bluuebunny/crossref_metadata_2025_split huggingface dataset:
PS-R04-7: UNSOLVED CASE OF RESISTANT HYPERTENSION: A CHALLENGING ISSUE IN A DEVELOPING COUNTRY
Authors: Tiksnadi Badai Bhatara , Jungjunan Ridho 
Published: January 2023

Introduction:
It is difficult to find a definite etiology of resistant hypertension (RH) in developing countries due to limited resources. We present a case report and discuss RH's diagnosis and treatment approaches, which we suspected owing to Obstructive Sleep Apnea (OSA) after extensive assessment, including nuclear imaging and renal arteriography.

Case presentation:
A 58-year-old female was referred to Hasan Sadikin General Hospital for RH assessment. Having conducted ambulatory blood pressure monitoring and echocardiography, which suggested hypertensive heart disease, we confirmed the diagnosis of RH in this patient. The patient has a 4-year history of hypertension, accompanied by throbbing headaches and snores. She underwent percutaneous coronary intervention two years ago due to angina. During the physical examination, she was fully alert with a blood pressure of 170/90 mmHg and a heart rate of 62 times/minute, mild exophthalmos, and cardiomegaly. Her renal (including proteinuria), and thyroid function were within normal limits. Echocardiography revealed concentric left ventricular (LV) hypertrophy with normal LV systolic function. An abdominal Computed Tomography indicated pheochromocytoma or adrenal tumor. Metanephrines examination was not feasible due to cost issues. Using metaiodobenzylguanidine scan (Tc-99 and I-131), nuclear imaging failed to establish diagnosis of pheochromocytoma. Renal artery ultrasonography increased the suspicion of renal artery stenosis; however, renal arteriography showed mild renal artery stenosis. We referred the patient to a neurologist for OSA screening, from STOP-Bang questionnaire result indicated that the patient was likely to have OSA. Unfortunately, the diagnosis was inconclusive due to unavailability of polysomnography facility. The unavailability of minoxidil, renal denervation and continuous positive airway pressure (CPAP) hinders the optimal treatment in this patient. The blood pressure target remains unachievable despite Amlodipine 1x10 mg, candesartan 2x16 mg, bisoprolol 1x10 mg, tamsulosin 1x400 mg, spironolactone 1x50 mg, dan isosorbide mononitrate 2x2.5 mg consumption. The unavailability of chromatography-mass spectrometry for evaluation of medication adherence was also a significant limitation.

Conclusion:
This case showed that the blood pressure remains uncontrolled despite six different medications, which may be due to the untreated etiology of secondary hypertension. Furthermore, although extensive examinations have been performed, a definite diagnosis could not be made due to cost/facility issues for other diagnostic approach. To further complicate matters, the evaluation of medication adherence and optimal treatment were not available. Therefore, RH remains a challenging issue in developing countries.
PS-R05-2: ESAXERENONE AMELIORATES EGFR DETERIORATION AND URINE PROTEIN SECRETION IN DIABETES MELLITUS (DM) NEPHROPATHY: LONG TIME FOLLOW-UP
Authors: Yamazaki Osamu , Yasukawa Minoru , Ochiai Fumika , Morimoto Chikayuki , Asakawa Shinichiro , Nagura Michito , Arai Shigeyuki , Tamura Yoshifuru , Fujigaki Yoshihide , Shibata Shigeru 
Published: January 2023

Introduction:
Mineralocorticoid antagonist (MRA) not only reduce cardiovascular event, but also may have the probable renoprotective events, likewise other RAAS inhibitors. Here we experienced that esaxerenone ameliorates eGFR deterioration and urine protein secretion in severe DM nephropathy.

Patient Presentation:
72-years-old, Female. She referred to our hospital in order to investigate DM retinopathy. She already had DM nephropathy (Cr 0.95 mg/dL, eGFR 44.4 mL/min/1.73m2) with severe urine protein (11.2 g/gCre), and eGFR was decreased -10 mL/min/1.73m2 per year. We started esaxerenone with conventional therapy using ARB. After initiation of esaxerenone, eGFR decreasing rate was significantly ameliorated (eGFR: -4 mL/min/1.73m2 per year). In addition, urinary protein levels were decreased by as much as 98% (urinary protein levels after the initiation were 0.25 g/gCre).

Discussion:
Esaxerenone may have the additional renoprotective effect with conventional RAAS therapy. The evidence on renoprotective effects of MRA will be reviewed along with the case presentation.
PS-R05-3: SEVERE GLOMERULAR MICROANGIOPATHY IN A PATIENT WITH NEPHROTIC SYNDROME FOLLOWING TAKAYASU ARTERITIS
Authors: Yamashita Yuya , Kodama Goh , Ito Sakuya , Kaida Yusuke , Taguchi Kensei , Fukami Kei 
Published: January 2023

Introduction:
Takayasu arteritis (TA) is a large vessel inflammation that predominantly involves aorta and its main arteries. TA-caused kidney injury is known to be mainly due to renal artery stenosis. However, glomerulonephritis including membranous proliferative glomerulonephritis, focal segmental sclerosis, or crescentic nephritis has been histologically identified in some TA cases.

Case description:
A 69-year-old female presented with leg edema and refractory hypertension with nephrotic range proteinuria (17.0 g/gCr). She exhibited > 10 mmHg blood pressure discrepancy between left and right upper limbs and severe aortic regurgitation. Lab test showed high level of C-reactive protein and high erythrocyte sedimentation rate. Contrast-enhanced computed tomography identified wall thickening of the left subclavian artery, which led to the diagnosis of TA. Renal biopsy demonstrated that double basement membrane, enlarged subendothelial space, and mesangiolysis with no immunoglobulin deposition. Although azilsartan 40 mg QD and nifedipine 30 mg BID had been prescribed, systolic blood pressure (sBP) was still > 160 mmHg. Thus, while oral prednisolone was started to suppress TA-induced inflammation, azilsartan was replaced with sacubitril valsartan, an angiotensin receptor-neprilysin inhibitor (ARNI), for treating refractory hypertension. After a few weeks, sBP was decreased to 130 mmHg with sacubitril valsartan 200 mg QD and proteinuria was dramatically improved to 0.5 g/gCr.

Discussion:
TA commonly involves the renal artery, leading to stenosis and subsequent ischemic nephropathy. However, no stenosis and occlusion were observed in renal artery of this case. In addition, small vessel inflammation in the kidney such as vessel wall necrosis and immune cells infiltration around arterioles was not found. Serum levels of pro-inflammatory cytokines including vascular endothelial growth factor and interleukin-6, a well-known contributors for progression of TA-related inflammation, were within the normal range. The results indicate that TA-caused hypertension, but not vessel inflammation induced by TA, seems to play a pathological role for development of glomerular microangiopathy in this case. A previous study showed that 70% of TA patients presenting with glomerular lesion has severe hypertension and intimal thickening in renal arterioles was observed more frequently in TA patients presenting with glomerular lesion when compared to those without glomerulonephritis, which supports our hypothesis. In the present case, ARNI significantly reduced sBP which might directly contribute to the improvement of proteinuria. ARNI can be potent to control hypertension more effectively than conventional hypertensive agents in TA patients.
PS-R05-7: MALIGNANT PHASE OF HYPERTENSION IN A PATIENT ON PERITONEAL DIALYSIS
Authors: Vitkauskaite Monika , Maliukeviciute Indre , Rimsevicius Laurynas , Avizienyte Eleonora , Janusaite Marta Monika , Asakiene Egle , Miglinas Marius 
Published: January 2023

Background:
Posterior reversible encephalopathy syndrome (PRES) describes a disorder of abrupt onset neurological symptoms due to potentially reversible lesions on brain imaging. Case reports of PRES in PD patients are scarce.

Case presentation:
A 42-year-old male presented to the emergency department (ED) with two weeks of worsening occipital headaches, nausea, vomiting and dizziness. The patient had a background of end-stage renal disease due to primary focal segmental glomerulosclerosis, and resistant hypertension. He had been receiving peritoneal dialysis (PD) for one month; hypertension was treated with torasemide 100 mg/day, perindopril 10 mg/day, amlodipine 10 mg/day, moxonidine 0.6 mg/day, doxazosin 8–16 mg/day. One week earlier, he was brought into ED due to hypertensive crisis (blood pressure (BP) was 190/120 mmHg); intravenous labetolol 20 mg, oral moxonidine 0.4 mg, doxazosin 8 mg were administered; afterwards he was released for outpatient treatment.
On admission, BP was 187/114 mmHg, heart rate - 75 beats/minute, oxygen saturation - 98% on room air, and body temperature - 36.5°C. Laboratory tests revealed severe renal dysfunction (serum creatinine: 1478 mcmol/l, serum urea: 29.1 mmol/l) and normal inflammatory indicators (WBC: 4.51 x 109/l, CRP: 0.65 mg/l) (Table). Head CT showed no obvious intracranial hemorrhage, ischemia, or mass lesion; PRES was suspected. Due to hypervolemia, he was temporarily transferred to hemodialysis. On day 12, fundoscopy revealed flame-shaped hemorrhages, microaneurysms, cotton wool patches in the posterior pole surrounding the optic nerve. On day 14, he was transferred to the intensive care unit (ICU) due to uncontrollable hypertension (BP was 202/129 mmHg) and epileptic seizure; MRI showed bilateral subcortical occipital and frontoparietal hyperintensity with vasogenic edema typical of PRES. BP was decreased to approximately 155/90 mmHg using a combination of anti-hypertensive medication and ultrafiltration. Subsequently he was discharged on day 28. Two months later he underwent cadaveric kidney transplantation. After the transplantation, his BP control improved and he was left with bisoprolol 5 mg/day, amlodipine 10 mg/day, and doxazosine 4 mg/day (office BP one month after the transplantation: 124/90 mmHg, after two months: 135/95 mmHg, after three months: 135/95 mmHg).

Conclusions:
This is to the best of our knowledge the fifth report of PRES in an adult patient undergoing PD, and the first presenting a PD patient with history of PRES whose hypertension control improved after kidney transplantation. It is likely that the cause of described PRES episode was multifactorial, originating from the complications of ESRD, hypertension and poor compliance with PD.
PS-B10-8: BLOCKADE OF AT1 RECEPTORS RESTORE P2/P1 WITHOUT CHANGING INTRACRANIAL PRESSURE IN RENOVASCULAR HYPERTENSIVE RATS WITH 0.3 M NACL AD LIBITUM
Authors: Lucera Gabriela Maria , Pontes Roberto Braz , Fernandes Marcos Vinicius , Frigieri Gustavo , Andrade Rodrigo , Colombari Eduardo , Menani Jose Vanderlei , Colombari Debora Simoes 
Published: January 2023

Objective:
Renovascular hypertension is characterized by activation of the renin angiotensin aldosterone system, elevated sympathetic nerve activity and sodium appetite behavior. The association of increased sodium intake and hypertension can worsen the injury to end organs. We tested the effects of AT1 receptors blockade (losartan, 10 mg/kg iv) on mean arterial pressure (MAP), intracranial pressure (ICP) and P2/P1 ratio (index of brain compliance) in 2K1C rats with 0.3 M NaCl ad libitum. Design and Methods: Male Holtzman rats (150 tp 180 g) with water and food ad libitum received a silver clip around the left renal artery to induce 2K1C or no clip (SHAM surgery) resulting 3 groups: SHAM (n = 9), 2K1C (n = 9) and 2K1C/Na (n = 7), which had an additional bottle of 0.3 M NaCl ad libitum. Six weeks after the renal surgery, MAP and ICP were recorded under urethane anesthesia (1.2 g/kg iv) and the P2/P1 was calculated offline from the waveform. Saline (0.2 ml/rat) was used as control injection before losartan.

Results:
In SHAM rats, ICP and P2/P1 were not changed by losartan (7.8 ± 1.1 and 0.88 ± 0.02; vs. saline: 7.9 ± 1.1 and 0.83 ± 0.01 mmHg, respectively), while MAP was decreased (104 ± 5, vs. saline: 120 ± 3 mmHg, p < 0.05). In 2K1C, MAP, ICP and P2/P1 values were greater than SHAM (respectively, 196 ± 6, 14.7 ± 2.7 and 1.1 ± 0.03 mmHg, vs. SHAM; p < 0.05) and all of them were decreased by losartan pre-treatment (137 ± 6, 8.6 ± 1.3 and 0.87 ± 0.05 mmHg, vs. saline, respectively). In 2K1C-Na MAP and P2/P1 were greater than in SHAM (186 ± 7 and 1.15 ± 0.06 mmHg, vs sham p < 0.05) and were decreased by losartan (162 ± 8 and 0.87 ± 0.02 mmHg, vs. saline; p < 0.05), although the decrease in MAP after losartan was lesser than the observed in 2K1C rats (p < 0.05). In 2K1C-Na rats, ICP was not different from SHAM (10.8 ± 1.2, vs. SHAM: 7.8 ± 1.1 mmHg, p > 0.05) and losartan had no effect on ICP (10.3 ± 1.7, vs. saline: 10.8 ± 1.2 mmHg, p > 0.05).

Conclusion:
Even without a change in ICP, AT1 blockade in 2K1C-Na was effective in restoring P2/P1 ratio, suggesting a beneficial effect on brain compliance in this situation.
PS-B10-10: MRI CEREBROVASCULAR CHARACTERIZATION IN A MOUSE MODEL OF HYPERTENSION-INDUCED BRAIN INJURY
Authors: Carnevale Lorenzo , Carnevale Raimondo , Mastroiacovo Francesco , Perrotta Marialuisa , Carnevale Daniela , Lembo Giuseppe 
Published: January 2023

Hypertension has been recognized as the main modifiable risk factor for vascular cognitive impairment (VCI), dementias and neurodegenerative pathologies as Alzheimer Disease (AD). As we previously demonstrated, Transverse aortic constriction (TAC) is a relevant mouse model of cerebral injury and cognitive impairment induced by vascular factors. In this work we characterize the effect of TAC procedure on cerebral injury leveraging Magnetic Resonance Imaging (MRI), and investigate the relationship between the alterations found by MRI and histological, cognitive and cardiac parameters of injury, to establish a framework of translational imaging biomarkers to be applied in human.
We subjected C57Bl/6J to TAC procedure, inducing severe cerebral hypertension. Thereafter, the brain injury was characterized by macro and microstructural MRI; cerebral blood flow (CBF) was analyzed by perfusion MRI. All neuroimaging scans were performed on a small-animal dedicated 7 Tesla MRI. The cognitive phenotype was characterized by Morris Water Maze (MWM) and Novel Object Recognition (NOR), while cardiac and carotid remodeling was assessed by ultrasound imaging. Finally, brains were analyzed for histological alterations in terms of microvascular density and integrity.
Structural MRI showed white matter microstructural degradation in the left Fimbria of TAC mice, evidenced by a reduction of Fractional Anisotropy, Mean Diffusivity and Radial Diffusiity, coupled with bilateral hypothalamic enlargement (Figure A). Hemodynamic alterations resulted in reduced global, cortical and hypothalamic CBF (Figure B). The histological microvascular analysis evidenced capillary rarefaction, reduced capillary-pericyte coverage and Blood-Brain Barrier leakiness in the neocortex (Figure C). Finally, we evaluated whether cerebral MRI parameters of injury were correlated with cardiac, carotid and cognitive alterations: CBF was significantly correlated with mouse performance at Probe trial of MWM test and correlated to cardiac remodeling and diastolic dysfunction. Diastolic disfunction was correlated also to hypothalamic swelling, and cardiac remodeling was significantly correlated to microstructural alterations in the fimbria. Finally, CBF was correlated to bilateral carotid remodeling.
In conclusion we have developed a mouse model of hypertension-induced brain damage that recapitulates typical traits of the human pathology and a pipeline of analysis that will ease allow to appreciate findings resulting from novel molecular targeting of the brain and translate them from bench to bedside.

JOURNAL/jhype/04.03/00004872-202301001-01152/figure1/v/2023-10-24T163949Z/r/image-jpeg
PS-B11-10: IRON DEFICIENCY AFFECTS CARDIAC FUNCTION BUT HAS NO EFFECT ON BLOOD PRESSURE IN MICE WITH METABOLIC SYNDROME
Authors: Naito Yoshiro , Yasumura Seiki , Tahara Saki , Asakura Masanori , Tsujino Takeshi , Ishihara Masaharu 
Published: January 2023

Objective:
Metabolic syndrome is a serious problem concerning public health, increasing the risk of cardiovascular diseases. Some epidemiological studies have reported that iron overload is associated with metabolic syndrome; however, it remains unknown whether iron deficiency affects the pathogenesis of metabolic syndrome. Therefore, in this study, we investigated the impact of dietary iron deficiency in genetically obese KKAy mice, a model of human metabolic syndrome.

Methods:
Four-week-old male KKAy mice and control C57BL/6J mice (wild-type mice, WT) were fed a normal or an iron-restricted diet, and the impact of dietary iron deficiency was investigated 12 weeks after diet initiation.

Results:
Compared with WT mice, systolic blood pressure presented an increasing trend in KKAy mice; however, the difference was not statistically significant between the two groups, and this trend did not change after iron restriction. Notably, some KKAy mice died following iron restriction, while no deaths were recorded in WT mice. Of interest, obese KKAy mice exhibited cardiac hypertrophy and cardiac dysfunction, thereby developing heart failure with pulmonary congestion after iron restriction.

Conclusions:
These results indicate that iron deficiency affects cardiac function in metabolic syndrome.
PS-B12-11: FUNCTIONAL VERSATILITY OF (PRO) RENIN RECEPTOR CLARIFIED BY STRUCTURAL AND EVOLUTIONARY ANALYSES
Authors: Sugihara Daiki , Matsuyama Makoto , Nakagawa Chiharu , Nabi AHM Nurun , Nakagawa Tsutomu , Nishiyama Akira , Suzuki Fumiaki , Ebihara Akio 
Published: January 2023

Objective:
(Pro)renin receptor [(P)RR] is a single-span membrane protein originally identified as a regulator of the renin-angiotensin-aldosterone system. (P)RR reportedly exerts various functions, including an accessory protein of vacuolar ATPase complex and a component of Wnt receptor complex. The soluble form of (P)RR [s(P)RR] which comprises of most of extracellular domain (ECD) exerts an antidiuretic action. although the versatile functions should be mediated through the interactions between (p)rr ecd and its respective binding partners, the one-to-many bindings has not been fully explained. Here we investigated the binding mode of this receptor by structural and evolutionary analyses using three-dimensional structural models of (P)RR, which were predicted by the AlphaFold2 (AF2) program, a machine learning-based algorithm capable of predicting protein structure to near experimental accuracy.

Design and method:
Monoclonal antibodies against (P)RR reduce the Wnt/beta-catenin-dependent development of pancreatic ductal adenocarcinoma (PDAC), the most common pancreatic cancer. Antibodies against two (P)RR regions (residues 47–60 and 200–213) located in ECD reduce the proliferation of human PDAC cells in vitro. The spatial distribution of the two regions was examined using human (P)RR AF2 structural models (monomer and dimer). The evolutionary conservation profile and hydrophobicity were mapped on the models.

Results:
The dimer structure predicted by AF2 shows that (P)RR homodimerizes via ECD, which explains the experimentally proven dimer formation. The 47–60 and 200–213 regions of (P)RR formed a continuous surface patch on the structural model, which comprised evolutionarily conserved hydrophobic residues. The dimer model revealed the presence of two hand-like grooves, with 47–60 and 200–213 regions as its palm and 270–296 region (intrinsically disordered region, IDR) as its fingers.

Conclusions:
Considering conformational flexibility of IDR allowing for multiple protein interactions, we propose that the grooves may act as a binding interface with Wnt signaling molecules and antibodies against the grooves probably interfere with the formation of Wnt receptor complex due to steric hindrance and direct competition with the binding interface residues. The hydrophobic nature of the grooves may explain why (P)RR shows one-to-many bindings underpinning its functional versatility. This study provides new insights into the binding mode of (P)RR for the first time. s(P)RR is considered a useful biomarker for diseases, including essential hypertension and cancer. Our findings may help explore a new treatment and biomarker testing of human diseases, and contribute to quality of life in a longevity society.
PS-C28-4: IMPACT OF SYSTOLIC BLOOD PRESSURE ON OUTCOMES IN ACUTE ISCHEMIC STROKE AFTER INTRAVENOUS THROMBOLYSIS: NCVC RT-PA REGISTRY
Authors: Yoshimoto Takeshi , Wada Shinichi , Yoshimura Sohei , Toyoda Kazunori , Ihara Masafumi , Koga Masatoshi 
Published: January 2023

Background:
The optimal management of systolic blood pressure (SBP) in acute ischemic stroke (AIS) patients receiving intravenous thrombolysis (IVT) remains unclear. We aimed to clarify the association between SBP parameters, including variability and clinical outcomes in AIS patients who received IVT.

Methods:
Data of AIS patients receiving intravenous alteplase at 0.6 mg/kg were extracted from the National Cerebral and Cardiovascular Center (NCVC) rt-PA Registry. SBP was measured seven times at admission and within 24 hours every 4 hours after IVT. SBP variabilities included maximum SBP, minimum SBP, mean SBP, standard deviation, coefficient of variation, and successive variation. Outcomes were defined as modified Rankin Scale score 3–6 at 90 days, representing unfavorable outcome, and symptomatic intracranial hemorrhage (SICH) within 36 hours.

Results:
Among 802 patients (303 women; median age, 76 years; median National Institutes of Health Stroke Scale score, 12), 424 (52.9%) AIS patients had unfavorable outcomes and 16 (2.0%) patients had SICH, respectively. In multivariable analyses, maximum (adjusted odds ratio per 10 mmHg 1.13, 95% confidence interval, 1.04–1.24), minimum (1.27, 1.14–1.42), and mean SBP (1.54, 1.35–1.77) were independently associated with unfavorable outcomes.

Conclusions:
SBP during the initial 24 hours after intravenous low-dose alteplase was associated with unfavorable outcomes.
PS-C28-5: ROLE OF SYMPATHETIC NERVOUS SYSTEM IN ATTENDED AND UNATTENDED BP LEVELS IN ESSENTIAL HYPERTENSION
Authors: Manta Eleni , Andrikou Ioannis , Konstantinidis Dimitrios , Thomopoulos Costas , Dimitriadis Kyriakos , Drogkaris Sotirios , Iliakis Panagiotis , Mantzouranis Emmanouil , Polyzos Dimitrios , Zammanis Ioannis , Tsioufis Konstantinos 
Published: January 2023

Objective:
It has been hypothesized that unattended blood pressure (BP) measurement may provide complementary clinical information to conventionally attended BP measurement. The role of sympathetic nervous system activation during attended and unattended BP measurements is largely undetermined.

Design and method:
We studied 161 untreated hypertensive patients undergoing attended and unattended office BP measurements. Patients were divided into two groups - group A, unattended systolic BP greater than the attended systolic BP (n = 79), and group B, unattended systolic BP equal or lower than the attended (n = 82). All participants underwent muscle sympathetic nerve activity (MSNA) estimation by microneurography. Unattended and attended BP measurements were performed with the same device in a random order for each patient on the day of MSNA recording. MSNA levels were compared between the two groups.

Results:
We examined 161 hypertensive patients [54% men, mean age 56 ± 12 years, BMI 29 ± 5 kg/m2, mean attended BP 140 ± 17 / 87 ± 13 mmHg, mean unattended BP 141 ± 20 / 85 ± 12 mmHg]. Group A and group B had statistically significant differences between attended systolic BP (136.7 ± 17.8 vs 143.7 ± 15.7 mmHg respectively, p = 0.009), attended diastolic BP (85.5 ± 14.7 vs 89.7 ± 11.4 mmHg respectively, p = 0.004), unattended systolic BP (145.5 ± 19 vs 135.7 ± 19.9 mmHg respectively, p = 0.002) and unattended diastolic BP (86.9 ± 13 vs 83.2 ± 11.2 mmHg respectively, p = 0.05). However, the two groups did not differ as regards MSNA levels (42.5 ± 10 vs. 41.6 ± 7.8 bursts per minute respectively, p = 0.5). MSNA levels did not correlate to attended and unattended systolic/diastolic BP in both groups.

Conclusions:
In conclusion, sympathetic nervous system activity may not contribute significantly to the differential BP levels during attended or unattended BP measurements.