bluuebunny/crossref_metadata_2025_split huggingface dataset:
#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

Abstract

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

Abstract

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 (&lt;500 mg/day), 12 KTRs with moderate proteinuria (500–1000 mg/day), and 4 KTRs with high proteinuria (&gt;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

Abstract

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

Abstract

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 (&lt;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&lt;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&lt;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

Abstract

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

Abstract

Background and Aims
In Japan, of the &gt;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

Abstract

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

Abstract

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

Abstract

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.