bluuebunny/crossref_metadata_2025 huggingface dataset:
#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

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<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<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

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 >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

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) >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

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

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 (>4.5%) and a lower (<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(>4.5% 18.63±22.84vs. <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 (>4.5% 1.31±1.38 vs.<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>4.5% 0.35±0.29 vs. <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

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

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<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.
#6465 MIR-451B AND CHRONIC KIDNEY DISEASE: A NOVEL TARGET TO MODULATE RENAL VEGF SIGNALING
Authors: Chade Alejandro , Sitz Rhys , Eirin Alfonso
Published: June 2023

Background and Aims

Chronic kidney disease (CKD) is a progressive disorder that affects over 15% of adults worldwide. A major component of CKD pathophysiology is renal microvascular rarefaction and loss that pairs the progression of the disease and complications. We developed a translational swine model of CKD and showed that loss of renal function associates with a significant decrease in renal vascular endothelial growth factor (VEGF) signaling and progressive microvascular (MV) rarefaction. VEGF is a key endogenous cytokine for MV proliferation and repair, but underlying mechanisms of renal VEGF downregulation in CKD are unknown. We hypothesized that micro-RNA (miRNA)-mediated processes contribute to the downregulation of renal VEGF signaling in CKD.

Method

Unbiased renal micro-RNA (miRNA)-seq was performed in a swine model of CKD stage 3 (14 weeks of bilateral renal artery stenosis + atherogenic diet) and normal controls (n = 5/group). Micro-RNAs up- (>1.4 FC, p<0.05) and down-regulated (<0.7 FC, p<0.05) were identified, followed by target prediction analysis (miRwalk 3.0, Target Scan 7.2). Renal gene and protein expression of VEGF was measured by qPCR and western blot, respectively, and renal MV architecture was studied by 3D micro-CT.

Results

Unbiased miRNA-seq and target prediction analysis identified four miRs upregulated in the kidney of CKD pigs vs. controls, of which miR-451b (validated by qPCR), broadly conserved among species, was capable of targeting VEGFA (FC = 4.46, p = 0.04). Renal gene and protein expression of VEGF was downregulated in CKD vs. controls, associated with significant cortical and medullary microvascular rarefaction (Figure 1).

Conclusion

Our data suggest that post-transcriptional modulation of renal VEGF signaling may serve as a prominent mechanism of VEGF downregulation, which leads to MV rarefaction and disease progression in CKD. Furthermore, this work in progress identified a novel candidate (miR-451b) and may set the stage for its targeted modulation to preserve VEGF signaling as a potential strategy to protect the renal microvasculature in CKD.
#6566 A STUDY OF CLINICAL PRESENTATION AND OUTCOME OF COVID 19 INFECTION IN KIDNEY TRANSPLANT RECIPIENTS
Authors: Parry Manzoor , Alam Shahzad
Published: June 2023

Background and Aims

Novel coronavirus 19 (coronavirus disease-19 [COVID-19]) disproportionately affects patients with various kidney diseases. Patients with kidney transplant are at higher risk of complications of COVID-19 infection. Our aim of this analysis was to study the clinical profile and outcome of COVID-19 infections in KTRs from Kashmir.

Method

Here we present a cohort study of 122 KTRs with polymerase chain reaction-confirmed COVID-19 positivity from March 31, 2020 to October 31, 2022. We detailed demographics, immunosuppression regimen, clinical profile, Covid 19 vaccination status, treatment given, and outcomes (acute kidney injury, graft failure and death) of our study population.

Results

Median age of the patients was 41 years and median age of disease was 2.9 years after transplant. Most common comorbidities included hypertension (65.6%) and diabetes (35.3%); presenting symptoms at the time of COVID-19 included fever (82.7%) and breathlessness (66.4%). Covid-19 vaccination was given to 81 patients (66.4%) with two doses in 26 patients and 55 patients received one dose. Clinical severity ranged from asymptomatic (4.1%), mild (36.1%), and moderate (28.7%), to severe (31.1%). Acute kidney injury developed in 46.7% of patients and mortality in 21 patients. Risk factors for mortality included higher age, severe disease, allograft dysfunction before COVID-19 infection, Obesity, acute kidney injury, absence of covid-19 vaccination (Table 1). At 3 months of follow-up, loss of graft function was seen in 19 patients of survivors.

Conclusion

Mortality rates in COVID-19-positive KTR appear to be higher than those in nonimmunosuppressed patients. Risk factors for mortality included higher age, severe disease, allograft dysfunction before COVID-19 infection, Obesity, acute kidney injury, absence of covid-19 vaccination.
#6573 ASSOCIATION BETWEEN SERUM TOTAL PROTEIN-TO-ALBUMIN RATIO AND PROGNOSIS IN SEPTIC ACUTE KIDNEY INJURY PATIENTS
Authors: Yin Ting , Wei Wei , Huang Xiaorong , Zhao Yuliang , Fu Ping , MA Liang
Published: June 2023

Background and Aims

Sepsis is the leading cause of acute kidney injury (AKI). Increasing evidence shows that serum total protein-to-albumin ratio (TAR) could serve as inflammation- and nutrition-based prognostic score. The purpose of this study was to assess the effect of TAR on predicting the clinical outcomes of septic AKI patients.

Method

A retrospective study between August 2015 and August 2021 was performed at West China Hospital of Sichuan University. The primary outcomes were 30-day and 90-day all-cause mortality of septic AKI patients. The secondary outcomes were septic shock, transfer to the intensive care unit, mechanical ventilation, requirement for renal replacement therapy, and stage 3 AKI.

Results

A total of 309 eligible patients with a median age of 58 years were enrolled. Among the patients, 70.2% were males. In multivariate analysis, after adjustments for age, sex, and other confounding factors, higher baseline TAR was associated with an increased risk of 30-day and 90-day all-cause mortality in septic AKI patients (HR 1.91, 95% CI 1.18–3.09, P = 0.008; HR 1.54, 95% CI 1.01-2.34, P = 0.043, respectively). Subgroup analysis revealed no significant interactions in most strata. We found no relationship between TAR and secondary outcomes. The Youden index of TAR was larger than total protein or albumin alone in predicting both 30-day and 90-day all-cause mortality.

Conclusion

Increased TAR is an independent predictor for 30-day and 90-day all-cause mortality in septic AKI patients. The predictive performance of TAR outperformed those of total protein and albumin. Further research is needed to corroborate our findings in other cohorts and to compare the predictive ability of baseline TAR and the change in TAR under treatments.
#6600 ASSOCIATION BETWEEN ADVANCED GLYCATION END-PRODUCTS AND SARCOPENIA IN PATIENTS WITH CHRONIC KIDNEY DISEASE
Authors: Molinari Paolo , Caldiroli Lara , Vettoretti Simone
Published: June 2023

Background and Aims

In patients with chronic kidney disease (CKD), there is an overproduction and accumulation of advanced glycation end-products (AGEs). Since AGEs may have detrimental effects on muscular trophism and performance, we evaluated whether they may contribute to the onset of sarcopenia in CKD patients.

Method

We enrolled 117 patients. The AGEs were quantified by fluorescence intensity using a fluorescence spectrophotometer and soluble receptor for AGE (sRAGE) isoforms by ELISA. As for the sarcopenia definition, we used the European Working Group on Sarcopenia in Older People (EWGSOP2) criteria.

Results

The average age was 80 ± 11 years, 70% were males, and the mean eGFR was 25 + 11 mL/min/1.73 m2. Sarcopenia was diagnosed in 26 patients (with a prevalence of 22%). The sarcopenic patients had higher levels of circulating AGEs (3405 ± 951 vs. 2912 ± 722 A.U., p = 0.005). AGEs were higher in subjects with a lower midarm muscle circumference (MAMC) (3322 ± 919 vs. 2883 ± 700 A.U., respectively; p = 0.005) and were directly correlated with the gait test time (r = 0.180, p = 0.049). The total sRAGE and its different isoforms (esRAGE and cRAGE) did not differ in patients with or without sarcopenia.

Conclusion

In older CKD patients, AGEs, but not sRAGE, are associated with the presence of sarcopenia. Therefore, AGEs may contribute to the complex pathophysiology leading to the development of sarcopenia in CKD patients.
#6635 ARNT AND ALK3 MEDIATE RENO PROTECTION AFTER ISCHEMIC PRECONDITIONING
Authors: Rapp Gregor Christof , Zeisberg Michael , Nyamsuren Gunsmaa
Published: June 2023

Background and Aims

Ischemia and following hypoxia are a common cause of acute kidney injury (AKI). Strategies for prevention and treatment of AKI are limited. In several animal models, ischemic preconditioning (IPC) has been established as an effective intervention to prevent ischemic organ injury. An IPC protocol of ischemia and reperfusion mediates organ protection for a few hours. This first phase of organ protection is followed by a second, protective phase occurring after 24–48 h. The second phase, named second window of protection (SWOP), persists for 3–4 d. Mechanisms and transcriptional mediators during SWOP are mostly unknown. The aim of the underlying study was to investigate effectors and target genes during SWOP and to identify a potential pharmacological therapeutic target.

Method

6–8-week-old C57BL/6 mice were undergoing an IPC intervention; five minutes of renal sinistra artery ischemia was followed by five minutes of reperfusion. This cycle was performed five times. Mice were sacrificed 2, 4, 8, 12, 25, 48, 72 h after IPC. Two additional groups of mice were pharmacologically preconditioned for 48 h with low dose FK506 and small molecule GPI1046. Analysis of murine kidneys were performed by SDS-Page and Western blot.

Results

The first phase after IPC (2–4 h) was characterized by an increasing expression of hypoxia inducible factor-1α (HIF1α); 48 h after intervention a significant increase of expression of aryl hydrocarbon receptor nuclear translocator (ARNT) and consecutive activin receptor-like kinase 3 (ALK3) was observed. Comparable induction of ARNT and ALK3 expression was obtained by pharmacological preconditioning with FK506 or GPI1046.

Conclusion

Affected by hypoxia, HIF1α activates transcriptional upregulation of ARNT 48 h after IPC. The increasing expression of ARNT, follows an increased ARNT homodimerization. ARNT homodimer binds to the palindromic E-box 5′-CACGTG-3′ of the proximal ALK3 promoter. By this it induces the expression of the renoprotective ALK3 during SWOP. The organ-protective effects of constitutively expressed ARNT during SWOP can be mimicked pharmacologically by administration of FK506 or GPI1046 and may be used as a future therapeutic target.
#6641 BONE MATERIAL STRENGTH INDEX AND DUAL ENERGY X-RAY ABSORPTIOMETRY IN EVALUATION OF BONE HEALTH IN AUTOSOMAL POLYCYSTIC KIDNEY DISEASE
Authors: Jankowska Magdalena , Wiśniewski Piotr , Evenepoel Pieter , Lindholm Bengt , Debska-Slizien Alicja , Stenvinkel Peter , Haarhaus Mathias Loberg
Published: June 2023

Background and Aims

Bone material strength measured with the use of impact microindentation technique (OsteoProbe®) has emerged recently as potentially beneficial tool in evaluating bone quality in metabolic bone disorders. Patients with autosomal polycystic kidney disease (ADPKD) carry an increased risk of skeletal complications, both due to deficiency of polycystins and development of chronic kidney disease-mineral bone disorder (CKD-MBD). In our preliminary study, we found that bone material strength index (BMSi) associated with bone mineral density (BMD) measured with the use of dual energy X-ray absorptiometry (DXA) in chronic kidney disese patients (CKD). The aim of the present study was to find if the same applies to patients with ADPKD. We evaluated bone health by measuring BMSi and performing DXA in patients with ADPKD.

Method

BMSi was measured (OsteoProbe®, Active Life Scientific, USA) in 64 adult patients (37 men, mean age 43 years) with ADPKD in CKD stages G1-4. The measurement of BMSi compared the resistance to impact of microindentation in bone and reference material. After applying local anaesthesia, we impacted the cortical bone in the midshaft tibia in 10 different points. BMD was measured using Hologic Discovery Wi densitometer in multiple sites: lumbar spine, hip, 1/3 distal non-dominant forearm and whole-body. Trabecular bone score (TBS) was calculated using Medimaps TBS iNsight software.

Results

Mean values of BMSi, TBS and BMD are presented in the Table 1. BMSi in ADPKD patients was lower than average value observed in healthy individuals (85 men and 80 women). A positive linear relationship between BMSi and BMD was found in all of the examined sites with the highest standardized regression coefficient for 1/3 distal forearm (R2 = 0.315, beta = 0.57, p < 0.001) and weakest for lumbar spine (R2 = 0.003, beta = 0.33, p = 0.003). There was no association between BMSi and TBS.

Conclusion

This is the first report on BMSi in ADPKD patients. In agreement with the notion of a distinct bone phenotype in ADPKD, we observed a median bone material strength index in patients with ADPKD that was lower than the reference value. BMSi associated with BMD, but not with TBS. However, the association with BMD overall is weak, with BMD explaining only 3 to 31% of the variability of BMSi. This observation suggests complementarity and warrants additional studies investigating whether BMSi associates with hard bone endpoints, independent of BMD.
#6690 THE ASSOCIATION BETWEEN SERUM CHEMERIN AND PERITONEAL MEMBRANE TRANSPORT FUNCTION IN INCIDENT PERITONEAL DIALYSIS PATIENTS: A PROSPECTIVE COHORT STUDY
Authors: Zang Zhiyun , Wu Xiaofang , Xia Xiaoxiao , Li Zi
Published: June 2023

Background and Aims

Some biomarkers in drained dialysate or peritoneal membrane have been found related to the dialysate/plasma ratio of creatinine at 4 h (D/P Cr) in patients undergoing peritoneal dialysis (PD). But so far, there is no report on serum markers. Some biomarkers are associated with cardiovascular diseases (CVDs). Chemerin is a multifunctional chemoattractant adipokine which plays roles in inflammation, adipogenesis and metabolism. In this study, we intended to investigate the role of chemerin in the peritoneal membrane transport function and CVDs in incident PD patients.

Method

This prospective cohort study was conducted in our PD center. The patients underwent initial standardized peritoneal equilibration test (PET) after PD for 4–6 weeks. Level of serum chemerin was determined via enzyme-linked immunosorbent assay (ELISA). The patients’ CVDs were recorded during the follow-up period.

Results

151 eligible patients with a mean age of 46.59±13.52 years were enrolled. And the median duration of PD was 25.0 months. The median concentration of serum chemerin was 29.09 ng/mL. Baseline D/P Cr was found to be positively correlated with serum chemerin (r = 0.244, p = 0.003). The multivariate analyses revealed that serum chemerin (p = 0.002), age (p = 0.041), albumin (p = 0.000), and high-density lipoprotein (HDL) (p = 0.022) were independent factors of D/P Cr. The serum chemerin level was significantly higher in diabetes mellitus (DM) patients than that of patients without DM (36.45 vs 27.37 ng/mL, p = 0.000). And there was a significant statistical difference in CVDs between the high chemerin group (≥29.09 ng/mL) and low chemerin group (<29.09 ng/mL) (42% vs 21%, p = 0.009).

Conclusion

Serum chemerin has a positive correlation with baseline D/P Cr in incident PD patients. It may be a biomarker that can predict the baseline transport function of peritoneal membrane. And serum chemerin may be a risk factor of CVDs for incident PD patients. Multicenter studies with a larger sample size are warranted in the future.
#6697 HIGHER PRO-INFLAMMATORY CYTOKINES IL-6 AND IFN-γ ARE ASSOCIATED WITH A HIGHER SEROCONVERSION RATE AGAINST SARS-COV-2 VIRUS SPIKE PROTEIN
Authors: Prasad Narayan , Yadav Brijesh
Published: June 2023

Background and Aims

Maintenance of Immunosuppressive regimen in renal transplant recipients (RTR), leads to a decreased immunogenic response to SARS-CoV-2 infection and vaccination than in the general population. In contrast, healthy people with SARS-CoV-2 infection often developed neutralizing antibodies and secrete copious quantities of cytokines leading to virus clearance and sometimes more severe immune-related complications. Associations of cytokines with seroconversion rate in immunocompromised renal transplant recipients are not clear. Therefore, in this study, we have determined the association of cytokines with seroconversion.

Method

In this study, 210 living-related RTRs who either acquired SARS-CoV-2 infection or were vaccinated with two doses of vaccine against SARS-CoV-2.Thirty-five healthy controls, who were non-vaccinated and had no anti-SARS-CoV-2 spike protein-specific antibodies, were also included as controls. Cytokines IL-6, IFN-γ, TGF-β, and IL-10 were measured using the enzyme-linked immunosorbent assay, and SARS-CoV-2 spike protein-specific IgG titer by chemiluminescent microparticle immunoassay methods.

Results

We found a seroconversion rate of 115/132 (87.12%), with a median antibody titer of 706.40 au/ml (IQR, 215.45-1844.42) in the infection group and 63/78 (80.76%) with a median titer 1454.20 (IQR, 80.52-3838.75) au/ml in the vaccinated group. The IL-6, IFN-γ, TGF-β, and IL-10 levels were significantly higher in both, the infection and vaccination groups as compared to the healthy control Fig. 1A-D. In the infection group, the proinflammatory cytokines IL-6 (55.41±24.30 vs. 31.64±16.98 pg/ml; p<0.001); IFN-γ (91.21±33.09 vs. 61.69±33.28 pg/ml; p = 0.001), were significantly high in the seroconverter group as compared to non-seroconverter. Anti-inflammatory cytokines TGF-β (730.48±400.47 vs. 765.47±366.39 pg/ml; p = 0.92), and IL-10 (91.31±48.54 vs. 96.73±59.53 pg/ml; p = 0.88) were not significantly different between the seroconverter and non-seroconverter group respectively. Similarly, in the vaccination group, the pro-inflammatory cytokines IL-6 (50.31±25.67 vs. 30.00±11.19 pg/ml; p = 0.002), and IFN-γ (65.70±39.78 vs. 32.14±17.48 pg/ml; p = 0.001) were significantly high in seroconverter post-vaccination compared to non-seroconverter. In contrast, TGF-β (820.96±415.78 vs. 1045.57±204.66; p = 0.046) was elevated in non-seroconverter, and although IL-10 (93.18±35.45 vs. 112.90±59.61 pg/ml; p = 0.11) was not significantly high in non-converter.

Conclusion

Inflammatory cytokines IL-6 and IFN-γ were significantly associated with seroconversion after SARS-CoV-2 infection and vaccination.
#6792 VASCULAR ACCESS SURVIVAL OUTCOME IN ELDERLY HEMODIALYSIS PATIENTS: A SINGLE-CENTER RETROSPECTIVE STUDY
Authors: Surattichaiyakul Bongkod
Published: June 2023

Background and Aims

Elderly hemodialysis patients usually have lower life patency of vascular access than another age-group. Our center, elderly patients are the most of population of hemodialysis patients. Prior to initiate hemodialysis, planning of first vascular access has been established by patients, nephrologist, and vascular surgeon. The canulation technique for arteriovenous fistula (AVFs) has been determined by experienced hemodialysis-nurse and patient preferences. The aim of this study was to analyze the survival outcome of the access depending on the vascular type in the elderly.

Method

The study was collected retrospective data between Jan 1, 2013, and December 31,2022. We identified elderly patient (age ≥65) who initiate in-center hemodialysis and first-use vascular access in our center, including arteriovenous fistulas, graft, tunnel-catheter. Outcomes were vascular access patency and subgroup analysis for non-extreme elderly group and extreme (age ≥80) elderly group. A χ2 test, Kaplan-Meier analysis were performed.

Results

Overall number of elderly patients who initiated hemodialysis are 170: 63 AVFs-first (74% buttonhole cannulation technique), 21 grafts-first and 86 for tunnel-catheters. Mean survival of vascular accesses are higher in AVFs group (78 months in AVFs, 52.5 months in grafts, 53.3 months in tunnel-catheter P = 0.012). The outcome was consistency in the subgroup age 65-80 (80.9 months in AVFs, 47.3 months in grafts, 47.2 months in tunnel-catheter P = 0.005). However, mean vascular access survival did not differ in subgroup age >80 (56.3 months in AVFs, 58.4 months in grafts, 56.4 months in tunnel-catheter P = 0.98).

Conclusion

In our single center data, vascular access patency of elderly patients was highest in AVFs-first group and AVFs should be the first choice for elderly patients who would initiate hemodialysis especially non-extreme elderly group.
#6817 ROLE OF THE CGAS-STING PATHWAY IN THE PROGRESSION OF DIABETIC NEPHROPATHY
Authors: Khedr Sherif , Palygin Oleg , Staruschenko Alexander
Published: June 2023

Background and Aims

Diabetic kidney disease (DKD) is the leading cause of chronic renal pathology. Understanding the molecular underpinnings of DKD is critical to designing tailored therapeutic approaches. We have demonstrated previously that type 2 diabetic nephropathy (T2DN) rats develop renal and physiological abnormalities similar to clinical observations in humans with DKD, indicating these rats are an excellent model for studying the progression of renal injury in type 2 DKD [1]. Furthermore, our recent studies revealed sexual dimorphism in this model, indicating that while both male and female T2DN rats developed non-obese DKD phenotype, females had significant protection from the development of severe forms of glomerular and tubular damage [2]. The potential role of the cyclic GMP-AMP synthase (cGAS) / Stimulator of interferon genes (STING) pathway in renal inflammation and fibrosis was also uncovered [3]. Here we focused on sex differences in DKD and the potential mechanisms leading to the progression of DKD.

Method

To explore the sexual dimorphisms in the development of DKD, we utilized young (12-week-old) and aged (>48 weeks old) type 2 diabetic nephropathy (T2DN) rats. To delineate transcriptional changes, RNA-Seq analysis was performed in the kidney cortex of T2DN rats of both sexes at a younger and older age. Western blotting, immunohistochemistry, and flow cytometry analyses were further used to identify specific pathways contributing to sexual dimorphism and disease progression in T2DN rats.

Results

We have revealed that the cGAS/STING signaling pathway is upregulated in T2DN rats compared to non-diabetic Wistar rats and in type 2 diabetic human kidneys. The expression of key proteins in the cGAS-STING pathway, such as cGAS, STING, phospho-IRF, mtTFA, and TREX1, was significantly different between male and female T2DN rats and following the progression of DKD. Proinflammatory genes were also upregulated in male T2DN rats compared to female rats of the same age, and their levels were further elevated in aged rats. RNA-Seq analysis also identified significant changes in genes participating in the cGAS-STING inflammatory pathway. Flow cytometry revealed a significantly greater number of infiltrating leukocytes in the male kidneys compared to their age-matched females. Moreover, the leukocytic count was significantly higher in old males versus young males, while it was almost the same in females of different ages. Approximately 50% of the renal leukocytic population was monocytes/macrophages (CD11b/c+), with fewer CD3+ T cells, both CD3+CD4+ T helper and CD3+CD8+ cytotoxic T cells, and CD45R+ B cells.

Conclusion

Our study provides critical insights into the sexual dimorphism and progression of DKD and identifies the cGAS-STING pathway as an essential contributor to disease development.
#6898 CATHETER RELATED BLOODSTREAM INFECTION IN NON-TUNNELED HEMODIALYSIS CATHETERS IN A RESOURCE-LIMITED HOSPITAL IN MERIDA, YUCATAN, MEXICO
Authors: Pech Julio , Tapia Leticia
Published: June 2023

Background and Aims

There is scarcity in epidemiological data regarding chronic kidney (CKD) disease in low- and medium-income countries, and information about vascular access infectious complications is limited. In Mexico, access to renal replacement therapy (RRT) is burdensome for the uninsured patients. The General Hospital Agustin O'Horán, is a secondary care level unit in Yucatan, which receives uninsured patients from southeast Mexico. In our hospital, patients who are not candidates for peritoneal dialysis start hemodialysis with non-tunneled hemodialysis central venous catheters (NTHC), mainly due to the late nephrology referral and the shortage of vascular access specialists in our unit which prevents for the timely creation of an arteriovenous fistula or the placement of a tunneled hemodialysis catheter (THC). Permanence of NTHC is the main risk factor for catheter related bloodstream infection (CRBI) and according to the literature, Gram positive microorganisms are the most common isolated microbes. The aim of our study was to describe the incidence and risk factors for CRBSI in our hospital, from January to December 2022.

Method

We conducted a prospective and observational study in patients older than 18 years with CKD who were candidates to start hemodialysis and who had a NTHC inserted in our hospital from January to December 2022. We evaluated the incidence, organisms and risk factors related to CRBSI.

Results

During the study period, 94 NTHC were placed, 63.8% of them were inserted in women. Median age of the population was 49.4 years, and the most frequent comorbidities were diabetes mellitus (63.8%), hypertension (86.2%) and renal lithiasis (27.7%). 73.4% of the NTHC were Mahurkar® catheters and most of the insertions (73.4%) were not ultrasound guided. The right jugular vein was the most common insertion site (72.3%), followed by the left jugular vein. Mean catheter use duration was 71 ± 66 days. 27 patients had evidence of CRBI, the incidence rate was 0.78 per 1000 catheters-day. CRBI was more frequent in patients with prolonged catheter use (more than 30 days) (p<0.001) (Table 1). In respect to blood cultures reports, 51.83% were Gram positive organisms and 48.12% were Gram negative (Table 2).

Conclusion

Vascular access survival without infectious complications is of paramount importance in hemodialysis patients. The prolonged used of NTHC with the associated risk for developing CRBI negatively impacts the health outcomes in our population. In accordance to previously published literature, the main isolated microbes in our hospital comprise Gram positive bacteria. One of the biggest challenges in our country is to provide our CKD population with better vascular access options like THC or arteriovenous fistula to improve the outcomes and reduce infectious complications.
#6963 OBESITY, METABOLIC SYNDROME AND THE RISK OF ADVERSE CLINICAL OUTCOMES IN PATIENTS WITH CHRONIC KIDNEY DISEASE
Authors: Kang Shinyeong , Hwang Hyeon Seok , Kim Jin Sug , Jeong Kyunghwan
Published: June 2023

Background and Aims

Obesity and metabolic syndrome are prevalent disorder in patients with chronic kidney disease (CKD). However, it is unclear whether obesity without metabolic syndrome is associated with higher risk of adverse clinical outcomes in patients with CKD.

Method

We reviewed the National Health Insurance Service database of Korea for people who received ≥2 national health screenings between 2009 and 2011. A total of 68,464 chronic kidney disease patients were identified with consecutive estimated glomerular filtration rate <60 ml/min per 1.73 m2. Obesity was defined as body mass index ≥25 kg/m2 and metabolic syndrome status was considered as the presence of three or more of the following metabolic factors; waist circumference, blood pressure, fasting blood sugar, triglyceride level, high-density lipoprotein cholesterol level. The primary outcomes were cardiovascular events, end-stage renal disease progression (ESRD) and all-cause mortality.

Results

Compared to non-obese patients without metabolic syndrome, obesity without metabolic syndrome did not increase the risk of cardiovascular event (HR 1.02, 95% CI 0.95–1.11) and progression to ESRD (HR 0.86, 95% CI 0.73–1.02). Risk of all-cause mortality was significantly decreased in these patients (HR 0.88, 95% CI 0.81–0.96). These findings were consistently observed in overweight, obese, morbid obese patients without metabolic syndrome. In addition, while linear increase of HRs for each additional metabolic abnormality was observed, HRs increase for cardiovascular event was significantly slower in obese patients than in non-obese (P for interaction = 0.035).

Conclusion

Obesity without metabolic syndrome did not confer excess risk for cardiovascular complication or ESRD progression and decreased the risk of all-cause mortality. Healthy effect of obesity against mortality risk and metabolic hazard on cardiovascular event is better to be considered in CKD patients.
#2572 CLINICAL CHARACTERISTICS OF ACUTE KIDNEY INJURY IN PATIENTS WITH GLUFOSINATE POISONING
Authors: Cho A Young , Sun In O , Oh Ju Hwan
Published: June 2023

Background and Aims

Glufosinate-containing herbicide is widely used in agriculture. According to previous reports, glufosinate poisoning causes various complications, but there are few reports of nephrotoxicity. In this study, we investigated the incidence and clinical characteristics of acute kidney injury (AKI) in patients with glufosinate poisoning.

Method

This study performed between 2008 and 2021 included 76 patients categorized into the AKI and the non-AKI groups. The incidence, clinical characteristics, and severity of AKI were compared between the AKI (n=54) and the non-AKI (n=22) groups, based on the Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease classification.

Results

The incidence of AKI was 71.1%, of which 40.9%, 26.3%, and 3.9% patients were classified into the Risk, Injury, and Failure categories, respectively. Patients in the AKI group were older (62.6±14.2 years vs. 54.9±16.2 years, P=0.045) and poorer renal function (73.9±25.2 mL/min/1.73 m² vs. 94.5±35.5 mL/min/1.73 m², P=0.006) on admission. The length of hospitalization was longer (17.2±17.2 days vs. 7.6±7.6 days, P=0.014) in AKI group, and the mean amount of glufosinate ingested was higher in AKI group than that in non-AKI group (250±172 mL vs. 152±121 mL, P=0.032). In addition, the serum bicarbonate level was lower in AKI group than in non-AKI group (19.9±4.7 vs. 23.0±3.3, P=0.006). Notably, intensive care unit admissions (81.5% vs. 40.9%, P=0.001) and mechanical ventilator support (68.5% vs. 22.7%, P<0.001) were more frequently required in the AKI group. Multivariate logistic regression analysis showed that serum bicarbonate concentration on admission remained significant predictors of AKI in patient with glufosinate poisoning.

Conclusion

Serum bicarbonate is helpful to predict the development of patients with glufosinate poisoning.