bluuebunny/crossref_metadata_2025 huggingface dataset:
PS-B08-2: EXOSOME-MEDIATED INTERCELLULAR CROSSTALK BETWEEN MESANGIAL CELLS AND MACROPHAGES PARTICIPATES IN THE PROGRESSION OF DIABETIC KIDNEY DISEASE.
Authors: Fujimoto Daisuke , Umemoto Shuro , Kuwabara Takashige , Date Ryosuke , Hata Yusuke , Mizumoto Teruhiko , Kakizoe Yutaka , Izumi Yuichiro , Mukoyama Masashi
Published: January 2023

Background:

Extracellular vesicles (EVs) are important mediators of intercellular communication and can play a key role in the regulation of pathophysiological processes. Particularly, exosome-mediated intercellular crosstalk has been addressed in several disorders such as cancer and lifestyle-related diseases including hypertensive and diabetic vascular diseases. In diabetic kidney disease (DKD), it has been reported that macrophages infiltrate the mesangial region and may play an important role through local inflammation in glomeruli.

Design and method:

In this study, we focused on exosome as a factor that acts in a paracrine manner in glomeruli and examined the effects of mesangial cell-derived exosomes cultured under high-glucose conditions on macrophages. In order to identify new therapeutic agents, we screened a validated compound library that can efficiently inhibit this mechanism and also studied their effects on DKD.

Results:

Exosomes released from mesangial cells induced inflammation in macrophages, as indicated by the NFκB transcriptional activity and TNFα and IL-1β mRNA expression. In addition, the effect was significantly enhanced in exosomes from mesangial cells cultured under high-glucose conditions compared to low-glucose conditions. We also observed that fluorescent-labeled (DiO) exosomes were endocytosed by macrophages in vitro and in vivo. Next, we conducted drug screening using a validated compound library to find compounds that could specifically and effectively inhibit the inflammation in macrophages induced by exosomes. The screening was divided into four steps, and we succeeded in narrowing down the list to 30 candidate compounds from a total of 1,364 compounds. Finally, an HSP90 inhibitor, alvespimycin, was identified as a compound with a strong inhibitory effect on both exosome uptake and the NFκB transcriptional activity. Treatment of a diabetic rat model with alvespimycin significantly reduced proteinuria, and showed a trend toward suppression of mesangial expansion.

Conclusions:

We found that mesangial cell-derived exosomes are important for inducing the local inflammation by intercellular crosstalk between mesangial cells and macrophages in DKD. Furthermore, alvespimycin, one of the HSP90 inhibitors obtained by drug screening, can effectively ameliorate the disease progression, suggesting that this mechanism could become a novel therapeutic target for DKD.
PS-B08-11: SALT DIRECTLY REGULATES UMOD TRAFFICKING IN A NORMOTENSIVE BACKGROUND
Authors: Boder Philipp , Mary Sheon , Mark Patrick B , Leiper James , Delles Christian
Published: January 2023

Objective:

Uromodulin (UMOD) is the most abundant protein secreted into urine of healthy individuals and is primarily produced by the renal thick ascending limb cells (TAL) of the loop of Henle. Genetic studies have demonstrated an association between UMOD risk variants, kidney diseases, and hypertension. We have previously demonstrated that salt induces a reduction in urinary UMOD excretion in normotensive rats after three weeks, which was exacerbated in a chronic hypertensive rat model. Our next objective was to determine the influence of salt on UMOD secretion independent of blood pressure effects. Here we investigate the underlying molecular differences in the effects of intermittent and chronic salt-loading on UMOD trafficking dynamics in the TAL.

Design and Methods:

Wistar-Kyoto (WKY) normotensive rats were maintained on 1% NaCl for three weeks in an intermittent pattern (one week on, one week off, one week on) or continuously (chronic) over three months. Urine was collected over a 24-hour period every experimental week. Total kidneys were harvested for lysate extraction, subcellular fractionation, and immunofluorescence analyses. UMOD levels were measured using ELISAs, qPCR, and Western blotting.

Results:

No abnormal changes in blood pressure, body weight, or renal parameters including albumin-creatinine-ratio and injury markers KIM-1 and NGAL were observed in either animal study group. During intermittent salt-loading, there was no significant difference in UMOD mRNA expression or total kidney UMOD protein levels. However, UMOD excretion significantly decreased after one week and remained lower than control levels even after salt removal. Similarly, chronic salt-loading did not alter UMOD mRNA levels, however total kidney UMOD protein levels were increased after three months. More specifically, analysis of subcellular fractions of the medulla from these salt-loaded animals showed higher levels of cytosolic UMOD compared to membrane-bound UMOD. Immunofluorescence analyses revealed a trend towards increased localisation of UMOD with endoplasmic reticulum (ER) marker calnexin.

Conclusions:

Our findings underline the effect of salt in molecular trafficking of UMOD in the kidney independent of blood pressure effects. Long-term salt exposure of TAL cells leads to intracellular accumulation of this abundant renal protein. The relationship between salt, UMOD accumulation, and renal end-organ damage in hypertension requires further research.
PS-B09-2: ENOS-NO PATHWAY MODULATES AKI TO CKD TRANSITION IN IRI MODEL MICE VIA REGULATION OF B;CATENIN TRANSLOCATION
Authors: Takasu Masanobu , Kondo Megumi , Nagasu Hajime , Kadoya Hiroyuki , Kishi Seiji , Kidokoro Kengo , Kashihara Naoki
Published: January 2023

Background:

The incidence of acute kidney injury (AKI) has increased over the past few decades. AKI is also currently recognized as an inducer of chronic kidney disease (CKD) through a process known as the AKI to CKD transition. It has been shown that aging and hypertension are risk factor for the AKI to CKD transition. Because these conditions are related to endothelial dysfunction, we hypothesized that the AKI to CKD transition is promoted by deficiency in the eNOS Nitric Oxide (NO) pathway as an endothelial dysfunction, and we used eNOS deficient mice (eNOSKO) and wild-type (WT) mice (C57B6/J: WT) to determine the mechanism of the AKI to CKD transition.

Methods:

WT and eNOSKO mice were used to determine the role of the eNOS NO pathway. Ischemic reperfusion was performed two weeks after uni-nephrectomization. The ischemic time was 20 min. The WT and eNOSKO mice were divided into four groups: WT sham, WT ischemic reperfusion injury (IRI), eNOSKO-sham and eNOSKO IRI. The first theses mice were sacrificed on Day 28 (D28) after the IRI (WT IRI D28 and eNOS IRI D28). Pathological analysis was conducted using Masson staining and KIM1 staining. Inflammation was assessed using quantitative PCR (qPCR) (IL1β;, IL6, and F4/80) and flow cytometry (FACS) analysis.

Results:

There was no evidence of kidney damage in the WT IRI D28 group. However, KIM1 staining detected tubular cell damage in the eNOSKO IRI D28 group. Fibrosis, which was assessed using the Masson staining, was also exacerbated in the eNOSKO IRI D28 group compared with the WT IRI D28 group. These results suggested that deficient eNOS NO signaling promoted the AKI to CKD transition. Next, the WT-IRI and eNOS IRI mice were sacrificed on Day 1 (D1) after the IRI (WT IRI D1 and eNOSKO IRI D1) to evaluate inflammation and kidney damage in the acute phase after IRI. There were no differences in kidney damage and inflammation between the WT-IRI-D1 and eNOSKO-IRI-D1 groups. In addition, at each time point (D7, Day 14 (D14), and D28) after IRI, qPCR was used to detect Wnt β;catenin related gene expression in the entire kidney. Expression of these genes was increased in the eNOSKO IRI D7 group compared with the WT IRI D7 group.

Conclusions:

Our results showed that after ischemic reperfusion, deficiency in the eNOS NO pathway promotes the AKI to CKD transition via acceleration of Wnt β;catenin. Therefore, activation of the eNOS NO pathway could be a potential therapeutic target in AKI.
PS-B09-5: THE LANDSCAPE OF HIGH-CONFIDENCE MICRORNA - GENE INTERACTIONS OPERATING IN THE HUMAN KIDNEY AND THEIR ROLE IN HYPERTENSION
Authors: Drzal Maciej Szymon , Xu Xiaoguang , Eales James M , Scannali David , Rainey Timothy , Bogdanski Pawel , Wystrychowski Wojciech , Szczechowska Ewa Zukowska , Zywiec Joanna , Guzik Tomasz J , Morris Andrew P , Charchar Fadi J , Tomaszewski Maciej
Published: January 2023

Objectives:

MicroRNAs (miRNAs) are short non-coding RNAs acting as post-transcriptional regulators of mRNAs. It is becoming increasingly clear that they play an important role as molecular drivers/mediators of complex human diseases including hypertension. Given the key role of the kidney in the pathogenesis and treatment of hypertension we sought (i) to comprehensively characterise the network of renal miRNA-mRNA interactions and (ii) evaluate their relevance to human hypertension.

Design and method:

Using poly-A RNA-sequencing and small RNA-sequencing we have identified 22,558 genes and 1,604 miRNAs in the discovery analysis of 328 human kidney samples (Human Kidney Tissue Resource). The outputs from these experiments have been normalised and adjusted by linear regression. We conducted a replication analysis of the identified miRNA-gene pairs in normal control kidney samples from two National Institutes of Health cohorts - CPTAC (n = 66) and TCGA (n = 83). We then examined the extent to which the expression of kidney genes known as targets of blood pressure lowering medications can be modulated by microRNAs. Finally, we investigated whether the effects of these interactions are observed at the protein level (CPTAC dataset).

Results:

We identified 186,192 unique statistically significant inverse miRNA-gene correlations in our discovery resource. Of these, 4,319 were replicated in both NIH kidney resources. 32.5% of kidney protein-coding genes and 12.2% of kidney long non-coding RNAs had at least one such high-confidence miRNA associated with their expression. SLC12A3 (Solute Carrier Family 12 Member 3) - kidney gene target for thiazides, SLC12A1 (Solute Carrier Family 12 Member 1) - gene target for loop diuretics and SLC5A2 (Solute Carrier Family 12 Member 2) - gene target for SGLT2 inhibitors showed consistent, negative correlations with four, five and five kidney miRNAs in each of three independent datasets, respectively. Some of the identified miRNAs showed negative correlations with more than one gene-drug targets. For example, miR-31-5p showed a strong, significant inverse association with SLC5A2 (R = -0.67, P = 9.41E-10) and SLC12A3 (R = -0.70, P = 5.80E-11) in the CPTAC resource. We confirmed that miRNA-31-5p also negatively correlates with the renal expressions of SLC12A3 and SLC5A2 at the protein level (R = -0.58, P = 3.5E-7 and R = -0.45, P = 1.51E-4, respectively).

Conclusion:

We characterised highly credible miRNA-gene interactions in the human kidney and mapped them onto genes and proteins of established relevance to blood pressure lowering treatment. These kidney miRNAs represent exciting targets for the development of novel antihypertensives.
PS-B09-13: PHARMACOLOGICAL INHIBITION OF INTERLEUKIN-18 REDUCES DEOXYCORTICOSTERONE/SALT-INDUCED HYPERTENSION AND RENAL INFLAMMATION
Authors: Wickramasinghe Buddhila , Jelinic Maria , Huuskes Brooke , Diep Henry , Drummond Grant , Vinh Antony
Published: January 2023

Objective:

Circulating levels of the pro inflammatory cytokine, interleukin18 (IL18), are elevated in patients with hypertension and chronic kidney disease (CKD). Moreover, genetic deficiency of IL18 prevents the development of one kidney deoxycorticosterone acetate and high salt (DOCA/salt) induced blood pressure (BP) elevation and renal injury. Thus, the current study aimed to determine if pharmacological inhibition of IL18 is similarly protective against elevations in BP, renal inflammation and dysfunction in the DOCA/salt model of hypertension and CKD.

Design and method:

Male C57BL/6 mice were randomly assigned to receive either control IgG or anti IL18 neutralising monoclonal antibody (control IgG and mAb; 30 mg/kg, i.p., Novartis, bolus every 3 days). Three days after the first injection, mice were uninephrectomised and treated for a further 21 days with either DOCA (2.4 mg/d, s.c. pellet) with high salt (0.9% in drinking water), or a placebo pellet (s.c.) plus normal drinking water. BP was measured weekly (tail cuff, starting at baseline). Transdermal glomerular filtration rate (tGFR) measurements were recorded at baseline and at endpoint to determine kidney function. Kidneys were harvested at endpoint for histopathological staining, quantitative reverse transcription PCR (RT qPCR) and flow cytometry to assess fibrosis, inflammation and immune cell infiltration, respectively.

Results:

Baseline systolic BP was not different between mice treated with anti IL18 mAb (118 ± 2 mmHg) versus control IgG (122 ± 3 mmHg). However, anti IL18 mAb treatment significantly blunted hypertensive responses to DOCA/salt, with systolic BP only reaching 139 ± 6 mmHg compared to 159 ± 6 mmHg in control IgG treated animals (Figure; n = 11–12; P < 0.05). Anti IL18 mAb treatment also significantly reduced DOCA/salt induced leukocyte (CD45+) accumulation in the kidneys (0.9 ± 0.1x105 cells/kidney) compared to control IgG treatment (1.6 ± 0.3x105 cells/ kidney; n = 11–12; P < 0.05), which was largely attributed to reduced macrophage accumulation (CD11b+/F4/80+; n = 11–12; P < 0.05). A ∼30% decline in kidney function was observed in DOCA/salt-treated mice that received control IgG, which was associated with renal fibrosis and injury. Impaired kidney function decline (but not fibrosis and injury) appeared to be less severe in DOCA/salt treated mice that received anti IL18 mAb (n = 7). DOCA/salt treatment increased expression of genes associated with renal fibrosis (Col1al, Col3a1 and Col5a1), injury (Kim1 and Ngal) and inflammation (Ifng, Mrc1, II6, Ccl2 etc.). Surprisingly, DOCA/salt induced changes in gene expression were not prevented by anti IL18 mAb treatment.

Conclusions:

IL18 neutralisation affords protection against DOCA/salt induced hypertension and renal inflammation. Thus. IL18 may represent a potential therapeutic target to treat hypertension and CKD.
PS-C17-4: ASSOCIATION BETWEEN SERUM INSULIN LEVELS AND HEART FAILURE-RELATED PARAMETERS IN PATIENTS WITH TYPE 2 DIABETES AND HEART FAILURE
Authors: Tanaka Atsushi , Node Koichi
Published: January 2023

Background:

Insulin resistance and hyperinsulinemia in patients with type 2 diabetes (T2D) are adversely associated with the development and worsening of heart failure (HF). Herein, we sought to investigate the effect of canagliflozin on insulin concentrations and the associations of changes in insulin concentrations with HF-related clinical parameters in patients with T2D and HF.

Methods:

This was a post hoc analysis of the investigator-initiated, multicenter, open-label, randomized, controlled CANDLE trial for patients with T2D and chronic HF (UMIN000017669). The endpoints were the effects of 24 weeks of canagliflozin treatment, relative to glimepiride treatment, on insulin concentrations and the relationship between changes in insulin concentrations and clinical parameters of interest, including New York Heart Association (NYHA) classification. The effects of canagliflozin on those parameters were also analyzed by baseline insulin level.

Results:

Among the participants in the CANDLE trial, a total of 129 patients (canagliflozin, n = 64; glimepiride, n = 65) who were non-insulin users with available serum insulin data both at baseline and week 24 were included in this analysis. Overall, the mean age was 69.0 ± 9.4 years; 75% were male; the mean HbA1c was 6.8 ± 0.7%; and the mean left ventricular ejection fraction was 59.0 ± 14.1%, with parameters roughly balanced between treatment groups. Canagliflozin treatment significantly reduced insulin concentrations at week 24 (p < 0.001), and the between-group difference (canagliflozin minus glimepiride) in those changes was -3.52 mU/L (95% confidence interval, -4.85 to -2.19; p < 0.001). Decreases in insulin concentrations, irrespective of baseline insulin level, were significantly associated with improvement in NYHA class in patients treated with canagliflozin.

Conclusion:

Our findings suggest that canagliflozin treatment in patients with T2D and HF ameliorated excess insulin overload, contributing to the improvement of clinical HF status.
PS-C18-6: THE IMPACT OF ANTIHYPERTENSIVE DRUG USE ON INTRADIALYTIC BLOOD PRESSURE DECLINE CONSIDERING SEASONAL VARIATION: A RETROSPECTIVE COHORT STUDY
Authors: Uchiyama Kiyotaka , Washida Naoki , Shibagaki Keigo , Yanai Akane , Nakayama Takashin , Morimoto Kohkichi , Itoh Hiroshi
Published: January 2023

Objective:

Risk factors of intradialytic systolic blood pressure decline remain less understood. We aimed to identify clinical and laboratory predictors of intradialytic systolic blood pressure decline, considering its seasonal variation.

Design and method:

In a retrospective cohort of 47,219 hemodialysis sessions from 307 patients undergoing hemodialysis for 1 year in three dialysis clinics, seasonal variation and intradialytic systolic blood pressure decline predictors (predialysis systolic blood pressure - nadir intradialytic systolic blood pressure) were assessed using cosinor analysis and linear mixed models adjusted for baseline/monthly hemodialysis-related variables, respectively.

Results:

Intradialytic systolic blood pressure decline was highest and lowest in the winter and summer, respectively, following a clear seasonal pattern. In both models adjusted for baseline and monthly hemodialysis-related parameters, calcium channel blocker use was associated with a smaller decline (-4.58 [95% confidence interval (CI), -5.84 to -3.34], P < 0.001; -3.66 [95% CI, -5.69 to -1.64], P < 0.001) and alfa blocker use, with a greater decline (3.25 [95% CI, 1.53–4.97], P < 0.001; 3.57 [95% CI, 1.08–6.06], P = 0.005). Baseline and monthly serum phosphorus levels were positively correlated with a decline (1.55 [95% CI, 0.30–2.80], P = 0.02; 0.59 [95% CI, 0.16–1.00], P = 0.007) and baseline and monthly normalized protein catabolic rate, inversely correlated (-22.41 [95% CI, -33.53 to -11.28], P < 0.001; 9.65 [95% CI, 4.60–14.70], P < 0.001)

Conclusions:

Calcium channel blocker use, alfa blocker avoidance, and serum phosphorus-lowering therapy may attenuate intradialytic systolic blood pressure decline and should be investigated in prospective trials.
PS-C18-11: HYPERTENSION AS A CAUSE OF MORTALITY IN PATIENTS WITH CKD ON DYALISIS; A REPORT ON RURAL HOSPITAL
Authors: Mulia Deddy Primadona , Rico Rico Irawan , Herleni Herleni Kartika , Wangsa Syahpri Putra , Akbar Kgs M Yusuf Arief , Ida Ida Trikandiani , Firda Firda Ariyanti , Sugihartono Sugihartono Sugihartono , Adhi Adhi Permana , Amrizal Amrizal Amrizal , Ian Ian Effendi , Novadian Novadian Suhaimi , Suprapti Suprapti Slamet , Zulkhair Zulkhair Ali
Published: January 2023

Objective:

Chronic kidney failure is an important issues because its increased in a recent years and impacted the high cost medical financing. This is directly related to social, economic and public health problems. it can be prevented as soon as possible to prevent progression to dialysis. A survey conducted by the Indonesian Nephrology Association stated that CKD occurred in 12.5 ‰ of the population with high risk, namely hypertension, proteinuria, and or diabetes.

The aetiology of CKD in Indonesia is different from other countries, One of the comprehensive efforts in the management of chronic kidney disease in Indonesia is an analysis of the causes of mortality in chronic kidney failure patients undergoing haemodialysis. Hypertension as the main cause of CKD is also important to study, especially the mortality rate is also a priority for health workers in hemodialysis installations.

Design and Method:

This research is descriptive analytic. The target population is all chronic kidney failure patients undergoing haemodialysis at the East OKU Hospital recorded in the Indonesian Renal Registry from 2020 to 2022, including 68 patients undergoing routine haemodialysis for more than 6 months.

Result:

The most common aetiology of CKD is hypertension with 34, followed by type II diabetes in 31 patients, and the rest are other diseases such as stones, gout, and others. There is no significant difference in the aetiology of CKD. Of the 34 patients who developed hypertension which resulted in end stage CKD with haemodialysis, more than 50 ‰ of patients were over 50 years of age. Unknown cause of hypertension causes complications of various diseases that aggravate the disease, such as kidney disease. The higher blood pressure measured for a many time, the more severe its complications, especially in the kidneys. If kidney failure continues and its progression continues, it will result in end-stage renal failure which requires renal replacement therapy, in this case was a haemodyalisis procedure. Patients with hypertension aetiology who underwent haemodialysis had a mortality rate of 20 patients or 58.8 ‰ and patients who survived as many as 41.2 ‰ patients.

Conclutions:

Hypertension as a cause of chronic kidney disease with haemodialysis is still the biggest contributor, followed by diabetes mellitus. The higher and longer the hypertension, the higher the risk of chronic kidney disease that requires renal replacement therapy in the form of dialysis. The mortality rate is also influenced by the aetiology of cardiovascular disease
PS-C19-2: AMLODIPINE/VALSARTAN EFFICACY IN HYPERTENSIVE PATIENTS - A REAL WORLD OBSERVATIONAL STUDY (ALERT)
Authors: Iqtadar Somia , Khan Khalid Mahmud , Malik Mahmood Nasir , Attiq ur Rehman Muhammad , Siddiqui Anum Sohail
Published: January 2023

Objectives:

Hypertension is a significant public health problem and one of the major non-communicable diseases at the endemic level in Pakistan. This study was done to determine the efficacy of amlodipine/valsartan (Aml/Val) once-daily dose in reducing blood pressure (BP) after eight weeks of therapy.

Methods:

This study is an open-labeled observational study carried out for a period of 12 months. Some 769 participants of either gender between the ages of 18 and 70 years selected after taking written informed consent had a BP of > 139/89 mmHg (not controlled) on monotherapy with a minimum 30 days of treatment. Therapy to control their high BP was initiated with Aml/Val at the time of their enrolment in the study. Pregnant females and patients with secondary hypertension were excluded. Data were analyzed using SPSS version 20.0 and chi-square test was used for inferential analysis. p-values less than 0.05 were considered significant.

Results:

At the end of week one, less than half of the patients achieved the desired level of BP while the majority achieved this level by the end of the study. Some 75.6% patients achieved targeted BP with Aml/Val 80/5 mg tablet, 18.5% achieved targeted BP with Aml/Val 160/5 mg tablet, and 5.9% achieved the targeted BP with Aml/Val 160/10 mg tablet at the end of the eighth week. The compliance rate was 99.2% at the first week, 98.9% at the fourth week, and 99.9% at the eighth week of treatment.

Conclusion:

Our study concluded that Aml/Val combination therapy was very effective in controlling BP among patients who were uncontrolled with other monotherapies for at least one month.
PS-C19-11: ASSESSMENT OF ADHERENCE TO ANTIHYPERTENSIVE THERAPY AND BLOOD PRESSURE TARGETS ACHIEVING AMONG HYPERTENSIVE PATIENTS IN THE REPUBLIC OF KAZAKHSTAN
Authors: Mukhtarkhanova Dilyara , Junusbekova Gulnara , Tundybayeva Mira , Leonovich Tatyana , Baglanova Lyazat
Published: January 2023

Introduction:

Arterial hypertension is one of most prevalent cardiovascular diseases and leading factor of mortality and morbidity due to higher cardiovascular risk. To prevent cardiovascular events: myocardial infarction, stroke, heart failure it is crucial to manage hypertensive patients carefully and to achieve blood pressure targets. The one of leading causes of not achieving control of blood pressure levels is low adherence to therapy.

Objective:

The objective of this investigation is to assess the level of adherence to antihypertensive therapy and blood pressure targets achieving.

Methods:

A prospective cross-sectional study was conducted from August 2021 to November 2021 in four regions of Kazakhstan, included 1805 adults of both sexes (1073 women (59.40%) and 732 men (40.60%)) of mean age 39 years. Special survey, including assessment of current antihypertensive therapy, blood pressure and heart rate measurement were performed. Statistical test was performed by the StatTech 2.6.1 (Russia, 2020), IBM SPSS statistics version 28.0, Epi Info, version 7.

Results:

The prevalence of arterial hypertension in the population was 37.06%. Of the 658 participants with hypertension, 333 (40.51%) were aware of their diagnosis and 227 (68.17%) of them were taking antihypertensive medications.

33.5% were on monotherapy; 36.1%, 17.6%, and 3% were taking 2, 3, and 4 classes of antihypertensive drugs, respectively. 113 (49.78%) had a blood pressure lower or equal to 140/90 mm Hg, and only 33 (14.54%) lower or equal to 130/80 mm Hg.

Among participants on monotherapy, 42% had blood pressure levels higher or equal to 140/90 mm Hg. Of all patients on therapy, only 152 (45.6%) were taking drugs regularly. A strong relationship was found between adherence to therapy and age (OR 1.049, 95% CI 1.031, 1.066, p < 0.001): adherence to therapy was higher in older patients.

It should also be noted that of the total number of participants on antihypertensive therapy, 95 (41.9%) were taking acetylsalicylic acid, of which only 16 (16.8%) had a history of myocardial infarction or stroke.

Conclusion:

To conclude, the level of adherence to therapy was 45.6%, more than half of the patients were not adherent to current antihypertensive therapy. When using the lower BP target of < 130/80 mm Hg as the definition of control, which more accurately reflects current guidelines the proportion controlled was 14.54%. It could be related to several different causes: low levels of adherence, little knowledge of healthcare specialists about target blood pressure levels and little knowledge of population about importance of control blood pressure. In conclusion, the study confirms the importance and relevance of arterial hypertension as socially significant disease.
PS-C20-3: MOBILE MEDICAL APP CAN BE MORE EFFECTIVE IN LONG-TERM MANAGEMENT OF HYPERTENSION PATIENTS
Authors: Li Na , Cheng wenli
Published: January 2023

Objective:

The application of mobile medical application, APP, to manage patients with hypertension makes the contact between doctors and patients more convenient, saves the economic cost and time cost of patients, and also makes it easier for doctors to manage patients and improve their compliance. This study investigated the effect of APP on long-term management of hypertension patients.

Design and method:

This trial was a randomized, single-blind, parallel, controlled study. A total of 302 patients with hypertension were included in this study and observed for one year. All the enrolled patients received antihypertensive treatment of nifedipine controlled release tablets with or without telmisartan in outpatient or ward. The APP of the experimental group could be used to push health education information, remind patients to measure their own blood pressure and take medication, and consult doctors online. Blood pressure, improvement of hypertensive target organ injury, and sodium intake were assessed in both groups after one year treatment.

Results:

There were no significant differences in blood pressure, urinary microalbumin and 24-hour urinary sodium levels between the two groups at baseline. APP information push was more helpful to the control of blood pressure, systolic and diastolic blood pressure decreased significantly, after treatment, systolic blood pressure of experimental group vs control group 133 ± 6mmHg vs 141 ± 11mmHg, P < 0.05; Diastolic pressure 83 ± 7mmHg vs 89 ± 9mmHg, P < 0.05. APP information push was more helpful to improve target organ injury (decrease of microalbuminuria), and microalbuminuria after treatment was 31 ± 12 mg/L vs 47 ± 14 mg/L, P < 0.05. APP information push helped control sodium intake, and the urine sodium level at 24 hours after treatment was 123 ± 31 mmol/24 h vs 148 ± 28 mmol/24 h, P < 0.05.

Conclusions:

Using mobile medical APP for patient management can help control patients’ blood pressure level, improve the degree of renal damage caused by hypertension, and help control sodium intake. APP can be used as an auxiliary means for long-term management of hypertension patients, which can improve the quality of blood pressure management of patients more effectively, conveniently and economically.
PS-C20-5: WARM IV INFUSION IN HYPERTENSIVE URGENCY
Authors: Ray Abhijit , Chandana Thota
Published: January 2023

Background:

Hypertensive Urgency is defined as marked elevation in systemic blood pressure without any evidence of end organ damage. At present, the condition is managed with intravenous (IV) antihypertensives, of which most common is Sodium Nitroprusside.

Aim:

In this abstract we explore the possibility of slow IV infusion of warm (37–38oC) Normal Saline along with IV antihypertensives for a better and faster management of Hypertensive Urgency.

Content:

The slow IV will gradually increase the core body temperature of the patient while preventing fluid overload. Homeostatic regulation of Systemic Blood Pressure is maintained by an intricate network of correlated mechanisms, most of which are temperature dependent. The raised body temperature will be useful to control the Blood Pressure through the following mechanisms -

Cardiac Output: reduces as core body temperature increases.

Baroreflex: decreased post-synaptic adrenergic vasoconstrictor responses.

Chemoreceptors: vascular responsiveness to adrenergic receptor stimulation reduces at higher temperatures.

RAAS: Kosunen et al recorded reduced Systolic and Diastolic Blood Pressures at raised body temperatures despite increased levels of Angiotensin II & Aldosterone.

Endothelin: Serum concentration of Endothelin-I reduces at higher temperatures.

Sweat: Thermal stimulation of sweat gland will help excretion of both salt and water, thus maintaining the sodium balance.

VEGF: VEGF-A, a potent vasodilator, is increased during elevated body temperature.

However, apart from Blood Pressure, a change in core body temperature causes change in many other parameters as well, which must be considered during this discussion.

Coagulation profile - Valeri et al noted no change in in-vivo coagulation states till 100oF

Effect on other visceral organs - Internal visceral organs like Liver, Kidneys and Brain were not affected till 100oF

Infection Control - Core body temperature close to 100oF has also been found to have a protective role against invasive fungal infections in the ICU

Discussion:

Though the effects of various antihypertensive drugs to raised body temperatures need to be tested, the above points prove that introducing a protocol of warm IV saline Infusion in patients of Hypertensive Urgency may be extremely beneficial, and also prevent clinical inertia.
PS-C21-2: PREDICTORS OF CLINICAL AND BIOCHEMICAL SUCCESS OF ADRENALECTOMY IN PATIENTS WITH UNILATERAL PRIMARY ALDOSTERONISM
Authors: Vaclavik Jan , Hartmann Igor , Hruska Frantisek , Kocianova Eva , Frysak Zdenek , Nesvadbova Marika , Tudos Zbynek , Ctvrtlik Filip , Benesova Klara
Published: January 2023

Objective:

Our study aimed to evaluate clinical and laboratory predictors of outcome of unilateral adrenalectomy in patients with primary aldosteronism (PA).

Design and method:

Data from patients with unilateral PA verified by adrenal venous sampling who subsequently underwent transperitoneal laparoscopic adrenalectomy between 2008 and 2019 were analyzed. We assessed patient demographics, preoperative and postoperative clinical, pharmacological, laboratory, and radiological data. Antihypertensive drug use was quantified by estimating the daily defined dose (DDD) of antihypertensive medication. Statistical assessments included univariable and multivariable logistic regression analysis.

Results:

87 patients with PA were enrolled. Complete biochemical success of surgery, defined as normalisation of the aldosterone-to-renin ratio and correction of hypokalaemia, was reached in 67 patients (77%), 19 patients (22%) had partial biochemical success (please see the Figure). Complete clinical success with normalization of blood pressure and withdrawal of all antihypertensive drugs was achieved in 19 patients (22%). 57 patients (65%) exhibited a reduction of DDD after surgery and/or improvement of blood pressure - partial clinical success. Multivariable logistic regression showed that complete clinical success was independently associated with female gender (odds ratio: OR 3.71, 95% CI 1.16–11.87, P = 0.027) and baseline sum of antihypertensive drugs DDD < 4 (OR 5.30, 95% CI 1.68–16.67, P = 0.004). None of the analysed clinical or laboratory parameters was found to be a significant predictor of biochemical success.

Conclusion:

A majority of patients undergoing unilateral adrenalectomy for PA achieved markedly improved hypertension control while almost halving their antihypertensive medication. Females and patients using lower number of antihypertensive drugs preoperatively were more likely to be completely cured by the surgery.
PS-C21-3: URINARY FREE CORTISOL EXCRETION AS A MARKER OF DECREASED BONE DENSITY IN PATIENTS WITH ADRENAL CUSHING'S SYNDROME
Authors: Takiguchi Miwa Kimura , Morimoto Satoshi , Watanabe Daisuke , Abe Koichiro , Ichihara Atsuhiro
Published: January 2023

Objective:

Patients with adrenal Cushing's syndrome (CS) have a poor prognosis due to the autonomous hypersecretion of endogenous cortisol from the adrenal gland. Although several clinical examinations have been developed to manifest the autonomous hypersecretion of endogenous cortisol in this syndrome, it is unknown which parameter of cortisol overproduction is best associated with adrenal cortisol content and the bone and vascular complications of this syndrome. Therefore, the present study was undertaken to evaluate the parameter(s) associated with adrenal cortisol content in patients with adrenal CS, as well as to assess the associations between these parameters and the vascular and bone complications of this syndrome.

Design and method:

Patients with CS who were over 18 years old and had undergone adrenalectomy for this syndrome were enrolled in this study. Patients who were pregnant, had an allergy to iodine, or who were receiving medications that may interfere with the evaluation of 131I-adosterol single-photon emission computed tomography (SPECT) /computed tomography (CT) were excluded. Those taking medications that may interfere with the evaluation for the diagnosis of CS were also excluded. Relationships between office blood pressure and pulse rate, urinary examinations, blood examinations, endocrinological examinations, CT and 131I-adosterol SPECT/CT data, bone density, physiological function tests, and adrenal cortisol concentration/content were examined. In addition, relationships between the parameter associated with adrenal cortisol concentration/content and complications of CS were investigated.

Results:

Cardiovascular factors, except for diastolic blood pressure, failed to show an association with adrenal cortisol content. 24-h urinary free cortisol excretion (ρ = 0.893, P = 0.007) and plasma cortisol levels after the 1 mg (ρ = 0.857, P = 0.014) or 8 mg (ρ = 0.900, P = 0.037) overnight dexamethasone suppression test, but not plasma cortisol levels in the morning or at late night or indices of 131I-adosterol SPECT/CT, were significantly and positively associated with adrenal cortisol content. 24-h urinary free cortisol excretion, and not plasma cortisol levels after the 1 or 8 mg overnight dexamethasone suppression test was significantly and negatively associated with lumbar spine bone density (lumbar spine T-score, ρ = -0.883, P = 0.009; lumbar spine Z-score, ρ = -0.883, P = 0.009).

Conclusions:

24-h urinary free cortisol excretion is best associated with a decrease in bone density via increased adrenal cortisol overproduction and suggested that it could be used as a marker for osteoporosis in these patients.
PS-C21-8: THE CHANGING CLINICAL SPECTRUM OF PSEUDOALDOSTERONISM IN JAPAN: ANALYSIS OF REPORTED ADVERSE DRUG REACTIONS DATABASE
Authors: Takahshi Katsutoshi , Ikeda Yuzuru , Kurihara Isao , Katabami Takuya , Ueshiba Hajime , Tanabe Akiyo
Published: January 2023

Background:

Pseudoaldosteronism is a severe primary aldosteronism-like syndrome with decreased plasma aldosterone levels. In Japan, it is often caused by herbal medicines containing licorice. However, there has been little evidence assessing the updated proportion of each drug and its recent trends.

Objective:

To identify recent major causes of pseudoaldosteronism in Japan and assess the possibility of chronological changes from 2005 to 2020.

Methods:

We collected data from the Japanese Adverse Drug Event Report (JADER) database, a spontaneous reporting system maintained at Japan's Pharmaceutical and Medical Devices Agency, reported between January 2005 and December 2020.

Findings:

In the JADER database, reported adverse events of pseudoaldosteronism, hypokalemia, rhabdomyolysis, and myopathy were extracted from 2016 to 2020. The drugs frequently implicated in the development of these pseudoaldosteronism-related events, including Syakuyakukanzoto, Yokukansan, Hochuekkito, Kakkonto, Rikkunshito, Daioukanzoto, Ryoukeijyutsukanto, Hangeshashinto, Bakumondoto, Saireito, were identified. Yokukansan, an herbal medicine increasingly used in the treatment of behavioral and psychological symptoms of dementia (BPSD), was shown to be the second most frequently associated drug with pseudoaldosteronism-related adverse events (232 cases), following Syakuyakukanzoto (255 cases). Furthermore, with regards to adverse events standardized by the content of licorice, Yokukansan was the most common. Between 2005 and 2020, the number of adverse events related to Yokukansan increased significantly, however, those associated with

Shakuyakukanzoto did not (Fig. 1).

Conclusion:

Yokukansan-induced pseudoaldosteronism appears to have increased significantly in Japan. Considering the aging population and limitations of conventional drugs for BPSD, this is an emerging trend and a potentially serious healthcare issue in Japan.
PS-C22-1: DIFFERENCE IN ALDOSTERONE DEPENDENCY BETWEEN CARDIOVASCULAR DISEASES AND RENAL IMPAIRMENTS IN PATIENTS WITH PRIMARY ALDOSTERONISM
Authors: Sone Masakatsu , Ohno Youichi , Kawashima Akiyuki , Inagaki Nobuya , Naruse Mitsuhide
Published: January 2023

Recently, we assessed the PA database established by the multicenter JPAS (Japan Primary Aldosteronism Study) and compared the prevalences of CVD (stroke, ischemic heart disease, and heart failure), cardiomegaly (left ventricular mass index: LVMI) and renal impairment (proteinuria and lowered eGFR) among patients with PA and those with essential hypertension (EHT). We also performed logistic regression analysis to determine which parameters significantly increased the odds ratio for these complications.

As the results, the prevalence of CVD was significantly higher among patients with PA than among matched patients with EHT. The prevalence of proteinuria was also significantly higher among PA than EHT patients, whereas there was no significant difference in the prevalence of lowered eGFR. Multivariable logistic regression analysis showed that the PAC was not linearly related to the adjusted odds ratio for CVD and cardiomegaly though the PAC after saline infusion test and captopril challenge test was positively related to LVMI. By contrast, regarding renal complications, the PAC significantly increases the adjusted odds ratios for proteinuria and lowered eGFR independent of other known risk factors. The mechanism underlying the kidney damage in patients with PA may thus differ from that affecting the cardiovascular system.
PS-C22-3: VALIDATION AND CLINICAL EVALUATION OF DIAGNOSTIC ABILITY OF NOVEL CHEMILUMINESCENT ENZYME IMMUNOASSAY OF PLASMA ALDOSTERONE CONCENTRATION.
Authors: Ono Yoshikiyo , Omata Kei , Tezuka Yuta , Morimoto Ryo , Yamazaki Yuto , Sasano Hironobu , Ito Sadayoshi , Takase Kei , Tanaka Tetsuhiro , Satoh Fumitoshi
Published: January 2023

Plasma aldosterone concentration has been usually measured by radioimmunoassay and chemiluminescent enzyme immunoassay which have demonstrated lack of high specificity and variability in assay performances. Liquid chromatography-tandem mass spectrometry is considered to be ideal measurement method of plasma aldosterone, however it takes relatively high cost and measurement time. We recently developed a novel non-competitive chemiluminescent enzyme immunoassay for plasma aldosterone concentrations by the fully automated assay system. We performed clinical validation of diagnostic ability of the new assay-based screening of 344 hypertensive patients including 133 patients with primary aldosterone producing adenoma, 100 patients with bilateral hyperaldosteronism, and 111 patients with essential hypertension. Passing-bablok analysis revealed that the new measurement of plasma aldosterone concentration was significantly correlated and almost equivalent to liquid chromatography-tandem mass spectrometry measurement of aldosterone; the regression slope and intercept were 0.962 and -0.043, and the correlation coefficient was 0.962, which is more similar than radioimmunoassay especially in lower range (< 10 ng/dL). Bland-Altman plot analysis with the mass-spectrometry measurement also demonstrated that both bias and limits of agreement with 95% confidence interval of the automated aldosterone assay were smaller than those of the radioimmunoassay, suggesting smaller systemic errors in the novel measurement. The lowest plasma aldosterone concentration and ratio of aldosterone-over-renin concentrations in aldosterone producing adenoma group were 6.0 ng/dL and 16.3 ng/dL per pg/mL/hr, respectively. We suggest if aldosterone-over-renin concentrations is over 15 ng/dL per pg/mL/hr, the patient should be performed confirmatory test for primary aldosteronism. The novel chemiluminescent enzyme immunoassay is clinically reliable alternative for conventional radioimmunoassay and liquid chromatography-tandem mass spectrometry to provide better throughput and cost-effectiveness in diagnosis of primary aldosteronism from larger number of hypertensive patients.
PS-C22-5: PLASMA METANEPHRINES PROVIDE GREATER SPECIFICITY THAN URINARY METANEPHRINES IN PATIENTS WITH OBSTRUCTIVE SLEEP APNEA: A PROSPECTIVE TRIAL
Authors: Puar Troy H , Lenders Jacques , Saffari Seyed Ehsan , Wong Hang Siang , Mok Ying Juan , Mae Lily , King Thomas F
Published: January 2023

Introduction:

Pheochromocytoma and paraganglioma (PPGL), and obstructive sleep apnea (OSA) are important secondary causes of hypertension. Both plasma and urinary metanephrines have high diagnostic sensitivity and specificity for diagnosis of PPGL. Patients with OSA have increased nocturnal catecholamine release, which can lead to increased metanephrines production over 24 hours. We hypothesized that morning plasma metanephrines have a higher diagnostic accuracy than 24-hour urinary metanephrines in patients with OSA.

Methods:

We recruited patients undergoing polysomnography for suspected OSA. Plasma and 24-hour urinary metanephrines were measured. Patients with elevated metanephrines had repeated measurements of metanephrines, imaging and follow-up, to diagnose, or exclude, PPGL.

Results:

Seventy-six patients completed polysomnography and biochemical testing, of which 68 had OSA. One patient had a PPGL, while PPGL was excluded in the remaining patients. At baseline, OSA patients were more likely to have falsely-elevated urinary (17 of 67, 25.4%), than falsely-elevated plasma metanephrines (2 of 67, 2.9%) (P < 0.01). Seven patients had normal metanephrines on repeat testing. Nine patients with persistently elevated metanephrines underwent abdominal imaging: six patients had no PPGL, one had lipid-rich adrenal adenomas, one had indeterminate adrenal adenoma, and one had bladder tumor. This final patient with biopsy-proven bladder PPGL had marginally-elevated urinary metanephrines, but false-negative plasma metanephrines, due to the small tumor size.

Falsely-elevated urine metanephrines were more common in patients with severe OSA (13 of 3, 38.2%), compared to moderate OSA (1 of 13, 7.7%) and mild OSA (3 of 20, 15%), P < 0.01. Falsely-elevated plasma and urine metanephrines were all due to elevation of normetanephrine, while metanephrine was normal in all patients. Declines in metanephrines were observed only in patients with OSA treated with continuous positive pressure ventilation, while those untreated had no improvements.

Conclusion:

In patients with OSA, metanephrines measured in plasma provide better specificity than those measured in urine for the diagnosis of PPGL. However, one patient with a small PPGL was missed by plasma metanephrines.
PS-C22-11: EFFICACY OF TRI-COMBINATION ACEI PLUS AMLODIPINE AND INDAPAMIDE VERSUS ARB AMLODIPINE AND THIAZIDE IN DIABETES WITH HYPERTENSION PATIENTS
Authors: Jain Rajesh , Shoghli Mohammadreza , Fesseha Hermon Eyob , Husseini Siyamal Jalal
Published: January 2023

Introduction:

Global Burden of Disease (GBD) Study has estimated that Hypertension leads to

1.6 million deaths and 118 million disability-adjusted life years in INDIA1

40% of diagnosed Hypertension patients are treated1. The poor control rates among treated Hypertension patients are around 40% in Indian3.

Plausible reasons for poor Hypertension control rates in INDIA. This is mainly because most treated patients only receive monotherapy despite guidelines recognizing that most patients require combination therapy 2 and 3.

ISH 2020 guidelines support initiating with A+C SPC in Hypertension patients For patients uncontrolled on two drugs, recommended approaches are to increase doses as step 2 and add a third drug as step 3. 4

Every third Hypertension patient needs three or more drugs to reach the BP Perindopril + Amlodipine + Indapamide offers better blood pressure control.

In studies such as the ADVANCE CCB study5. Active treatment with Perindopril + Indapamide + CCB reduced the relative risk of death by -28%.

-The recent Mazza et al. study provides evidence for Cardiovascular risk reduction with Perindopril + Indapamide + Amlodipine combination. Left ventricular hypertrophy (LVH) regression was greater in the SPC group of Perindopril+ Indapamide+ Amlodipine vs. the FCT group (43.5% vs. 30.4%, P < 0.05).6

In our Indian study from 2019 to 2022, 110 patients with Diabetes with Moderate to severe Hypertension on Perindopril with Amlodipine and Indapamide were able to achieve a blood pressure target of < 130/80 mmHg with Minimum 6 months to a maximum of 2 years on this combination therapy, whereas Target of < 130/80 mmHg with ARB with Amlodipine and thiazide were achieved in 54% only, which was significant (Figure 1).

Indian patients are well Tolerated with triple single Pill, and adherence to therapy was Good.