bluuebunny/crossref_metadata_2025 huggingface dataset:
#2605 Evaluation of cardiac fetal gene program in experimental uremia
Authors: Chinnappa Shanmugakumar , Maqbool Azhar , Viswambharan Hema , Mooney Andrew , Denby Laura , Drinkhill Mark
Published: May 2024

Background and Aims

Heart failure (HF) and uremia share several potent cardiac hypertrophic stimuli such as wall stress, sympathetic activation, renin angiotensin system activation and oxidative stress. In heart failure, induction of fetal gene program is one of the major processes through which such stimuli lead to progressive pathological hypertrophy and myocardial dysfunction. The fetal genes are activated by the transcription factor, myocyte enhance factor 2 (MEF2) which is a downstream target of the Ca++- Calmodulin Dependent Kinase II (CAMKII) pathway. The CAMKII pathway has been shown to be the major transduction pathway of the hypertrophic stimuli in HF [1, 2]. We hosphorzed that such mechanisms are also at play in uremic cardiomyopathy and tested the hypothesis in a rodent model of experimental uremia.

Method

Wistar rats (n = 18) had subtotal nephrectomy (STNx) or sham surgery (sham) and were followed up for 10 weeks. In vivo and in vitro cardiac assessments were performed. Cardiac tissue was extracted, and protein expression of CAMKII and hosphor-CAMKII were quantified using immunoblotting. Protein expression of MEF2 and its target fetal genes were also studied. Histological analyses were performed to quantify myocardial fibrosis. Data was analysed using an independent sample t-test with Welch's correction and expressed as mean± SEM.

Results

STNx resulted in higher echocardiographic left ventricular mass, heart weight to tibia length ratio and myocardial fibrosis in the STNx group (Fig. 1) demonstrating cardiac pathological hypertrophy. CaMKII signalling was activated and the expression of MEF2 was also increased following STNx (Fig. 1). There was trend towards increased expression of fetal genes (Fig. 1). However, the difference did not reach statistical significance.

Conclusion

The study shows that experimental uremia induces cardiac pathological hypertrophy along with activation of intracellular pathways involved in fetal gene induction. Further studies evaluating fetal genes at an earlier time course in the evolution of pathological hypertrophy will be worthwhile.
#2387 Case study of a patient with gouty nephropathy treated with immunosorbent therapy
Authors: Xu Xuecheng , Lei Yu
Published: May 2024

Background and Aims

Gouty nephropathy is a kidney disease caused by chronic hyperuricemia, in which uric acid crystals are deposited in the kidneys leading to tubular and glomerular damage, which in turn affects kidney function.

Patient

female, 68 years old, 7 years ago, no obvious cause of the first toe joint of the right foot, the right ankle joint redness, swelling and pain, the local skin temperature increases, serious limitation of activities, had checked the high uric acid (specific unknown), diagnosed as “gout”, simple treatment after the symptoms are relieved, but did not have systematic treatment, and gradually appeared in the left foot, the first toe joint, the left ankle joint, double knee joint redness, swelling and pain, oral pain medication treatment, pain disappears after still no systematic treatment. After that, redness, swelling and pain appeared gradually in the first toe joint of the left foot, left ankle joint and both knee joints, and the pain disappeared without systematic treatment after taking pain-relieving medicines. He was admitted to our hospital as an outpatient with the diagnosis of “gout”.

Method

Immunosorbent therapy was given once/day on days 1-3, along with Jinshuibao and urotoxin clearing granules. Immunosorbent therapy was given again three times on the 8th-10th day of admission.

Results

Before admission, uric acid: 899.3 µmol/L; creatinine: 586.1 µmol/L, both seriously out of the normal range. 3 days later, uric acid: 770.4 µmol/L, creatinine: 468.7 µmol/L. At the time of discharge, serum uric acid: 298.5 µmol/L and creatinine: 182.6 µmol/L were detected and restored to the normal range.

Conclusion

The case demonstrated the presence of gout with arthritic symptoms, vascular damage, anemia, and hepatic and renal impairment. The patient's gout progressively worsened due to prolonged absence of systemic treatment. After admission, the levels of uric acid and creatinine were effectively controlled and restored by immunosorbent therapy. This indicates that immunosorbent therapy plays a positive role in removing uric acid from the body and improving renal function. Meanwhile, the management and control of gout was further strengthened by combining the comprehensive treatment with Jinshuibao and uremic acid granules.
#376 Self-efficacy, social support and hemodiafiltration are independently associated with better Self-Reported Health Status over time
Authors: Cromm Krister , Pham Ngoc , Jaha Hanna , Schappert Anna , Liegl Gregor , Fischer Kathrin I , Fischer Felix , Rose Matthias
Published: May 2024

Background and Aims

Patients with kidney disease receiving dialysis are a highly vulnerable population. Psychosocial determinants of Self-Efficacy (SE) and Social Support (SS) have been suggested as potentially important outcomes for people with end stage kidney disease. We investigated whether these variables could explain differences in Health-Related Quality of Life (HRQL) outcome domains over time independently or in interaction with treatment modality of high-flux hemodialysis (HD) versus high-dose hemodiafiltration (HDF).

Method

HRQL in 1264 participants from the international multi-centre, prospective, randomized, open label, controlled CONVINCE trial were assessed, using screening and quarterly follow-up data up to 24 months. Measures included the MOS Social Support Scale, General Self-Efficacy Scale, and PROMIS short forms for fatigue, physical function, pain interference and intensity, sleep disturbance, anxiety, cognitive function, depression, ability to participate in social roles. SE, SS and interactions with modality were included as independent variables and HRQL domains as dependent variables in a linear mixed effects model with random intercept and slope for SE and SS.

Results

Participants were 20-92 (M=62.33, SD=13.50) years old, 62.9% were male. Linear mixed effect regression models showed significant main effects for self-efficacy (β = −0.15-1.09, all p < .0001) on all HRQL domains. Significant SE × time interactions were found for all variables (β = −0.02-0.04, all p < .01) but pain intensity. Main effects for SS were found for cognition (β = 0.31, p = .00) and sleep disturbance (β = −0.21, p = .00). A significant SS × time interaction was found for anxiety (β = 0.01, p = .02) and sleep disturbance (β = 0.02, p = .00).

Plots for these associations can be found in Figs 1 and 2. Marginal means were plotted and 25%, 50% and 75% quantiles were used to separate the different levels of SE and SS.

There were no significant interactions between treatment modality (HDF vs. HD) and SE/SS.

Conclusion

Our results indicate that higher SE and better SS are independently associated with higher HRQL of dialysis patients over time, showing no significant interactions with HDF. SE had the largest effects on HRQL. This bears the chance to develop targeted psychosocial interventions to improve health outcomes when introducing new therapy options for patients. However, patients achieving higher HRQL over the course of the treatment may also experience higher SE and SS over time. Future research should include longitudinal assessments on these psychosocial determinants to evaluate their effect further.
#2575 GFR in onco-nephrology: the innovative use of measured GFR in the management of oncological solitary kidney
Authors: Trevisani Francesco , Floris Matteo , Trevisani Francesco , Angioi Andrea , Cinque Alessandra , Bettiga Arianna , Capitanio Umberto , Salonia Andrea , Locatelli Massimo , Pizzagalli Giorgio , Simeoni Mariadelina , Montorsi Francesco
Published: May 2024

Background and Aims

A reliable assessment of renal function in onco-nephrology and especially in oncological solitary kidney (SK) is of paramount importance. Nowadays, the use of estimated GFR is predominant in clinical practice because it is fast, easy and cost-effective. However, eGFR harbours a significant error in comparison to gold standards methods using exogenous molecules such as iohexol or iothalamate (mGFR). Aim of this study was to determine the extent of the error of eGFR compared to the mGFR in onco-nephrological patients with a solitary kidney (SK) after nephrectomy (RN).

Method

A total consecutive cohort of 200 SK who previous underwent RN for renal cancer was enrolled in a single tertiary institution from 2017 to 2023 to compare the most used eGFR formulas (MDRD, CKD-EPI crea 2012, CKD-EPI 2021 crea, CKD-EPI cyst 2012, CKD-EPI Cyst 2021, CKD-EPI cyst/creat, Cockroft-Gault) with a mGFR method using Iohexol Plasma Clearance. Clinical and laboratory data were reported for each patient. True positives (TP) and False positives, (FP) were classified in CKD stages based on eGFR and mGFR. Comparisons between groups were performed using Wilcoxon ranks sum test for numerical variables and Pearson's Chi square test for categorical ones.

Results

Overall median age was 67 years (IQR: 56.75), median BMI 24.8 (IQR: 22.8; 27.7), Male: 74.9%,F: 25.1% Diabetes: 10.9% Hypertension: 53.8%, CKD stage I: 3.7%, II: 25.5%, IIIA:28,IIIB: 27.5%, IV: 13.4%, V: 1.74%, mean Creatinine:1,46 mg/dl (1.16-1,84), cystatin: 1.23 (0.95-1.56). Surprisingly, SK cohort harboured a non-negligible errors in each CKD class with a huge discrepancy between the eGFR formulas and the gold standard method (Figs 1 and 2), suggesting the great relevance of mGFR in the clinical decision making algorithm.

Conclusion

The use of mGFR in nephrectomized patients for RC remains fundamental to avoid misleading evaluations and to perform correct personalized pharmacological therapies.
#2243 The experience from the use of citric acid blood purification solution (CD) with l-ascorbic acid (Vitamin-C) in patients under HD
Authors: Griveas Ioannis
Published: May 2024

Background and Aims

The use of CD offers anticoagulation with a reduced dose of heparin while the use of L-Ascorbic acid offers better management of the patients' anemia. The purpose of the study is to record the experience of using CD solution with Vitamin-C in patients with ESRD under HD

Method

45 patients with ESRD under HD (40 new recruits) with an average weight of 75 kgrs received CD solution with vitamin-C (2 g/lt) for a period of 12 months. All changes in heparin dose as well as patients' anemia profile (Hb, Hct, ferritin, TSAT, rhEPO dose) were recorded.

Results

The initial cumulative heparin dose of 1818 ± 659.28 iu (24 iu/kgrBW) was progressively increased to 2677.41 ± 1053.15 iu (36 iu/kgrBW) at 6 months and to 3323.52 ± 1467.79 iu (44 iu /kgr/GB) at 12 months. With no observed thrombotic events or bleeding tendency, the dose of heparin used was significantly lower than the recommended doses with the classical solution (loading dose 30-50 IU/kgBW and then 10 IU/kgBW/hour). Patients' Hb and Hct progressively increased significantly (10.63 ± 1.55 start-11.79 ± 0.91 end, p < 0.05, 32.25 ± 4.45 start-36.5 ± 2, 92 end, p < 0.05) with constant weekly erythropoietin dose (14000 ± 9500 iu start-14000 ± 10000 iu end, p = NS) and stable ferritin levels (526.73 ± 498.72 iu start-690.44 ± 470.32 iu end, p = NS). The above observation was combined with a significant reduction in monthly iron administration (from 700 mg monthly initially to 200 mg monthly after one year).

Conclusion

Our findings suggest that the use of CD solution and vitamin C compared to the classic one offers anticoagulation with a significant reduction in the dose of heparin used, while simultaneously increasing hemoglobin with a fixed dose of erythropoietin and reduced iron administration.
#806 Predicting arteriovenous fistula success using ferumoxytol-enhanced MRI (Fe-MRI) and computational flow dynamics (CFD)
Authors: Ker Robert , Hyde-Linaker George , Barrientos Pauline Hall , Kingsmore David , Kazakidi Asimina , Stoumpos Sokratis
Published: May 2024

Background and Aims

Arteriovenous fistula (AVF) failure is common and is invariably associated with preexisting anatomic problems of the inflow and outflow circuit. Ferumoxytol, an iron oxide nanoparticle, provides a safe alternative to gadolinium contrast material for MR angiography in chronic kidney disease (CKD). Computational fluid dynamics (CFD) has been utilised to virtually demonstrate the haemodynamics within AVFs using high-quality vascular mapping obtained with ferumoxytol-enhanced MRI (Fe-MRI). Using Fe-MRI and CFD we aimed to assess AVF haemodynamics and identify flow patterns and geometries associated with AVF success.

Method

In this pilot study we used Fe-MRI datasets of CKD patients who had vascular mapping 6 weeks after AVF creation. Using CFD methods we performed vessel segmentation to construct three-dimensional (3D) patient-specific geometries from images obtained with Fe-MRI (Fig. 1). We then completed a detailed CFD analysis for each AVF geometry to establish the associations of haemodynamic (mean wall shear stress (WSS), oscillatory shear index (OSI), blood flow velocity, and areas of abnormal flow) and anatomical parameters (anastomosis angle, feeding artery diameter, feeding artery curvature, draining vein diameter, and draining vein curvature) with AVF outcomes. The primary outcome was AVF success defined as AVF use (assisted or unassisted) for dialysis for a minimum of 3 months. ROC analysis was used to assess anatomical predictors of AVF flows of ≥1000 ml/min.

Results

The study included 17 patients with CKD who had AVF creation between 2018 and 2020. From these, 13 AVFs were successfully used for dialysis and 4 failed to mature or were used for dialysis for <3 months before failure. Compared to failed fistulas, successful AVFs had higher mean WSS and OSI. Failed AVFs were characterised by different haemodynamic patterns including lower flow rates with less helical flows. On ROC analysis the three metrics with the highest area under the curve (AUC) values were the feeding artery curvature (0.82), feeding artery diameter (0.76), and draining vein diameter (0.74) with a combined AUC value of 0.83 (Fig. 2).

Conclusion

Using Fe-MRI and CFD in the post-surgical juxta-anastomotic environment higher mean WSS and OSI were predictive of AVF success. In addition, the feeding artery curvature, feeing artery and draining vein diameters are strongly correlated with high venous flow rates, one of the key factors of AVF success. Although vessel diameters are routinely measured as part of pre-operative vascular mapping, a greater emphasis should be given on mean WSS, OSI and feeding artery vessel curvature when selecting vessels for AVF creation.
#1711 The impact of a multidisciplinary vascular access team on haemodialysis vascular access-related outcomes
Authors: Figueiredo Rafael , Fernandes Bernardo , Relvas Miguel , Diniz Hugo , Pinho Ana , Coentrao Luis
Published: May 2024

Background and Aims

Autologous arteriovenous fistulae (AVF) are considered the vascular access (VA) of choice for most haemodialysis (HD) patients. Timely AVF creation, adequate AVF maturation and assurance of long-term functional patency significantly benefit this population. International guidelines suggest the creation of multidisciplinary VA programs to improve access-related outcomes. This study aims to evaluate the results of the institution of a multidisciplinary VA team at our center.

Method

A retrospective case-control study was performed, comparing our center's incident HD patients from years 2019 and 2022. A multidisciplinary VA team was created in 2021. Patient data was collected from their electronic health record, namely demographic variables, comorbidities, prior nephrology (NA) and vascular access appointments (VAA), and access typology at the beginning of HD. The primary outcome was VA used for HD initiation. Secondary outcomes were time until multidisciplinary VAA, AVF creation and maturation, and the prevalence of AVF at six months for patients who initiated HD with a central venous catheter (CVC). Analysis of the results was performed using SPSS v28.0. A p-value < 0.05 was considered statistically significant.

Results

184 and 169 incident HD patients were included from years 2019 and 2022, respectively. There were no significant differences regarding demographic variables, comorbidities and prior NA. 42.4% and 37.3% of patients had been observed in a VAA at least 6 months before HD initiation, in 2019 and 2022 respectively (p = 0.095). Significantly more patients started HD with an AVF in 2022 (37.5% vs 50.9%, p = 0.011), regardless of demographic variables, VAA and AVF creation prior to HD institution. For those who started HD with a CVC (62.5% in 2019 and 49.1% in 2022), the median time until VAA (33 vs 25.5 days, p = 0.045), AVF placement (87 vs 46 days, p < 0.001) and puncturable AVF (203 vs 132 days, p < 0.001) were significantly lower in 2022. At 180 days post-HD initiation with CVC, the number of puncturable AVFs was also significantly higher in 2022 (26.1% vs 38.6%, p = 0.002).

Conclusion

Multidisciplinary VA teams have a positive impact on the number of patients who start HD with AVF. For those who initiate HD using a CVC, these teams are also a major determinant in the number of functional AVFs.
#1129 Systematic reporting of extracorporeal blood losses in a large dialysis provider organization
Authors: Beige Joachim , Jüttner Katrin , Göbel Kati , Masanneck Michael
Published: May 2024

Background and Aims

The assessment of adverse safety events is important for the risk assessment of major blood loss from the extracorporeal blood circuit during hemodialysis (HD). Such blood loss has been proven to result in a low double-digit number of fatal events per year in the USA. The frequency in Europe is not mandatorily recorded. The mechanisms of blood loss in the venous leg of the system, undetected by the alarm system of the dialysis machines, are not generally known and further patient and structure-related risks are not yet systematically recorded, evaluated and improved.

Method

We set up a web-based intranet database (“Event Management”) to record serious adverse events affecting patients during or around dialysis treatments in all 174 kidney centers of the Kuratorium für Dialyse und Nierentranspantation in Germany (KfH). This system is accessed via intranet within the KfH organization. Nursing and medical staff are regularly trained and informed about this system. The entry of event data that have endangered or harmed patients is mandatory.

Results

141 reports of blood loss were identified for a total of approximately 3 million hemodialysis treatments performed in 174 renal centers in between 2020 and 2022, including venous needle loss due to complications in the extracorporeal blood circuit, 15 of which required inpatient treatment. The breakdown of the causes and consequences of blood losses is shown in the Figure.

Conclusion

Venous disconnection must be reduced by earlier detection with appropriate technical and patient-adapted measures. Patients should be educated about their individual risk and about individual measures to manage risk. Identification of patient-specific and shunt-specific risk factors is necessary. Patient-related risk factors include cognitive impairment, frailty, and dialysis in special areas (ICU, isolation area, nocturnal dialysis). Monitoring systems (blood sensors) currently on the market have good technical blood detection sensitivity. Such systems should be investigated with regard to their clinical benefit according to the rules of evidence-based medicine before their broad introduction into routine care.
#470 Relationship between intraperitoneal volume and intraperitoneal pressure during peritoneal dialysis
Authors: Zhu Fansan , Merlo Laura Rosales , Tisdale Lela , Villamar Maricar , Yi Jun , Wang Xiaoling , Grobe Nadja , Fischer Karsten , Plahey Kulwinder , Chamney Paul , Schiller Brigitte , Kotanko Peter
Published: May 2024

Background and Aims

Monitoring intraperitoneal pressure (IPP) has been advocated to quantitate intraperitoneal volume (IPV) during peritoneal dialysis (PD). The aim of this study was to investigate the relationship between IPV and IPP during a short PD dwell.

Method

Thirteen patients (age 60.2 ± 13.8 years, 5 females, BMI 28.6 ± 7.8 kg/m2) were studied during a 2-hour dwell (2 L dialysate, 2.5% dextrose) in a sitting position. IPP was measured 4x per minute by a pressure sensor integrated in the Liberty Cycler (Fresenius Medical Care, Waltham, MA, USA). Segmental abdominal bioimpedance (Hydra 4200, Xitron Technologies, San Diego, CA, USA) was done concurrently to measure IPV. Serum and dialysate creatinine and glucose concentrations were measured before and after the dwell. Dialysate density (ρ) was measured by a handheld density meter (Mettler-Toledo, Columbus, OH USA). Ultrafiltration volume (UFV) was recorded by the Liberty Cycler. A simple physical model (IPP = ρ × h × g) was used to explore the relationship between IPP and IPV (Fig. 1). Based on the model, a change in IPP (ΔIPP) depends on the change of apparent dialysate height (Δh) and dialysate density (Δρ); g is the gravity constant. The apparent cross-sectional area (A) of the peritoneal cavity was calculated as IPV/h.

Results

Average UFV was 0.31 ± 0.25 L (range 0.03 to 1.03 L). During the dwell, IPP decreased in 12 patients (UFV 0.03 to 0.49 L; Fig. 2) and increased in one (UFV 1.03 L). The IPP decrease (−3.81 ± 2.78 cmH2O; −21.2 ± 18%, p < 0.01) was accompanied by a decrease of apparent h (−0.04 ± 0.03 m; −20.9 ± 18.5%, p < 0.01) and ρ (−3.41 ± 0.56 kg/m3; −0.34 ± 0.06%, p < 0.0001). In patients with a decrease in IPP, the apparent dialysate h decreased from 0.19 ± 0.04 to 0.14 ± 0.04 m, and the apparent A increased from 107.8 ± 23 to 154.7 ± 34 cm2. In the patient with IPP increase, the apparent h increase from 0.14 to 0.18 m, and the apparent A from 138.4 to 164.6 cm2. ΔIPP inversely correlated with Δρ (Fig. 3) and UFV (Fig. 4). Moreover, ΔIPP correlated with D/P creatinine (Fig. 5) and with D/D0 glucose (Fig. 6).

Conclusion

In this proof-of-concept study, a simple physical model was used to explore the relationship between IPP and IPV. Contrary to our expectation, we found that IPP declines in most patients during the dwell. Decrease in IPP is related to increase in the apparent cross-sectional area of the peritoneal cavity. We hypothesize that during the dwell additional spaces of the peritoneal cavity become accessible to IPV. To what extent this opening of peritoneal space is associated with membrane characteristics warrants further studies.
#1470 Study of limitations for the implementation of an assisted peritoneal dialysis program in Spain
Authors: Escuredo Ana Sánchez , Nuñez Sara , Tango Ariel , Ramos Maria Quero , Sanchez-Alvarez Jose Emilio , Fontan Miguel Perez , Macia Manuel , Roblero Maria Fernanda Slon
Published: May 2024

Background and Aims

Assisted peritoneal dialysis (APD), whether partial or total, is a home-based technique for patients who have lost their independence due to age or comorbidities, requiring some assistance to manage their treatment. It is also a viable option for patients ineligible for Peritoneal Dialysis (PD) due to social, cognitive, or physical barriers or those approaching the end of life. Moreover, APD has demonstrated lower hospitalization and mortality rates, lower costs, and similar quality of life compared to in center Hemodialysis (HD).

To understand the usual clinical practice in PD and the limitations for the implementation of an APD program in Spain.

Method

Cross-sectional observational study conducted through a survey with closed-ended questions distributed by email to the PD working group of the Spanish Society of Nephrology. Participation was voluntary and anonymous. The survey included four questions about the center's structure, six about usual practices, and six about potential barriers to the implementation of APD.

Results

A total of 74 responses from 59 centers were analyzed. Average PD programs were 40 ± 26 [2-100]. The median number of patients undergoing APD is 5 [3-10] per program. Among the respondents, 73% believe that APD should include support in organizing and preparing materials at home, connecting and disconnecting in APD/CAPD, and documenting the treatment.

Regarding the offering of APD, 48% of respondents answered it should be provided to patients who have initiated PD and need assistance to continue the technique, 47% in cases of family surrender, 39% to all patients wishing to undergo PD despite physical or mental impairment, 38% at any time if the patient requires it, and 22% during information sessions on techniques in CKD clinic.

Regarding who should perform APD, 73% responded with a caregiver, 63% with external nursing/assistant personnel not affiliated with the PD unit, 52% with a family member, and 48% with nursing/assistant personnel from the PD unit itself.

Perceived limitations by the respondents include lack of funding (80%), lack of experience in PD units (15%), lack of motivation in PD units (11%), lack of trained personnel (5%), and none of the above (7%).

Eighty percent of the respondents believe that implementing APD would increase the number of PD patients in their program.

Conclusion

Seventy-three percent considers that APD should include support in material preparation at home, connection-disconnection, and treatment documentation. There is no consensus on who should be offered APD or who should perform the treatment at the patient's home.

The primary perceived limitations are program funding and a lack of training and motivation among the teams.
#2857 Home hemodialysis training time: associated factors and impact on technique survival
Authors: Quilis Aina , Castillo Belén Vizcaino , Moya Mercedes González , Hernandis Amanda , Pascual Pilar , Alba Amparo , Ureña Paula Gandía , Parra Manuel , Saura Laura Porcar , Barrilero Elena Galván , Sancho Asunción , Molina Pablo
Published: May 2024

Background and Aims

The optimal training time for Home Hemodialysis (HHD), its related factors and its impact in the technique survival are not well established.

Our objective was to analyze the risk factors associated with longer duration of HD training and to assess the impact of training time on the survival of the technique.

Method

Single-center observational study in which all patients seen in our HHD program from January 2013 to November 2023 were included. Training time was defined as the total number of dialysis treatments undertaken for instructional purposes, regardless of prior experience. Patients were divided into two groups, according to standard (≤31 days) or prolonged (>31 days) training duration. Sociodemographic and clinical variables were compared between the two groups, and the factors associated with prolonged training were analyzed using binary logistic regression. HDD failure was the composite of technique failure (defined as transfer to in-center HD for ≥ 30 consecutive days) and death.

Results

We analyzed 50 patients (women: 18, 36%) with a mean age of 55.1 ± 12.6 years and a median length of time on dialysis of 33 (IQR 3-369) months. The median training time was 31 (IQR 24-45) days. 14 (28%) patients were single, 22 (44%) were actively working and the percentage of primary, middle and university education was 20%, 56% and 24%, respectively.

In the univariate analysis, a younger age, and the presence of a care partner were associated with a shorter HHD training time, whereas the type of vascular access, the educational level, the marital status, the gender, and the need for a care partner were similar in both standard and prolonged training duration groups. After a multivariate logistic regression analysis, the only factor independently associated to a longer training time was the age (OR: 1.08, 95% CI: 1.02-1.14; p = 0.01). After a median follow-up of 27 (IQR: 15-50) months, HDD failure was observed in 12 (27%) of patients. Although in the crude analysis the technique survival tended to be lower in the prolonged training duration group (Fig. 1), this finding was not confirmed after adjusting for age.

Conclusion

In our experience, the older age was the only factor independently associated with longer HDD training time, whereas a longer training time did not impact in the HDD survival. These data suggest that HHD training should be especially careful in elderly patients, whose learning may require greater use of time and resources.
#2806 Role of non-HLA antibodies in pre-transplant evaluation of antibody-mediated damage risk
Authors: Solà-Porta Eulàlia , Pérez-Saéz María José , Redondo-Pachón Dolores , Eguía Jorge , Caro José Luis , Federico-Vega Judith , Gimeno Javier , Buxeda Anna , Burballa Carla , Crespo Marta
Published: May 2024

Background and Aims

Donor-specific HLA antibodies (HLA-DSA) contribute to antibody-mediated rejection (ABMR) after kidney transplantation (KT) and worse graft-survival. Non-HLA antibodies may play a role in the development of ABMR in the presence of HLA-DSA or in the development of microvascular inflammation (MVI) in the absence of HLA-DSA. Considering both antibodies in potential recipients before or after KT could enhance the prediction of post-KT ABMR/MVI.

Method

Retrospective study of a cohort of 169 KT recipients with: a) pre- and post-KT sera; b) follow-up HLA antibody monitoring; and c) follow-up biopsies. We determined the presence of 60 non-HLA antibodies in sera with a multiplex test: the Single Non-HLA Beads kit (LIFECODES®) on a Luminex® platform. We obtained an absolute number of positive antibodies and a sample MFI ratio sum according to which we stratified results into quartiles.

Results

Pre-KT, we detected a 15.4% of KT recipients with high HLA sensitization (cPRA >50%), being 8.3% HLA-DSA, and non-HLA antibodies in 85% of KT recipients, with a median of 3 (2-5) antibodies and a median MFI ratio sum of 10.1 (2.9-18.5). During a median follow-up of 60 (18.5-89) months 73 patients developed ABMR/MVI. We observed that a high burden of pre-KT non-HLA antibodies was associated with a higher risk of ABMR/MVI, regardless of HLA sensitization and pre-KT HLA-DSA. Notably, 57% of patients with ABMR/MVI had a high non-HLA burden before KT and 24.6% had a HLA cPRA >50%. Altogether, 68.5% of these patients showed either a high HLA sensitization or a high non-HLA burden before KT (Figure).

Conclusion

A high non-HLA preTR non-HLA antibody burden detected with a multiplex panel allows identification of patients more likely to develop ABMR/MVI, irrespective of the presence of anti-HLA antibodies.
#1996 Identification of the biological bases associated with the mTOR-I-related podocytopathy through high-resolution mass spectrometry
Authors: Candiano Giovanni , Granata Simona , Bruschi Maurizio , Zaza Gianluigi
Published: May 2024

Background and Aims

mTOR inhibitors (mTOR-I) often cause podocytopathy with the development of proteinuria (sometimes in the nephrotic range) in kidney transplant patients, but the biological mechanisms underlying this effect have been only partially defined.

Method

Immortalized human podocytes were treated in vitro with different everolimus (EVE) doses (10, 100, 200, 500 nM) for 24 h. Total cell lysates and supernatants were subjected to high-resolution mass spectrometry (Proteomics analysis). Innovative tests were used for bioinformatics analysis, including the Support Vector machine (SVM) and partial least squares discriminant analysis (PLS-DA). The results were validated in vitro and in human urine samples from 30 patients treated with EVE-based immunosuppressive treatment, using various molecular biology techniques (western blot, ELISA).

Results

Proteomic evaluation identified more than 7000 differentially expressed proteins. Among these, after a conservative statistical analysis, 78 showed an expression level significantly and directly correlated with EVE dosage. Functional analysis of the selected proteins showed a biological interconnection that involved several pathways, including kinases, cell cycle regulation, epithelial–mesenchymal transition, and protein synthesis. Osteopontin (SPP1) and Polo Like Kinase 2 (PLK2) were two of the most significantly correlated proteins (p < 0.00001, FDR<0.5%). The data were then confirmed through biomolecular experiments in vitro and in vivo in urine samples from kidney transplant recipients who received immunosuppressive treatment with EVE.

Conclusion

This study, for the first time, analyzed the biological impact of mTOR-I on podocytes, helping to understand not only the molecular basis of its therapeutic effect but also the biological reasons underlying their adverse events (particularly proteinuria). Validation of our data on larger cohorts of patients treated with this category of drugs will help identify new therapeutic targets to minimize adverse effects.
#2313 Perspectives in immunosuppression management following post renal graft failure: a Portuguese national survey
Authors: Venda João , Dos Santos Henriques Andreia , Leal Rita , Alves Rui
Published: May 2024

Background and Aims

The best approach to immunosuppression withdrawal post renal graft failure is controversial. Maintaining immunosuppressive therapy may preserve residual diuresis and prevent allosensitization, which is beneficial for a subsequent transplant. However, prolonged maintenance is associated with an increased risk of infection, metabolic side effects and neoplasia. No standardized protocol exists and immunosuppression is center and nephrologist dependent. Our aim was to document immunosuppression practices nationally amongst Portuguese nephrologists.

Method

A national survey of 5 short questions was conducted among residents and specialists in Nephrology in Portugal through email distribution by the Portuguese Society of Nephrology.

Results

We received a total of 90 responses, with 54.4% (n = 49) of participants working at a renal transplant unit. When faced with a patient returning to dialysis after graft loss, 66.7% (n = 60) immediately discontinue the antimetabolite, maintaining the calcineurin inhibitor and prednisolone, 33.3% (n = 30) maintain only the prednisolone and no respondent maintains mycophenolate mofetil or equivalent. Among those who maintain calcineurin inhibitors and steroids, 46.6% (n = 28) wean calcineurin inhibitor within 6 months to 1 year following graft loss, 23% (n = 14) discontinue calcineurin inhibitor within 3 to 6 months, and 30% (n = 18) discontinue calcineurin inhibitors before the first three months after graft loss. Considering steroids, 36.7% (N = 32) discontinue prednisone after one year post graft loss, and 64.3% (N = 58) of the Nephrologists maintain steroids indefinitely or until graft removal or steroid associated complications. The majority (83.3%, n = 75) agreed that the risk of the toxic rejection of the graft is the main factor deciding to maintain immunosuppression, followed by the possibility of re-transplantation (56.7%, n = 51) and the risk of infection was the major concern to withdrawal (55.6%, n = 50). All the participants considered this is an important or very important issue in kidney transplantation, that needs further investigation.

Conclusion

Immunosuppression management is one of the most challenging issues in patients with a failing or failed graft. Several working groups are being developed to discuss the best approach of the patients with a failing graft but only the British Transplantation Society have published guidelines. In this survey we can observe important disparity of different approaches, mostly physician/centre dependent. The current evidence is weak, calling the need for larger studies and a standardized protocol-based approach.
Rethinking food policy framework to tackle childhood obesity in the Italian context
Authors: Loperfido Federica , Vincenti Alessandra , Basilico Sara , Conti Maria Vittoria , Orsini Francesca , Franchi Carlotta , Sossan Cristina , Magarini Andrea , Zuccotti Gianvincenzo , Calcaterra Valeria , Cena Hellas
Published: May 2024

Pediatric obesity has been described by the World Health Organization as 1 of the most serious public health challenges of the 21st century. Projections of increasing burdens of pediatric obesity and its related diseases on society highlight the need for urgent and substantial action. Many scientific and public debates about the prevention of childhood obesity are centered around simple dichotomies presenting a single-level solution. In contrast, efficient prevention programs should overcome these overly simplistic dichotomies and proceed in the early years of life within the family environment and the whole society, throughout one's lifetime. Food policies have the potential to counteract pediatric obesity by creating healthy food environments. However, the current food policies approach lacks monitoring indicators to assess short- and long-term impact, and is not well integrated into regional, national, and cross-cutting initiatives. Therefore, redesigning and rethinking food policy strategies and goals is an important opportunity to address childhood obesity, safeguard the planet, and contribute to economic and social prosperity.
Work and Retirement Among Women: The Health and Employment After Fifty Study
Authors: Palermo G , D’Angelo S , Ntani G , Bevilacqua G , Walker-Bone K
Published: May 2024

Background

Women increasingly work beyond age 50+ but their occupational health is under-researched.

Aims

To investigate what jobs older contemporary women do, when they exit their jobs and what factors predict job exit.

Methods

Data came from the Health and Employment After Fifty cohort, which recruited women aged 50–64 at baseline in 2013–14 and has followed them up annually collecting: demographic, lifestyle and work information. Exits from employment were mapped longitudinally over five follow-ups. Time-to-first event Cox regression analyses were used to identify risk factors for job exit.

Results

At baseline, 4436 women participated, 64% of whom were working. The proportions of women working at 50–54, 55–60 and over 60 years were 86%, 79% and 38%, respectively. Amongst all women, after adjustment for age, managing comfortably financially and not coping with the mental demands of the job were associated with exit. Risk factors for job exit differed in the age bands: 50–54; 55–59 and >60 years, reflecting socio-economic status, markers of health (musculoskeletal pain and poor self-rated health) and work factors (under-appreciation, job dissatisfaction, temporary/permanent contracts, coping with work’s physical demands).

Conclusions

Factors contributing to exit from work among older women differ by age group, after controlling for perceived financial position, age and mental demands of the job. A number of work characteristics predict job exit and suggest that employers can play an important role in supporting women to continue working until older ages. Identification and treatment of musculoskeletal pain could also enable work amongst older women.
Privacy and Confidentiality
Authors: Miller Seumas , Bossomaier Terry
Published: May 2024

Important privacy and confidentiality issues arise from bulk data, surveillance, and encryption. Thus, analyses of the key ethical notions of privacy (and, relatedly, autonomy, confidentiality and anonymity) but also of security are required; and required in the context of bulk databases and the use of machine-learning techniques (ML), by governments and their security agencies, on the one hand, and by market-based global technology companies (e.g., Google), on the other hand. Ethical issues also arise from the use of high-level encryption. In considering privacy rights and security needs in these contexts, and in offering some ethical guidelines to inform policies in this area, a range of ethical principles are discussed, such as the principles of necessity and proportionality. For instance, in the context of current level of cybercrime in liberal democracies, is the use of end-to-end encryption necessary and, if so, in what specific security settings?
Freedom of Political Communication and Computational Propaganda
Authors: Miller Seumas , Bossomaier Terry
Published: May 2024

Freedom of political communication on the internet now exists in the context of an explosion of disinformation, propaganda, and hate speech that has been accelerated by a largely unregulated social media in which social bots, AI, and so on, are used. While there is a presumption in favour of freedom of political communication in liberal democracies, this right brings with it a moral responsibility to comply with principles of evidence-based truth telling. How can disinformation, propaganda, and hate speech be countered without compromising the right to freedom of political communication? Ethical analysis of freedom of communication, disinformation, and ideology are provided. Various practical recommendations are offered for policymakers and regulators with an emphasis on the role to be played by epistemic institutions, such as news media organizations and universities, in the context of a more effectively regulated cyberspace.
Individual and Collective Responsibility for Cybersecurity
Authors: Miller Seumas , Bossomaier Terry
Published: May 2024

In this final chapter, it is argued that the ethical issues in cybersecurity can be framed as dual-use issues: various cybertechnologies, including social bots, automated drones and blockchains, can be used to achieve great benefits, but in the hands of malevolent state and nonstate actors, they can cause great harm. The satisfactory resolution of the resulting ethical issues involves the discharging of collective moral responsibilities. These collective responsibilities need to be institutionally embedded in webs of prevention. Cybersecurity is, in the end, a collective moral responsibility of both individual citizens and organizations, but a collective responsibility that requires new regulation and the redesign of institutional roles, as well as technical countermeasures to cyberattacks (e.g., passwords, encryption, firewalls, patching, and the like) in order to be discharged. It also involves at times, we suggest, offensive as well as defensive measures.
Replication
Authors: Kane Brian
Published: May 2024

This chapter introduces the concept of musical replication, the first of two key processes involved in the emergence of a standard from a network of musical performances. Replication is the process of producing an artifact that can substitute for another within a particular social context of use. By replicating particular aspects, not essential properties, musicians can fashion substitutes that allow for morphological difference while still maintaining identity. The use of chord substitutions in jazz can be understood as a form of musical replication, yet replication is not limited to chords. Throughout the chapter, the standard “Body and Soul” is used as a “case study” to demonstrate how jazz musicians produce both harmonic and melodic replications. This chapter also introduces a major claim of the book: that work-determinative properties of a jazz standard are not necessary properties but rather sufficient properties—that is, properties sufficient for grounding judgments of identity and individuation. Alongside a theory of nomination, or the “naming” of a musical work, a theory of replication helps to explain why two performances of a standard can be performances of one and the same work even though their musical properties (or their musical morphology) might be radically distinct.
Transformations
Authors: Schofield John
Published: May 2024

Chapter 8 draws together the ideas and thematic discussions covered in this book in the context of some alternative approaches and frameworks for archaeological and heritage research. In terms of approaches, a missions approach is one example while creative practice is another. In terms of the frameworks within which such approaches might be adopted, the notion of Doughnut Economics and the Rainbow Model are examples borrowed from other disciplines. Both relate directly to policymaking, and to influence this area of practice the notion of policy entrepreneurs is discussed again. This is a vital role that some future archaeologists and heritage practitioners may be well suited to fulfilling. Concluding comments are specifically about the future, addressing both leadership within this field of practice, and also pedagogy and the world of archaeology that students should be prepared for. The futures of archaeology and of wicked problems should be closely entangled.
Could a Good God Permit So Much Suffering?
Authors: Sterba James , Swinburne Richard
Published: May 2024

James Sterba argues that the evils of the world are so horrendous that their occurrence conclusively shows the non-existence of the all-good, all-powerful God of traditional theism. Specifically, Sterba argues that his three necessary moral evil prevention requirements (MEPR I–III) that are exceptionless minimal components of the Pauline Principle never to do evil that good may come of, it as well as the basic normative principles that Swinburne employs in his own argument, are logically incompatible with the God of traditional theism’s permitting all the horrendous evil consequences that occur in our world. In response, Richard Swinburne argues that our major benefactors, our parents and the State, have rights to permit us to suffer if doing so is necessary to secure some good for ourselves or others. Hence, Swinburne claims, since God, if he exists, is so much greater a benefactor than are parents and the State, that he has a far greater right to allow us to suffer a lot if allowing such suffering is the only logically possible way for him to secure some very great goods for ourselves or others. Swinburne then argues that the goods made possible by allowing humans to cause or cope with great evils, such as that we can make great differences to ourselves and others, and thereby make ourselves very saintly people, are very great goods.
Rewriting Geoffrey of Monmouth
Authors: Henley Georgia
Published: May 2024

This chapter considers the Epitome historiae Britanniae, an abbreviation of Geoffrey of Monmouth’s Historia regum Britanniae written from a South Welsh perspective in the late fourteenth century. The chapter contrasts the way the history was read in Wales (as an explanation for Welsh loss with a promise of future regeneration in the era of rapid political change leading up to the rebellion of Owain Glyndŵr) with how it was read in the March of Wales (as an outline of the historical past and royal lineage that the marchers had now inherited). The Epitome historiae Brianniae’s explanation of the classical origins of the Britons, the loss of Welsh independence, and the foundation of the church in South Wales was adapted to fit the political geography of the early fifteenth century, when control over South Wales was reasserted after the Glyndŵr rebellion’s failure. The transmission of this text from South Wales to the March of Wales is a primary example of how marcher interest in the Welsh past drew Welsh historical texts out of Wales.
Royal Aspirations
Authors: Henley Georgia
Published: May 2024

This chapter focuses on the reimagining of British historical memory by the Mortimers of Wigmore in the late fourteenth century. At this time, Roger Mortimer, 4th earl of March, became the presumptive heir to Richard II, prompting chroniclers at Wigmore Abbey to draw together a compilation of historical texts and genealogies, several of which are edited by the author for the first time. These genealogies emphasized his right to rule in an elaborate presentation of hybrid English and Welsh ancestry. Using Welsh textual sources, genealogists traced his Welsh and English ancestry back to the legendary founders of Britain, doubling his claim to the throne. This creative refashioning of the past on the part of family chroniclers illustrates the leverage of Welsh familial connections by marcher baronial families. Their efforts positioned Roger Mortimer as uniquely qualified to unite the kingdoms of Britain and offered an important model for Edward IV’s and Henry Tudor’s later uses of Welsh ancestry to support their own royal claims.