bluuebunny/crossref_metadata_2025_split huggingface dataset:
#1945 Comparative analysis of kidney transplantation modeled using precision-cut kidney slices and kidney transplantation in pigs
Authors: Moor Matthias , Nordström Johan , Burmakin Mikhail , Raki Melinda , Al-Saad Samer , Nowak Greg , Wennberg Lars , Patrakka Jaakko , Olauson Hannes 
Published: May 2024

Abstract

Background and Aims
Kidney transplants are at risk for so far unavoidable ischemia-reperfusion injury. Several experimental kidney transplantation models are available to study this injury, but all have their own limitations. Here, we describe precision-cut kidney slices (PCKS) as a novel model of kidney ischemia-reperfusion injury in comparison with pig and human kidney transplantation.

Method
Following bilateral nephrectomy in pigs, we applied warm ischemia (1 h), cold ischemia (20 h) and a reperfusion period (4 h) to one whole kidney undergoing transplantation to a recipient pig and, in parallel, established PCKS undergoing ischemia and modeled reperfusion. Tissues were analyzed using standard histopathology assessment by two blinded pathologists, and bulk RNAseq with gene set enrichment analysis with comparison to human kidney biopsy gene sets obtained from Gene Expression Omnibus.

Results
Histopathological assessment revealed the presence of some but not all morphological features of tubular injury in PCKS as seen in pig kidney transplantation. RNAseq demonstrated that the majority of changes occurred after reperfusion only, with a partial overlap between PCKS and kidney transplantation, with some differences in transcriptional response attributable to systemic inflammatory responses and immune cell migration. Comparison of PCKS and pig kidney transplantation with RNAseq data from human kidney biopsies by gene set enrichment analysis revealed that both PCKS and pig kidney transplantation reproduced the post-reperfusion pattern of human kidney transplantation. In contrast, only post-cold ischemia PCKS and pig kidney partially resembled the gene set of human acute kidney injury.

Conclusion
Overall, the present study established that a PCKS protocol can model kidney transplantation and its reperfusion-related damage on a histological and a transcriptomic level. PCKS may thus expand the toolbox for developing novel therapeutic strategies against ischemia-reperfusion injury.
#2819 The association between oral proteome and microbiome in kidney transplant recipients: 24-months prospective study
Authors: Ribas Ana Merino , Sampaio Susana , Araujo Ricardo , Azevedo Maria João , Alencastre Ines , Pestana Manuel , Ximénez-Embún Pilar , Muñoz Javier , Sampaio-Maia Benedita , Trindade Fabio 
Published: May 2024

Abstract

Background and Aims
Recent evidence observed changes in saliva composition and an oral dysbiosis in end-stage renal disease (ESRD) patients. Despite of that, the relationship between oral microbiome and oral peptidome in kidney transplant recipients (KTR) is still unexplored. Therefore, the aim of this study is to investigate the interplay between oral microbiome and oral peptidome in KTR from live kidney donors (LKD) and to analyze their relevance on the recovery of renal function.

Method
This prospective study enrolled 11 adult KTR/LKD pairs to whom saliva was collected before organ transplant/donation (T0) and at 6 (T6), 12 (T12), and 24 (T24) months after (dropout rate up to 45% at T24). Saliva microbiome was evaluated by throughput sequencing (16SrRNA gene) and low-molecular weight salivary proteome by LC-MS/MS analysis.

Results
The glomerular filtration rate (GFR) of KTR recover to normal levels after transplant. Oral microbiome of ESRD differ significantly from healthy donors (T0; p = 0.04), however these differences fade away progressively post-transplant, presenting only a slight difference at T6 (p = 0.046) but no differences at T12 and T24. Also, 21 proteins were found dysregulated in ESRD and after protein-protein interaction analysis were organized into two functional clusters: one mainly composed by cysteine protease inhibitors, and another mainly composed by metabolism-related enzymes (lactate dehydrogenase, catalase, and arginase-1). Almost all differences between LKD and KTR became elusive at 6 months. It was found an inverse correlation between Streptococcus and peptidyl-prolyl-cis-trans-isomerase-A, a protein with a strong chemotactic effect on leukocytes, and a positive correlation between Bergeyellaand cystatin-D (CST5), a cysteine proteases-protective protein. The remaining secreted cystatins (CST1/2/4), but not CST5 were found significantly correlated with GFR, suggesting that renal function recovery is paralleled related to an increase in oral cystatins. Also, an inverse relationship between Bergeyella and GFR suggests that the renal function recovery has implications in the composition of oral microbiota.

Conclusion
This study may provide relevant clues about the oral cavity-kidney axis dynamics and pinpoint potential markers of renal function impairment and/or recovery in KTR.
#856 Performance of ex vivo confocal microscopy in the assessment of Remuzzi score in preimplantation biopsies
Authors: Andujar Alicia Molina , Larque Ana Belen , Paredes David , Cucchiari David , Barnadas Esther , Diekmann Fritz , García-Herrera Adriana 
Published: May 2024

Abstract

Background and Aims
Confocal microscopy (CM) is a technique that generates digital images from fresh tissue samples with resolution comparable to that obtained with conventional stains. These images are digitally stained with Hematoxylin/Eosin-like. The clear advantage of this technique with respect to conventional staining is the speed in obtaining results which is of great importance in the donation process, as well as their digitalization. The aims of the present study were two: 1) to assess reproducibility for CM between two nephropathologist in preimplantation biopsies and 2) to describe the correlation between gold standard for preimplantation biopsies in our institution performed in frozen block and CM.

Method
Donor biopsies were reviewed according to Remuzzi score (RS) by on-call pathologist for frozen block and two nephropathologist for CM, blinded to the original frozen block report. The intraclass correlation coefficient (ICC) for every variable in RS was calculated for the two nephropathologists. Later, concordance between the techniques was evaluated by the κ index.

Results
We included 50 preimplantation biopsies between January and October 2023. Median donor age was 74 years (IQR 62-77.3), 56% were male, 74% had arterial hypertension and 24% had diabetes mellitus. Number of glomeruli were 23 (IQR 14.25-30.25). ICC was excellent for glomerulosclerosis (0.755) and total RS (0.787) and good for interstitial fibrosis (0.536), while fair for tubular atrophy (0.412) and poor for vascular narrowing (0.14). There was excellent agreement between frozen block and CM for interstitial fibrosis (κ 0.898) and global RS (κ 0.898) and substantial for glomerulosclerosis (κ 0.694) while it failed to moderate for vascular narrowing (κ 0.522) and fair for tubular atrophy (κ 0.37).

Conclusion
CM proved to have reproducibility between nephropathologists and comparability to our gold standard technique in evaluating preimplantation biopsies. The ease of acquisition of CM images suggests that it may be useful for rapid evaluation of graft histology.
#1155 Outcomes after kidney transplantation in anti-glomerular basement membrane disease
Authors: Brilland Benoit , Traversat Priscille , Dekervel Marine , Piccoli Giorgina , Assia Djema , Gatault Philippe , Thierry Antoine , Bertrand Dominique , Golbin Leonard , Anglicheau Dany , Duveau Agnès , François Augusto Jean 
Published: May 2024

Abstract

Background and Aims
Anti-glomerular basement membrane antibody disease-associated glomerulonephritis (anti-GBM-GN) can lead to end-stage kidney disease (ESKD), requiring replacement therapy with dialysis or kidney transplant (KT). Few studies evaluated the outcome of these patients after KT. Our aim was to describe, in comparison with a control group, the occurrence of the following events: delayed graft function recovery, graft survival, relapse, acute rejection, overall survival; and to study the risk factors associated with these events.

Method
This was a retrospective, multicenter (6 French centers), observational study including patients who received a KT between 2005 and 2023 for ESKD secondary to anti-GBM-GN. Each vasculitis case receiving a KT was matched with 2 controls, matched on gender, center, recipient age (±5 years) and transplant period (±1 year). Event-free survival and the associated risk factors were analyzed.

Results
126 patients were included, including 42 with anti-GBM-GN and 84 control patients. The median post-KT follow-up for vasculitis patients was 95 months. There was no difference in the occurrence of DGF between the groups (24 vs 18%, p = 0.5). There was no difference in graft survival when comparing both groups (78% vs 82% at 10 years, p = 0.48) (Fig. 1A). Only one patient experienced a relapse after KT (being anti-GBM negative at the time of transplantation). There was no difference in the incidence of acute rejection between the groups (p = 0.82). There was no difference in overall survival when comparing both groups (83% vs 89% at 10 years, p = 0.76) (Fig. 1B).

Conclusion
Kidney transplantation is an interesting option for patients with anti-GBM-GN: outcomes are similar to those of a matched population with similar occurrence of acute rejection, graft loss or death. Moreover, relapse rate is low. Comparison with a matched anti-GBM-GN population remaining on dialysis would be of interest to go further.
#725 Incorporating molecular rejection patterns to differentiate histologic activity and chronicity features in antibody-mediated rejection
Authors: Harmacek Dusan , Lopez Kai Castrezana , Weidmann Lukas , Rho Elena , von Moos Seraina , George Britta , Gaspert Ariana , Helmchen Birgit , Schachtner Thomas 
Published: May 2024

Abstract

Background and Aims
Biopsy-based transcripts associated with antibody-mediated rejection (AMR) hold promise as substitutes for C4d positivity, according to the Banff Meeting Report of 2022. However, incorporating histologic and molecular features of disease activity and chronicity is crucial to potentially guide patient management.

Method
We analyzed 365 kidney allograft biopsies by histology and the Molecular Microscope Diagnostic System (MMDx) at the University Hospital Zurich from July 2021 to November 2023. Histologic findings were classified according to Banff 2022 into (1) active AMR (n = 24), (2) chronic active AMR (MVI, n = 47), and (3) chronic AMR (n = 30). The corresponding histologic subgroups with DSA negativity were used for comparison.

Results
Fourteen out of 24 cases (58%) with active AMR, 28 of 47 cases (60%) with chronic active AMR, but only 1 of 30 cases (3%) with chronic AMR showed molecular AMR. Among cases with molecular AMR the sum of the fully-developed AMR-related (R5) and late-stage AMR-related (R6) phenotype scores was significantly higher in chronic active AMR compared to active AMR cases (p = 0.0017). This finding was even more pronounced in chronic active AMR cases with double contours (cg)&gt;1 (p = 0.00062). Similarly, in the cases without molecular AMR the sum of the fully-developed AMR-related (R5) and late-stage AMR-related (R6) phenotype scores was higher in chronic active AMR compared to active AMR cases (p = 0.039) and more pronounced in cases with cg&gt;1 (p = 0.008). However, rejection phenotype scores (R1-R6) among chronic AMR cases did not differ from DSA-positive or DSA-negative cases without microvascular inflammation (p = 0.705 for R5+R6).

Conclusion
Incorporating molecular rejection phenotype patterns may further differentiate disease activity and chronicity in cases with active and chronic active AMR by histology. However, molecular subthreshold findings do not appear relevant in chronic AMR cases.
#2414 Hypertension resolution after kidney transplantation is associated with better kidney transplant outcomes in patients with pre-transplant hypertension
Authors: Lee Kyungho , Kim Bong-Sung , Jeong Seoin , Jang Minyoung , Jeon Junseok , Shin Dong Wook , Lee Jung Eun , Huh Wooseong , Han Kyungdo , Jang Hye Ryoun 
Published: May 2024

Abstract

Background and Aims
Hypertension is prevalent in patients with advanced chronic kidney disease (CKD), and kidney transplantation (KT) can potentially improve hypertension. Although hypertension is expected to be resolved after KT in many recipients with pre-transplant hypertension, little is known about the hypertension resolution rate and its prognostic role in KT outcomes.

Method
We retrospectively identified KT recipients (between 2006 and 2015) who had pre-transplant hypertension using Health Insurance Review & Assessment Service and Korea National Health Insurance System. The recipients were categorized into two groups based on their post-KT hypertension status: “persistent hypertension” and “resolved hypertension”. Cox proportional hazard analyses were performed to assess the risk of death-censored graft failure and all-cause mortality with adjusting various clinical, immunological risk factors, and socioeconomic status.

Results
Among 11,342 KT recipients with pre-transplant hypertension, 8,233 (73%) remained hypertensive, while 3,109 (27%) experienced hypertension resolution after KT. Recipients with resolved hypertension had lower rates of delayed graft function and major comorbidities, including diabetes mellitus, ischemic heart disease, and stroke compared to recipients who remained hypertensive. After adjusting for multiple covariates, the resolved hypertension group had 0.59-fold (95% confidence interval [CI] 0.49–0.73) lower risk for graft failure and 0.59-fold (95% CI 0.48–0.73) lower risk for all-cause mortality compared to the persistent hypertension group. Subgroup analyses revealed that the protective effect of resolved hypertension on graft survival was more pronounced in females (P for interaction = 0.045), and on overall survival was weaker in recipients with diabetes (P for interaction = 0.033).

Conclusion
A significant proportion of patients experienced hypertension resolution after KT, which is associated with improved graft survival and overall patient survival. The post-KT hypertension status can be used as a prognostic indicator for predicting better outcomes in KT recipients with pre-transplant hypertension.
#3009 The impact of living donor hypertension on later function of kidney graft in kidney transplantation
Authors: Jaques David , Huegli Sophie , Grouzmann Noémie , Pasquier Théodore , Hirt Patricia , de Seigneux Sophie , Ponte Belen , Haidar Fadi 
Published: May 2024

Abstract

Background and Aims
Living donor (LD) selection is a crucial step in kidney transplantation (KTX). The impact of hypertension (HT) of LD on later kidney graft function remains insufficiently understood.

Method
We retrospectively reviewed recipients of LD KTX at a single tertiary center (Geneva University Hospitals, Geneva, Switzerland) from January 2003 to December 2021 with a follow-up until December 2022. LD blood pressure (BP) values obtained with office measurement and 24 h ambulatory BP monitoring (ABPM) were the main predictors, while recipients estimated glomerular filtration rate (eGFR) and proportion of kidney fibrosis on biopsies were the outcomes. Multivariate analyses were adjusted for the following pre-KTX donor characteristics: Age, gender, ethnicity, body mass index and eGFR.

Results
In total, 212 LD KTX recipients were included with LD mean age 51 ± 11 and 133 women (62.7%). According to European guidelines definition, 73 (34.4%) LD were hypertensive based on office BP. On a sub-group of 112 LD with ABPM, 64 (57.1%) were hypertensive. Systolic office BP was negatively associated with eGFR at 6 months, 1 year, 5 year and 10 year follow-up (p &lt; 0.05 for all). Systolic office BP was positively associated with kidney fibrosis at 1 year follow-up (p &lt; 0.05). Those associations were not significant after multivariate adjustment. Age at donation remained significantly associated eGFR and kidney fibrosis after multivariate adjustment (p &lt; 0.05 in both models).

Conclusion
Based on our experience, a significant proportion of LD are hypertensive at kidney donation. While an adverse impact of HT on later kidney function and fibrosis could be measured, this effect seemed negligible after accounting for other more relevant clinical characteristics, with age at donation being decisive.
#2586 Time to event prediction of new-onset diabetes after transplantation in kidney transplant recipients using machine learning models
Authors: Szili-Torok Tamas , Suleja Agata M , Verbeek Max J , Guo Jiapan , Bakker Stephan J L , Tietge Uwe J F , de Borst Martin H 
Published: May 2024

Abstract

Background and Aims
New-onset diabetes after transplantation (NODAT) is a common and serious complication of kidney transplantation that contributes to long-term morbidity and mortality after the transplant procedure. Conventional methods may predict the risk of, but not time to developing NODAT. We aimed to develop a machine learning model that predicts the time to NODAT in kidney transplant recipients (KTR).

Method
Two large prospective cohort studies of stable KTR (inclusion &gt;1 year after transplantation) from the University Medical Center Groningen were combined. Data collection took place between 2001 and 2003 for cohort A, and between 2008 and 2011 for cohort B, resulting in the inclusion of 750 KTR free of NODAT at baseline. To predict absolute time to NODAT, a bootstrap aggregating (bagging) approach was utilized which consisted of several extreme gradient boosting (XGBoost) models with the accelerated failure time (AFT) objective. The performance of the resulting bagging model was internally evaluated by assessing the concordance index (c-index) in 20% of the dataset not used for training.

Results
From the 750 KTR included, 76 (10.1%) developed NODAT during a median (interquartile range [IQR]) follow-up of 5.8 (4.7 to 9.2) years. The median (IQR) age was 51.2 (40.5 to 60.7) years and 342 (45.6%) of the KTR were female. During feature engineering, 18 features from 53 were selected. After hyperparameter tuning, model performance during internal validation was 0.84. Furthermore, SHapley Additive exPlanations (SHAP) values were used to estimate feature importance, which revealed that glucose, HbA1c, mean arterial pressure, cyclosporine concentrations and daily vegetable intake were the most important features.

Conclusion
The developed machine learning model shows good discriminative ability of time to NODAT prediction. Due to the methodology used, the model allows for flexible incremental learning, meaning that the bagging model can be retrained with additional data without compromising on performance.
#1860 Oral semaglutide in diabetic kidney transplant recipients: Evaluating effectiveness and safety
Authors: Singh Arshdeep Singh , Vigara Luis Alberto , Mozo Marta Alonso , Amaro José Manuel , Fernández Florentino Villanego , Alonso Myriam Eady , Márquez Maria Gabriela Sánchez , Chavez Cristhian Orellana , Garcia Teresa , Blanca María Auxiliadora Mazuecos 
Published: May 2024

Abstract

Background and Aims
Glucagon-like peptide 1 receptor agonists (GLP1-RA) have demonstrated cardiovascular and renal benefits in obese diabetic patients. However, the evidence for oral semaglutide in kidney transplant (KT) patients is very limited. Our study aims to analyze the effectiveness and safety of oral semaglutide in diabetic KT patients.

Method
Retrospective cohort study of KT with diabetes who started oral semaglutide in 3 Spanish hospitals (Puerta del Mar University Hospital, Jerez de la Frontera University Hospital and Puerto Real University Hospital) between December 2021 and December 2023. None of them had previously received subcutaneous GLP1-RA. Clinical and demographic variables were analyzed. Glomerular filtration rate (eGFR), proteinuria, and weight were collected at the start of the treatment and after 6 and 12 months. We analyze glycemic control, blood pressure, lipid profile and trough level, dose and C/D ratio of tacrolimus. Acute rejections (AR), de novo donor-specific antibodies (dnDSA) and adverse effects were documented. Parametric and non-parametric tests were performed according to the normality of the sample.

Results
In this period, 22 KT with DM started treatment with oral Semaglutide, of which 16 patients completed follow-up for 6 months and 11 patients for 1 year. Fourteen (63.6%) had developed post-transplant DM. The mean age was 61 years, and 77% were men. The mean baseline estimated glomerular filtration rate (eGFR) was 46.1 ml/min/1.73 m2, the baseline body mass index was 34.7 kg/m2 and the median KT vintage was 45 months. Three patients were on treatment with SGLT2i at the start of the drug. Variables compared during the follow-up are shown in Table 1. Four patients (18%) suffered gastrointestinal side effects. No dnDSA were documented during follow-up. One episode of AR was documented after drug initiation.

Conclusions
We show the longest series of oral semaglutide in KT patients. Our results support that it can be a good option for managing DM in KT, especially in obese patients.
#535 Roxadustat as a treatment of anemia after kidney transplantation
Authors: Beliančinová Monika , Blichová Tímea , Kleinova Patricia , Graňák Karol , Vnučák Matej , Dedinska Ivana 
Published: May 2024

Abstract

Background and Aims
Roxadustat is a recently approved hypoxia-inducible factor prolyl hydroxylase inhibitor that has demonstrated favourable safety and efficacy in the treatment of renal anaemia.
The goal of this study is to analyse the effect of roxadustat on the level of hemoglobin in a group of patient with chronic kidney disease with or without kidney transplantation.

Method
This is a monocentric study conducted on the patients of Transplant-nephrology department and/or Transplant-nephrology out-patient clinic of University Hospital Martin, Slovakia who have been treated with roxadusat since August 1st, 2022.

Results
33 patients were included in the study. The average follow up of treatment with roxadustat was 4.2 months. The following parameters were recorded at the baseline: age, gender, estimated glomerular filtration rate—eGFR (CKD-EPI), treatment with iron and level of iron in serum, level of C-reactive protein, level of hemoglobin, starting dose of Roxadustat.
We discovered a significant improvement in the levels of hemoglobin after one month of roxadustat treatment (P &lt; 0.0001) and another significant improvement in follow-up (P ‚0,0373). There was no significant difference in eGFR, CRP or iron levels during follow up, so hemoglobin levels were not affected by inflammation or kidney function. In the next step the group of patients was divided based on history of kidney transplantation. Again, we confirmed significant improvement in hemoglobin levels in kidney transplantation group in first month of treatment (P &lt; 0.0001) as well as in follow up (P &lt; 0.0001). There was a significant improvement in hemoglobin levels in the first month of roxadustat treatment in the group of patients who did not undergo kidney transplantation (P = 0.0261). However, there was no significant difference between hemoglobin levels in month 1 and follow up in this group.

Conclusion
Roxadustat—as a new treatment option of anaemia for patients with chronic kidney diseases. Our first analysis confirmed that roxadustat is very effective not only in patients with CKD, but also in patients with anaemia after kidney transplantation.