bluuebunny/crossref_metadata_2025 huggingface dataset:
CURRENT PERSPECTIVES FROM THE 2020 VIRTUAL INTERNATIONAL HEART FAILURE SUMMIT FOR THERAPEUTIC HEART RATE REDUCTION WITH CARVEDILOL AND IVABRADINE IN THE FOREFRONT
Authors: Bansal Sandeep , Chaurasia Ajay , Rao Nageshwara , Aravindakumar S. , Dasbiswas Arup , Malhotra Ashish , Khera Ashok , Kumbala Dayanand , Trivedi Ak , Sinha Ajay
Published: April 2021

Objective:

Disseminate the contemporary global evidences and practices among experts for management of management of (reduced) HFrEF, (mid-range) HFmrEF/ (recovered) HFrecEF and the role of Carvedilol and Ivabradine in the forefront through live webinar

Design and method:

A virtual learning collaborative educational initiative was convened on September 27, 2020 by Prof Michael Bohm live from Germany with high expertise rank within 0.02% of 158,672 published authors worldwide on heart failure in last one decade, with 1853 continuous active participants at forefront of HF management across India. The first module focused on need to target Ejection Fraction (EF) as a measure for improvement in outcomes in HF and second for evidence for the novel combination approach to utilise beta blockers with Ivabradine to improvise the outcomes in HF

Results:

Analysis of ESC HF long term registry represents diverse phenotypes of demography, clinical presentation, aetiology with continuum in HFmrEF and HFrEF. Elevated HR in failing heart is a maladaptation which when lowered to 55 to 65 beats per minute (bpm), with beta blockers, helps improve myocardial oxygen demand and coronary perfusion time with independent effects on heart failure. Therapeutic heart rate reduction is strongly correlated with reduced mortality and HR reduction of 5 bpm using beta blockers provide 14% risk reduction in mortality. Ivabradine mechanistically enables unloading of heart by facilitating the acceptance of higher doses of carvedilol as the drop in HR in tolerated better by conserving energy during systolic phase and improves contractility during diastolic phase. Pharmacokinetic properties of extended release formulation through logical technological innovation enhances the release of Ivabradine which mitigates the levels to fall below the critical levels. Secondary analysis of large trials show that combination works efficiently, and this is substantiated by the 2016 ESC guidelines for acute and chronic HF, which suggests higher level of evidence for the rationale

Conclusions:

Ivabradine improves uptitration of beta blockers in HF. Distinctive pharmacological properties of Carvedilol for unloading the heart makes it an evidence-based choice for the combination with Ivabradine, which antagonises spontaneous depolarisation for effective therapeutic heart rate reduction for managing heart failure.
EARLY AND CONTINUOUS DETECTION OF LEFT ATRIAL PHASIC DYSFUNCTION IN THE PROGRESSION OF HYPERTENSIVE CARDIAC REMODELING
Authors: Liu Yan , Zhao Yixiao , Sun Qiaobing , Lu Yan , Zhang Ying , Song Wei , Cheng Yunpeng , Cong Tao , Jiang Yinong
Published: April 2021

Objective:

Objective: The left atrium (LA) modulates left ventricular (LV) filling and cardiovascular performance with its reservoir, conduit, and booster pump functions. We used two dimensional speckle tracking echocardiography (2DSTE)-based strain and strain rate to evaluate LA mechanics in hypertensive patients with or without LA/LV structural remodeling.

Design and method:

Design and Method: We enrolled 30 healthy controls (Group I) and 302 HT patients, and we divided HT patients according to LV and LA structural remodeling. Group II (n = 101), HT without LVH and LA volume index (LAVI) < 28 mL/m2; Group III (n = 82), HT without LVH and LAVI > 28 mL/m2; Group IV (n = 98), HT with LVH and E/e‘ < 13; Group V (n = 21), HT with LVH and E/e‘ > 13. The strain and strain rate images were studied, and the following parameters were measured: LA reservoir strain and strain rate (LAS-S, LASR-S), LA conduit strain and strain rate (LAS-E and LASR-E), LA booster strain and strain rate (LAS-A and LASR-A). LA stiffness index (LASI) was defined as the ratio of E/e‘ to LAS-S.

Results:

Results: LASI was significantly higher in Group II than Group I (p < 0.05), and further increased in Group III and IV. LASI is the highest in Group V (p < 0.001 vs Group I and II, p < 0.05 vs Group III and IV). Generally, All strain and strain rate parameters, including LAS-S, LASR-S, LAS-E, LASR-E, LAS-A and LASR-A, gradually and significantly decreased from Group I to Group V. We also explored the correlation between LASI and cardiovascular risk factors as well as the other markers of TOD in HT. LASI was correlated with age, diabetes, hemoglobin A1c, systolic blood pressure, BMI, LVMI, Ma/Cre, carotid IMT, PWV, Triglycerides and eGFR. Multivariate regression analysis revealed that age, BMI, PWV and Ma/Cre were independent factors related to LASI.

Conclusions:

Conclusions: The abnormality of LA mechanics precedes LA enlargement and LVH in HT, and strain-derived LA phasic function declined further along with LA and LV remodeling and diastolic dysfunction. LASI can be identified as a detective biomarker of left cardiac remodeling and diastolic dysfunction in HT.
DOES ALDOSTERONE VIA MINERALOCORTICOID RECEPTORS AND ENAC PROMOTE INTERLEUKIN-17 PRODUCTION IN LYMPHOCYTES?
Authors: Thangaraj Sai Sindhu , Oxlund Christina , Mortensen Line Aas , Thiesson Helle , Abildgaard Ib , Jensen Boye
Published: April 2021

Objective:

Despite availability of antihypertensive therapeutic strategies, 20% of hypertensive patients remain resistant towards conventional treatment. Studies have shown that interleukin 17 (IL-17) from Th17 lymphocytes may be an important factor in the pathophysiology of hypertension. IL-17 plasma concentration is increased in hypertensive type 2 diabetes (T2D) patients compared to non-hypertensive diabetes patients. In vitro studies have shown the epithelial sodium channel ENaC to be expressed in lymphocytes. Activation of the mineralocorticoid receptor (MR) promotes pro-inflammatory Th17 lymphocyte differentiation in a spironolactone-sensitive way. We therefore hypothesized that aldosterone and ENaC may promote IL-17 production in lymphocytes ex vivo and from T2D hypertensive and kidney transplant patients in vivo.

Design and method:

Treatment resistant hypertensive T2D patients were included in a randomized double blinded study where patients were allocated to receive either spironolactone or placebo for 16 weeks (n = 116). After a two-week wash-out period the patients were included in an open label non-controlled follow-up study receiving amiloride for 8 weeks (n = 60). In a third randomized double blinded study, kidney transplant patients were allocated to receive either placebo or spironolactone for 1 year (n = 80). Plasma samples were available from all trials before and after intervention.

Key cytokines involved in Th17 differentiation (IL-17, IL-6, IL-1β, IL-10, IFN-γ, TNF-α) were measured in plasma samples from the three interventional studies using ELISAs from Mesoscale.

Results:

Spironolactone intervention in T2D hypertensive patients lead to a decrease in plasma IFN-γ and IL-6. Amiloride intervention in the same patient group showed with a decrease in plasma IL-6 and TNF-α and an increase in IL-10 levels

Conclusions:

Spironolactone and amiloride treatment of hypertensive and kidney transplant patients had no effect on IL-17 concentrations in plasma. Spironolactone suppressed the cytokines IFN-γ and IL-6, whereas amiloride decreased the levels of IL-6 and TNF-α and cause an increase in the anti-inflammatory cytokine IL-10. Since these are key cytokines of macrophage activation, MR and ENaC may be relevant for monocyte-macrophage activation. Future ex vivo experiments will be performed to elucidate the effect of amiloride and spironolactone on cytokine release from Th17 cells and macrophages.
IL-6 AND IL-10 ACTIVITY IN HYPERTENSIVE MEN WITH MODERATE OR HIGH CARDIOVASCULAR RISK
Authors: Orlova Natalya , Goryaynova Svetlana , Khachirova Asiyat , Spiryakina Yana , Posokhov Igor
Published: April 2021

Objective:

To assess IL-6, IL-10 activity in hypertensive men with moderate or high cardiovascular risk (CVR).

Design and method:

60 hypertensive men with moderate and high CVR were included. Two groups were formed: 1st - 30 hypertensive men with moderate CVR; 2nd - 30 men with high CVR. Control group - 15 men, 45–62 years old, without chronic diseases and hypertension. Anamnesis collection, CVR study, general examination, biochemical blood test, ECG, ECHO were held. IL-6, IL-10 were determined by the enzyme-linked immunosorbent assay method. The Mann-Whitney nonparametric test was used for groups comparison. The statistical significance of different values was determined by using the Pearson's Chi-square test. Correlation analysis was carried out on the basis of Spearman's nonparametric rank correlation.

Results:

IL-10 activity: moderate risk group - 5.18 [3.74; 7.03] pg/ml, high-risk group - 4.92 [2.96; 6.36] pg/ml, control group - 6.63 [5.90; 9.07] pg/ml. There was a statistically significant IL-10 decrease in the high-risk group in comparison with the control group (p = 0.0175). IL-6 activity: moderate risk group - 1.55 [0.75; 2.68] pg/ml, high-risk group - 1.16 [0.48; 2.41] pg/ml, control group - 1.02 [0.00; 9.83] pg/ml, there were no statistically significant differences in the groups. Correlation analysis revealed a multidirectional relationship between IL-10 and the hypertension duration in two groups: with a high risk a negative correlation was revealed (R = - 0.5, p < 0.01), with a moderate risk a positive correlation was revealed (R = 0.46, p < 0.05). IL-6 positively correlated with the thickness of the carotid artery intima-media complex (R = 0.41, p < 0.05) in men with moderate CVR.

Conclusions:

IL-10 decrease was revealed in hypertensive men with high CVR as compared to the healthy people. It can be used as an additional criterion for high CVR. The negative IL-10 correlation with the hypertension duration reflects the unfavorable development of hypertension in hypertensive men with high CVR. The detection of high IL-6 values in hypertensive men indicates the risk of endothelial dysfunction.
LONG-TERM CALORIC RESTRICTION IMPROVES MYOCARDIAL SIRT1/AMPK/PGC-1A PATHWAY IN C57BL/6J MICE
Authors: Ma Lina , Wang Rong
Published: April 2021

Objective:

Caloric restriction (CR) is capable of improving heart function, there is as yet no consensus on the mechanism of effect of CR. Silent mating-type information regulation 1 (SIRT1), adenosine monophosphate-activated protein kinase (AMPK), and mTOR are key players in metabolic stress management. We aimed to explore the effect of CR on myocardial SIRT1/AMPK/mTOR pathway in mice.

Design and method:

Thirty 6-week-old male C57BL/6J mice were randomly divided into three groups: normal control group (NC group, n = 12), high-energy group (HE group, n = 12) and CR group (n = 12) according to different diet. After 11 months, western blot was used to examine proteins such as p-AMPK, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1a), SIRT1, and p-mTOR, whereas real-time PCR was used to examine the expression of AMPK, PGC-1a, and SIRT1 transcripts.

Results:

Compared with NC group, the CR group displayed increased expression of myocardial p-AMPK, SIRT1 protein and mRNA, and PGC-1a mRNA. However, no difference was observed in the expression of p-mTOR protein and mTOR mRNA in the myocardium among the three groups.

Conclusions:

CR improves SIRT1/AMPK/PGC-1a pathway in mice myocardium with no effect on the mTOR pathway.
HYPERTENSIVE PATIENTS AS CANDIDATES FOR RENAL SYMPATHETIC DENERVATION: CONSENSUS OPINION OF HYPERTENSION EXPERTS IN GREECE
Authors: Doumas Michael , Andreadis Emmanouil , Davlouros Periklis , Dimitriadis Kyriakos , Gkaliagkousi Eugene , Grassos Harris , Hatzitolios Apostolos , Imprialos Konstantinos , Kalaitzidis Rigas , Kallistratos Emmanouil , Konstantinidis Dimitrios , Kotsis Vasilios , Makris Thomas , Manolis Athanasios , Marketou Maria , Papadakis Ioannis , Papadopoulos Dimitrios , Poulimenos Leonidas , Sanidas Ilias , Savopoulos Christos , Stavropoulos Konstantinos , Stergiou George , Thomopoulos Konstantinos , Triantafyllidi Helen , Triantafyllou Areti , Vlachakos Dimitrios , Zebekakis Pantelis , Ziakas Antonios , Tsioufis Costas
Published: April 2021

Objective:

Several studies have evaluated the efficacy and safety of renal sympathetic denervation (RSD) in patients with hypertension and other conditions characterized by sympathetic overactivity. However, to date there is no consensus in the literature about which patients are the most appropriate candidates for RSD. This analysis presents the opinions of hypertension experts in Greece regarding potential candidates for RSD.

Design and method:

Chairpersons of ESH Hypertension Excellence Centers in Greece and their senior clinical research fellows, were invited to participate in a meeting aiming to discuss the current evidence on the clinical utility of RSD. Individual responses were recorded and qualitatively analyzed, in order to reach consensus about potential RSD candidates.

Results:

Twenty-five experts participated in the meeting (cardiologists 52%, internists 40%, nephrologists 8%). (i) 84% of the experts agreed that patients with resistant or uncontrolled hypertension are the most eligible candidates for RSD. (ii) Patients who are either non-adherent to treatment (72%) or discontinued antihypertensive drugs due to adverse events (64%) were suggested as potential candidates. (iii) Patients with severe left ventricular hypertrophy or other TOD were also proposed as potential candidates (24%). (iv) Individuals with diseases associated with sympathetic overactivity (72%), such as obstructive sleep-apnea syndrome, chronic kidney disease, heart failure, arrhythmias, and polycystic ovary syndrome. (v) Patients at the initial stages of hypertension (12%), women of child-bearing potential (4%), drug naïve patients (16%), and patients of young age without TOD were also considered (12%). (vi) Hypertensive patients with increased sympathetic activity, such as patients with excessive white-coat hypertension or sodium sensitivity, were also proposed as potential candidates (8%). (vii) Patients preferring RSD over life-long drug treatment might also be eligible (24%).

Conclusions:

Seven patient groups were identified as potential candidates for RSD. Experts agreed on the eligibility of patients with resistant hypertension, yet other groups of patients were also proposed. More data are needed to properly identify those patients who will benefit the most from RSD, aiming towards personalized therapy in this field.
A 3-YEAR DURABILITY OF POWERFUL BLOOD PRESSURE LOWERING EFFECT OF DISTAL RENAL DENERVATION
Authors: Pekarskiy Stanislav , Baev Andrei , Falkovskaya Alla , Sitkova Ekaterina , Zubanova Irina , Lichikaki Valeria , Mordovin Viktor
Published: April 2021

Objective:

To evaluate efficacy and safety of anatomically optimized distal renal denervation (RDN) in segmental branches of renal artery.

Design and method:

We performed a double blind, randomized control study of the efficacy and safety of distal RDN versus conventional main trunk treatment in patients with true resistant hypertension (NCT02667912) with 3 year follow-up period. The efficacy of the RDN was evaluated by changes in ambulatory and office BP at 6, 12 and 36 month. The safety was assessed by a number of procedure-related adverse events, changes in the 24-h protein excretion, serum creatinine and eGFR during the same time periods.

Results:

Of 55 randomized patients who undergone RDN (28 - distal denervation vs 27 - main trunk treatment) 51 completed 6 month (27 vs 24), 47 - 12 month (23 vs 24), and 39 - 36 month follow-up (21 vs 18).

There was a powerful significant decrease in 24-h mean ambulatory systolic BP at 6 month after distal RDN that was, also, maintained throughout the follow-up, and remained statistically significant at the end of the study, -21.1 (95% CI -28.9;-13.3), -18 (95% CI -27.6;-8.5), -16.9 (95% CI -27.3;-6.5), mmHg, at 6, 12, and 36 month, respectively. In group of conventional main trunk treatment the same BP decreased substantially less at all study periods, and lost significance at 36 month. -10.3 (95% CI -17.8;-2.8), -12.1 (95% CI -19.2;-5.0), -8.7 (95% CI -19.7;2.2). Other ambulatory BP indices changed accordingly.

eGFR decreased in group of distal RDN at 1 year post-procedure -8.9 (95% CI -14.8;-3.1), mL/min/sq.m, however, slightly increased during next 2 years with finally non-significant change at the end of the study, -6.5 7 (95% CI -13.2;0.3). In contrast, in group of main trunk treatment eGFR remained unchanged during 1st year, -1.3 (95% CI -6.6;4.0) but progressed to statistically significant decrease at 3-year post-procedure, -5.0 (95% CI -9.6;-0.3).

Conclusions:

Anatomical optimization of renal denervation by redistributing treatments to segmental branches of renal artery produces a durable increase in the efficacy of the intervention without additional risk to the kidney.
EFFECT OF CHILD-TO ADULT RESTING HEART RATE TRAJECTORY ON SUBCLINICAL RENAL DAMAGE IN MIDLIFE
Authors: Yuan Yue , Mu Jian-Jun , Chu Chao , Zheng Wen-Ling , Ma Qiong , Hu Jia-Wen , Wang Yang , Yan Yu , Liao Yue-Yuan , Chen Chen
Published: April 2021

Objective:

It has been well established that an elevated resting heart rate (RHR) is associated with the development of chronic kidney damage (CKD), but the relationship between the developmental patterns of RHR and CKD has not been studied before.

Design and method:

A total of 2339 participants enrolled in the large-scale Hanzhong Adolescent Hypertension cohort study, which was established in 1987 and was followed up over 30 years, were included in the final analysis. Latent mixture modelling was used to explore the child-to-adult trajectories of the RHR.

Results:

We identified four RHR trajectories from childhood to adulthood: a low-stable group (class 1, n = 1104), a moderate-stable group (class 2, n = 1098), an increasing-decreasing group (class 3, n = 78), and a decreasing-increasing group (class 4, n = 59). Individuals in class 4 had the highest risk ratio (RR) of incident subclinical renal damage (SRD) after they were fully adjusted compared with those in class 1 [RRs = 4.12 (1.65–10.33), P < 0.01], and individuals in class 3 had nearly 1.43 times the risk of prevalent SRD compared with those in class 1. Significant differences existed in body mass index (BMI) by RHR trajectory groups in prepuberty, puberty and middle-aged adulthood (all P < 0.05). In subjects who were overweight, those in class 2 and class 4 had significantly higher risk of prevalent SRD when compared with those in class 1 [RRs = 1.65 (1.09–2.50), RRs = 5.39 (1.45–20.11), respectively].

Conclusions:

RHR lacks stability in middle-aged segments of the population. Elevated RHR and increasing RHR in midlife are independently associated with the development of SRD, particularly in overweight participants.
ANGIOTENSIN II-INDUCED EPITHELIAL-MESENCHYMAL TRANSITION IN PODOCYTES IS AGGRAVATED BY HOMOCYSTEINE VIA PI3K/AKT SIGNALING PATHWAY
Authors: Xu Rui , Zhao Xuan
Published: April 2021

Objective:

To evaluate the effects of Ang II on epithelial-mesenchymal transition (EMT) in podocytes and to explore whether homocysteine (Hcy) could aggravate it and the possible mechanisms.

Design and method:

A recently generated conditionally immortalized mouse podocyte cell line was cultivated as described before. Podocytes were divided into three groups, control group (CG), Ang II group (AG) and Hcy + Ang II group (H + A G). Podocytes of AG and H + A G were exposed to Ang II (10–6 mol/l) for 24 h, and meanwhile podocytes of H + A G were exposed to Hcy (8∗10–4 mol/l) for 24 h. All cells were FBS-deprived for 12 h before each experiment. EMT is characterized by loss of nephrin and observation of mesenchymal marker such as desmin. The expression of nephrin and desmin were assessed by quantitative real-time PCR (qRT-PCR) and Western blotting. The expression of AKT and p-AKT were assessed by Western blotting.

Results:

(1) Compared with CG, nephrin mRNA and protein were obviously decreased and desmin mRNA and protein were increased significantly (P < 0.05) in AG. (2) The decrease in nephrin and the increase in desmin were much more significant in H + A G than those in AG (P < 0.05). (3) An increased expression of P-AKT/AKT was observed in podocytes in H + A G, when compared with that in AG (P < 0.05).

Conclusions:

Ang II is a contributing factor to EMT in podocytes and Hcy could aggravate Ang II induced EMT via PI3K / AKT signaling pathway.
ASSOCIATION OF URIC ACID IN SERUM AND URINE WITH SUBCLINICAL RENAL DAMAGE: HANZHONG ADOLESCENT HYPERTENSION STUDY
Authors: Wang Yang , Chen Chen , Yan Yu , Yuan Yue , Wang Ke-Ke , Chu Chao , Hu Jia-Wen , Ma Qiong , Liao Yue-Yuan , Fu Bo-Wen , Gao Ke , Zhu Wen-Jing , Yang Lei , Sun Yue , Mu Jian-Jun
Published: April 2021

Objective:

Uric acid (UA) has been proposed as an important risk factor for cardiovascular and renal morbidity. The aim of the study was to examine the associations of UA in blood and urine with subclinical renal damage (SRD) and its progression in a Chinese cohort.

Design and method:

In 1987, we established the Hanzhong Adolescent Hypertension Study cohort based on a baseline survey of 4623 adolescents aged 6–15 years in Hanzhong, Shaanxi, China.

1) 2342 participants from our previously established cohort who were followed up in 2017 were included. Cross-sectional analysis was used to examine the relationships between serum and urinary UA and the risk of SRD.

2) A total of 266 participants were recruited from the same cohort in 2013, and followed up in 2017. Longitudinal analysis was used to determine the relationships of serum and urinary UA with progression of SRD, which was defined as urinary albumin-to-creatinine ratio (uACR) progression or estimated glomerular filtration rate (eGFR) decline.

Results:

In cross-sectional analysis, uACR levels were positively correlated with serum UA (β = 0.093, P < 0.001), and urinary uric acid/creatinine ratio (uUA/Cre) (β = 0.042, P = 0.041). eGFR was negatively associated with serum UA (β = −0.300, P < 0.001) but positively associated with uUA/Cre levels (β = 0.086, P < 0.001) in all subjects. Furthermore, the multivariate-adjusted odds ratios for SRD compared with non-SRD were 3.574 (2.255–5.664) for uUA/Cre. We further assessed the effect of UA excretion on the risk of SRD when uUA/Cre was modelled in quartiles. After adjusting for multiple confounders, the ORs (95% CIs) of SRD across increasing quintiles of uUA/Cre were 1.00, 1.122 (0.756–1.664), 1.362 (0.928–1.998) and 2.480 (1.719–3.578) (P for trend < 0.001). In longitudinal analysis, 4-year changes in uUA/Cre (β = −0.114, P = 0.040) and serum UA (β = 0.187, P = 0.001) were significantly associated with eGFR decline.

Conclusions:

This study suggested that urinary UA excretion was significantly associated with the risk of SRD in Chinese adults. Furthermore, 4-year changes of serum and urinary UA were associated with SRD progression. These findings suggest that UA, especially urinary UA, may be used as a simple, noninvasive marker for early detection of decreased renal function in otherwise healthy subjects.
RENAL PROTECTIVE EFFECTS OF URIC ACID-LOWERING THERAPY IN HYPERTENSIVE PATIENTS BY TOPIROXOSTAT AND FEBXOSTAT, NEWLY AVAILABLE XANTHINE OXIDASE INHIBITORS
Authors: Satoh Fumitoshi , Tezuka Yuta , Omata Kei , Ono Yoshikiyo , Yamanami Hiroaki , Morimoto Ryo , Ito Sadayoshi
Published: April 2021

Objective:

Elevated serum uric acid were related not only with cardiovascular disease but also with higher incident of chronic kidney disease in many cohort studies. Lower eGFR and higher urine albumin to creatine ratio (UACR) are associated with all-cause and cardiovascular mortality as well as future renal end-stage. Febxostat (FBX) and topiroxostat (TPX), new xanthine oxidase inhibitors with much less side effects as comparison to allopurinol, are available now. To demonstrate the effects of FBX and TPX on renal functions (eGFR and UACR) in well-controlled hypertensive patients.

Design and method:

We retrospectively collected 252 well-controlled hypertensive patients with hyperuricemia (HU) who newly received a prescription of FBX or TPX and continued 24 weeks without the addition of any other drugs. Those who had other uric acid-lowering drugs, diabetes mellitus or severe proteinuria were excluded. Total 252 Participants were selected and divided into FBX (128 patients) group and TPX (124 patients) group, both of who were matched for % mean dose/dairy conventional dose, age, sex, uric acid (UA), blood pressure (BP), UACR and eGFR. The changes of UA, BP, eGFR and UACR were evaluated between at the baseline and at the 24-week treatment by FBX and TPX.

Results:

The baseline characteristics were not significantly different between both treatment groups, which were analyzed by Mann-Whitney U test. Administration of FBX and TPX lowered UA significantly (p < 0.0001). Decrements of UA in both group were not significantly different. Diastolic BP of FBX group was only significantly reduced (BP129.3 ± 17.8/78.7 ± 12.4 mmHg to BP126.1 ± 16.3/76.2 ± 11.1 mmHg, p = 0.049). The eGFR in both FBX group and TPX group were significantly increased from 55.2 ± 15.0 to 56.8 ± 15.7 mL/min/1.73m2 (p = 0.0082) and from 57.3 ± 16.3 to 61.5 ± 16.3 mL/min/1.73m2 (p = 0.0002), respectively. In TPX and FBX groups, there were no significant differences in change of eGFR between patients using high and low amount of TPX and FBX, respectively. UACR was significantly decreased only in TPX group(90.0 ± 336 mg/gCr to 48.9 ± 171 mg/gCr, p = 0.027), while UACR in FBX group was not reduced (113 ± 376 mg/gCr to 120 ± 488 mg/gCr).

Conclusions:

FBX could improve eGFR and diastolic BP, and TPX could renoprotectively reduce UACR as well as increase eGFR.
HEALTH RELATED QUALITY OF LIFE AMONG HAEMODIALYSIS AND KIDNEY TRANSPLANT RECIPIENTS FROM NEPAL: A CROSS SECTIONAL STUDY USING WHOQOL-BREF
Authors: Ranabhat Kamal , Mishra Shiva Raj , Khanal Pratik , Adhikari Bhoj Raj , Sigdel Mahesh Raj , Pradhan Bandana
Published: April 2021

Objective:

Very less is known about health-related quality of life (HRQOL) among patients with kidney diseases in Nepal. This study examined HRQOL among haemodialysis and kidney transplant recipients in Nepal.

Design and method:

The Nepali version of World Health Organization Quality of Life Instruments -(WHOQOL-BREF) questionnaire was administered using face to face interviews among end stage renal disease (ESRD) patients, from two large national referral centers in Nepal. The differences in socio-demographic characteristics among ESRD patients were examined using the Chi-square test. The group differences in quality of life (QOL) were examined using the Mann-Whitney U test and Kruskal-Wallis tests.

Results:

Of the 161 participants, 92 (57.1%) were renal transplant recipients and 62 (42.9%) patients were on maintenance haemodialysis. Hypertension (70.9%) was the most common co-morbidity among ESRD patients. Haemodialysis patients scored significantly lower than the transplant recipients in all four domains as well as in overall perception of quality of life and general health. Ethnicity (p = 0.020), socio-economic status (p < 0.001), educational status (p < 0.001) and employment status (p = 0.009) were significantly associated with the overall QOL in ESRD patients. Across patient groups, educational status (p = 0.012) was positively associated with QOL in dialysis patients, while urban residence (p = 0.023), higher socio-economic status (p < 0.001), higher educational status (p = 0.004) and diabetes status (p = 0.010) were significantly associated with better QOL in transplant recipients.

Conclusions:

The overall QOL of the renal transplant recipients was higher than that of the patients on maintenance haemodialysis; this was true in all four domains of the WHOQOL-BREF. ESRD patients with low HRQOL could benefit from targeted risk modification intervention.
ORAL ETHINYLESTRADIOL-LEVONORGESTREL COUNTERACTS FRUCTOSE IMPACTS ON RENAL METABOLIC FUNCTION IN FEMALE WISTAR RATS
Authors: Olaniyi Kehinde , Olatunji Lawrence
Published: April 2021

Objective:

Renal function is critical in the regulation of cardiovascular parameters such as blood pressure and endothelial factors. However, evidence suggests that the excessive intake of fructose (FRU) induces insulin resistance (IR)-associated renal impairment, which perhaps contribute to global increase in cardiovascular disease (CVD). Similarly, the use of estrogen-progestin formulation of oral contraceptive (EEL) has been associated with metabolic disruption with consequent attendant CVD risk factors, and its non-contraceptive benefits especially in metabolic pathologies remain inconclusive. Therefore, the present study was designed to investigate the effects of EEL on renal metabolic function in female rats exposed to high fructose drink.

Design and method:

Female Wistar rats weighing 140–170 g were randomly allotted into control, EEL, FRU and EEL+FRU groups (6 rats per group). The groups received vehicle (p.o.), EEL containing 1.0 μg ethinylestradiol plus 5.0 μg levonorgestrel (p.o.), fructose (10%; w/v) and EEL plus FRU respectively, daily for 8 weeks. Insulin resistance, pancreatic beta-cell function and insulin sensitivity were estimated by homeostatic model of assessment (HOMA-IR), HOMA-beta and quantitative insulin sensitivity check index (QUICKI) respectively. Plasma and tissue biochemical parameters were determined using enzyme-linked immunosorbent assay kits or fluorescence assay as appropriate.

Results:

Data revealed that FRU or EEL caused IR, impaired glucose tolerance and hyperinsulinemia with corresponding increase in plasma or renal triglyceride, total cholesterol, atherogenic lipid, xanthine oxidase, uric acid, lactate synthesis, renal glycogen synthesis, decreased plasma or renal adenosine, glucose-6-dehydrogenase (G6PD) and glutathione (GSH). High fructose but not EEL increased plasma glucose, urea and creatinine, plasma or renal gamma-glutamyl transferase, malondialdehyde and decreased plasma or renal NO and pancreatic beta-cell function. Interestingly, these alterations were attenuated when EEL was concomitantly administered with FRU exposure.

Conclusions:

The results of the study demonstrate that high fructose intake causes renal impairment, attributable to lipid and glycogen deposition, and collectively accompanied by excessive lipid peroxidation, impaired NO/adenosine-dependent endothelial function and defective G6PD/GSH-dependent antioxidant defense. The findings also suggest that EEL blots the renal effects of high fructose by possibly improving insulin sensitivity, endothelial function and antioxidant defense.
THE INFLUNECE OF PULSE WAVE VELOCITY ON RENAL FUNCTION IN CHINESE EARLY KIDNEY DYSFUNCTION POPULATION: RESULTS FROM A LARGE-SCALE CROSS-SECTIONAL AND A 5-YEAR LOGITUDINAL STUDY
Authors: Len Yiming , Lu Yao , Yuan Hong
Published: April 2021

Objective:

Extensive researches show that arterial stiffness has been associated with chronic kidney disease, but the association with deterioration of renal function and its progression still remains unclear. We sought to investigate the relevance between arterial stiffness and the dynamic changes of renal function in Chinese populations,with or without chronic kidney disease.

Design and method:

This large-scale observational study comprised one cross-sectional and one longitudinal population samples totalling 655289 individuals, aged 21 to 74 years (mean age = 42.8 ± 12.7 years) from the Health Management Center in the Third Xiangya Hospital of Central South University with brachial-ankle pulse wave velocity (baPWV) measurements available. Associations with potential risk conditions were analysed using linear regression and linear mixed-effects models.

Results:

After adjusted for age,sex, BMI and MAP,baPWV showed a negative correlation with individuals with renal dysfunction (−0.01,−0.015∼-0.004,p < 0.001).Notably,it did not show significant correlation with individuals whose renal function was normal. The change of PWV was negatively associated with eGFR. The 5-year increase in PWV was associated with decrease in eGFR (−0.02,−0.035∼−0.012,p < 0.001) in mixed effect models adjusted for age, sex, ethnicity, age, BMI, and MAP.

Conclusions:

The increase of PWV showed extraordinary relevance among patients with the progression of kidney dysfunction rather than patients with normal kidney function,suggesting PWV measurement may help prompt the deterioration of kidney function. The current study may unravel a new understanding of the role arterial stiffening played in kidney dysfunction and set ground for the further clinical use as an early warning indicator.
LOCALIZATION OF NATRIURETIC PEPTIDE RECEPTORS IN HUMAN KIDNEY TISSUE
Authors: Jensen Mia , Frees Andreas , Assersen Kasper Bostlund , Madsen Kirsten , Lund Lars , Zamani Reza , Toft Anja , Hansen Pernille B. Lærkegaard , Schweda Frank , Jensen Boye Lagerbon
Published: April 2021

Objective:

Subsequent to partial and total nephrectomy, the remaining kidney tissue compensates by functional adaption. The glomerular filtration rate (GFR) and the renal blood flow increases. The post-nephrectomy GFR increases rapidly (as early as 8 h) from 50% up to 65–80% compared to pre-nephrectomy. The molecular mechanism is still unexplained. We hypothesized that the cardiac hormones atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) could mediate this response and thus, that their receptors would be expressed in the human kidney preglomerular vasculature, both in smooth muscle and in endothelial cells.

This study was conducted to localize the Natriuretic Peptide Receptor A (NPRA) and C (NPRC) at mRNA and protein level in human kidney tissue.

Design and method:

The localization of the receptors was investigated by; 1) determining vascular reactivity ex vivo in human intrarenal arteries in response to ANP and BNP; 2) microdissection of vessels and glomeruli from nephrectomy specimens followed by polymerase chain reaction (PCR); 3) immunohistochemistry and fluorescence analyses of fixed-paraffin embedded kidney sections and 4) RNAscope detection of mRNA in tissue sections.

Results:

ANP and BNP caused relaxation of K+-precontracted human arteries. NPRC mRNA was uniformly present in all arteries whereas NPRB was not detected and NPRA was seemingly less abundant in microvessels NPRC. Both NPRA and -C were observed in isolated glomeruli by PCR. NPRA was associated with glomeruli, glomerular podocytes and parietal layer of Bowman's capsule but not mesangial cells. Arteries, arterioles and vasa recta displayed uniform immunolabeling associated with endothelium across sex and age of the patients whereas vascular smooth muscle cells were more faintly and non-uniformly labeled. NPRA was detected in both the descending and ascending vasa recta. No labeling of tubular compartment for NPRA was seen. NPRB was not detected in human kidney tissue. By RNAscope on kidney sections, NPRC was observed in glomeruli but also in proximal tubules and collecting ducts.

Conclusions:

We conclude that functional NPRA and NPRC are located in human renal tissue, both NPRA and -C are found in the vasculature and could be involved in the acute increase of the GFR following nephrectomy.
EFFECTS OF NUCLEAR FACTOR OF ACTIVATED T-CELLS 5 (NFAT5) KNOCKOUT IN RENAL TUBULAR CELLS ON RENAL FIBROGENESISNFAT5 (NUCLEAR FACTOR OF ACTIVATED T-CELLS 5) IS A TRANSCRIPTION FACTOR
Authors: Izumi Yuichiro , Ono Makoto , Eguchi Koji , Matsuo Naomi , Hiramatsu Akiko , Nakayama Yushi , Inou Hideki , Kakizoe Yutaka , Kuwabara Takashige , Mukoyama Masashi
Published: April 2021

Objective:

NFAT5 (nuclear factor of activated T-cells 5) is a transcription factor that stimulates the expression of osmoprotective genes in response to extracellular hypertonicity, contributing to cell survival even in extreme hypertonic conditions as seen in renal medulla. Recent studies have suggested that activation of NFAT5 in macrophages in the skin induces lymphangiogenesis in response to high-salt diet, alleviating salt-sensitive hypertension. Pathophysiological roles of NFAT5 in the kidney, however, are still obscure. Not only hypertonicity but also hypoxia, oxidative stress, and toll-like receptor signaling, which promote fibrogenesis in the kidney, have been suggested to increase the NFAT5 activity. In the present study, the role of NFAT5 in renal fibrogenesis was examined using renal tubular cell-specific NFAT5 conditional knockout mice.

Design and method:

We generated renal tubular cell-specific NFAT5 conditional knockout (cKO) mice by crossing NFAT5 floxed mice with Pax8-rtTA/LC-1 mice, in which Cre recombinase was specifically expressed in renal tubular cells by the treatment with doxycycline. Wild-type (WT) mice and NFAT5 cKO mice were subjected to unilateral ureteral obstruction (UUO) or sham-operation. After 7 days, mice were sacrificed and kidneys were removed. The mRNA expression levels of NFAT5 and markers for fibrogenesis (TGF-beta, alfa-SMA, CCL2, Col1, Col3, KIM-1, and NGAL) in the kidney were examined by real-time PCR. Renal fibrosis was evaluated by Azan staining.

Results:

In WT mice, the expression of NFAT5 mRNA was two times greater in the kidney from UUO mice than that from sham-operated mice. Expressions of fibrogenesis-related genes were significantly increased in the kidney from UUO mice compared with those from sham-operated mice. In the UUO groups, the expressions of fibrogenesis-related mRNAs were significantly higher in the kidney from NFAT5 cKO mice compared with those from WT mice. Azan staining showed that UUO-induced renal fibrosis tended to get worse in NFAT5 cKO mice compared to WT mice.

Conclusions:

NFAT5 in renal tubular cells may exert protective actions against the development of renal fibrosis caused by UUO.
EPIDEMIOLOGY OF HYPERTENSION AMONG PATIENTS ON HEMODIALYSIS AND THE SIGNIFICANCE OF VOLUME OVERLOAD
Authors: Tsikliras N. , Georgianos P. , Karpetas A. , Minasidis E. , Syrganis C.H. , Anagnostara A. , Chatzidimitriou C. , Pikilidou M. , Liakopoulos V. , Zebekakis P. , Balaskas E.
Published: April 2021

Objective:

Earlier cross-sectional studies provided variable estimates of the prevalence and control of hypertension among patients on hemodialysis due to their heterogeneity in definitions and because they were based mainly on routine blood pressure (BP) recordings obtained within the dialysis-unit. The aim of the present study was to explore the epidemiology of hypertension in hemodialysis using home BP monitoring (HBPM).

Design and method:

A total of 120 prevalent hemodialysis patients underwent HBPM over 1 week with the validated automatic device HEM-705 CP (Omron, Healthcare). BP was recorded 3 times daily — on awaking up, between noon and at bedtime. The volume status of participants was assessed via bioelectrical-impendence-analysis (BIA) after the completion of the mid-week dialysis session using the BCM monitor (Fresenius Medical Care, Germany).

Results:

Hypertension (defined as 1-week averaged home BP higher than 135/85 mmHg or current use of antihypertensive medications) was detected in 88.8% of participants. Although 92.2% of hypertensives were being treated with an average of 2.0 BP-lowering medications, adequate control of home BP was achieved in only 32.6%. In multivariate logistic regression analysis, compared with those participants not receiving antihypertensive treatment (reference category), the odds ratio (OR) for uncontrolled hypertension was 3.15 for those receiving 1 antihypertensive, 3.85 for those receiving 2 antihypertensives and 18.1 for those receiving above 3 antihypertensives (P = 0.028 for the interaction). Each 1 L higher postdialysis overhydration was associated with 1.72 higher OR for uncontrolled home BP (P = 0.002).

Conclusions:

Hypertension in hemodialysis diagnosed by HBPM is highly prevalent and remains poorly controlled. Excessive antihypertensive drug use and extracellular volume expansion appear to be the strongest determinants of inadequate BP control in this population.
THE ROLE OF CALCIUM IN UROMODULIN EXPRESSION AND SECRETION FROM RENAL MEDULLARY EPITHELIAL CELLS OF HYPERTENSIVE AND NORMOTENSIVE RATS
Authors: Boder Philipp , Mary Sheon , Graham Lesley , Delles Christian
Published: April 2021

Objective:

Uromodulin (UMOD) is the most abundantly secreted protein found within the urine, primarily produced by medullary thick ascending limb (mTAL) epithelial cells of the kidneys. There is accruing genetic evidence implicating UMOD in blood pressure regulation and consequently hypertension. The aim of this study was to investigate the potential role of extracellular calcium and the calcium-sensing receptor (CaSR) on UMOD production and secretion in TAL cells with the hope of defining novel clinical targets for the treatment of hypertension.

Design and method:

mTAL tubules from Wistar-Kyoto (WKY) and stroke-prone spontaneously hypertensive (SHRSP) female rats were incubated with calcium, nifedipine (calcium channel blocker), CaSR agonist (spermine) and antagonist (NPS2143). UMOD protein levels were detected by Western blot. Gene expression of Umod was determined by qRT-PCR.

Results:

Calcium increased mTAL UMOD secretion in WKY and SHRSP. Nifedipine slightly decreased UMOD secretion in WKY without calcium. In both strains, NPS2143 increased calcium-induced UMOD secretion, with an enhanced effect in SHRSP. Stimulation of CaSR with spermine decreased UMOD secretion in WKY. Analysis of intracellular UMOD levels in these conditions demonstrated increased accumulation when extracellular secretion was low, and vice versa. Incubation of primary mTAL cells with calcium confirmed increased localisation of UMOD at the membrane compared to cytosol. The Umod mRNA level changes were not statistically significant among conditions.

Conclusions:

Trafficking of UMOD is influenced by the CaSR ligand and the biased nature of G-protein coupled CaSR signalling. Unravelling the signalling events post-calcium will be necessary for identification of key regulators of UMOD secretion.
SERUM ANTI-AGING PROTEIN - SIRTUIN 1 CONCENTRATION CORRELATES WITH IMPAIRED KIDNEY FUNCTION
Authors: Bielach-Bazyluk Angelika , Zbroch Edtra , Czajkowska Katarzyna , Koc-Zorawska Ewa , Rydzewska-Rosolowska Alicja , Kakareko Katarzyna , Hryszko Tomasz
Published: April 2021

Objective:

To compare serum concentration of sirtuin 1 between patients suffering from chronic kidney disease, conservatively treated and healthy volunteers. In addition, our aim was to establish its possible relation to kidney function, pharmacological treatment and demographic data.

Design and method:

Sirtuin 1 concentration was estimated in 102 patients suffering from stable chronic kidney disease and 26 healthy volunteers using commercially available assays. The correlation between sirtiuin 1 level, estimated glomerular filtration rate based on cystatin C, hypotensive therapy, statins use status, age and sex were analysed.

Results:

The median sirtuin 1 concentration in the study group was significantly higher than in the control group (2237.5 pg/mL vs 444.9 pg/mL, p < 0.001). Sirtuin 1 concentration positively correlated with CKD-EPI cystatin C eGFR (R = 0.51, p < 0.001), age (R = 0.23, p = 0.008), creatinine (R = 0.21, p = 0.038) and parathormone level (R = 0.26, p = 0.017). Statin and beta-blockers use were associated with decreased sirtuin concentration (p < 0.001 and p = 0.006, respectively). There were no differences in sirtuin 1 level between men and women (p = 0.779)

Conclusions:

Serum sirtuin 1 concentration was elevated in patients with chronic kidney disease and was dependent on the degree of kidney impairment. Statins and beta-blockers therapy was associated with decreased sirtuin 1 level. Patients with chronic kidney disease have excessive cardiovascular risk, which can be reduced by statins and beta-blockers use. Sirtuin 1 concentration may reflect high risk for cardiovascular disease. It could indicates individuals, who may benefit from more rigorous chronic kidney disease management. Further studies are warranted to establish if sirtuin 1 may become a novel, alternative marker of kidney function and cardiovascular risk.
CAPILLARY DENSITY DURING POSTOCCLUSIVE REACTIVE HYPEREMIA AND VENOUS CONGESTION DETERIORATES WITH ADVANCING CKD STAGES
Authors: Schoina Maria , Memmos Evangelos , Loutradis Charalampos , Dimitroulas Theodoros , Pagkopoulou Eleni , Theodorakopoulou Marieta , Binas Athanasios , Doumas Michael , Karagiannis Asterios , Garyfallos Alexandros , Papagianni Aikaterini , Sarafidis Pantelis
Published: April 2021

Objective:

Cardiovascular disease is the main cause of mortality in CKD patients. Endothelial dysfunction and capillary rarefaction are established cardiovascular risk factors. Nailfold video-capillaroscory provides a thorough assessment of capillary density and microcirculation changes. The aim of this study is to examine structural and functional capillary density in CKD patients of stages 2 to 4.

Design and method:

A total of 96 CKD patients were included in the study. The population consisted of 4 equal groups according to CKD stage (2, 3a, 3b and 4). All patients underwent nailfold video-capillaroscopy, during which capillary density was measured at baseline, after a 4-minute arterial occlusion (postocclusive reactive hyperemia) and at the end of a 2-minute venous occlusion (congestion phase). Arterial stiffness and arterial wave parameters were measured with applanation tonometry and common carotid intima-media thickness (IMT) with a 2D ultrasound device.

Results:

Capillary density at baseline showed a progressive reduction with advancing CKD stages (stage 2: 32.63 ± 2.79, stage 3a: 31.23 ± 3.84, stage 3b: 32.48 ± 3.34, stage 4: 28.50 ± 3.09, p < 0.001). Similar reductions were observed in capillary density during postocclusive hyperemia (39.42 ± 3.00, 37.63 ± 4.24, 38.35 ± 3.83, and 33.77 ± 3.34, respectively, p < 0.001) and after venous congestion (41.10 ± 3.09, 39.02 ± 4.41, 39.90 ± 3.51, and 35.21 ± 3.40, p < 0.001). Office pulse wave velocity showed a non-significant increasing trend with advancing CKD, but carotid IMT did not. In multivariate regression analysis, eGFR showed a positive association (per ml/min increase; OR: 0.053, 95%CI: 0.004 to 0.101), whereas diabetes (OR: -1.706, 95%CI: -3.176 to -0.236), and parathormone (PTH) (per pg/ml increase; OR: -0.022, 95%CI: -0.036 to -0.008) negative associations with post-occlusive capillary density.

Conclusions:

Both structural and functional capillary density progressively decrease with advancing CKD stages. Apart from reduced eGFR, the presence of diabetes and increased PTH levels are independently associated with this reduction. This capillary rarefaction may play a central role in the increased burden of cardiovascular events in CKD patients.