bluuebunny/crossref_metadata_2025_split huggingface dataset:
#3421 MRI PREDICTORS OF DIASTOLIC DYSFUNCTION OF THE LEFT VENTRICLE
Authors: Egamberdieva Dano , Ruzmetova Iroda , Khodjibekova Yu M , Karimova Yu A 
Published: June 2023

Abstract

Background and Aims
Non-invasive assessment of diastolic dysfunction remains challenging, this study aims to identify the most informative cardiac magnetic resonance imaging (CMR) parameters for assessing left ventricular diastolic dysfunction (LVDD).

Objective
To study MRI parameters as predictors of left ventricular diastolic dysfunction (LVDD) in patients with suspected heart failure.

Method
The study included 39 patients with CHF, 25 were men (61%), and the average age of patients was 48.12 ± 16.79 years. The study was based on a retrospective examination of patients who underwent MRI in the period from April 2021 to August 2022. All patients underwent a comprehensive clinical and instrumental examination taking into account such factors as age, gender, nationality, smoking, diabetes mellitus (DM), arterial hypertension (AH), lipid profile, body mass index (BMI). A total of 39 patients, 28 of them with suspected myocarditis, 7 patients with fibrosis in heart failure, 4 patients with congenital heart disease identified during the study. The CMR measurements of the patients' heart chambers were obtained from an independent manual examination using an image archiving and transmission system. CMR measurements were performed as follows. The patients were examined with a 1.5 Tesla MRI machine and eight-channel cardiac coils were used to acquire the image. The position and orientation of the heart in the chest were determined after serial reference images of the chest were taken. Using stationary free precession sequences, a two-chamber image of the left ventricle was obtained with a breath hold of 10 – 15 seconds at the end of exhalation (image parameters: repetition time 3.6 ms; echo time 1.6 ms; 350 mm; slice thickness 6 mm; gap 2 mm; angle of rotation 45°, 14 projections per segment, matrix 224 160). Four-chamber short axes and three-chamber sequences were then obtained. The right ventricular end-diastolic size (EDD) diameter was measured between the right ventricular endocardium and the interventricular septum, parallel to the tricuspid valve and 1 cm distal to the valve on four-chamber sinusoids with free precession (SSFP).

Results
As a result the left atrial enlargement is the most prognostic factor for diastolic dysfunction (DD) among the assessed complex MRI parameters. TBI and tissue tracking reflect internal aberration, revealing abnormal deformity patterns in the basolateral segments compared to patients with normal diastolic function. Based on the quantitative assessment of the size of the LA, it is possible to determine the threshold value for the detection of DD. In addition, it was found that the quantitative assessment of LV diastolic deformity is predictive for identifying patients with DD. Increased LA dimensions have a diagnostic accuracy according to our data for detecting diastolic dysfunction (DD).

Conclusion
Tissue tracking and TRM reveal impaired diastolic deformity of the basal-lateral wall in DD+ as a direct sign of DD.
#3424 RENAL OUTCOMES IN THE ELDERLY WITH ANTINEUTROPHIL CYTOPLASMIC AUTOANTIBODY-ASSOCIATED VASCULITIS: A NEW PREDICTION MODEL
Authors: Zhang Shuo , Chen Xin , Hou Zuoxian , Xia Peng , Shi Xiaoxiao , Ting Wuhai , Wen Yu-Bing , Qin Yan , Tian Xinping , Chen Limeng 
Published: June 2023

Abstract

Background and Aims
Antineutrophil cytoplasmic autoantibody-associated vasculitis (AAV) is a type of necrotizing small vessel inflammatory disease, including alveolar hemorrhage and rapidly progressive glomerulonephritis. Elderly patients with antineutrophil cytoplasmic autoantibody-associated vasculitis (AAV) commonly experience renal impairment and poor prognosis. Based on the cohort of inpatients with AAV in Peking Union Medical College Hospital, this study aimed to analyze the clinical manifestations, diagnosis and treatment characteristics of elderly patients compared with non-elderly patients, and establish a risk scoring system for predicting composite renal outcomes in patients with AAV in elderly patients.

Method
This retrospective observational study included all AAV patients hospitalized in a single-center tertiary hospital in China between January 2013 and April 2022. Patients aged ≥ 65 years were defined as elderly and randomly divided into development and validation cohorts (2:1). Logistic regression analysis was performed in the development cohort to analyze risk factors. The scoring system was established accordingly and further validated in the validation cohort.

Results
A total of 1203 patients were enrolled in the study, among whom the elderly group accounted for 36% with a mean age of 71.4 ± 0.3 years. The elderly group had a worse prognosis, a higher mortality rate (8.9% vs. 3.5%, P &lt; 0.001), a higher rate of end-stage renal disease (17.6% vs. 10.2%, P &lt; 0.001), and worsening renal function (7.4% vs. 4.5%, P = 0.04). Logistic regression showed that age &gt; 75 years, chronic heart disease, elevated serum creatine, and D-dimer values were risk factors for poor prognosis in patients with AAV. The development and validation cohorts in AAV patients produced area under the curve values of 0.823 (0.784–0.862) and 0.833 (0.777–0.888), respectively (Figure 1). When the risk score was ≥ 2 points, the risk of acquiring composite renal outcomes increased significantly with a sensitivity and specificity of 75.0% and 79.9%, respectively.

Conclusion
We established risk-scoring systems based on baseline clinical characteristics to predict composite renal outcomes in patients with AAV. Our results suggest that more attention should be paid to elderly patients who have severe renal impairment and active inflammation.
#3467 INHIBITION OF ACYL-COA SYNTHETASE MEDIUM CHAIN FAMILY MEMBER 3 PROMOTES RENAL FIBROSIS BY ACCELERATING CELLULAR SENESCENCE IN TUBULAR EPITHELIAL CELLS
Authors: LI Lingzhi , Wu Yiting , MA Liang , Fu Ping 
Published: June 2023

Abstract

Background and Aims
Cellular senescence is associated with renal disease progression. Accelerated tubular cell senescence promotes the pathogenesis of renal fibrosis no matter caused by natural aging or disease. However, the underlying mechanism is unknown.

Method
Proteomic analysis of natural aging kidney from 20-week mice was used to find potential target protein which is acyl-CoA synthetase medium chain family member 3 (Acsm3). After finding it, two Acsm3 inhibitor (4-Methylsalicylic acid and 2-hydroxyoctanoic acid) were used separately to treat natural aging and pathological aging (unilateral ureteral obstruction induced renal fibrosis) mice. Renal histological injury was measured by HE and Masson's trichrome staining. SA-β-gal staining was used to check cellular senescence. Renal tissues of the mice were analysed by western blot and qPCR assay for the expression of Acsm3, fibrosis and cellular senescence related proteins and genes. In order to avoid drug toxicity, tubular epithelial cells were treated with Acsm3 SiRNA to explore the effects of Acsm3 in vitro.

Results
Firstly, we confirmed that cellular senescence happened in both elderly mice and UUO mice and found SA-β-gal positive cells were mainly tubular epithelial cells. After analysing proteomic sequencing data, Acsm3 is the protein which increased dramatically as the top one protein in elderly mice. We also found Acsm3 increased in tubular cells specifically in adult mice compared with fetal mice from KIT single cell database, which suggested that Acsm3 might have effects for kidney development. After validating changes and location of Acsm3, we treated natural aging and UUO mice with two Acsm3 inhibitor to check the function of Acsm3, separately. Administration of Acsm3 inhibitor (no matter 4-Methylsalicylic acid or 2-hydroxyoctanoic acid) could induce renal histological injuries, renal fibrosis, with significantly increased COL6, α-SMA and FN expression in both natural aging and UUO induced renal fibrosis. The cellular senescence was also observed to increase after Acsm3 inhibitor treatment with growth P21 and P16 expression. In addition, pro-inflammatory senescence-associated secretory phenotype (SASP) including IL6 and MCP1 increased as well. In order to avoid kidney injury induced by drug toxicity instead of by inhibition of Acsm3, we transfected Acsm3 SiRNA in tubular epithelial cells to check in vitro. Similarly, the inhibition of Acsm3 augmented cellular senescence and SASP of tubular epithelial cells as what we found in vivo. It supported that inhibition of Acsm3 could induce senescence of tubular epithelial cells and thus to promote kidney fibrosis.

Conclusion
These findings suggested that Acsm3 could be an important protector for renal fibrosis by inhibiting cellular senescence of tubular epithelial cells. The underlying mechanism needs to explore more.
#3471 INCIDENCE, RISK FACTORS AND OUTCOMES ASSOCIATED WITH ACUTE KIDNEY INJURY IN COVID-19 AT THE NATIONAL KIDNEY AND TRANSPLANT INSTITUTE
Authors: Altillero Melchor , Danguilan Romina , Arakama Melhatra 
Published: June 2023

Abstract

Background and Aims
Acute kidney injury (AKI) in COVID-19 leads to an increase in patient mortality especially among chronic kidney disease (CKD) patients. This study aims to determine the incidence and risk factors for AKI and compare renal outcomes and survival among patients with and without AKI admitted for Covid-19 at a tertiary renal center.

Methods
A retrospective cohort of 519 adult patients admitted from March 1,2020 to March 1, 2022, reviewed baseline characteristics and their association with renal outcomes. Patients were divided according to diagnosed CKD, undiagnosed CKD and normal eGFR. Chronic dialysis and kidney transplant patients were excluded. Kaplan-Meier survival at 7, 14 and 30 days from admission was performed. Patients were followed up to 14 days from discharge.

Results
Overall incidence of AKI was 45.66%; 76.64%, 38.75%, 7.59% among patients with diagnosed CKD, undiagnosed CKD and normal eGFR respectively (p&lt;0.0001). Multivariate analysis showed males and inotrope use were significant risk factors for AKI, while higher eGFR was protective. AKI was associated with dialysis, invasive ventilation (p&lt;0.0001), prolonged hospitalization (p = 0.0001) and mortality (p&lt;0.0001). Renal recovery was 64%, 59%, 23% in stage 1, 2 and 3 AKI respectively, until 14 days from discharge (p&lt;0.0001). No significant difference was observed with renal recovery and COVID-19 severity. Patient survival was lower with AKI, 83.16%, 70.59%, 47.5% compared to non-AKI, 91.27%, 87.82, 76.95% at 7, 14, and 30 days respectively (p = 0.0001).

Conclusion
There was a higher incidence of AKI with worsening renal function. Intensified preventive measures for AKI is crucial to prevent its devastating consequences.
#3475 NOVEL OPTIMISED PROTOCOL FOR ISOLATION OF PTEC AND SYSTEMATIC CHARACTERISATION FROM HUMAN KIDNEY BIOPSY
Authors: Petreski Tadej , Varda Luka , Gradišnik Lidija , Maver Uroš , Ekart Robert , Hojs Radovan , Bevc Sebastjan 
Published: June 2023

Abstract

Background and Aims
Human kidneys have a role in water homeostasis, acid-base control, reabsorption of compounds, and secretion of xenobiotics and endogenous metabolites, exposing them to substances that could cause harm. This results in an alarming number of acute kidney injuries (AKI) worldwide, estimated at 13%. Furthermore, one-quarter of hospitalised cases are due to drug-induced AKI [1]. Current methods for nephrotoxicity assays are based on animal testing and/or the use of simple human cell lines. Meta-analyses show that we can correctly predict human drug responses in only 10–50% [2]. Our work aimed to develop a novel and optimised protocol for isolating proximal tubular epithelial cells (PTEC) from human kidney biopsy to aid future research regarding AKI and nephrotoxicity studies.

Method
Isolation and cultivation of primary human adult PTEC obtained with biopsy during the regular diagnostic procedure was performed. We used a protocol consisting of micro-dissection of a tissue sample to get ∼1 mm3 fragments, enzymatic dissociation with 0.2% collagenase type 1, and use of selective culture media (Advanced DMEM/F12 with added insulin, transferrin, and selenite (all three together termed ITS), epidermal growth factor (EGF), and hydrocortisone). Light microscopy was used for morphologic characterisation. Some cells were cultured on Transwell inserts, and the transepithelial electric resistance (TEER) was measured in mature cells that formed a confluent culture. For phenotypic characterisation, several markers characteristic of PTEC were chosen [3], and immunocytochemical staining was performed using a fluorescent microscope to evaluate the PTEC phenotype.

Results
Following the described protocol resulted in isolating cells that formed first colonies after 24 h. Using light microscopy, the cells exhibited a cobblestone appearance, reached confluence after eight days, and showed dome (hemicysts) formation after 13 days. TEER reached 169 Ω/cm2 after 14 days. The isolated cells were marked positive using immunocytochemistry for sodium-glucose cotransporter 2 (SGLT2), multidrug-resistant protein 4 (MRP4), organic anionic transporter 1 and 3 (OAT1 and OAT3), organic cationic transporter 2 (OCT2), p-glycoprotein (p-gp), multidrug and toxin extrusion protein 1 (MATE1), and N-cadherin.

Conclusion
In this study, we developed a protocol for isolating and cultivating primary human PTEC from biopsy samples. To the best of our knowledge, we have performed the most extensive systematic characterisation following the isolation of PTEC from kidney biopsy reported to date.
#3480 PATIENT REPORTED OUTCOMES IN GLOMERULAR DISEASES: A NEW MODEL OF CARE BASED ON MEDICAL CARE, TELEHEALTH AND NURSE COACHING: THE HUMAN-C PROJECT
Authors: Couso Elena Seren , Rivera Miguel Giovanni Uriol , Arias-Camisón Paloma Livianos , Mulet Aina Obrador , Ojeda Felipe Ignacio , Rodenas Estela de Los Angeles Mas , Mendoza Sonia Cleofe Jimenez , Losa Franciso Fanjul , Mendez Isabel Garcia 
Published: June 2023

Abstract

Background and Aims
Glomerular diseases (GD) affect young and working-age people. Questionnaires for assessing health-related quality of life in GD patients are scarce. The implementation of telehealth and nurse coaching support (Humanization Coaching Project: Human-C Project) in a multidisciplinary team may influence the patient-reported outcomes (PROs), patient-reported experiences (PREMs) and could open new perspectives on these patients, which should be taken into account We report the results of PROMs and PREMS after the introduction of the Human-C Project. The objective of the study was to describe PROMs and PREMs in a glomerular disease unit of a third-level hospital after the implementation of the Human C-Project.

Method
Telehealth was implemented in 2019, and nurse-coaching support in 2021. The survey was online and anonymous to improve the accuracy of self-reports. The questionnaire consists of 15 items (based on Promis-29 (3 questions), SF-36 (2 questions) scales, and 10 questions previously obtained through personal interviews during nurse-coaching support). The questionnaire was sent to 233 patients included in our telehealth program.

Results
89 (38%) patients responded to the questionnaire. The mean (SD) age was 46(14). The questionnaire was stratified into 6 domains and the percentage of responses preference were: employment status (100%), knowledge of the disease (94%), social function (96%), psychological health (86%), type and periodicity of the medical appointments (84%), and therapy preferences (80%). 87% of the patients are of working age, 16% consider that they know little or nothing about their disease, 20% know little or do not know its severity, 53% reported fatigue, 50% their sleep quality is regular or very poor, 40% are not satisfied with their work performance (including at home), 34% reported poor health status, 34% reduced their activity (at work and home) due to emotional problems, 19% do not ask all questions or do not come up with clear information during the appointment, 80% report taking the medication correctly, 80% knows what each pill is for, 35% want to retire and or reduce the number of tablets even adding intravenous mediation, 33% develop anxiety about the disease, 72% consider that telehealth helps to reconcile work schedule and illness and helps to clarify doubts and in remission period 67% prefer to have an appointment as long as 6-9 months if they can directly access their health team if necessary.

Conclusion
A relevant percentage of GD patients reported health-related quality-of-life problems. Telehealth and nurse coaching support are opening specific perspectives of care in GD patients, with important implications for the health system.
#3500 CENTRAL DIABETES INSIPIDUS ASSOCIATED WITH ACUTE MYELOID LEUKEMIA
Authors: Mareedu Neeharik , Jat Asadullah 
Published: June 2023

Abstract

Background and Aims
Central Diabetes Insipidus (CDI) is a rare condition in which there is decreased release of antidiuretic hormone (ADH) from the posterior lobe of the pituitary gland resulting in polyuria. CDI is most commonly idiopathic with other known causes being primary or secondary tumors, cranial nervous system (CNS) infiltrative diseases, head trauma or neurosurgical procedures. Acute Myeloid Leukemia (AML) is rarely associated with CDI. We report a case of elderly male patient with recently diagnosed AML who developed polyuria due to CDI.

Method
Review of medical literature and hospital patient case workup based on reviewed medical literature.

Results
A 78-year-old male patient diagnosed with acute myeloid leukemia was started on treatment with Decitabine and Venetoclax 4–6 weeks prior to his hospitalization with chief complaints of back pain and oropharyngeal mucositis. The patient was also noted to have significant polyuria with hypernatremia during his hospitalization. His urine output ranged around 6–7 liters per day and his serum sodium levels were noted to be elevated to 162 mmol/L. 24-hour urine osmolality was calculated at around 1700 milliosmoles/day. Though patient's initial labs were suggestive of osmotic diuresis as a cause of his polyuria from ongoing hyperosmolar IV fluids input and significant increased oral dietary osmolar input, his polyuria persisted despite decreased total daily osmolar input. Further investigation with desmopressin suppression testing was notable for doubling of his urine osmolality with 10 mcg intranasal desmopressin administration with urine osmolality reaching to a peak of 447 mOsm/kg, indicating CDI as a reason for patient's ongoing polyuria. Patient's urine output as well as hypernatremia improved with initiating the patient on daily Desmopressin. MRI head with and without contrast ruled out any intracranial masses or infiltrative CNS diseases.

Conclusion
The pathogenic mechanism for association between CDI and AML is not completely clear, but it is thought to be secondary to infiltration of the central nervous system with leukemic cells, especially Sella Turcica, though this may not be evident on CNS imaging studies in all the cases, like in our patient. Polyuria can present in patients with AML either before or after the diagnosis of AML and sometimes it might be the only presentation in patients with AML which would lead to further workup and diagnosis of AML. Early identification of CDI in these patients lead to prompt management and avoidance of any significant electrolyte imbalances which could be sometimes attributed to patient's chemotherapeutic agents rather than to the patient's disease process itself.
#3508 FUROSEMIDE DECREASES KYNURENIC ACID SYNTHESIS IN RAT KIDNEY IN VITRO
Authors: Zakrocka Izabela , Załuska Wojciech 
Published: June 2023

Abstract

Background and Aims
Loop diuretics are highly potent agents, particularly beneficial in patients with impaired kidney function or heart failure exacerbation. Furosemide, due to fast onset and short time of action, remains the most commonly used drug from this class of diuretics. Inhibition of sodium-potassium-chloride cotransporter (NKCC2) in the thick ascending limb of Henle's loop is the main mechanism of furosemide's action. Other effects of furosemide, like modulation of potassium channels activity or activation of prostaglandin synthesis, were previously described. It was postulated that furosemide may exacerbate kidney injury in a dose dependent manner. Kynurenic acid (KYNA) is a tryptophan derivative synthesized from L-kynurenine (L-KYN) by kynurenine aminotransferases (KATs). KAT I and KAT II are the main KAT isoenzymes. Non-selective antagonism towards ionotropic glutamatergic receptors, as well as activation of aryl hydrocarbon receptors and the α7 nicotinic acetylcholine receptors are known mechanisms of KYNA’s action. KYNA was shown to regulate water and electrolyte balance through natriuretic effect. By some researchers KYNA, together with other tryptophan metabolites, is classified as uremic toxin. We aimed to analyze the influence of furosemide, widely used loop diuretic, on KYNA’s synthesis and the activity of both KATs in rat kidney in vitro.

Method
The influence of furosemide on KYNA’s production with KAT I and KAT II activity was tested in rat kidney homogenates in vitro after 2 hours incubation in the presence of KYNA precursor L-KYN and furosemide. Diuretic was examined at increasing concentrations: 1 μM, 10 μM, 50 μM, 100 μM, 500 μM and 1 mM. Enzymatic KYNA’s production was measured by high performance liquid chromatography (HPLC) with fluorometric detector. All applicable international, national and institutional guidelines for the care and use of animals were followed.

Results
Furosemide at 500 μM and 1 mM lowered KYNA formation in kidney homogenates in vitro to 80% (p &lt; 0.05) and 70% (p &lt; 0.05) of control value, respectively. At 1 mM concentration furosemide inhibited kidney KAT I activity in vitro to 38% (p &lt; 0.01) of control value. Similarly, furosemide at 500 μM and 1 mM concentration decreased kidney KAT II activity in vitro to 53% (p &lt; 0.01) and 18% (p &lt; 0.001) of control value, respectively.

Conclusion
Our study presents a novel mechanism of action of furosemide. Inhibition of KYNA synthesis in the kidney by furosemide may have influence on kidney function.