bluuebunny/crossref_metadata_2025_split huggingface dataset:
#2589 TIMING OF ATRIAL FIBRILLATION OCCURRENCE IN HEMODIALYSIS PATIENTS WITH CARDIAC IMPLANTABLE ELECTRICAL DEVICES
Authors: Kida Hirota , Kikuchi Yoshitaka , Sato Nobuhiroo , Kawasaki Masato , Watanabe Tetsuya , Yamada Takahisa 
Published: June 2023

Abstract

Background and Aims
Hemodialysis (HD) patients has the high prevalence of atrial fibrillation (AF), and the procedure of HD itself might be related to risk factors for the onset of AF. On the other hand, cardiac implantable electronic devices (CIEDs), such as pacemaker, implantable cardioverter-defibrillators (ICD) and cardiac resynchronization therapy (CRT) have the function for arrhythmia detection. However, in HD patients with CIEDs, there are no studies that observe AF over long periods of time. The aim of this study is to investigate AF onset and duration of HD patients with AF, using the AF detection and memory function of CIEDs.

Method
Consecutive HD patients who were newly implanted with CIEDs between January 2008 and December 2021 were retrospectively analyzed in this study. Patients with chronic AF, with leadless pacemaker and without post-implantation follow-up were excluded from this study. Subclinical AF was defined from previous studies as atrial tachyarrhythmia lasting more than 6 minutes in memories of devices. The primary endpoint of this study was the subclinical AF within one year after CIESDs implantation. HD week was defined as follows according to HD schedule, HD1: Monday or Tuesday; HD1+1: Tuesday or Wednesday; HD2 Wednesday or Thursday; HD2+1 Thursday or Friday; HD3 Friday or Saturday; HD3+1 as Saturday or Sunday; and HD3+2 Sunday or Monday. We examined the association between onset and duration of AF and HD.

Results
Fifty-four HD patients who had been implanted with CIEDs (pacemaker: 37, ICD: 6, CRT: 11) were enrolled in the study. During a mean follow-up period of 352 ± 36 days, in 26 of 54 (48.1%) patients, 124 subclinical AF events (1-8 events / patient) were detected with CIEDs. History of clinical AF (46.2% vs 7.1%, p = 0.003) and sick sinus syndrome (53.8% vs 10.7%, p = 0.005) were significantly higher in HD patients with than without subclinical AF. The frequency of subclinical AF onset on HD day was approximately twice higher than on non-HD day (83 episodes [27.7 episodes/day] vs 41 episodes [10.3 episodes/day]), and subclinical AF onset on HD1 day was most frequent among a week (Figure 1a). Limited to HD day, subclinical AF events were observed more frequently especially during HD (30/86 events: 34.9%) and five hours after HD (28/86 events: 32.6%) (Fig. 1-b). Subclinical AF duration was significantly longer during HD compared to non-HD time (216 [90, 1066] min vs 96 [30, 418] min, p = 0.008).

Conclusion
In HD patients, subclinical AF occurred more frequently on HD day, especially during HD and several hours after HD. Careful observation during and after HD might help early diagnosis of clinical AF.
#2622 COST-EFFECTIVENESS OF SGLT2 INHIBITORS FOR THE TREATMENT OF TYPE 2 DIABETES AND ITS COMPLICATIONS
Authors: Igarashi Ataru , Tachimori Hisateru , Maruyama-Sakurai Keiko , Kubota Anna , Segawa Yasumasa , Akiyama Hiroki , Imai Naohiko , Kohsaka Shun , Miyata Hiroaki 
Published: June 2023

Abstract

Background and Aims
Diabetes and its complications (e.g. chronic kidney disease [CKD] and cardiovascular disease [CVD]) impose significant clinical and financial burden. Recent large-scale randomized controlled trials have demonstrated cardiorenal benefit of the anti-diabetic drug sodium glucose co-transporter 2 (SGLT2) inhibitors, and they are approved for the treatment of CKD and/or heart failure (HF) in many countries. In the present study, we assessed the economic effectiveness of SGLT2 inhibitors for patients with type 2 diabetes (T2DM) using a cost-analysis model that adopts CKD-dependent increases in the risk of developing CVD.

Method
We constructed a natural history model for T2DM patients incorporating CKD, end-stage renal disease, and CVD including myocardial infarction, HF, and stroke as diabetic complications. All diseases except for CKD were considered independent (i.e., the development of CKD increases the risk of CVD manifestation but a patient who develops one disease does not present with another disease). By using a population-based microsimulation, we estimated the 10-year medical costs in Japanese Yen (JPY) and outcomes (development of complications and quality-adjusted life years [QALY]) for patients who initiated antidiabetic therapy with SGLT2 inhibitors or conventional therapy. Probabilistic sensitivity analysis (PSA) was performed with 1,000,000 iterations.

Results
The total medical costs per person were JPY 1,193,000 versus JPY 1,160,000 and the QALYs were 8.13 versus 8.02 years for the SGLT2 inhibitor strategy versus the conventional strategy, respectively. As a result, the incremental cost-effectiveness ratio (ICER) was 302,000 JPY/QALY, well below the threshold value of JPY 5,000,000/QALY. The PSA revealed that the probability of ICER being below the threshold was 97.7%.

Conclusion
We demonstrated that the use of SGLT2 inhibitors was cost-effective compared to the conventional strategy for treating patients with T2DM, and these results suggest clinical and financial benefit of SGLT2 inhibitors that can holistically approach T2DM and its renal and cardiovascular complications.
#2629 ROS-SCAVENGING BLOCKS GLUCOSE INDUCED OXIDATIVE PERITONEAL CELL DAMAGE IN VITRO
Authors: Oberacker Tina , Schricker Severin , Schanz Moritz , Ketteler Markus , Latus Jörg 
Published: June 2023

Abstract

Background and Aims
Peritoneal dialysis (PD) is an effective method of renal replacement therapy (RRT). The long-term use of PD as RRT is limited due to adverse effects of high glucose-based PD fluids (PDFs) to the structure and function of the peritoneal membrane. Our group recently elucidated one pathological mechanism showing that glucose-based PDFs enhance oxidative DNA-damage in PD patients due to reduced thioredoxin (TRX) activity trigged by thioredoxin-interacting-protein (TXNIP) upregulation (Oberacker et al., 2022). Therefore, the aim of this in vitro study was to investigate drug treatments to mitigate oxidative stress and oxidative DNA-damage due to glucose-dependent induction of TXNIP expression.

Method
Using a mesotheliomal cell line (NCl-H28, ATCC) we performed in vitro studies mitigating reactive oxygen species (ROS) production and oxidative DNA damage as well. Cells were treated for three and eight hours with high-glucose media (1.5%, 2.3% and 4.25% glucose; glucose concentrations were adapted to PDFs from Fresenius Medical Care) compared to control media (normal glucose concentration). mRNA expression of TXNIP, TRX and further redox-related genes like superoxide dismutases (SODs) or catalase were analyzed by qPCR. Since TRX is negatively regulated by TXNIP, we investigated TRX activity in cell lysates. ROS production was monitored using a bioluminescent assay and immunofluorescence using the redox dye CellRoxGreen as well. The content of oxidative DNA-damage was investigated by immunofluorescence. Furthermore, we have preliminary analysis using primary human peritoneal mesothelial cells derived from PD effluent (PDF).

Results
We demonstrated a dose-dependent upregulation of round 1.5 fold TXNIP expression on mRNA level. However, no change in the expression of TRX, SODs and catalase could be observed. Interestingly, we observed a 20% reduction in TRX activity upon glucose stimulation compared to cells treated with control media. These findings are consistent with the previously published data on human peritoneal biopsies. Beyond, we demonstrated a dose-dependent increase in ROS production and increase in oxidative DNA-damage. However, ROS production and oxidative DNA damage could be prevented upon pre-incubation with the ROS-scavenger N-acetylcysteine (NAC).

Conclusion
Here, we show that enhanced levels of ROS and oxidative DNA damage due to glucose induced TXNIP expression could be diminished using ROS scavengers. These findings show that further antioxidative substances may be potential drugs, which could also be potential drug candidates for use in clinical practice to treat PD patients.
#2633 ROLE OF INTRAVENOUS ASCORBIC ACID IN THE MANAGEMENT OF ANEMIA IN HEMODIALYSIS PATIENTS
Authors: El Shinnawy Howayda , Alghitany Ahmed , Ishak Marina , Khedr Abdelrahman , Attallaha Aber 
Published: June 2023

Abstract

Background and Aims
Patients with end-stage kidney disease (ESKD) suffer from functional iron deficiency where despite the presence of sufficient iron stores in the body, adequate iron is unavailable for heme synthesis. This study hypothesis was that in patients undergoing hemodialysis (HD), administration of intravenous (IV) ascorbic acid (AA) exerts a good effect on the management of anemia, either by increasing the mobilization of iron from tissue stores or acting as an antioxidant to overcome the inflammatory block and increase the erythropoietin sensitivity.

Method
Fifty patients with ESRD who were on regular HD were included in the study. Patients’ ferritin levels ranged from 500 to 1200 ng/mL with transferrin saturation of 30% or more. However, all patients were anemic and received erythropoietin therapy. Iron therapy was discontinued in the first group, whereas it was continued in the second group that received IV AA.

Results
A significant increase in the levels of Hb was observed in the second group after 6 months despite the decrease in ferritin levels in both the groups. Transferrin saturation decreased in both groups, the decrease being more in the first group. The levels of C-reactive protein (CRP) decreased in the second group, whereas these increased in the first group.

Conclusion
Intravenous AA as an adjuvant therapy with iron exerts a favorable and significant effect on the Hb, serum ferritin, and CRP levels in patients with ESKD having anemia. The discontinuation of iron therapy only decreases the serum ferritin levels and does not improve the Hb or CRP levels.
#2634 ROLE OF LIGHT CHAIN CLEARANCE IN THE RECOVERY OF RENAL FUNCTION IN MULTIPLE MYELOMA: ANOTHER POINT OF VIEW
Authors: Liébana Marc Patricio , Senin Alicia , Azancot Maria , Gironella Mercedes , Gaibor Néstor Toapanta , Garcia Sheila Bermejo , Martin Lucia , Caravaca-Fontán Fernando , Pérez-Ávila Clara Cuéllar , Martínez-López Joaquin , Rodríguez-Garcia Eva , Matamoros Oriol Bestard , Romeo Maria José Soler , Terrades Natàlia Ramos 
Published: June 2023

Abstract

Background and Aims
Acute Kidney Injury (AKI) in patients with multiple myeloma (MM) requiring renal replacement treatment (RRT) is associated with high morbidity and mortality. Early reduction of serum free light chains (FLC) using both targeted therapy against MM and intensive hemodialysis (IHD) may improve renal outcomes. We evaluated the effectiveness of two different RRT techniques on renal recovery in a MM patient population: standard dialysis procedure versus IHD with either PMMA or hemodiafiltration with endogenous reinfusion (HFR).

Method
Multicentric retrospective study with severe AKI related to MM, between 2011 and 2018. Twenty-five consecutive patients with AKI secondary of MM requiring RRT were included. Patients that underwent IHD received 6 dialysis sessions per week during the first 14 days (PMMA vs HFR). All patients were diagnosed with de novo MM or first relapsed MM. Primary outcome was renal recovery defined as dialysis-free at six months follow-up.

Results
A total of 25 patients were included. Seventeen patients received IHD and 8 standard dialysis. All patients were treated with targeted therapy, 84% bortezomib-based. Of the 25 patients included, fourteen (56%) became dialysis independent. We observed a higher proportion of patients who received IHD in the group who recovered kidney function compared to those who remained in HD (92.9% vs 36.4%, p:0.007). In our study, the use of IHD to remove FLC had a statistically significant association with renal recovery compared to standard dialysis group (p = 0.024).

Conclusion
Early reduction of FLC with IHD as an adjuvant treatment along with MM targeted therapy may exert a positive impact on renal recovery.
#2635 ASSOCIATION BETWEEN PLASMA LYSO-GB3 LEVELS AND BONE MINERAL DENSITY IN PATIENTS WITH FABRY DISEASE
Authors: Nose Yuma , Fujii Hideki , Goto Shunsuke , Kono Keiji , Okamoto Hayaki , Watanabe Kentaro , Nishi Shinichi 
Published: June 2023

Abstract

Background and Aims
Fabry disease is a rare X-linked genetic disorder that contributes to various clinical manifestations including cardiac hypertrophy, renal dysfunction, cerebrovascular disease, angiokeratoma, and anhidrosis. Several previous reports showed that male patients with Fabry disease had decreased bone mineral density (BMD). However, the association of BMD with clinical characteristics and biomarkers of organ damage in patients with Fabry disease has not been sufficiently studied. Therefore, we aimed to investigate their associations in patients with Fabry disease.

Method
Patients with Fabry disease who attended our hospital from January 2008 to June 2021 were included in this study. Patients without enough clinical and laboratory data were excluded from the present study. The remaining fifteen patients were assessed in this study. We examined clinical characteristics, biomarkers including blood globotriaosylsphingosine (lyso-Gb3) levels, and BMD, and compared them between male and female patients. We measured the lumbar spine and femoral BMD by dual-energy bone X-ray absorptiometry and calculated the Z-score. Furthermore, we also examined ΔBMD, defined as the two-year change in the Z-score, for ten patients who underwent BMD measurement before and after starting ERT. Because two patients already had received ERT, two did not undergo BMD measurement, and one took an anti-osteoporotic agent, they were excluded from the analysis.

Results
Both lumbar spine BMD and femoral BMD decreased in male patients, while they were preserved in female patients (lumbar spine Z-score: -1.9 ± 2.0 versus 0.8 ± 0.8, p &lt; 0.05; femoral Z-score: -1.0 ± 1.4 versus 0.6 ± 0.6, p &lt; 0.05) among all the study patients. Lumbar spine and femoral BMD showed a significantly negative correlation with blood lyso-Gb3 levels. Moreover, blood lyso-Gb3 levels were significantly correlated with the lumbar spine BMD (r = -0.92; p &lt; 0.01) and femoral BMD (r = -0.91; p &lt; 0.01) in male patients. On the other hand, there was no significant correlation of blood lyso-Gb3 levels with the lumbar spine BMD (r = 0.66, p = 0.18) and femoral BMD (r = 0.11; p = 0.99) in female patients. After starting ERT, blood lyso-Gb3 levels were significantly reduced in both male and female patients. The lumbar spine ΔBMD in male patients improved whereas that in female patients remained unchanged despite no changes in kidney function and serum calcium and phosphate levels.

Conclusion
Our findings suggested that lumbar spine BMD and femoral BMD decreased in male patients with Fabry disease possibly due to the deposition of lyso-Gb3 in bone tissue and ERT could improve BMD in these patients.
#2648 IMPACT OF ACUTE AND CHRONIC KIDNEY FUNCTION ON THE SIZE AND PROGNOSIS OF ISCHEMIC STROKE AFTER THROMBECTOMY
Authors: Bobot Mickaël , Hak Jean-François , Burtey Stephane , Doche Emilie , Suissa Laurent 
Published: June 2023

Abstract

Background and Aims
Patients with Chronic Kidney Disease (CKD) have an increased risk of ischemic and haemorrhagic stroke and CKD seem associated with worse outcome after a stroke. Few studies specifically investigated the impact of mechanical thrombectomy on outcomes after an ischemic stroke. The main objectives of our study RISOTTO were to evaluate the influence of CKD (eGFR &lt; 60 mL/min/1.73m²) and Acute Kidney Injury (AKI) on the size of cerebral ischemic lesions and their outcome.

Method
Multicenter cohort study. Patients with at the acute phase of ischemic stroke following a large artery occlusion managed with mechanical thrombectomy were included. CKD was defined as eGFR &lt; 60 mL/min/1.73m² for more than 3 months, AKI by 2012 KDIGO score, infarcted volume by ASPECTS and functional prognosis at 3 month by modified Rankin Scale (mRS).

Results
296 patients were included. Sixty-three patients (22.8%) had CKD. In univariate analysis, patients with CKD had more white matter vascular lesions (Fazekas 1.7±0.8 vs. 1.0±0.8, p&lt;0.0001), had lower initial infarcted volume (ASPECTS 7.6±1.7 vs. 6.7±1.8, p = 0.003), for equivalent severity (NIHSS: 9.2±7.0 vs. 10.1±7.7, p = 0.404), had more thrombectomy failure (12.7% vs. 3.8%, p = 0.008) compared to non-CKD patients. At 3 months, CKD was associated with equivalent functional prognosis (mRS 3–6: 51.6% vs. 42.2%, p = 0.193) but higher mortality: 24.2% vs. 9.5%, p = 0.004. Forty-eight patients (19.6%) developed an AKI. AKI was associated with increased initial gravity (NIHSS 18.8±5.2 vs. 16.7±5.7, p = 0.014, equivalent stroke volume (ASPECTS 7.3±1.9 vs. 6.8±1.8, p = 0.254. At 3 months, CKD was associated with poorer functional prognosis (mRS 3–6: 64.6% vs. 39.4%, p = 0,002) and mortality: 25.0% vs. 8.4%, p = 0.003. In multivariate analysis, AKI appeared as a independent risk factor of poor neurological outcome (OR 2.16 [1.05-4.46], p = 0,036 and mortality: OR 2.47 [0.96-6.35], p = 0.059 at 3 month, as CKD was not.

Conclusion
CKD was associated with smaller initial ischemic lesions for equivalent neurological severity, and more recanalization failures. CKD was not an independent risk factor for mortality or poor functional prognosis at 3 months. CKD patients seem to benefit from thrombectomy and should not be contraindicated to this technique. AKI is associated with greater initial neurological severity, poorer functional prognosis and increased mortality at 3 months and is an independent risk factor for poor prognosis.
#2652 ANTIPROTEINURIC EFFECT OF SODIUM-GLUCOSE COTRANSPORTER 2 INHIBITORS IN GLOMERULAR AND SYSTEMIC DISEASES: A REAL-WORLD CLINICAL STUDY
Authors: Caravaca-Fontán Fernando , Stevens Kate , Kronbichler Andreas , Anders Hans Joachim , Floege Jürgen , Juarez Gema Maria Fernandez , Praga Manuel 
Published: June 2023

Abstract

Background and Aims
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have recently begun to be used in glomerular/systemic autoimmune diseases with glomerular involvement for the treatment of proteinuria, although the information on real-world clinical settings is very scarce.

Method
Retrospective, observational, international cohort study. Adult patients with biopsy-proven glomerular diseases were included. The main outcome was the percentage reduction in 24-hour proteinuria from SGLT2i initiation to 3, 6, 9, 12 months. Secondary outcomes included percentage proteinuria reduction by type of disease and a reduction of proteinuria ≥30% from SGLT2i initiation.

Results
The study group consisted of 493 patients with a median age of 55 years. All patients were on renin-angiotensin system blockade. Geometric mean percentage change of proteinuria from baseline was –35%, –41%, –45% and –48% at 3, 6, 9 and 12 months after SGLT2i initiation, respectively. Geometric mean percentage change of eGFR was –6%, –3%, –8%, –10.5% at 3, 6, 9 and 12 months, respectively. Results were similar irrespective of the underlying disease. However, a significant correlation was found between body mass index (BMI) and percentage proteinuria reduction at last follow-up (R = –0.11; p = 0.02). By mixed-effects binomial logistic regression model, serum albumin at the onset of SGLT2i emerged as the main predictor of a ≥30% proteinuria reduction (odds ratio for albumin &lt;3.5 g/dl: 0.53; 95% CI 0.30–0.91; p = 0.02). Finally, a slower eGFR decline over time was observed in patients achieving a ≥30% proteinuria reduction: –3.7 versus –5.3 ml/min/1.73m2/year (p = 0.001).

Conclusion
The use of SGLT2i was associated with a significant reduction of proteinuria, irrespective of the underlying glomerular/systemic disease. This percentage change was higher in patients with higher BMI. Higher serum albumin at SGLT2i onset is associated with higher probability of achieving a ≥30% proteinuria reduction.
#2685 SLC34A2 EXACERBATES TUBULAR INTERSTITIAL FIBROSIS VIA INDUCTION OF APOPTOSIS AND CELL CYCLE ARREST IN S PHASE
Authors: Hu Liang-Shuan , Chang Sheng-Cheng , Tsai Chia-Hui , Wu Chun-Ching , Nguyen Phuong Thao Hoang , Chang Wei-Che , Chang Wei-Ya , Yang Ya-Chien , Jao Tzu-Ming 
Published: June 2023

Abstract

Background and Aims
Chronic kidney disease (CKD) is an urgent public health issue in the world. However, effective treatments for intervention of CKD remain undefined. Phosphate (Pi) is an essential element for synthesis of DNA, RNA, ATP, phospholipid membranes, and for regulation of phosphorylation/dephosphorylation, cellular signaling and metabolic pathways. Solute carrier family 34 (SLC34) is responsible for Pi absorption in the small intestine. However, the role of SLC34 in progression of CKD is still unknown.

Method
A membrane protein, solute carrier family 34 member 2 (SLC34A2), was discovered by using big data mining from the National Center for Biotechnology Information (NCBI). SLC34A2 was overexpressed in human proximal tubular cells, HK-2, by Lipofectamine 3000. RNA sequencing was carried out to uncover SLC34A2-mediated signaling pathways by using Illumina platform. Apoptosis was evaluated by Annexin V-PI staining and TEUNEL assay in cells and mouse kidneys, respectively. Cell cycle was measured by flow cytometry. Unilateral ureteral obstruction (UUO) and bilateral renal ischemia-reperfusion injury (bIRI) were employed to generate CKD mouse models.

Results
By using big data mining from the NCBI, we identified a membrane protein, SLC34A2, was upregulated in various types of nephropathies including diabetic nephropathy, focal segmental glomerulosclerosis, minimal change disease, ANCA-associated vasculitis. Overexpression of SLC34A2 suppressed viability of HK-2 cells. RNA sequencing revealed that apoptosis and cell cycle are high scored pathways modulated by SLC34A2. The results were further verified in HK-2 cells. Ectopic SLC34A2 promoted apoptosis via downregulation of BCL-2. Moreover, SLC34A2 induced cell cycle arrest in S phase via downregulation of CDK2. CKD mouse models of UUO and bIRI were carried out to confirm in vitro findings. In mice kidneys, the expression of Slc34a2 in UUO and bIRI groups was superior to that in sham groups. Enriched Bax and TUNEL-positive cells were observed in the fibrotic kidneys of mice. Moreover, increased expression of p21 and downregulated Cyclin A2 in the fibrotic kidneys further confirmed that Slc34a2 induced cell cycle arrest in S phase.

Conclusion
Slc34a2 induced apoptosis and halted cell cycle in S phase, resulting in subsequent tubulointerstitial fibrosis in mice. Our results suggest that targeting SLC34A2 might be a promising strategy for intervention of CKD.