bluuebunny/crossref_metadata_2025_split huggingface dataset:
#5904 COMPARATIVE TRANSCRIPTOMICS OF THREE CANONICAL MOUSE MODELS OF CHRONIC KIDNEY DISEASE
Authors: Christensen Michael , Marstrand-Jørgensen Adam Bøgh , Sembach Frederikke Emilie , Ougaard Maria , Christensen-Dalsgaard Mikkel , Madsen Martin Rønn , Bak Stine , Jensen Ditte , Hansen Henrik Björk , Dalbøge Louise S 
Published: June 2023

Abstract

Background and Aims
A range of mouse models are available in preclinical chronic kidney disease (CKD) research but differ in their disease etiology and pathological hallmarks. To enable better selection of the mouse CKD model optimal for preclinical drug discovery studies, we characterized the kidney transcriptome signature of three well-established models of CKD induced by unilateral ureter obstruction (UUO), unilateral ischemic reperfusion injury (uIRI) and adenine-supplemented diet feeding (ADI).

Method
Male C57BL/6JRj mice were used in all studies. UUO or sham surgery was performed in 9 weeks old mice, which were terminated two weeks post-surgery. uIRI or sham surgery was performed in 10 weeks old mice terminated 6 weeks post-surgery. 12 weeks old mice received an adenine-supplemented diet or a control diet for 6 weeks. Endpoints included plasma biochemistry, kidney histology and RNA sequencing on kidney samples.

Results
Compared to corresponding controls, plasma urea was only increased in ADI mice. All three models presented with increased inflammation (F4/80, UUO&gt;ADI&gt;uIRI) and fibrosis (COl1A1, UUO = uIRI&gt;ADI) in the histological analysis. Compared to corresponding controls, all three models demonstrated substantial increases in differential expressed genes (DEGs, UUO, n = 12,046; uIRI, n = 12,236; ADI, n = 11,468), with significant overlap in transcriptome signatures between the models. Gene expression markers of inflammation (e.g., Ccl2, Cd68 and Il1b), fibrogenesis (e.g., Tgfb1, Serpine1 and Col1a1) and kidney injury (e.g., Havcr1, Lcn2 and Spp1) supported histological findings in the three models. Interestingly, several molecular targets pursued in CKD drug discovery were significantly regulated, however with different directionality, in UUO (upregulated Atg7, Bax, Ednra/b, Gli2, Ifng, Shh; downregulated Glp1r, Nr3c2, Ptch1, Slc5a2), uIRI (upregulated Ednra, Gli2, Glp1r, Ifng, Nr3c2; downregulated Agt, Egfr, Slc5a2), and ADI mice (upregulated Agt, Atg7, Bax, Ednra; downregulated Ednrb, Egfr, Flt1, Nr3c2, Ptch1, Slc5a2).

Conclusion
UUO, uIRI and ADI mouse models demonstrate histopathological hallmarks of CKD, characterized by increased macrophage infiltration and fibrosis, which was corroborated by their individual transcriptome signatures. Despite similarities in histological phenotype, the models were distinguished based on kidney transcriptome changes, with several current drug targets regulated in a model-specific fashion. In conclusion, the current work will enable researchers to select the mouse model optimal for profiling individual preclinical test drugs with therapeutic potential in CKD. Also, our data may serve to enable further development of CKD mouse models with improved clinical translatability.
#5907 RENAL INJURY IN RELATION TO OBESITY AND THE ADDITIVE EFFECT OF HYPERTENSION IN FEMALE AND MALE OBESE AND LEAN ZSF1 RATS
Authors: Nguyen Isabel T N , Cramer Maarten Jan , Joles Jaap A , Verhaar Marianne 
Published: June 2023

Abstract

Background and Aims
Chronic kidney disease co-exists with heart failure with preserved ejection fraction (HFpEF), which is characterized by the presence of obesity, hypertension, and diabetes mellitus type 2. Obese ZSF1 rats, a model of HFpEF, exhibit multiple of these comorbidities that can disturb cardiac function. Little attention has been paid to how these comorbidities affect renal disease in the ZSF1 rats. HFpEF is found predominantly in women in whom obesity and hypertension are particularly prevalent. Therefore, we aimed to characterize the renal phenotype in female and male, lean and obese, ZSF1 rats and investigated additional effects of worsened hypertension on disease severity.

Method
Systolic blood pressure and renal function were assessed biweekly in female and male, lean and obese, ZSF1 rats from 12 to 26 weeks of age by tail-cuff plethysmography, urine collection via metabolic cages and plasma collection, respectively. From 19 weeks of age, rats were implanted with either a deoxycorticosterone acetate pellet (DOCA) and fed high salt diet (6% NaCl) or with a placebo pellet and fed a normal salt diet. At 26 weeks of age, terminal GFR was assessed via inulin clearance under isoflurane. Renal sections were processed for histological analysis.

Results
Lean and obese placebo ZSF1 rats, both female and male, were mildly hypertensive (systolic blood pressure 140-150 mmHg). All obese rats showed HFpEF, evidenced by elevated E/e’ ratio. In female normoglycemic ZSF1 rats, obesity associates with mild proteinuria, decreased GFR and glomerular hypertrophy. The addition of DOCA-salt worsened hypertension in female obese ZSF1 rats, but not in their lean counterparts. DOCA-salt-worsened hypertension enhanced proteinuria and triggered glomerulosclerosis in female obese rats. Male obese placebo ZSF1 rats were hyperglycemic and showed proteinuria, glomerular hypertrophy and sclerosis, and tubulo-interstitial damage. DOCA-salt worsened hypertension in both male lean and obese rats and further aggravated proteinuria, tubulo-interstitial damage, glomerular hypertrophy and sclerosis in obese male rats. No effect of DOCA-salt was observed on GFR in both male and female ZSF1 rats.

Conclusion
Female obese ZSF1 rats developed mild renal disease and DOCA-salt-worsened hypertension deteriorated renal function and structure in normoglycemic female obese ZSF1 rats similar to hyperglycemic male obese ZSF1 rats.
#6039 EPIDEMIOLOGY AND OUTCOMES OF ACUTE KIDNEY INJURY: DON'T FORGET THE CHILDREN
Authors: Chisavu Flavia , Stroescu Ramona , Chisavu Lazar , Gafencu Mihai , Schiller Adalbert 
Published: June 2023

Abstract

Background and Aims
Acute kidney disease (AKI) has evolved from a primary single renal disease to a syndrome secondary to other systemic illness. The aim of this study is to asses AKI epidemiology in a large East European country database comprising a mixt paediatric population (critically ill and non-critically ill) and the impact on mortality and hospitalization length.

Method
We conducted a retrospective observational study on all the admitted paediatric patients from 1 day to 18 years old between first of January 2014 until 31 December 2021. Out of 137760 admissions, 2194 patients were included in the study. We classified the different age groups as: premature (all the babies born before 37 weeks of gestation), full-term new-borns, infants (between 28 days and 12 months of life), toddlers (over 12 months up to 3 years), pre-schoolers (between 3 and 5 years), scholars (6 years to 11 years) and adolescents (12 to 18 years).

Results
The overall incidence of AKI was 15.92/1000 hospital admissions with a 4.77 times fold increased incidence over the 8 year period, from 6.72 in 2014 to 32.12/1000 admissions in 2021. The most prevalent age group, accounting for almost half the AKI cohort (49.49%), was represented by the neonatal setting with 527 (24.02%) preterm and 559 (25.47%) full-term neonates. The paediatric age groups were represented by 10.84% infants, 8.29% toddlers, 6.65% pre-schoolers, 10.57% school aged children and 14.17% adolescents. Staging AKI according to AKIN, stage 1 was identified by us in 24.24% of the AKI cases, stage 2 in 31.03% and stage 3 in 44.71%. Only 25 patients (1.1%) required RRT. Dividing the cases by AKI causes, the most common was represented by prerenal AKI in 85.64% of the cases, followed by 12.16% renal causes respectively 2.18% postrenal causes. Over the 8-years period, from the 137 760 admitted children, 0.32% (449 patients) died of whom 255 (56.79%) presented AKI diagnosis. The risk of death in the presence of AKI was 109 times higher than in the no-AKI group (p&lt;0.0001, 95% CI: 90-132), mortality in the AKI group being 11.62%. Stage 3 AKI group had a higher risk of death than stage 1 with an OR of 3.31 (CI = 2.516-4.355, p&lt;0.001). The average hospitalization period for all admitted patients (137 760) was 5.76 days. In the presence of AKI the average hospitalization period increased to 20.9 days ± 19.3 days.

Conclusion
The neonatal setting portends poor outcomes with the highest incidence of AKI. We can state that in the 21st century patients do no die of AKI but with AKI. Hospitalization increased significantly in the presence of AKI.
#6068 ERYTHROPOIETIN RESISTANCE IN HAEMODIALYSIS PATIENTS POST SARS-COV-2 INFECTION
Authors: Gembillo Guido , Labbozzetta Vincenzo , Peritore Luigi , Giuffrida Alfio Edoardo , Romeo Adolfo , Lipari Antonella , Spinella Claudia , Tigano Alessia , Spallino Eugenia , Calabrese Vincenzo , Santoro Domenico 
Published: June 2023

Abstract

Background and Aims
During the SARS-CoV-2 pandemic, patients undergoing chronic haemodialysis treatment were at particularly high risk of infection. This was due to their vulnerability given their state of immunosuppression and multiple comorbidities, on the one hand, and the circumstances that limited physical distancing during treatment, on the other. Even after negativation, patients with a previous infection experience symptoms such as persistent asthenia, muscle weakness, widespread pain and deterioration in perceived health status. In our study, we aimed to investigate the parameters of anaemia and the change in the erythropoietin resistance index (ERI) in haemodialysis patients with previous infection.

Method
We included 25 patients with a dialysis age &gt;6 months, giving a total of 72 measurements. The distribution was assessed with the Kolmogorov-Smirnov test and with a graphical evaluation of the same. We calculated the ERI 3 months before the date of infection and in the 3 and 6 months after. These data were also compared with a control group. Patients were divided into 2 groups: Group A (patients with previous infection) and Group B (control group). Linear mixed models were performed to calculate the slope between the group and the ERI index.

Results
No statistically significant differences were found. The LMMs showed a significant interaction between the scores obtained at the visits performed and the study group, with a decrease in ERI over time of 0.21 at each visit.

Conclusion
Our results show that patients with previous Covid 19 infection have higher resistance to erythropoietin and require higher doses even months after infection. The response to erythropoietin in this population should be investigated in studies with larger cohorts, as anaemia is an important factor affecting the quality of life of our patients.
#6073 MAGNETIC RESONANCE RADIOMIC ANALYSIS FOR THE PREDICTION OF GRAFT FAILURE IN PATIENTS WITH KIDNEY TRANSPLANTATION
Authors: Fontana Francesco , Alfano Gaetano , Monelli Filippo , Besutti Giulia , Trojani Valeria , Donati Gabriele 
Published: June 2023

Abstract

Background and Aims
Prediction of future graft failure with non-invasive investigations is a relevant objective for transplant clinicians. We previously demonstrated a promising discrimination capacity for interstitial fibrosis / tubular atrophy (IFTA) &gt;50% in kidney biopsy of a machine learning (ML) based magnetic resonance imaging (MRI) radiomic algorithm. Aim of the present study is to evaluate accuracy of MRI radiomic-based ML algorithms in predicting future graft failure.

Method
Single-center retrospective observational cohort study on a previously characterized cohort of kidney transplant recipients who underwent graft biopsy and graft MRI imaging within 6 months from biopsy, both on clinical indication, at the “Azienda Ospedaliero-Universitaria di Modena”, Italy, from 1/1/2012 to 1/3/2021. The primary outcome was to identify the best combination of MRI radiomic features for the prediction of graft failure during follow-up. Segmentation of renal parenchyma, cortex and medulla on MRI sequences was performed using the 3DSlicer software. Radiomic features were then extracted using an in-house software based on pyradiomics applying Wavelet and Gaussian filters. LASSO algorithm was employed to select correlated features with outcome and summarize them in a radiomic signature. Using radiomic signature alone and then merged with meaningful clinical data we trained ML-algorithms using 70% of cases for training/validation, with a 10-fold internal cross-validation, and 30% for model testing. Model performance was assessed using AUC with a 95% confidence interval (CI).

Results
Seventy coupled tests (63 patients) were included and randomly subdivided into a training/validation cohort (n = 50) and a test cohort (n = 20). Median follow-up was 24.73 months (interquartile range 13.64-46.57). Radiomic model had an AUC of 0.88 (95%_CI 0.70-0.97) in training and 0.57 (95%_CI 0.23-0.86) in test cohort. Radiomic-clinical mixed model had an AUC of 0.90 (95%_CI 0.73-0.98) in training and 0.66 (95%_CI 0.33-0.88) in test cohort.

Conclusion
We produced an MRI radiomic-based ML algorithm with good prediction ability for future graft failure in patients with kidney transplant. Given the limited number of enrolled patients, validation in larger (and ideally prospective) cohorts is required to confirm our findings. Comparison of radiomic-based ML with histological parameters (i.e., IFTA) for the prediction of graft failure in our cohort is currently under assessment.
#6118 ALTERNATIVE SPLICING IN MECHANICALLY STRETCHED PODOCYTES AS A MODEL OF GLOMERULAR HYPERTENSION
Authors: Mattias Francescapaola , Kliewe Felix , Hammer Elke , Ameling Sabine , Lio Chit Tong , Endlich Karlhans , Zimmermann Uwe , Stracke Sylvia , Capasso Giovambattista , Baumbach Jan , Tsoy Olga , Völker Uwe , Endlich Nicole 
Published: June 2023

Abstract

Background and Aims
It has been shown that mRNA splicing plays a relevant role in disease pathophysiology. However, the possible role of alternative splicing (AS) in hypertensive nephropathy (HN) has not been investigated. The purpose of the Sys_CARE (Systems Medicine Investigation of AS in Cardiac and Renal Diseases) project is to investigate the possible implication of AS events in HN development and progression.

Method
Differentiated murine podocytes were seeded on a flexible silicone membrane, and mechanically stretched using the Stretchy apparatus (NIPOKA GmbH, Greifswald). Cells were stretched for 3 days under low and high stretch conditions with a frequency of 0.5 Hz. The mRNA and proteins were isolated and analyzed using RNA_Seq and LC-MS/MS techniques. Enrichment analysis identified proteins which were classified according to the related biological processes, molecular function and cellular components. Splicing and transcript expression were evaluated with bioinformatical tools (rMATS, leafcutter, Whippet, MAJIQ, IsoformSwitchAnalyzeR).

Results
Proteomic analysis of cultured podocytes revealed significant different expression levels for 135 proteins (54 increased and 81 decreased) and 424 proteins (195 increased and 229 decreased) under low and high stretch conditions, respectively, compared to unstretched conditions. Interestingly, most of the proteins with decreased intensity upon stretch are cytoskeleton and actin-binding proteins. In contrast, the up-regulated proteins are more associated in clusters affecting mRNA processing and splicing. By RNA_Seq we identified over 1000 different splicing events including all types of alternative splicing events. We screened for candidates that showed an alternative splicing event in multiple tools, were found in the proteomics, were podocyte-specific, or showed altered expression in glomerulopathies such as diabetic nephropathy. In this regard, we found an isoform switch of Myl6 and Shroom3 after mechanical stretch.

Conclusion
Using mechanically stretched podocytes as a model of HN, we found significant up- and down-regulated proteins. In addition, by RNA_Seq we identified an isoform switch of Myl6 and Shroom3 that might be essential for the development of HN.
#6201 CHANGES ON LEFT VENTRICULAR FUNCTION AND CHARACTERISTICS ACCORDING TO THE DEGREE OF INTERDIALYTIC WEIGHT GAIN IN MAINTENANCE HEMODIALYSIS PATIENTS
Authors: Anastasiou Vasileios , Alexandrou Maria Eleni , Kamperidis Vasileios , Daios Stylianos , Tsilonis Konstantinos , Theodorakopoulou Marieta , Moysidis Dimitrios , Iatridi Foteini , Giannakoulas George , Ziakas Antonios , Sarafidis Pantelis 
Published: June 2023

Abstract

Background and Aims
Pronounced pulmonary circulation overloading has been observed in hemodialysis patients with higher fluid intake over the long interdialytic interval. This study aimed to evaluate the impact of the degree of fluid accumulation on left ventricular (LV) systolic and diastolic function and sizing characteristics.

Method
For the present analysis, 41 patients receiving maintenance hemodialysis thrice-weekly were divided by the recommended threshold of interdialytic-weight-gain corrected for dry weight (IDWG%) into a higher (&gt;4.5%) and a lower (&lt;4.5%)IDWG% group. All participants underwent 4 echocardiographic assessments at the start and the end of the 3-day and the 2-day interdialytic interval in a cross over design.

Results
Over the 3-day interval, significant increments in stroke volume (SV) were observed for both groups, but were more prominent in the higher IDWG% group(&gt;4.5% 18.63±22.84vs. &lt;4.5% 12.6±14.48mmHg, p = 0.04). Similarly, a greater increase in cardiac output was evidenced in patients with higher IDWG% over the 2-day interval (&gt;4.5% 1.31±1.38 vs.&lt;4.5% 0.36±2.08L/m2, p = 0.012). With regards to diastolic function, a significant increase in E/A and E/E’m ratios was observed over the 3-day interval, but significant between-group differences in interdialytic changes were detected only for the E/A ratio (IDWG&gt;4.5% 0.35±0.29 vs. &lt;4.5% 0.06±0.44, p = 0.035). Left atrial dimensions and LV mass were enlarged to a similar extent in both study-groups during both intervals.

Conclusion
Patients exceeding the recommended threshold of interdialytic fluid accumulation experience higher increases in SV and deterioration of preload-dependent indexes of diastolic function, particularly during the 3-day interval.
#6327 ACCEPT OR DECLINE? A STATISTICAL APPROACH TO AID DECISION MAKING
Authors: Ibrahim Maria , Mehew Jenny , Utley Martin 
Published: June 2023

Abstract

Background and Aims
The clinician-patient decision of whether to accept or decline an offered deceased donor kidney is one of the most complex in transplantation. Though many attempts have been made to risk stratify based on donor and recipient characteristics as well as other methods, reliance on clinical intuition remains high. We used a novel statistical modelling technique to better understand potential outcomes for patients following acceptance or decline of a deceased donor organ offer in the UK.

Method
We obtained UKTR data held by NHS Blood and Transplant (NHSBT) on adult patients listed for kidney transplantation in the UK, deceased donor kidney offers and post-transplant outcomes. Multivariable models to demonstrate 5-year transplant survival (a composite of graft and patient survival) for patients from the point of offering and post-transplant survival were developed using a Cox proportional hazard techniques. Waiting time to a “better” offer was modelled using a micro-simulation approach for patients and donors with different profiles, incorporating the points system from the current UK kidney offering scheme. Rates of patients arriving on the waiting list, leaving the list and being transplanted were obtained to facilitate this, as well as characteristics of waitlisted patients and organ donors. Simulations were then run to ascertain potential outcomes from the point of offer for an index patient for scenarios characterised by offers from donors with differing profiles.

Results
Figure 1 demonstrates the outcomes of an index patient if they accept an organ offer from a donor with the demonstrated characteristics compared with potential outcomes if the next offer is accepted. Figure 2 uses the same techniques but demonstrates outcomes if a kidney from a donor with ‘worse’ characteristics is offered.

Conclusion
This study demonstrates a novel method to help visualise potential outcomes for patients listed for deceased donor kidney transplantation. With further input from patient and clinician perspectives, this work has potential to be beneficial in facilitating discussions between patients and clinicians regarding decision making at the time of organ offering and may ultimately improve organ utilisation.
#6373 EFFECT ON BLOOD PRESSURE AND CARDIOVASCULAR RISK FACTORS IN PEDIATRIC PATIENTS DURING COVID-19 PANDEMIC CONFINEMENT (COBECOR STUDY)
Authors: Sampera Elena Codina , Sancho Pedro Arango , Rodríguez Ana Cristina Aguilar , Herrera Bernat Gómez , Moreno Marta Jiménez , Baños Yolanda Calzada , García Raquel Jiménez , Brito Verónica Coll , González Osmar Davíd , Aris Álvaro Madrid 
Published: June 2023

Abstract

Background and Aims
Patients monitored in the cardiovascular risk (CVR) consultation usually present overweight/obesity, metabolic syndrome, tendency to hypertension (HT), poor eating habits and sedentary lifestyle, with great resistance to change, great influence of the environment and, frequently, psychosocial limitations. We asked whether home confinement for COVID-19 (March-May 2020) could have negative effects in relation to CVR in these patients. The main objective of this work is to assess this hypothesis with respect to HTN and the use of antihypertensive drugs in these patients. As a secondary objective, we assessed changes in other parameters: body mass index (BMI), level of physical activity and diet.

Method
Retrospective cohort study with review of 738 ambulatory blood pressure monitoring (ABPM) between 2019-2022 obtaining, after applying the exclusion criteria (no overweight/obesity, poor therapeutic compliance, underlying renal pathology or failure to perform two ABPM in the study period), a final cohort of 46 patients divided into two groups (23 each): one group exposed to home confinement (G1) with one ABPM before and after home confinement and another group not exposed to confinement (G2) with two ABPM in different periods between 2021-2022. Blood pressure (BP) percentile values, dipper pattern, variability and blood pressure load, as well as the rest of the CVR parameters were compared in both periods.

Results
The mean age was 13 years (13.8 G1/13.2 G2) with a mean time between the 1st and 2nd ABPM of 11 months (11.08 G1/10.95 G2) and a greater reduction in BMI in G2 than in G1 (1.05 G1/1.21 G2). Despite this, the results were not statistically significant. Nor were the results significant in terms of differences in AT or worsening of the dipper pattern (30.4% in G1 and 21.7% in G2). We did observe differences (p&lt;0.022) in the use of antihypertensive drugs, although contrary to our initial hypothesis, with greater use of drugs in G2.

Conclusion
Although the low sample size, the biases inherent in the design and the lack of previous studies make the interpretability and statistical significance of some results difficult, they reinforce that the measures during confinement did not contemplate all spheres of health and the need to implement specific CVR consultations. Obesity and its associated pathologies are an important public health problem that pediatricians have the responsibility to address.