent culture. Lower PAI-1 effluent levels were associated with mesothelial cell loss and higher effluent CDH-13 levels were related to peritoneal fibrosis.
#4412 URINARY SODIUM-TO-POTASSIUM RATIO DOES NOT ACCURATELY REFLECT DIETARY SODIUM-TO-POTASSIUM RATIO
Authors: van Vliet Anne Myrthe , Zwager Charlotte , Rauh Manfred , Titze Jens , Engberink Rik Olde 
Published: June 2023

Abstract

Background and Aims
Low sodium intake is associated with a lower blood pressure and less proteinuria, which are important therapeutic targets in chronic kidney disease. In contrast, a low potassium intake has been associated with higher blood pressure and a higher incidence of chronic kidney disease and cardiovascular events. Counselling of patients regarding their sodium and potassium intake requires accurate estimation of their intake, but 24-hour urinary sodium and potassium excretion can deviate substantially from actual intake. Urinary sodium-to-potassium (Na/K) ratio is a promising alternative as it is less affected by incomplete urine collections and additionally captures both the effect of sodium and potassium. Our study aimed to assess whether the Na/K ratio in 24-hour urine reflects dietary intake more accurately than separate measurement of sodium or potassium in 24-hour urine.

Method
We performed a post-hoc analysis on data from the long-term sodium balance studies Mars105 and Mars520. Ten healthy participants consumed a diet with a known sodium and potassium content and collected 24-hour urine samples for 105 or 205 days. We calculated the log fold difference between dietary intake and urinary excretion of sodium, potassium and Na/K ratio. A mixed-effects model with a random intercept per subject was used to compare these estimates of accuracy. Subsequently, we performed a subgroup analysis per salt intake level (i.e. 6, 9 or 12 grams per day) and assessed the effect of increasing the number of 24-hour urine collections.

Results
Overall, the urinary Na/K ratio underestimated dietary Na/K ratio with a median difference of -0.21 (IQR -0.47 to 0.09). Estimation of dietary Na/K ratio intake using the urinary Na/K ratio was significantly less accurate compared to using urinary sodium or potassium measurement for estimation of sodium or potassium intake (Figure 1A). Only during a salt intake of 6 grams per day, the urinary Na/K ratio did not perform significantly worse than sodium measurements. Although increasing the number of 24-hour urine measurements to three or seven improved the accuracy of the urinary Na/K ratio, it remained inferior to separate assessment of urinary sodium and potassium excretion (Figure 1B).

Conclusion
The 24-hour urinary Na/K ratio is less accurate than 24-hour urinary sodium or potassium excretion for estimation of dietary intake in a controlled setting in healthy volunteers.
#4414 GLOMERULONEPHRITIS DIAGNOSIS AND MANAGEMENT: IMPROVING KNOWLEDGE AND COMPETENCE AMONGST NEPHROLOGISTS THROUGH ONLINE CME CASE CHALLENGES
Authors: Bahra Sukhbir , Stan Adriana , Schoonheim Peter , Da Silva Rita Moreira , Kavanagh David 
Published: June 2023

Abstract

Background and Aims
Continuing medical education (CME) aims at modeling best practice in promoting positive behavior. We hypothesized that participation in the case-based medical education “Challenging Cases of Glomerulonephritis: How Would You Diagnose and Manage These Patients?” would lead to improved knowledge and competence of nephrologists in the diagnosis and management of glomerulonephritis.

Method
The online CME activity consisted of 2 patient case scenarios, and it was delivered as an interactive, text-based format. Using a “test and teach” methodology to elicit cognitive dissonance, clinicians completed multiple-choice questions to test their application of evidence-based recommendations. Each response was followed by detailed, referenced, feedback to improve learners’ knowledge, competence, and confidence on the diagnosis and management of glomerulonephritis. The educational effect was assessed using a repeated-pairs design with pre-/post-assessment, where 3 multiple choice questions assessed knowledge/competence and 1 question assessed confidence. Significance was assessed using paired samples t-test for overall average number of correct responses and for confidence rating, and the McNemar's test for individual questions (5% significance level, P &lt;0.05). Cohen's d estimated the effect size impact on number of correct responses (&lt;.20 modest, .20-.49 small, .59-.79 moderate, ≥.80 large). Data were collected between July 15 2022 and September 27 2022.

Results
Comparison of responses to questions before and after education demonstrated a large educational effect for nephrologists (n = 119; d = 1.36; P &lt;.001). Overall 84% nephrologists improved their knowledge/competence related to the diagnosis and management of glomerulonephritis (P&lt; .001), showing a 76% relative increase in correct responses from pre- to post-CME (51% pre, 90% post). Significant increases in knowledge/competence on rare complement-mediated kidney diseases were reported (P &lt;.001 for all comparisons) for:
- Clinical manifestations (64% pre; 97% post)
- Diagnosis (18% pre; 84% post)
- Management (71% pre; 90% post)
Around 55% of nephrologists showed a measureable confidence increase (P&lt;.001) in their ability to recognize clinical information suggestive of rare complement-mediated kidney diseases.

Conclusion
This online, interactive, case-based CME activity significantly improved the ability of nephrologists to diagnose and manage patients with glomerulonephritis. Additional gaps were identified for future education.
#4445 ANAEMIA MANAGEMENT IN PERITONEAL DIALYSIS: FROM GUIDELINES TO ROUTINE CLINICAL PRACTICE
Authors: Portoles Jose , Quiroga Borja , Salazar Maria Luisa Serrano , Peña Olga González , Domínguez María Sandra Gallego , Vera Manel , Espada Paula Jara Caro , Garcia Maria Alba Herreros , Vila Maria Antonia Munar , Amenos Aleix Cases 
Published: June 2023

Abstract

Background and Aims
The evidence on the management of renal anemia in peritoneal dialysis (PD) is much weaker than in hemodialysis (HD). Current guidelines establish the same haemoglobin (Hb) target for patients under eritropoietin stimulating agents (ESAs) in both dialysis techniques (PD, HD), although patients in PD are usually younger, more active and lesss comorbid. Unfortunately, there is not randomized controlled trials evaluating the efficacy and safety the effect of different Hb target on clinical outcomes. The aim is to describe the current situation of anaemia prevalence, treatments, and achievement of clinical guidelines recommendations in this population.

Method
Retrospective nationwide multicenter study including patients from 19 PD units. All prevalent PD patients that were active in the technique in November 2019 for at least 3 months was included (to avoid COVID pandemic interferences). Exclusion criteria were a previous kidney transplant failure and being on PD due to a cardiorenal syndrome with a residual renal function over 20 ml/min/1.73 m2. The nephrologists collected baseline data, demographics, comorbidities, and data related to anemia management (ie, laboratory values, previously prescribed treatments, and subsequent adjustments) from electronic medical records. The European adaptation of KDIGO guidelines was the reference for iron and Hb limits, prescriptions and targets.

Results
A total of 343 patients (mean age 62.9 years, 61.2% male) were included. Regarding anaemia-treatment prescription, 72.9% were receiving ESAs and 33.2% iron therapy (20.7% intravenously-IV and 12.5% orally). Eighty-two (32.8%) patients were receiving ESA without iron therapy, despite to have an indication to do it according ERBP guidelines in 53 out of them. After knowing lab results, iron therapy was only started in 8 (15%) patients. Among ESA-treated patients, 58.8% had an optimal control (Hb 10–12 g/dl). Seventeen patients had haemoglobin over 13 g/dl, and 12 of them continued receiving ESA after knowing lab results. Only three patients had persistent haemoglobin &lt;10 g/dl. Seven patients (2%) met criteria for ESA resistance (epoetin dose &gt;300 IU/kg/week). Patients in the highest tertile of erythropoietin resistance index (ERI) (&gt;6.3 UI/kg/week/g/dl) were more inflamed, had lower albumin levels and lower residual renal function.

Conclusion
Anaemia prevalence is high in this population and its management in PD Units could be improved according to the ERBP guidelines. The lack of iron therapy in patients who should have received it and the excessive tolerance to high Hb levels are the most relevant opportunities to improve compliance with clinical guidelines.
#4447 EFFECT OF RENAL IMPAIRMENT ON IPTACOPAN PHARMACOKINETICS
Authors: Schmouder Robert , Lestini Giulia , Bartels Christian , Baltcheva Irina , Junge Guido , Kulmatycki Kenneth 
Published: June 2023

Abstract

Background and Aims
Iptacopan (LNP023) is a first-in-class, oral, proximal complement inhibitor that specifically binds to Factor B and inhibits the alternative complement pathway (AP). Current Phase III studies of iptacopan focus on diseases associated with AP activation, such as paroxysmal nocturnal hemoglobinuria (PNH), C3 glomerulonephritis (C3G), IgA nephropathy (IgAN), and atypical hemolytic uremic syndrome. The liver is the primary route of iptacopan elimination. Based on a previous healthy volunteer pharmacokinetic (PK) study, the contribution of the renal route of iptacopan elimination was measured to be low, approximately 14%. A population PK (PopPK) analysis was done to further quantify the effect of renal impairment on iptacopan PK.

Method
A PopPK dataset pool was created by pooling across 6 Phase II/III studies in PNH, C3G, and IgAN indications. The pool comprised patient data on the two highest dose levels (100 and 200 mg bid) and included 2439 datapoints in 234 unique patients. Factors (baseline characteristics) that could possibly affect exposure, body weight, age, gender, ethnicity, and eGFR (mL/min/1.73 m2) at baseline were investigated. The range of eGFR was 27.4 to 142.8 mL/min/1.73 m2. Age, ethnicity, and body weight were included as the significant covariates in the final model.

Results
The median eGFR was 87.5 mL/min/1.73 m2. As shown in the table below, the PopPK model detected a significant (p = 4.3 × 10−11) but modest effect of eGFR on simulated mean AUC0-24. At an eGFR of 34.3, AUC0-24 is expected to increase by only 38%, compared with median eGFR. Changes of eGFR of ≤15% with respect to median eGFR were observed with eGFR range between 59.7 and 132.0 mL/min /1.73 m2.

Conclusion
Consistent with previously observed primarily hepatic clearance of iptacopan in preclinical and clinical studies, renal impairment down to an eGFR of 34.3 did not have a clinically meaningful effect on iptacopan PK. Currently, iptacopan PK in patients with eGFR &lt;30 mL/min/1.73 m2 is being explored. These results support the use of iptacopan in patients with mild and moderate renal impairment.
#4451 MONOCYTE MIGRATION AND ACTIVATION IN ANCA-ASSOCIATED GLOMERULONEPHRITIS
Authors: Vegting Yosta , Hanford Katie , Jongejan Aldo , Moerland Perry , Gajadin Gayle , van der Bom-Baylon Nelly , Dekker Tamara , Vogt Liffert , Bemelman Frederike , Kroon Jeffrey , Hilhorst Marc 
Published: June 2023

Abstract

Background and Aims
Glomerular injury in Anti-Neutrophil Cytoplasmic Antibodies (ANCA)-associated glomerulonephritis (AGN) is associated with macrophage infiltration. To date, their role and origin remain to be fully elucidated. Activated blood monocytes likely transmigrate and differentiate into kidney macrophages depending on the local microenvironment. Even in remission, some studies indicate sustained monocyte activation and upregulation of adhesion markers. The aim of this study was to research the intrinsic migration capacity of monocytes in AGN. Targeting monocyte migration might open new therapeutic avenues in the treatment of AGN.

Method
Transendothelial migration of monocytes was tested in AGN patients with active disease (n = 2), in remission (n = 8) and healthy controls (n = 6). To assess their adhesive and migratory capacity, freshly isolated CD14 positive monocytes were added to confluent TNF-α or IL1β overnight-stimulated Human Aortic Endothelial Cell (HAEC) for 30 minutes and subsequently fixed. Monocyte adhesion and transmigration was visualized by phase-contrast microscopy and quantified using ImageJ. To unravel the potential mechanisms driving these differences in monocyte migration, we performed bulk RNA-sequencing of monocytes from AGN patients with active (n = 4) and stable (n = 10) disease, and healthy controls (HC) (n = 6).

Results
Monocyte adhesion, but not migration, was significantly increased during active disease, independently of the stimuli used to mimic the pro-inflammatory phenotype of endothelial cells (EC) (Figure 1). During remission, decreased adhesion was found on the IL1β-stimulated ECs. While CD11b mRNA expression was upregulated, CD11a expression was downregulated in monocytes from active AGN patients compared to HC. Two genes involved in paracellular monocyte transmigration (JAML, PECAM-1) were significantly decreased. Most AGN patients were treated with corticosteroids at time of experiments.

Conclusion
These results suggest a remarkable increase in monocyte adhesion, but lower intrinsic migration capacity, in a 30 minute time-frame during active AGN. Our findings on migration are surprising in the light of theorized enhanced monocyte extravasation towards diseased AGN kidneys. Therefore, it could be speculated that after a longer period of time, a subset of the adherent monocytes would ultimately migrate and differentiate into kidney macrophages. In remission, long-term immunosuppressive treatment or chronic inflammation might decrease monocyte adhesion. This was the first ex-vivo study to research monocyte migration in AGN, further research is required to validate findings and to develop new therapies targeting monocyte migration.
#4472 POLYMORPHISMS OF THE GENE FOR GALECTIN-3 IN PATIENTS IN THE TERMINAL PHASE OF RENAL INSUFFICIENCY
Authors: Kovacevic Zoran , Lazarevic Tatjana , Ljujic Biljana , Canovic Petar , Kovacevic Marina Miletic , Maksimovic Nela , Jankovic Marina Gazdic , Djukic Svetlana , Glisic Milos 
Published: June 2023

Abstract

Background and Aims
Chronic kidney disease (CKD) is a major health problem worldwide. The last stage of CKD is end-stage renal disease (ESRD), which is characterized by a progressive decrease in glomerular filtration rate (GFR). End-stage renal failure is often complicated by anemia, uremic cardiomyopathy, and renal osteodystrophy, which can be fatal. Therefore, it is necessary to identify the risk factors that can lead to ESRD or death. In addition to well-defined early markers such as diabetes, hypertension, and obesity, it is necessary to identify other markers that would help in the prediction of the disease. It has been shown that genetic factors also have an influence on renal function, pathogenesis, and disease progression, which is confirmed by the results of genome-wide association studies (GWASs). The results of GWASs show that glomerular filtration rate and renal function are affected by several gene loci. Galectin 3 (Gal-3) is the only representative chimera type of the galectin family, which forms a pentameric structure on the cell surface after binding to glycoproteins or glycolipids. The results of numerous studies have shown that Gal-3 plays a significant role in fibrosis, inflammation, and proliferation. Increased circulating levels of Gal-3 have been associated with various diseases, including cancer, immunological disorders, and cardiovascular disease.

Method
A total of 108 ESRD patients and 38 healthy controls were enrolled in the study. Genotyping of LGALS3 geners 4644, rs4652, and rs11125 polymorphisms was performed by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP).

Results
By multivariate logistic regression analysis, we found that LGALS3 rs4644 CC and rs4652 AA genotypes were significantly associated with a higher risk for lower hemoglobin, higher level of parathyroid hormone, and also occurrence of diabetes mellitus and arterial hypertension. The CAA haplotype was significantly more common in patients with diabetes, low hemoglobin level, and normal PTH level. It has been observed as well that the ACT haplotype was more common in patients with low glomerular filtration, lowPTH, and normal hemoglobin level.

Conclusion
We found that the LGALS3 rs4644 and rs4652 gene polymorphism may be involved in the pathogenesis and appearance of complications in ESRD patients and thus could be considered a new genetic risk factor in this population.