bluuebunny/crossref_metadata_2025_split huggingface dataset:
#2784 Deep learning algorithm predicts individual ultrafiltration trajectories for patients on automated peritoneal dialysis 12 weeks ahead
Authors: Eibensteiner Fabian , Unterwurzacher Markus , Herzog Rebecca , Kratochwill Klaus , Aufricht Christoph , Vychytil Andreas 
Published: May 2024

Abstract

Background and Aims
Adequate small solute clearance and ultrafiltration (UF) are the main requirements for fluid and salt homeostasis on peritoneal dialysis (PD). New automated peritoneal dialysis (APD) systems that allow remote patient monitoring in terms of PD treatment analysis have the potential to improve clinical outcomes. UF on APD although dependent on PD prescription, i.e. fill volumes and glucose concentration, exhibits substantial intra- and interindividual variation, even day-by-day. As conventional statistical methods are not able to assess these complex non-linear relationships adequately, we aimed to build a deep learning algorithm to predict ultrafiltration trajectories of individual patients 12 weeks ahead.

Method
Data on daily UF and PD prescriptions (i.e., glucose concentration, fill volumes) was extracted from the APD cycler management software (PD Link, Baxter, IL, USA) and patient charts at the Medical University of Vienna, for a secondary analysis of this cohort. The Keras high-level API for TensorFlow in R software (R Core Team 2023) was used to create a Long Short-Term Memory (LSTM) recurrent neural network based on historic prescription and gcUF data of 26 weeks (after the first 90 days of APD) to predict individual UF trajectories for the following 12 weeks.

Results
APD machine readouts from a total of 123 patients, with a mean time on PD of 117 (±73) days, were retrieved. The final recurrent neural network consisted of four LSTM layers with 64 cells each, sigmoid activation. The final model was fit using 30 epochs, 49 steps per epoch, and recurrent dropout to avoid overfitting. A 40-40-20% data split was used to train, validate, and test the model adequately. This deep learning algorithm was able to predict individual UF values, for each day of the upcoming 12 weeks, with an accuracy of at mean 201ml. Upon visual inspection, predicted individual UF trajectories smoothly resemble the overall day-by-day trajectory of the patient but fail to account for extreme spikes in either direction.

Conclusion
In conclusion, historic daily APD cycler and prescription data in coalescence with respective daily measurements of membrane function (i.e., gcUF) can be used to predict individual daily ultrafiltration values and trajectories of APD patients 12 weeks ahead using a deep learning algorithm. Therefore, continuous collection of PD prescription data and UF measurements may be used to monitor peritoneal membrane function of patients on APD and alert clinical teams upon detection of relevant changes of UF trajectories already 12 weeks ahead to facilitate early intervention. In contrast to current “screening” methods on PD, i.e., Peritoneal Equilibrium Test, these methods could reduce treatment burden.
#3090 Parvovirus infection in renal transplant recipients: a systematic review of clinical profile and treatment strategies
Authors: Subbiah Arunkumar , Govindarajan Srinivasavaradan , Durgam Yashwant 
Published: May 2024

Abstract

Background and Aims
Parvovirus B 19 (PVB-19) virus infection can cause severe, persistent and/or refractory anaemia in kidney transplant recipients (KTR). There is paucity of data on the clinical manifestations, diagnosis and management of this infection and limited to case reports and case series.

Method
We performed a literature search of kidney transplant recipients infected with PVB-19 in MEDLINE, EMBASE and Cochrane databases and 93 articles were identified as suitable for assessment. The review was conducted in accordance with PRISMA statement.

Results
A total of two hundred and eighty-two patients were included from the studies assessed in the review. The mean age of the cohort was 37.05 years. The infection was more common in males when compared to females. The median onset of PVB-19 infection post transplantation was at 5 weeks (2, 15 weeks). One fourth of the recipients had at least one episode of rejection prior to PVB-19 infection. Majority of the patients were on Tacrolimus, MMF and corticosteroids maintenance. One third of the patients had co-infections with other organisms (EBV, CMV, etc.). Anemia and fever were the most common manifestations among all the kidney transplant patients infected with PVB-19 while CNS manifestations and rash were least reported. Hemoglobin was low (&lt;10 mg/dl) in ninety eight percent of the patients (n=151). The lowest hemoglobin reported in the due course of illness was 6 mg/dl (5, 7.2 mg/dl) and with corrected reticulocyte count being only 0.2% (0.1%, 0.6%). The most consistent finding on peripheral smear was normocytic, normochromic anemia while a few reported helmet cells too. Pure Erythroid hypoplasia alone (45.3%) combined with giant pronormoblasts and inclusion bodies (49%) were the most common findings on bone marrow aspirate. Majority of PVB-19 diagnosis was made with the help of multiple methods of detection like IgM assay, PCR—qualitative and quantitative (42.2%). The average PCR copies detected were 1.3*107 (4.28*105, 2.53*109). IVIG only (47.2%) and combined IVIG + immunosuppression reduction (41.2%) was the mainstay of the treatment in majority. The median time to recover was 8 weeks (3, 16 weeks). One fourth of the patients had recurrence after recovery. A majority of the patients (96.7%) recovered from reactivation of PVB-19.

Conclusion
Parvovirus infection is not uncommon in the early post-transplant period. Though data is insufficient, immunosuppression reduction with IVIG remains the treatment of choice for affected patients. Prospective studies to assess the hemoglobin cutoffs and dose of IVIG are needed to frame screening and treatment protocols.
#1214 Post-kidney transplant cancer: incidence, risk factors and future perspectives. Real-world analysis of a single Italian center
Authors: Alfieri Carlo , Sartò Giulia Vanessa Re , Cosmai Laura , Campise Maria Rosaria , Regalia Anna , Verdesca Simona , Molinari Paolo , Pisacreta Anna , Gallieni Maurizio , Castellano Giuseppe 
Published: May 2024

Abstract

Background
Our retrospective observational study aims to describe the epidemiology of cancer after KTx and to investigate its risk factors and the impact on therapeutic management and survival, in a big monocentric cohort of kidney transplant patients (KT-ps). The association between a specific modification of immunosuppressive therapy after cancer diagnosis and survival outcomes will be analyzed.

Methods
Retrospective collection of data in KTx-ps transplanted between January 2004 and December 2021, subjected to outpatient follow-up with a median follow-up of 7 [1-19] years.

Results
We included 930 KTx-ps with mean age at KTx of 49 years. 91% had received pre-TR dialysis, for an average of 52 months. The majority had received KTx from a deceased donor (84%). 74% had undergone induction therapy with Basiliximab and 26% ATG. Maintenance therapy included in most cases the use of steroids (87%), calcineurin inhibitors (tacrolimus 92%, ciclosporin 8%), and mycophenolate (94.6%). Patients with at least one cancer (CAN+) were 177 (19%). The mean time from TR to oncological diagnosis was 83 months. Non-melanoma skin cancers (NMSC) were the most common tumors (55%), while solid tumors were observed in 38.6% of cases. Deceased donor was more represented in CAN+. CAN+ were older and with higher BMI. They had greater presence of vasculitis as basic nephropathy. In the period between 2016 and 2021, induction therapy with ATG was significantly associated with CAN+. In multivariable analysis, ATG emerged as an independent risk factor for CAN+ (p=0.014) and, in survival analyses, ATG was strongly and significantly related to the earlier development of CAN+ (p=0.010). During follow up, cancer-related causes were the second cause of mortality (23%); the average time from cancer diagnosis to death was 23 months. The median survival from TR was 148 (CAN+) and 82 months (CAN−). After oncological diagnosis, significant evidence on tumor survival was derived from the shift to mTOR inhibitors compared to the group with definitive drug suspension (p=0.004).

Conclusion
The data reported by our study confirm the relevance of cancer as a complication in KTx. ATG represent an independent risk factor for cancer; in this context, a personalized choice of immunosuppressive therapy to be proposed at the time of TR represents a crucial point in the prevention of neoplastic risk. In the KTx-ps, therapeutic strategies with antineoplastic agents and management of immunosuppression therapy after malignancy remain important research perspectives in the near future.
#3048 Short and long term follow up of living Tunisian kidney donors
Authors: Dziri Sonia , Awatef Azzabi , Wissal Sahtout , Abdellaoui Imen , Asma Fradi , Sanda Mrabet , Yosra Guedri , Zellama Dorsaf 
Published: May 2024

Abstract

Background and Aims
Over the years, concerns have increased about the harmlessness of kidney donation. This is more relevant in an Arab Muslim developing country like Tunisia, where lack of cadaveric donors is continuously leading to an increase in living donor numbers. The aim of this study is to evaluate the safety of nephrectomy as well as medical and surgical outcomes among LKDs, both short and long terms.

Method
Longitudinal monocentric study, involving a cohort of 106 LKDs in which nephrectomies were performed between November 2007 and April 2015. Donors that attended their follow-up visits after donation as per the European Renal Best Practice group recommendations by the European Renal Disease Association were included.10 Because of the irregularity of visits, we defined visits as follows: M1=from hospital discharge to the 3rd month, M3=from the 3rd month to 6th month, M6=from the 6th month to the 1st year, Y1=from the 1st year to 2nd year, Y2=from the 2nd year to the 4th year, and Y4=4 years and more. At the time of evaluation, we looked for the presence or history of renal events (i.e., elevation of serum creatinine level or proteinuria). We also detected by periodical check- up the presence or history of other physical or biological affections such as the presence of hypertension (HTN), diabetes mellitus (DM), sugar intolerance, hyperlipidemia, or hyper-uricemia (Table 1).

Results
92 donors were included in the follow-up analysis after following exclusion criteria. The mean age at the time of nephrectomy was 42.8 ± 10 years with the sex ratio 0.6. and 27% of our donors were mothers. Twenty-two percent of the donors were obese and 4% were hypertensive. The median initial glomerular filtration rate (GFR) was 105 mL/min/1.73 m2. The surgical approach was costal lumbotomy in 96% of cases and laparoscopy for four cases. The kidneys were removed from the left side in 93% of cases. Postoperative mortality was zero and early postoperative morbidity was low. The median duration of hospital stay was nine days. During follow-up, 14% attended all recommended visits. The median follow- up duration was 26 months. After two years post donation, the prevalence of HTN was 28% and obesity was 26%. The prevalence of GFR decline (50–59 mL/min) was 14% using formula by modification of diet in renal disease. None of our donors reached stage 4 or 5 CKD. Twelve had proteinuria and one donor had diabetes, a comparable prevalence of morbidities to the general population

Conclusion
Our results are strong arguments for harmlessness of renal donation but emphasize the importance of a careful and science-based selection process. Post donation follow-up, seemingly insufficient in our study, is the only guarantor of short- and long-term safety for donors and therefore helps to encourage the act of donating in other potential donors.
#555 Acute graft pyelonephritis in a kidney transplant recipient—a single centre experience in northern India
Authors: Mittal Ankur , Bansal Shyam , Rana Abhyuday Singh , Mahapatra Amit 
Published: May 2024

Abstract

Background and Aims
Urinary tract infections (UTI) are the most common infections after kidney transplantation. Although clinical spectrum of pyelonephritis after kidney transplantation remain less clear. This study was conducted to evaluate the prevalence, clinical and microbiological profile with antibiogram of post-transplant pyelonephritis.

Method
We retrospectively reviewed and analysed the charts of 1684 patients, who underwent kidney transplantation at Medanta—The Medicity between January 2015 and May 2023. Patients were screened for the diagnosis of pyelonephritis and their clinical characteristics and outcome were evaluated.

Results
93/1684 (5.5%) patients with a mean age of 41 ± 13.57 years had developed at least one episode of Pyelonephritis. 68 were males and 25 females. Older age, female gender, hyperglycaemia, use of induction immunosuppression were the risk factors for Pyelonephritis. Median time of occurrence was 44 days after transplantation. Most common symptoms were fever (n=64) followed by dysuria (n=40), and abdominal pain (n=11). Most common organism isolated was Escherichia coli (51.6%) followed by Klebsiella pneumonia (30.1%), and Pseudomonas aeruginosa (11.8%). This study showed a high percentage of resistance to commonly used antibiotics like Carbapenems (61.3%), third generation cephalosporin (49.5%). 41/93 (44%) patients had acute graft dysfunction at the time of presentation. Median duration of hospital stay was 7 days. 90/93 patients had graft recovery and one patient lost his graft after episode of UTI.

Conclusion
Pyelonephritis is a common cause of morbidity after kidney transplantation and occurs in an early post-transplant period. Gram negative bacilli are the major pathogens and carbapenems as an empirical therapy might be useful choice for management of Pyelonephritis and coverage of majority pathogens.
#1511 The immune cell ‘signature’ of incident hypertension
Authors: Murray Eleanor , Delles Christian , Virlan Aysin Tulunay , Nosalski Ryszard , Guzik Tomasz 
Published: May 2024

Abstract

Background and Aims
Hypertension results from complex genetic and environmental interactions, mediated by cardiac, vascular, endocrine, and renal systems. The immune system may modulate all of these, though the exact mechanisms linking immune activation with hypertension and organ damage remain poorly defined. We aimed to identify the immune cell ‘signature’ in patients with newly diagnosed, untreated hypertension (HTN; n=76) compared to normotensive controls (NTN; n=67), as well as in relation to nocturnal dipping status.

Method
Flow cytometry of peripheral blood mononuclear cells (Attune, Thermo Fisher) characterising B cell, T cell, monocyte and dendritic cells (DC) subsets, including activation signature with intracellular staining, in an exploratory comparative analysis.

Results
The proportion of CD4+ naïve T cells (CD45RA+CCR7+) was lower in hypertension, with CD45RO+CD62L+ cells attaining nominal statistical significance between NTN and HTN groups (1.3 ± 1.1 vs 1.2 ± 1.0, p=0.039). CD4+ T central memory cells were expanded (TCM, 23.1 ± 7.2 vs 27.7 ± 10.0, p=0.002, Figure) in HTN along with T effector memory (TEM) cells lacking CD62 in an adjusted model, (TEM, CD4+CD45RA-CCR7-CD62l-; 31.4 ± 7.5 vs 33.7 ± 10.3, p0.035; CD8+CD45RA-CCR7-CD45RO+CD62l− 48.9 ± 10.5 vs 52.2 ± 13.3, p=0.011). Hypertensive group had proportionally fewer CD4+CD28+ cells (95.1 ± 9.8 vs 92.0 ± 13.5, p=0.034) and CD8+CD28+ (68.0 ± 19.7 vs 62.0 ± 21.0, p=0.011), as well as CD8+ TEMRA cells (Figure). In a fully adjusted model, the CCR7-CD45RO-CD62L+ (52.2 ± 14.5 vs 50.2 ± 16.1, p=0.036), and CD8+CD28+CD45RA+CCR7- significantly differed between groups (23.1 ± 14.7 vs 25.0 ± 17.8, p=0.008). On the molecular level, T cells were polarised in HTN towards a Th1/Tc1 and Th17.1/Tc17.1 pro-inflammatory milieu (Figure). No differences were detected in B cell subsets.
The innate immune ‘signature’ was characterised by intermediate monocytes with a differing pattern of CCR2 and CCR5 chemokine receptor expression (Table 1), and alterations in STAT1 and STAT6 phosphorylation cascades. NK cell CD56+Dim expression and fewer CD122-expressing NKT (0.13 ± 0.0 vs 0.08 ± 0.1, p=0.046) and CD122+ T lymphocytes (1.3 ± 3.4 vs 0.6 ± 0.4, p=0.019) further supported pro-inflammatory milieu in hypertension.
Finally, in an exploratory nominal statistical analysis, nocturnal non-dipping was associated with particular changes in immune cell signature, including expanded CD4+TCM (CD4+CD45RO+CD62L-, 9.4 ± 4.3 vs 8.0 ± 3.3, p=0.04) and reduced CD4+TEM and TEMRA compartments; polarisation towards Th17 and Tc1; and altered Monocyte CCR2 and CCR5 expression. Additionally, non-dipping was linked to dendritic cell mannose receptor downregulation e.g. mDC non-dipper 10.9 ± 5.8 vs dipper 13.6 ± 9.7, p=0.03.

Conclusion
These exploratory data support alterations of circulating innate (monocytes) and adaptive (T cells) immune compartments in newly diagnosed untreated, and uncomplicated hypertension.
#1870 Uninephrectomized diabetic rats delay onset of hyperglycemia via down-regulation of SGLT2 mRNA
Authors: Ishizaki Yuri , Kikuchi Masao , Fujimoto Shouichi , Kaikita Koichi 
Published: May 2024

Abstract

Background and Aims
The kidney is essential for glucose metabolism. Reabsorption of almost all the glucose filtered by the glomerulus is performed by the sodium-glucose cotransporters (the SGLTs) in the proximal tubules, with SGLT2 responsible for about 90%. In addition, the kidney, along with the liver, plays an important role in gluconeogenesis, especially in the long fasting state. SGLT2 inhibitors originally developed for the treatment of type 2 diabetes mellitus (DM) are clinically very effective drugs halting chronic kidney disease progression. The underlying mechanisms are, however, not fully understood. Furthermore, SGLT2 expression in diabetic patients has been reported to increase and decrease but remains unclear. Therefore, this study aimed to evaluate how uninephrectomy (UNx) and SGLT2 inhibitor treatment affects the dynamics of blood glucose and SGLTs in SDT fatty rats with obese type 2 DM (leptin receptor mutation), which is hyperglycemic from an early stage.

Method
24 male SDT fatty rats were divided into four groups: sham + placebo group (n=6); sham + dapagliflozin (dapa, 1.5 mg/kg/day) group (n=6); UNx + placebo group (n=6); UNx + dapa group (n=6). UNx or sham operations were undergone at week 6. Measurements included body weight, food intake, water consumption, urine output, blood pressure, serum creatinine, and blood glucose in the experiment. At week 12, the rats were sacrificed, and the kidneys were sampled to measure SGLT1 and SGLT2 mRNA in the renal cortex by real-time PCR quantification.

Results
Blood glucose levels continued to rise from week 7 in the sham + placebo group, but the rate of increase was still slower in the UNx + placebo group, and the increase in blood glucose levels was mostly suppressed with dapa administration (Fig. 1). Only the Sham + placebo group showed increased urinary volume and weight loss after week 10 due to hyperglycemia. There were no significant differences in serum creatinine or blood pressure during the study. Real-time PCR results showed that SGLT2 mRNA in the renal cortex was significantly decreased by 26% in the UNx group (P=0.0386), but SGLT1 mRNA was not significantly different.

Conclusion
Uninephrectomized diabetic rats delayed onset of hyperglycemia and reduced SGLT2 mRNA; SGLT2 inhibitor treatment further delayed the onset of hyperglycemia but did not alter SGLT2 mRNA expression. In animal models of diabetes, renal glucose reabsorption appeared to be a major contributor to the development of hyperglycemia.
#2239 Identification of non-HLA antibodies associated with the development of antibody-mediated damage after kidney transplantation
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

Abstract

Background and Aims
Non-HLA antibodies may play a role in the development of antibody-mediated rejection (ABMR) in the presence of donor-specific anti-HLA antibodies (HLA-DSA) or microvascular inflammation (MVI) without HLA-DSA in kidney transplantation (KT). The development of multiplex panels allowed the analysis of multiple antibodies simultaneously and new antibodies potentially related to ABMR/MVI have been identified.

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 using a multiplex test: the Single Non-HLA Beads kit (LIFECODES®) suitable for the SAB assay performed using Luminex® technology.

Results
Pre-KT, we detected non-HLA antibodies in 85% of the recipients, with a median of 3 (2-5) positive antibodies. During follow-up, 73 patients developed ABMR/MVI. Pre-KT, in a univariate analysis including the presence of HLA-DSA (8.3% in the cohort) we detected 7 antibodies individually associated with ABMR/MVI. In multivariate analysis (Figure) GSTT1, NCL, PLA2R1 and Thyroglobulin antibodies together with HLA DSA were significantly associated with the development of ABMR/MVI, although only GSST1 and Thyroglobulin appear in a relevant number of patients (&gt;10 patients) involved in 32 cases of ABMR and 6 cases of MVI. Post-KT, only the detection of anti-GSTT1 antibodies in sera 1- and 3-years post-TR was associated with ABMR/MVI in 3-year biopsies.

Conclusion
Pre-KT the detection of antibodies against GSST1 and Thyroglobulin using a multiplex non-HLA antibody detection panel is independently associated with the development of ABMR/MVI during follow-up. Post-KT detection of GSST1 is also associated with ABMR/MVI in 3-year biopsies.