bluuebunny/crossref_metadata_2025 huggingface dataset:
#3125 EXTERNAL VALIDATION OF A NOVEL MULTIMARKER GFR ESTIMATING EQUATION
Authors: Tio Maria Clarissa , Zhu Xiaoqian , Lirette Seth , Rule Andrew , Butler Kenneth , Hall Michael , Dossabhoy Neville , Mosely Thomas , Shafi Tariq
Published: June 2023

Background and Aims

The use of multiple markers may improve the accuracy in glomerular filtration rate (GFR) estimation especially when the interpretation of creatinine and cystatin C is limited. We sought to externally validate a recently developed multi-marker nuclear magnetic resonance (NMR)-based estimated GFR equation (eGFR-NMR) using the biracial Genetic Epidemiology Network of Arteriopathy cohort.

Method

We included 224 sex, race/ethnicity, and mGFR-category-matched participants. GFR was measured using urinary clearance of iothalamate (mGFR). We calculated eGFR-NMR using serum creatinine, valine, myo-inositol, and cystatin C, age, and sex. We compared the reliability of eGFR-NMR with current eGFR equations (2021 Chronic Kidney Disease Epidemiology Collaboration equations for creatinine [eGFR-Cr] and creatinine with cystatin C [eGFR-Cr-CysC]) using median bias, precision, and accuracy metrics. In particular, we evaluated its performance in age, sex, and race subgroups.

Results

In the overall cohort, mean age was 63 (±8) years, 54% were females, 49% were Black individuals, and mean mGFR was 78.7 (±24.3) ml/min/1.73 m2. eGFR-NMR overestimated mGFR by 2 mL/min/1.73 m2 (95% CI, 4 to 0.7) while eGFR-Cr-CysC underestimated mGFR by −5 mL/min/1.73 m2 (95% CI, −2 to −7). All equations had acceptable accuracy metrics. When stratified by age, sex, and race, eGFR-NMR performed the best among Black males age <65 years compared to current equations (Figure 1). In this subgroup, eGFR-NMR was unbiased (bias, 2mL/min/1.73 m2 [95% CI, -3 to 10]) compared to substantial biases of eGFR-Cr (bias, 17 mL/min/1.73 m2 [95% CI, 9 to 24]) and eGFR-Cr-CysC (bias, 15 mL/min/1.73 m2 [95% CI, 6 to 20]). In other subgroups, measures of accuracy for eGFR-NMR, eGFR-Cr, eGFR-Cr-CysC were generally similar.

Conclusion

eGFR-NMR can be used to estimate mGFR and was more accurate than CKD-EPI equations among Black males age <65 years.
#3145 ASSOCIATION OF ENDOTHELIAL NITRIC OXIDE SYNTHASE GENE POLYMORPHISM WITH ENDOTHELIAL DYSFUNCTION IN DIABETIC NEPHROPATHY AMONG AZERBAIJANIS
Authors: Ismayilova Shalala , Mammadzada Ayten , Kuliyev Orxan , Jabrayilov Jabrayil
Published: June 2023

Background and Aims

Vascular endothelial dysfunction resulting from impaired nitric oxide synthase (NOS) activity in the endothelial cells of blood vessels has been suggested as playing an important role in the pathogenesis of Diabetic nephropathy (DN). It regulates endothelial function and maintains endothelial-dependent vasodilation in multiple organs, including the kidney. The study was carried out to investigate the association of T-786C single nucleotide polymorphisms with the flow mediated dilation (FMD) in DN among type 2 diabetic subjects.

Method

90 patients (45 male and 45 female) with diabetic nephropathy were recruited from Nephrology and Endocrinology departments of the Azerbaijan Medical University hospital. As a control group the results were compared with the findings in 100 healthy Azerbaijani individuals (50 males and 50 females). The study was approved by ethics committee and informed consent was obtained from all patients in written form. Brachial endothelial function was determined by brachial artery vasodilator response or brachial FMD in the dominant arm according to previously validated techniques. T786C polymorphism was detected using polymerase chain reaction-restriction fragment length polymorphism analysis.

Results

The results showed significant differences between DN group and control group regarding the genotype and allele distributions of the T786C single nucleotide polymorphisms. The CC genotype was significantly more frequent in diabetics nephropathy patients than in control group (42% vs. 8%, p = 0.01). FMD in allele homozygote T786C(TT), T786C(CC) and heterozygote T786C(CT) were respectively 13.5 ±0.16%, 12.3±0.19%,13.9 ±0,28%. In the study groups, Azerbaijani patients showed dominance of the C allele and a mutant homozygous genotype CC of the T786C gene of eNOS. Subjects with the 786C(CC) (n = 48) showed significantly reduced FMD with those with T786C (TT) (n = 7) (p = 0.021) and T786C (CT) (n = 35) (p = 0.023), whereas there was no significant difference in endothelial-independent vasodilation between these groups. Although subjects with homozygote T786C(TT), did not show significantly reduced levels of FMD. Who were carriers of the T786C allele demonstrated markedly reduced levels of FMD compared with noncarriers (p = 0.019).

Conclusion

The data suggest that in diabetic nephropathy, the eNOS T786C allele may be involved in endothelial dysfunction. Azerbaijani patients showed dominance of the C allele and a mutant homozygous genotype CC of the T786C gene of eNOS.
#3148 PROTEINURIA AND TYPE OF KIDNEY ALLOGRAFT INJURY IDENTIFY KIDNEY TRANSPLANT RECIPIENTS BENEFITING MOST FROM BELATACEPT CONVERSION
Authors: Weidmann Lukas , Schmid Nicolas , Lopez Kai Castrezana , Mueller Thomas , Schachtner Thomas
Published: June 2023

Background and Aims

Belatacept conversion is associated with an improvement in kidney allograft function. Yet, not all kidney transplant recipients (KTRs) seem to benefit equally from this alteration of maintenance immunosuppression. Both type (alloimmune vs. non-alloimmune) and severity (assessed by proteinuria) of kidney allograft injury may impact the functional response to a belatacept conversion.

Method

We studied 37 KTRs from belatacept conversion to 1-year post-conversion. KTRs were categorized concerning pre-conversion proteinuria: 21 KTRs with low proteinuria (<500 mg/day), 12 KTRs with moderate proteinuria (500–1000 mg/day), and 4 KTRs with high proteinuria (>1000 mg/day). KTRs were analyzed concerning the change of kidney allograft function, change of proteinuria, and type of allograft injury (alloimmune vs. non-alloimmune).

Results

17 of 21 KTRs (81%) showed low proteinuria pre- and post-conversion, and 5 of 16 KTRs (31%) with moderate/severe proteinuria pre-conversion showed low proteinuria post-conversion (group 1, n = 22). 8 of 12 KTRs (67%) showed moderate proteinuria pre- and post-conversion, and 1 of 21 KTRs (5%) with low proteinuria pre-conversion developed moderate proteinuria post-conversion (group 2, n = 9). 3 of 4 KTRs (75%) showed high proteinuria pre- and post-conversion, and 3 of 21 KTRs (14%) with low proteinuria pre-conversion developed high proteinuria post-conversion (group 3, n = 6). 16 of 22 KTRs with low proteinuria post-conversion (73%; group 1) showed an increase in eGFR at 1-year post-conversion (≥10% from pre-conversion baseline eGFR) compared to 6 of 9 KTRs (66%, group 2) with moderate proteinuria post-conversion, and 1 of 6 KTRs (17%, group 3) with high proteinuria post-conversion (p = 0.008). Alloimmune injury was assumed in 5 of 22 KTRs (23%, group 1), 3 of 9 KTRs (33%, group 2), and 4 of 6 KTRs (75%, group 3), respectively.

Conclusion

KTRs with low proteinuria and non-alloimmune injury benefit most from belatacept conversion concerning the improvement of kidney allograft function. While aggravation of proteinuria post-conversion is rare, some KTRs may show improvement of proteinuria post-conversion. If belatacept conversion is still beneficial compared to calcineurin inhibitor-based immunosuppression among KTRs with high proteinuria and alloimmune injury needs to be studied.
#3243 CANCER PATIENTS WITH END-STAGE KIDNEY DISEASE ON CHRONIC HEMODIALYSIS: CHANGING THE PARADIGM
Authors: Roldão Marisa , Ávila Gonçalo , Coelho Inês , Ferreira Hugo , Chuva Teresa , Paiva Ana , Costa José Maximino
Published: June 2023

Background and Aims

In the last decade, new therapeutic regimens have dramatically improved the prognosis of cancer patients and changed the paradigm of a previously highly lethal disease, increasing the number of cancer patients with chronic kidney disease (CKD) who progress to end-stage kidney disease (ESKD). However decision-making regarding dialysis initiation in patients with cancer and ESKD remains however controversial. The aim of our study was to characterize the clinical course and evaluate survival outcomes of cancer patients on chronic hemodialysis (HD).

Method

We conducted a retrospective study of chronic HD patients in a single oncology hospital unit between January 1991 and November 2022. Outpatients on HD for more than one month, who underwent dialysis after the diagnosis of cancer were included. Univariate and multivariate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality were estimated using the Cox proportional hazards risk model.

Results

Two hundred and twelve patients were recruited. Mean age at HD initiation was 65.7±14.7 years. The most prevalent ESKD etiologies were cast nephropathy, chronic interstitial nephritis, and surgical removal of the kidney. The most common tumors were genitourinary, multiple myeloma (MM) and gastrointestinal corresponding to 80.6% of all cancers. There were 143 deaths over a median follow-up period of 23 months (IQR: 7.25 – 54). The overall survival rates were 76.5% at 1 year, 59.6% at 3 years and 39.2% at 5 years. The median survival time was 44 months (95% CI: 30.58 – 51.42). An increased mortality risk was observed in patients with MM (HR: 3.38; 95% CI: 1.01-11.39; p = 0.045) and in those who started HD from 2001 to 2011 (HR: 1.60; 95% CI: 1.06-2.42; p = 0.001). The presence of metastasis or multiple tumors was not associated with all-cause mortality.

Conclusion

Our results highlight the importance of considering cancer patients for renal support therapies, including those with multiple tumors and metastatic disease. In fact, with the new treatments available, many patients have chronic oncological disease non-fatal in the short term. To the best of our knowledge, this is the largest study of cancer patients on chronic HD.
#3255 BETA2 MICROGLOBULIN IS AN INDEPENDENT PARAMETER RELATED WITH DYSFUNCTION OF NATURAL KILLER CELL ACTIVITY IN HEMODIALYSIS PATIENTS
Authors: Park Hyeong Cheon , Oh Donghwan , Jhee Jong Hyun , Lee Jung Eun , Choi Hoon Young , Kim Hyung-Jong , Han Sang-Woong
Published: June 2023

Background and Aims

End-stage renal disease patients are characterized by immune dysfunction. Natural killer (NK) cells area lymphocytes of innate immune system that play a key role in an immune response towards viral infections and tumors. We aimed to analyze clinical factors related to the NK cell activity in chronic hemodialysis (HD) patients.

Method

Clinically stable 196 patients who were treated by HD for more than 3 months were enrolled from 4 outpatient HD clinics. NK cell activity was assessed using NK Vue assay (NKMAX, Sungnam, Korea) that uses serum of ex-vivo stimulated whole blood to detect interferon (IFN)-γ secreted from NK cells as an indicator of NK cell activity. All patients were stratified as abnormal (<250 pg/ml) and normal (≥250 pg/ml) groups according to NK cell activity.

Results

Mean age of the HD patients was 62.7 years [range 31 to 95 years] and mean HD duration was 49.2 months [range 3 to 221 months]. In total, 68 (35%) of HD patients showed abnormal NK cell activity. The abnormal NK cell activity group showed significantly increased age and shorter HD duration compared to the normal NK cell activity group (66.7 ± 11.9 vs. 60.6 ± 13.4 years, p = 0.001; 33.8 ± 33.0 vs. 57.5 ± 48.5 months, p<0.001, respectively). The serum albumin and parathyroid hormone levels were significantly lower in the abnormal NK cell activity group (3.7 ± 0.4 vs. 3.9 ± 0.3 g/dL, p = 0.005 and 176 ± 153 vs. 240 ± 260 pg/mL, respectively). In contrast, hemoglobin, blood urea nitrogen, urea reduction ratio, and C-reactive protein levels were comparable between the two groups. In multivariate regression analysis, old age, short dialysis duration, low serum albumin and high beta2 microglobulin levels were independent risk factors of abnormal NK cell activity in HD patients (adjusted odd ratio [AOR], 1.033; 95% confidence interval [CI], 1.005-1.062, p = 0.02; AOR, 0.981; 95% CI, 0.971-0.992; p<0.001, AOR, 0.395; 95% CI, 0.157-0.995; p = 0.049, and AOR, 1.042; 95% CI, 1.011-1.075; p = 0.008, respectively).

Conclusion

Our results suggest that young age and good nutrition as well as lower burden of middle molecule uremic toxin is associated with greater NK cell activity in HD patients.
#3261 SAR131675, A SELECTIVE VEGFR3 INHIBITOR, AMELIORATES RENAL INFLAMMATION AND LYMPHANGIOGENESIS IN THE MURINE LUPUS NEPHRITIS MODEL
Authors: Kang Kyung Pyo , LI Wenjia , Wang Tian , Yeom Ji-Hyun
Published: June 2023

Background and Aims

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by immune-complex deposits and inflammatory cell infiltrations in multiple organs, and approximately half of lupus patients have nephritis. Lymphangiogenesis is the proliferation of pre-existing lymphatic vessels (LVs), which regulate tissue fluid homeostasis and immune cell trafficking, responding to the tissue environment. In this study, we evaluated the therapeutic effect of SAR131672, a selective VEGFR3 inhibitor, on the murine lupus nephritis model by regulating inflammation and lymphangiogenesis.

Method

First, we reviewed medical records for the biopsy-proven lupus nephritis and performed an immunohistochemistry study for D2-40. For animal experiments, seven to eight-week-old male BALB/c mice were used. The back area's skin was shaved and treated topically three times per week, with 100 μg of resiquimod in 100 μl of acetone for eight weeks and concomitantly treatment of VEGFR3 inhibitor, SAR 131672 by oral gavage. We evaluated renal histology and immunofluorescent study for inflammatory cells and lymphatic vessels. We also evaluated inflammatory cytokines and chemokines, lymphangiogenic factors by qRT-PCR.

Results

In a human study, we found that the higher lupus activity index, the more D2-40(+) lymphatic vessels are expressed in the tubulointerstitial areas. In an animal study, eight weeks of topical treatment of resiquimod to Balb/c mice induces lupus-like symptoms such as weight loss, splenomegaly, and glomerular immune complexes deposits such as IgG, IgM, and C3 in immunofluorescent staining. Histologically, glomerular mesangial cell proliferation and increased inflammatory cells in tubulointerstitial areas were noted in the H&E stain. Inhibition of VEGFR3 by oral SAR131672 treatment decreases glomerular and tubulointerstitial inflammation and decreases LYVE-1(+) lymphatic vessels. The pro-inflammatory cytokines and chemokines such as ICAM-1, VCAM-1, MCP-1, CCL19, CCL21, CCR7, CXCL13, and BAFF mRNA levels were increased compared with the vehicle-treated group. Treatment SAR131672 decreases pro-inflammatory cytokines and chemokine.

Conclusion

Inhibition of VEGFR3 by SAR131672 decreases the resiquimod-induced lupus nephritis model by regulating inflammation and lymphangiogenesis.
#3312 EFFICACY OF TRANSCATHETER AORTIC VALVE IMPLANTATION FOR SEVERE AORTIC VALVE STENOSIS IN HEMODIALYSIS PATIENTS
Authors: Nakagaki Masahiro , Harada Kenji , Kanai Hidetoshi
Published: June 2023

Background and Aims

In Japan, of the >340,000 chronic dialysis patients, approximately 60% have lifestyle-related diseases including diabetes and nephrosclerosis. Two-thirds of maintenance dialysis patients (age, ≥65 years) often develop aortic stenosis (AS) and other serious and complex systemic cardiovascular disease complications associated with chronic kidney disease mineral and bone disorder (CKD-MBD). Furthermore, renal function loss and a prolonged state of renal failure are observed requiring renal replacement therapy (RRT). AS in dialysis patients progresses quickly, and the frequency of hospitalized treatment for heart failure increases with the worsening condition, leading to ADL deterioration, which may subsequently cause dialysis hypotension/interruption. At our hospital, of the 420 maintenance dialysis patients who died during hospitalization in 5 years before 2020 (420/2,637 = 16%), 32 cases (8%) developed AS complications, which became their direct cause of death in 12 cases (3%), and aortic valve replacement (AVR) was performed in 5 cases (1%). Maintenance hemodialysis patients (HD) are at high risk group and have a poor prognosis for life. Previously, transcatheter aortic valve implantation (TAVI) was not indicated., but recently TAVI has been approved in Japan. Efficacy of TAVI for HD patients remains unclear, here we investigated several outcomes.

Method

A total of 123 maintenance dialysis patients with severe AS were included in 2019–2021. We examined TAVI group and AVR group for length of hospital stay, hospitalization costs, life expectancy, and rates of complications such as occurrence of arrhythmias.

Results

Over a 3-year period, we performed TAVI for 58 maintenance dialysis patients (mean age, 81 years); their median duration of hospitalization was 14 days for a median cost of 6,259,350 JPY. The mean age was older than that of 66 patients who underwent open-heart AVR during the same period (mean age, 73 years; 35 days for 7,192,570 JPY); therefore, the cost was less, and the rate of complications, including vital prognosis and arrhythmia, was not inferior in hospitalization period.

Conclusion

In conclusion, TAVI is effective for elderly maintenance dialysis patients with severe AS and has a positive health care economics, ADL maintenance.
#3330 INFLAMMATION SECONDARY TO CHRONIC KIDNEY DISEASE AND PERITONEAL DIALYSIS ACCELERATES ATHEROSCLEROSIS IN A NEW MOUSE MODEL
Authors: Kane Jamie , den Toom Myrthe , Bosmans Laura , van Os Bram , Vos Winnie , Beckers Linda , Jakulj Lily , Lutgens Esther , Vervloet Marc , Eringa Etto
Published: June 2023

Background and Aims

Inflammation is an established contributor to accelerated atherosclerosis, which is highly prevalent in people with chronic kidney disease (CKD) and even more so in those treated with peritoneal dialysis (PD). We therefore hypothesised that PD-induced systemic inflammation is essential in the development of atherosclerosis. To study this we developed a novel mouse model of CKD and PD accelerated atherosclerosis.

Method

We performed a 5/6ths nephrectomy in ApoE deficient “black 6” mice, fed these mice a high-cholesterol diet (HCD), and intraperitoneally administered 3.86% Physioneal daily for 67 days. There were three groups of mice: control (HCD-only), CKD+HCD, and CKD+HCD+PD, with relevant shams. Tissues were harvested twelve weeks after the nephrectomy. Assessments of residual kidney function, atherosclerotic plaque pathology and immunology, and systemic immune responses were performed.

Results

Atherosclerotic plaque size in the aortic arch was larger in the PD group compared to the control, increasing from 83,779 μm2 ±18,430 to 109,973 μm2 ±25,602 (p = 0.0349), whilst plaque size was unchanged in the CKD group. In contrast, both the CKD and PD groups displayed altered plaque stability. There was less collagen in the plaque vs control, decreasing from 43.54% ±10.65 to 29.71% ±9.43 and 29.73% ±10.18 respectively. Additionally, fibrous cap thickness decreased in both groups vs control. The plaques from only the PD group showed infiltration by T-cells compared to control, with no changes in macrophage content in either the CKD or PD group. In the spleen in the CKD and PD groups, naïve CD4 cells increased and effector CD4 cells decreased compared to control, with the latter change also occurring in the circulation. Central memory CD4 cells, terminally differentiated Th1 cells, Th17 cells, and ‘vascular homing’ cells all increased in the PD group compared to control mice. These homing cells also increased in circulation. The PD group showed decreases in the spleen of regulatory T-cells, effector Th1 cells, and effector CD8 cells. Notably, all of these changes were absent from the mesenteric lymph node. There was a large drop in monocytes in the spleen and a loss of immature and mature dendritic cells in the PD group.

Conclusion

Combining CKD, a high-cholesterol diet, and exposure to PD fluids in ApoE−/-mice successfully generated a new model for cardiovascular disease in human PD patients. This new model is in a widespread and well-understood mouse line representative of human atherosclerosis. Here we demonstrate the pronounced effects of CKD and PD on the innate and adaptive immune response which increases atherosclerotic burden and leads to larger more vulnerable plaques
#3390 ADPKD PREDICTOR: A CLOUD-BASED PROGNOSTIC TOOL FOR AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE
Authors: Carbone Vincenzo , Gazzin Matteo , Bursi Roberta , Magistroni Riccardo , Corsi Cristiana
Published: June 2023

Background and Aims

ADPKD is a progressively debilitating genetic disease characterized by the growth of numerous cysts in the kidneys, leading eventually to end-stage renal disease. Total Kidney Volume (TKV) is accepted by FDA and EMA as a prognostic biomarker and quantitative predictor of kidney function decline, and is currently used to select patients to receive Tolvaptan treatment. However, TKV calculation from manual tracing of medical images is labor-intensive; for better accuracy, current available methods involve the injection of an iodinated contrast medium for CT scan, with important limitations in patients with impaired renal function. We developed ADPKD Predictor, a user-friendly cloud-based tool for fast and accurate estimation of disease classification and progression, based on automated kidney and cysts segmentation from MRI data.

Method

An online tool was designed on Microsoft Azure Cloud to automatize the set-up and running of a previously developed algorithm implemented in MATLAB to automatically detect kidneys and cysts contours from MRI data (T2-weighted turbo-spin-echo SPIR), based on advanced image processing techniques [1]. Through the web interface, the user is requested to upload the MRI data and select one point inside kidney's parenchyma in the central slice (Figure 1). Then, TKV is automatically calculated and eGFR based on CKD-EPI equation, ADPKD Imaging Classification and future eGFR [2], estimated Tolvaptan treatment effect [3], and GFR Category based on KDIGO CKD staging system are obtained (Figure 2). The MRI dataset is anonymized before upload to the cloud; data and results are stored in a secure and reliable environment controlled by the user.

Results

The proposed solution is very fast and precise compared to manual segmentation of medical images (absolute mean error 2.4% ± 2.7%) [1]. Moreover, it is faster and more accurate than the commonly used ellipsoid-based method, resulting in a manifold reduction of misclassification error (2.5%) [1] and therefore potential therapeutic consequences. Another advantage is its usability, with no specific computational expertise, numerical software or dedicated hardware required, since all computations are run remotely in the cloud.

Conclusion

ADPKD Predictor provides a fast and reproducible assessment of risk classification and disease progression, based on precise morphologic classification of the renal and cysts volume of patient. The proposed solution represents an extremely useful tool for researchers and clinicians to easily obtain an accurate estimation of risk classification potentially helping in a correct and effective stratification of patients, and monitor patient's disease progression, hence supporting a correct and effective therapy administration. Also, it would represent a great benefit for the patient, since the tool analyzes medical images obtained without the use of contrast medium.
#3394 THE VALUE OF ADVANCED CARDIAC MAGNETIC RESONANCE IN DETECTING THE CHARACTERISTICS OF CARDIAC INVOLVEMENT IN ANDERSON-FABRY DISEASE
Authors: Yang Junlan , Zhang Xiao Liang
Published: June 2023

Background and Aims

Anderson-Fabry disease (AFD) is a rare X-linked inherited lysosomal storage disorder caused by GLA gene mutations. With the progression of the disease, end organ damages (such as renal and cardiac) will impair quality of life. For nephrologists, it is necessary to improve the early diagnosis ability of AFD and the ability to assess the involvement of multiple organs (especially the heart). Cardiac magnetic resonance (CMR) is more accurate than echocardiography in measuring myocardial thickness and mass. Moreover, with the gradual maturation of T1 Mapping and gadolinium-enhanced cardiac magnetic resonance, CMR has also been applied to evaluate cardiomyocyte injury. In this study, clinical data of patients with AFD were collected in order to study the value and advantages of advanced CMR technologies in evaluating cardiac function, cardiac structure and cardiomyocyte injury.

Method

In this prospective observational study, clinical and echocardiography data were collected from patients with AFD diagnosed at this center from January 2022 to September 2022. T1 Mapping and gadolinium-enhanced cardiac magnetic resonance were used to evaluate the cardiac function and the degree of cardiac structural lesions, and to analyze characteristic CMR findings of cardiac involvement in AFD. To clarify the value of CMR for the assessment of cardiac involvement in AFD compared with echocardiography.

Results

13 patients (five women, eight men) with AFD were included (Table 1). When diagnosing reduced ejection fraction, two (15.4%) met CMR, and zero (0%) met echocardiography. When diagnosing left ventricular hypertrophy, 12 (92.3%, 18.56±2.74mm) met CMR, and ten (76.9%, 16.37±2.71mm) met echocardiography. Compared with CMR, echocardiography can significantly underestimate the severity of left ventricular hypertrophy (P = 0.043). Using T1 Mapping and gadolinium-enhanced cardiac magnetic resonance, characteristic CMR findings of cardiac involvement in AFD were found in all patients (Fig.1), included decreased T1 values (12 cases, 92.3%, 1104.00±44.69ms) and late gadolinium enhancement (LGE) (six, 46.2%).

Conclusion

Characteristic CMR findings of cardiac involvement in AFD are left ventricular hypertrophy, decreased T1 values, and LGE associated with myocardial fibrosis. Advanced CMR holds promise in subclinical detection of AFD.
#3421 MRI PREDICTORS OF DIASTOLIC DYSFUNCTION OF THE LEFT VENTRICLE
Authors: Egamberdieva Dano , Ruzmetova Iroda , Khodjibekova Yu M , Karimova Yu A
Published: June 2023

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

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 < 0.001), a higher rate of end-stage renal disease (17.6% vs. 10.2%, P < 0.001), and worsening renal function (7.4% vs. 4.5%, P = 0.04). Logistic regression showed that age > 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

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

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<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<0.0001), prolonged hospitalization (p = 0.0001) and mortality (p<0.0001). Renal recovery was 64%, 59%, 23% in stage 1, 2 and 3 AKI respectively, until 14 days from discharge (p<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

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

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

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

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 < 0.05) and 70% (p < 0.05) of control value, respectively. At 1 mM concentration furosemide inhibited kidney KAT I activity in vitro to 38% (p < 0.01) of control value. Similarly, furosemide at 500 μM and 1 mM concentration decreased kidney KAT II activity in vitro to 53% (p < 0.01) and 18% (p < 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.