bluuebunny/crossref_metadata_2025_split huggingface dataset:
PS-B08-8: THERAPEUTIC STRATEGIES TARGETING RAGE IMPROVES RENAL OUTCOME IN LUPUS NEPHRITIS
Authors: Taguchi Kensei , Ito Sakuya , Yokota Yunosuke , Kodama Goh , Higashimoto Yuichiro , Fukami Kei 
Published: January 2023

Introduction:
Lupus nephritis (LN) is present in 60% of patients with systemic lupus erythematosus (SLE). Despite of current development of immunosuppressant agents, LN still impairs the survival and quality of life in SLE patients. Receptor for advanced glycation endproducts (RAGE) is a multi-ligand receptor that belongs to the immunoglobulin superfamily, which is strongly associated with innate immune system. In the present study, we examined whether RAGE is involved in the development of LN. Further, we explored the therapeutic impact of DNA-aptamer directed against RAGE on lupus-related kidney injury.

Methods:
[Protocol 1] RAGE expression in kidneys and urinary RAGE excretion (uRAGE) were determined at 8, 12, 16, 18, 20-week-old by real-time PCR and ELISA, respectively in MRL/lpr, SLE-prone mice. [Protocol 2] LN was induced by peritoneally injecting pristane in wild type and RAGE globally knockout mice. [Protocol 3] MRL/lpr mice were subcutaneously administrated with DNA-aptamer raised against RAGE (RAGE-apt) or Control-aptamer (Ctrl-apt) for 10weeks.

Results:
[Protocol 1] uRAGE levels, but not urinary protein excretion, were significantly increased in 8-week-old MRL/lpr mice when compared to those in control MRL/MPJ mice, suggesting that uRAGE could be an early marker of LN.. Immunofluorescence staining demonstrated that RAGE was upregulated in distal tubules but not in glomerulus in 8-week-old mice. Glomerular RAGE expression was increased from 12-week-old with mesangial matrix expansion and formation of cellular crescents. RAGE expression was also found in endothelium and infiltrated macrophages in glomerulus while RAGE was merged with cathepsine D, a lysosomal aspartyl protease, and Rab7, a marker of late endocytosis in tubular epithelial cells. [Protocol 2] Pristane-induced increase in systolic blood pressure was reduced with improvement of renal dysfunction in RAGE knockouts. RAGE knockouts also showed less fibrosis with decrease in macrophage infiltration when compared to wild type mice in pristane-induced lupus nephritis. [Protocol 3] Administration of RAGE-apt ameliorated mesangial expansion, crescent formation, and macrophage infiltration into glomerulus in MRL/lpr mice. RAGE-apt, but not Ctrl-apt, reduced the level of pro-inflammatory cytokines gene expression including IL-6, TNF-α, and MCP-1 in renal cortex of MRL/lpr mice.

Conclusion:
RAGE could be involved in the pathogenesis of LN, and RAGE-DNA aptamer might be one of the promising therapeutic strategies for preventing the development of LN.
PS-B08-13: PLASMIN INHIBITION ALLEVIATES HYPERTENSION AND PODOCYTE INJURY IN DAHL SALT-SENSITIVE RATS
Authors: Deng Qinyuan , Kakizoe Yutaka , Iwata Yasunobu , Nakagawa Terumasa , Miyasato Yoshikazu , Nakagawa Miyuki , Nishiguchi Kayo , Nagayoshi Yu , Adachi Masataka , Narita Yuki , Izumi Yuichiro , Kuwabara Takashige , Tsuda Yuko , Mukoyama Masashi 
Published: January 2023

Objective:
The epithelial sodium channel (ENaC) in the kidney plays pivotal roles in blood pressure regulation, and the γ subunit is activated by extracellular serine proteases. In proteinuric renal diseases, plasmin filtered through injured glomeruli proteolytically activates γENaC. In addition, filtered plasmin directly causes podocyte injury. We previously reported that Dahl salt-sensitive (DS) rats fed a high-salt (HS) diet developed severe hypertension and proteinuria together with γENaC activation, and that a synthetic serine protease inhibitor, camostat mesilate, mitigated these changes. However, the role of plasmin in DS rats remains unclear. In this study, we evaluated the relationship between plasmin and hypertension as well as glomerular injury and the effects of plasmin inhibitors in DS rats.

Design and method:
Five-week-old male DS rats were divided into normal-salt (NS) diet, HS diet, and HS + plasmin inhibitors [tranexamic acid (TA, 2 mg/mL TA in drinking water) and synthetic plasmin inhibitor YO-2 (4 mg/kg/day, intraperitoneal injection)] groups. After systolic blood pressure measurement and 24-h urine collection over time for 5 weeks, the rats were sacrificed for biochemical examination.

Results:
The HS group displayed severe hypertension and proteinuria together with activation of plasmin in urine and γENaC in the kidney, which were not attenuated by TA. On the other hand, YO-2 mitigated both hypertension and proteinuria [SBP (mmHg): NS, 130.8 ± 7.5; HS, 209.0 ± 14.2; HS+YO-2, 183.8 ± 8.4; Urinary protein (mg/day): NS, 15.4 ± 3.2; HS 259.0 ± 129.3; HS+YO-2, 94.5 ± 31.5]. YO-2 inhibited the attachment of plasmin(ogen) to podocytes and alleviated podocyte injury by reducing glomerular apoptotic cells. Furthermore, YO-2 suppressed the upregulation of protease-activated receptor-1 and phosphorylated ERK1/2 as well as mRNA expression of inflammatory and pro-fibrotic cytokines in the kidney.

Conclusion:
These results indicate that plasmin plays important roles in the development of salt-sensitive hypertension and glomerular injuries in a rat model of hypertension, and suggest that plasmin inhibition could be a potential therapeutic strategy against salt-sensitive hypertension.
PS-B09-3: EXAMINATION OF ALBUMINURIA REDUCTION EFFECT THROUGH IMPROVEMENT OF ENOS UNCOUPLING BY SGLT2 IN TYPE 2 DIABETIC MICE
Authors: Iwakura Tsukasa , Kondo Megumi , Kidokoro Kengo , Kashihara Naoki 
Published: January 2023

Background and Aims:
One of the main mechanisms of the renoprotective effects of SCLT2is in DKD is considered the ability of these inhibitors to improve glomerular hyperfiltration. We previously demonstrated that the adenosine/adenosine A1 receptor pathway played a pivotal role in the tubuloglomerular feedback(TGF) system in a type 1 diabetic model, Akita mice (Circulation, 2019). We also reported that the uncoupling of endothelial nitric oxide (NO) synthase (eNOS) via oxidation of tetrahydrobiopterin (BH4), a cofactor required for NO production, played a major role in generation of oxidative stress (AJPRP, 2005; JASN, 2013). In the present study, we explored the renal protective effects of SGLT2 inhibition, with a focus on glomerular oxidative stress and glomerular hemodynamics.

Methods:
This study used type 2 diabetic db/db mice and db/m+ mice as a control (male, 8wk old). In the first experiment, we measured the glomerular filtration rate of single nephrons (SNGFRs) using in vivo imaging technique in 12 wk-old db/db and db/m+ mice to confirm glomerular hyperfiltration. Next, we evaluated the SNGFRs change before and after the administration of a single dose of canagliflozin (CANA) (10 mg/kg). The SNGFRs, glomerular permeability of macromolecules, glomerular reactive oxygen species (ROS) and NO production, and tetrahydrobiopterin (BH4) level in serum and kidney were evaluated after the CANA treatment for 8 wk. Finally, human glomerular endothelial cells (hGECs) were exposed to normal glucose (5 mmol/L), high glucose (30 mmol/L of D-glucose), or a hyperosmotic control (5 mmol/L of D-glucose plus 25 mmol/L of L-glucose) in the presence or absence of CANA (10umol/L).

Results:
The CANA treatment ameliorated glomerular hyperfiltration in the db/db mice. In the db/db mice, glomerulus ROS production increased, and NO production decreased as compared with the levels in the control mice. CANA improved the imbalance between ROS and NO production. The serum and kidney concentrations of BH4 declined in the non-treated db/db mice, whereas the CANA treatment preserved the BH4 level. Leakage of 70-kD FITC-labeled albumin into the urinary space was observed in the db/db mice. The CANA treatment reduced the amount of FITC-labeled albumin in the urinary space of the db/db mice. The CANA treatment also alleviated vascular endothelial damage in glomeruli. BH4 levels decreased in the hGECs exposed to high glucose. CANA did not improved BH4 level in the hGECs exposed to high glucose.

Conclusions:
SGLT2i improved glomerular ROS/NO imbalance by suppressing eNOS uncoupling of glomerular endothelial cells in type 2 diabetic mice.
PS-B09-7: NON-DIPPER BLOOD PRESSURE CAUSED BY INTERMITTENT HYPOXIA AND ITS POSSIBLE MECHANISM IN THE KIDNEY
Authors: Ueda Kohei , Yeerbolati Alimila , Lijuan Liang , Ogura Sayoko , Takase Mai , Goda Nobuhito , Shimosawa Tatsuo 
Published: January 2023

Background:
Non-dipper, less than 10% decrease of blood pressure in nighttime than daytime, is one of the strongest risk factor of cardiovascular diseases among hypertensive disorders. High prevalence of non-dipper among patients of sleep-apnea syndrome suggests intermittent hypoxia in nighttime as the mechanism of non-dipper, although it is still to be revealed.

Purpose:
To identify the mechanism of non-dipper caused by intermittent hypoxia in nighttime.

Method:
C57Bl/6-background male mice were kept under 8AM-8PM of light and 8PM-8AM dark cycle in closed air-conditioned system which could decrease the O2 level from 21% room air to 5% every 3 minutes. Mice were divided into two groups, normoxia (NX) or intermittent hypoxia (IH), and were kept for two weeks under room air thoroughly or under the IH only during 8 AM to 5 PM respectively. The mice were euthanized at 12PM and kidneys were obtained. Blood pressure (BP) of left carotid artery was recorded by radio-telemetry during the latter one week. To evaluate diurnal change in BP, BPs of 8AM-5PM (inactive) and 5PM-8AM (active) were compared in each of NX and IH mice. Kidney lysate was fractionated by ultracentrifuge to obtain membrane fraction of protein.

Result:
BP of NX mice in the active phase was significantly higher than the inactive phase, although such diurnal change was not observed in IH mice, demonstrating a development of non-dipper pattern by IH. In the kidney lysates, membrane protein expression levels of phosphorylated-Na+-Cl- cotransporter (NCC) and Na + -K+-Cl- cotransporter 2 (NKCC2) were significantly increased in IH mice compared to NX mice, but those of full-length and cleaved form of ENaCα were not changed. Transcriptional expression levels of Sgk1, Gilz, Per1/2 and Cry1/2 were significantly increased and those of Bmal1 and Clock were decreased in IH mice compared to those of NX mice.

Conclusion:
These data suggest that defect in molecular clock of the kidney and sodium reabsorption augmented by NCC and/or NKCC2 in the kidney contributes to the development of non-dipper.
PS-C18-2: BODY MASS INDEX TRAJECTORY AND TECHNIQUE FAILURE OR DEATH IN PATIENTS INITIATING PERITONEAL DIALYSIS
Authors: Kojima Daiki , Uchiyama Kiyotaka , Hama Eriko Yoshida , Nagasaka Tomoki , Kusahana Ei , Nakayama Takashin , Morimoto Kohkichi , Kanda Takeshi , Washida Naoki , Itoh Hiroshi 
Published: January 2023

Objective:
A decreased body mass index (BMI) over time, as a nutritional status marker, is associated with the poor prognosis of patients undergoing hemodialysis; however, this association has not been studied in patients with peritoneal dialysis (PD). Thus, this study aimed to evaluate the association between BMI trajectory and survival of patients initiating PD.

Design and Method:
BMI trajectory was defined as percent changes in BMI before PD catheter insertion until six months after insertion. The association of BMI trajectory with technique failure or all-cause death at six months after PD catheter insertion until October 2021 was analyzed.

Results:
This retrospective cohort study included 122 patients (aged 61.1 ± 12.1 years; 90 males) who underwent PD catheter insertion between January 2008 and March 2020. The median follow-up period was 43.1 (interquartile range, 21.2 - 78.8) months. The mean 6-month percent change in BMI was - 1.98% ± 6.91%, and patients were categorized into tertiles based on BMI trajectory. The adjusted Cox regression analysis for age, sex, Charlson comorbidity index, estimated glomerular filtration rate, and geriatric nutritional risk index revealed a significantly higher rate of technical failure or all-cause mortality (hazard ratio, 2.48; 95% confidence interval: 1.41 - 4.37) in patients with the lowest tertile (T1, BMI trajectory: < - 4.13%) compared to patients with middle tertile, the reference group (T2, BMI trajectory: - 4.13 - 0.67%). The risk was not significantly higher in patients with the highest tertile (T3, BMI trajectory: > 0.67%) than T2 group (hazard ratio: 1.18; 95% confidence interval: 0.66 - 2.11).

Conclusions:
A decreased BMI (not increased) over time is independently associated with technique failure or all-cause death among patients initiating PD, highlighting the importance of BMI trajectory as a novel prognostic marker. Moreover, further studies are warranted to investigate the interventions, including BMI optimization, as a novel therapeutic target to improve technique and patient survival.
PS-C20-11: ANTIHYPERTENSIVE TREATMENT IMPROVES LEFT VENTRICULAR DIASTOLIC FUNCTION AND INDICES OF ARTERIAL STIFFNESS IN YOUNGER MEN WITH GRADE 1 HYPERTENSION
Authors: Jedrzejewski Dawid , McFarlane Ewan , Lacy Peter , Williams Bryan 
Published: January 2023

Background:
Hypertension is a major risk factor for diastolic dysfunction which, once established, is essentially irreversible. However, it is unclear whether early manifestations of diastolic dysfunction in younger people with mild hypertension can improve with antihypertensive treatment.

Objectives:
Evaluate whether one-year antihypertensive treatment in younger men (age < 55 years) with low-risk (no evidence of hypertension mediated organ damage) grade 1 hypertension improves diastolic function and indices of arterial stiffness.

Methods:
105 treatment-naive men (mean age: 47 ± 6 years) with grade 1 hypertension (confirmed on ABPM) were recruited. Patients were randomised using a PROBE design to one-year antihypertensive treatment (ARB and/or CCB) or no treatment (control). Cardiac function was assessed at baseline and study end via 1.5-Tesla cMRI (MAGNETOM Avanto; Siemens Healthineers AG, Germany) using prospectively gated mid-left-ventricular golden angle tissue phase mapping (primary outcome). Arterial stiffness was measured using CAVI device (VS-1500N; Fukuda Denshi, Japan).

Results:
Diastolic (longitudinal E/A ratio) and systolic (longitudinal S peak velocity) function improved with treatment (n = 38; 0.11 ± 0.24 and 0.38 ± 1.19 cm.s−1, P = 0.01 and 0.05, respectively) but deteriorated in the control group (n = 44; -0.06 ± 0.33 and -0.13 ± 1.12 cm.s−1, P = 0.01 and 0.05, respectively). Improvement in diastolic function was significantly influenced by baseline bodyfat % and BMI (20 ± 8 versus 27 ± 10%, P = 0.04 and 27.8 ± 3.4 versus 31.0 ± 5.3 kg.m−2, P = 0.03, respectively). CAVI pre-ejection period (-9 ± 15 versus 1 ± 13 ms, P = 0.006), pre-ejection-period.ejection-time−1 (-0.03 ± 0.06 versus 0.00 ± 0.05, P = 0.02), upstroke time (-33 ± 50 versus -8 ± 45 ms, P = 0.03), pulse wave velocity (-0.89 ± 0.64 versus -0.02 ± 0.64 m.s−1, P < 0.001), CAVI (-0.40 ± 0.65 versus 0.03 ± 0.62, P = 0.005) and CAVI estimated vascular age (-3 ± 7 versus 1 ± 7 years old, P = 0.02) all improved with TREATMENT (n = 40) versus CONTROL (n = 44).

Conclusions:
Early treatment of Grade 1 hypertension improves left ventricular diastolic function. Treated patients with E/A improvements were leaner, which highlights the importance of a healthy lifestyle. Treatment also improved arterial stiffness, however it is unclear whether those changes were predominantly structural and/or functional. Further work is warranted to establish whether an even earlier intervention is needed to restore diastolic function to the level of normotensive age-matched controls.
PS-C23-2: GUT MICROBIOTA AND SUBCLINICAL CORONARY ARTERY CALCIFICATION IN A GENERAL POPULATION OF JAPANESE MEN
Authors: Okami Yukiko , Arima Hisatomi , Kondo Keiko , Hexun Zhang , Yano Yuichiro , Kadota Aya , Torii Sayuki , Hisamatsu Takashi , Fujiyoshi Akira , Kadowaki Sayaka , Watanabe Yoshiyuki , Ando Akira , Nakagawa Yoshihisa , Ueshima Hirotsugu , Miura Katsuyuki 
Published: January 2023

Objective:
The gut microbiota of patients with coronary artery disease is being shown to differ from that of healthy individuals. However, it is unclear whether it is altered before the onset of the disease. The aim of this study is to investigate the association between gut microbiota and subclinical coronary artery calcification (CAC) in general Japanese men.

Design and method:
We randomly selected men from the general Japanese population, who underwent computed tomography and gut microbiology tests between 2010 and 2016. Among participants who underwent both tests, excluding those with myocardial infarction history, leaving a sample size of 653 participants in the analysis. DNA was extracted from fecal samples, the bacterial 16S ribosomal RNA gene was amplified using a two-step tail polymerase chain reaction method, and DNA sequencing was performed on a MiSeq System, followed by data analysis using QIIME2 algorithm. Agatston scores > = 100 was defined as the presence of CAC. LEfSe identified different taxa between with and without CAC, and Poisson regression analysis examined them when logarithmic LDA score was > = 3.5 and phylogenetic levels > = 3. Each taxon was ranked in quartiles (Q1–4) and the relative risk (RR) of CAC was calculated. Adjustment factors were age, smoking, drinking, body mass index, use of medication to treat hypertension, dyslipidemia, or diabetes, and history of cardiovascular events. Sensitivity analysis also delimited Agatston scores by 0 or 10.

Results:
Mean age of the participants was 68.3 years, and 215 (32.9%) participants had a CAC score > = 100. Relative abundance of phylum level was 55.1% and 53.2% for Firmicutes, and 32.4% and 34.3% for Bacteroidetes among participants with versus without CAC score > = 100, respectively. Among taxa identified by LEfSe, Poisson regression analysis revealed the genus Bacteroides was inversely associated and genus Ruminococcus was positively associated with CAC after multivariable adjustment (Bacteroides: RR [95%CI] = 0.62 [0.45–0.86] (Q4) vs. ref (Q1)) (Ruminococcus: RR [95%CI] = 1.69 [1.25–2.29] (Q4) vs. ref (Q1)). Sensitivity analysis showed similar results.

Conclusions:
The ratio of Firmicutes to Bacteroidetes was high from the beginning of atherosclerosis. Higher genus Ruminococcus and lower genus Bacteroides were associated with a CAC score > = 100 in general Japanese men.
PS-C23-10: STUDY TO ASSESS THE TYPE OF MEAL SKIPPED AND CHOICE OF FOOD OUTLET (FOOD OUTSIDE HOME) BY COLLEGE GOING GIRLS
Authors: Sahu Poonam 
Published: January 2023

Background:
Obesity and hypertension are important public health issues. Most of the population does not consume the recommended daily amount of fruit and vegetables, nuts, and seeds. It has been shown that after the transition from adolescence to young adulthood, when independency increases, young adults are continuously challenged to make unhealthy food choices.

Aim:
To assess the type of meal skipped and choice of food outlet (food outside the home) by college-going girls.

Material & Method:
This study was conducted on 96 college-going girls between the age group of 18–25 years who were selected by a random sampling method. The data was collected with the help of a questionnaire.

Results:
Results showed that 30% of girls skipped their breakfast while 22% skipped their lunch and 26% were not skipping any of their meals. It was found that 43% of the college-going girls chose to eat food in the canteen during the college hours while 41% chose to eat in the cafeteria/ restaurant.

Conclusion:
The skipping of meals and consumption of food in food outlets (food outside the home) seem to contribute to reducing the consumption of nutrient dense food because majority of college canteens have few choices of healthy food options. Hence, this can lead to obesity, and the pathway from obesity to hypertension will most likely become one of the major health issues of twenty-first century.
PS-C26-8: UNIQUE PROPERTIES OF DEPRESSOR, RENAL, AND ALDOSTERONE RESPONSES TO ALISKIREN THERAPY IN HYPERTENSIVE PATIENTS WITH NEPHROPATHY
Authors: Saita Mitsuhiko 
Published: January 2023

Objective:
Blood pressure (BP) control using renin-angiotensin system (RAS) inhibitor as a first choice is recommended in hypertension accompanied by chronic kidney disease (CKD), and RAS localized in the kidney is known to exist independent of circulating RAS. Aliskiren, direct renin inhibitor (DRI), is most excellent in kidney tissue migration among RAS inhibitors despite it has been reported to cause aldosterone breakthrough like angiotensin II receptor blocker (ARB) in essential hypertension. Therefore, DRI-induced antihypertensive, renoprotective and aldosterone-suppressing effects were investigated as compared to those of ARB in hypertensive CKD patients.

Design and method:
168 hypertensive patients with CKD (stage G1–4) were employed in this study. Home BP in the morning, estimated glomerular filtration rate (eGFR), urinary protein/creatinine ratio (UPCR), urinary liver-type fatty-acid-binding protein (U-LFABP) as an indicator of tubular dysfunction, plasma and urinary aldosterone concentration (PAC and UAC) were measured before and 0.5 to 5 years after administration of ARB or DRI and assessed retrospectively. Aldosterone breakthrough was defined as any increase in PAC from the baseline level following treatment with a RAS inhibitor.

Results:
In ARB-treated group, BP and UPCR decreased significantly at 6 months, but sufficient declines were not observed 1st year onward. In DRI-treated group, a significant reduction in BP was sustained until 3 years and BP unchanged decreasing tendency even 4 years later, meanwhile UPCR decreased significantly for 2 years and was below the pretreatment value 3 years after. ARB raised BP and UPCR again in patients with CKD G3–4 prior to those with CKD G1–2, however, DRI expressed no difference between stages. Although PAC diminished up to 6 months in ARB group and 1 year in DRI group, it turned up 1 year and 2 years after, respectively. PAC-ascensive rate and maximum elevation in PAC were higher and greater in ARB group than in DRI group (48.7 vs 22.6%, 56.1 vs 29.3pg/ml). All significant differences in rising PAC cases disappeared by 5 years, whereas in non-rising PAC cases, only DRI reduced U-LFABP without deterioration in eGFR and UAC further lowered while PAC was maintained.

Conclusions:
In comparison with ARB, aliskiren prolongs hypotensive and proteinuria-lowering effects with retained eGFR regardless of CKD severity possibly via improvement of tubular disorders and less PAC reascent in hypertensive nephropathy. Aliskiren given to CKD patients might elicit mild and delayed aldosterone breakthrough rather than ARB due to a direct action against aldosterone derived from the kidney.