bluuebunny/crossref_metadata_2025_split huggingface dataset:
LONGER TELOMERE LENGTH IN BALKAN ENDEMIC NEPHROPATHY PATIENTS UNDERGOING CHRONIC HEMODIALYSIS IS ASSOCIATED WITH LOWER CARDIOVASCULAR MORTALITY
Authors: Toupance Simon , Premuzic Vedran , Hollander Allyson , Stipancic Zelimir , Bukal Nikolina , Jelakovic Ana , Brzic Ivan , Benetos Athanase , Jelakovic Bojan 
Published: June 2023

Objective:
Balkan endemic nephropathy (BEN) is characterized with later onset, milder forms of hypertension and lower pulse wave velocity (PWV) than other end-stage kidney disease (ESKD). We hypothesized that telomere length (TL) would be longer in BEN patients and associated with lower PWV and less cardiovascular (CV) mortality.

Design and method:
124 patients undergoing hemodialysis (HD) (68 BEN, 56 non-BEN; 48.4% men; 65±14 years) were enrolled and followed-up for 72 months. Blood pressure and PWV were determined before mid-week dialysis. TL was measured in leukocytes by Southern blot.

Results:
Age and sex-adjusted TL was significantly longer in the BEN group (7.19 kb vs 6.79 kb; p<0.001). TL was associated in the BEN group with PWV, and in the non-BEN group with age. BEN patients presented significantly lower CV mortality than non-BEN patients (p<0.001). In the BEN group shorter TL was the only determinant of shorter survival (HR 0.11 [95% CI 0.03, 0.35]). To analyze the diagnostic value of TL for CV mortality we used ROC analysis that revealed TL < 6.21 kb to be useful for prediction of CV mortality in patients undergoing chronic HD.

Conclusions:
Shorter TL is associated with CV mortality in patients undergoing chronic HD. BEN patients had longer TL and longer survival than other ESKD patients. In BEN patients, TL was negatively associated with PWV. This study confirmed our hypothesis that BEN is associated with slower vascular aging and that longer TL may partially explain this phenomenon.
EFFECTS OF SODIUM-GLUCOSE CO-TRANSPORTER 2 INHIBITORS ON CARDIOVASCULAR MORTALITY IN CHRONIC KIDNEY DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Alexandrou Maria Eleni , Pella Eva , Tsitouridis Alexandros , Theodorakopoulou Marieta , Sampani Erasmia , Georgiou Areti , Kamperidis Vasileios , Papagianni Aikaterini , Sarafidis Pantelis 
Published: June 2023

Objective:
In studies of patients with chronic kidney disease (CKD), recommended nephroprotective therapy with ACE-inhibitors or ARBs has not been shown to reduce cardiovascular (CV) events or mortality. Sodium-glucose co-transporter 2 (SGLT-2) inhibitors reduce cardiovascular events and death in patients with diabetes and established CV disease; evidence from studies in populations with CKD has been inconsistent. The aim of this meta-analysis was to evaluate the effect of SGLT-2 inhibitors on cardiovascular (CV) mortality in patients with CKD.

Design and method:
Studies were identified by search in major electronic databases (PubMed/MEDLINE, Scopus, Cochrane Library and Web of Science) (PROSPERO ID: CRD42022382863). We included randomized controlled trials assessing the effect of SGLT-2 inhibitors on the primary outcome, time to cardiovascular death, in patients with CKD at baseline. Secondary outcomes included all-cause mortality and major adverse cardiac events (MACE).

Results:
Eleven studies with 83,203 participants with CKD were eligible for inclusion in the meta-analysis. Treatment with SGLT-2 inhibitors, compared to placebo, reduced the risk of CV death by 14% (hazard ratio [HR] 0.86; 95%CI 0.79-0.94), of all-cause death by 15% (HR 0.85; 95%CI 0.79-0.91) and of MACE by 13% (HR 0.87; 95%CI 0.81-0.93). A consistent treatment effect on the primary outcome was observed with all SGLT-2 inhibitors (canagliflozin: HR 0.84; 95%CI 0.69-1.02, dapagliflozin: HR 0.89; 95%CI 0.78-1.01, empagliflozin: HR 0.82; 95%CI 0.69-0.97 sotagliflozin: HR 0.90; 95%CI 0.73-1.12) studied (p-subgroup-differences = 0.85). Sensitivity analysis pooling data from studies including only diabetic patients with CKD yielded similar results (HR 0.86; 95%CI 0.77-0.97).

Conclusions:
Treatment with SGLT-2 inhibitors led to a significant reduction in the risk for CV and all-cause mortality in CKD patients. These findings support the use of these agents also for protection against cardiovascular events and death in CKD.
HOW TO INTERPRET URINARY PROTEINURIA AS A MARKER OF HYPERTENSIVE NEPHROPATHY?
Authors: Nawal Habak , Nadjet Rouibah , Ammar Chikouche 
Published: June 2023

Objective:
Proteinuria may be the first sign of underlying nephropathy. It is pathological when the value is higher than 0.15 g/24h.
The gold standard of quantification is the determination of proteinuria on the collection of urine for 24 hours, however, in view of the errors related to the collection and storage, we adopted another mode of expression.
The objective of our work is to evaluate the correlation between the results of the 24 hours proteinuria and the proteinuria calculated by ratio (proteinuria/creatinuria).

Design and method:
Our prospective comparative study was performed on 100 24-hour urine samples (100 patients).
We recorded the 24h diuresis and we determined the proteinuria by the pyrogallol red method (Advia 1800) and the urinary creatinine by the compensated jaffa method (Cobas 6000). Statistical evaluation was performed using GraphPad Prism software7

Results:
Our results show: the average proteinuria of 24 h is 309.7 mg/24H (the norms lower than 150 mg/24H) and the average proteinuria/creatinine ratio is 283.7 mg/g (the norms lower than 300 mg/g).
Of the 100 samples, only 5 patients (5%) showed pathological 24-hour proteinuria with a proteinuria/creatinuria ratio within the norms, and one patient (1%) had 24-hour proteinuria within the norms and a high proteinuria/creatinuria ratio, 25 patients (25%) had a simultaneous increase in 24-hour proteinuria and in the proteinuria/creatinuria ratio The remaining 69 patients (69%) had 24-hour proteinuria and a proteinuria/creatinuria ratio within the physiological norms
The comparative study found a significant difference p<0.0001 with a significant positive Pearson correlation R 2 = 0.92. The agreement of the 24 h proteinuria tests and the Proteinuria/creatinuria ratio is modelled by the Bland and Altman diagram which finds a bias of 1.02 and a Confidence interval 95%] 0.046-1.36 [.

Conclusions:
Therefore it is not necessary to carry out a 24-hour urine collection, preferring measurements on urine samples from the first morning micturition. In order to overcome the numerous false positives and negatives linked to the collection of 24-hour urine, this examination is a good alternative.
INTRARENAL RESISTANCE INDEXES AND NONALCOHOLIC FATTY LIVER DISEASE IN UNTREATED HYPERTENSIVE PATIENTS
Authors: Bulfone Luca , Vacca Antonio , Catena Cristiana , Cicco Sebastiano , Soardo Giorgio , Donnini Debora , Bortolin Giulia , Candusso Giulia , Baiano Valeria , Comand Jacopo , Sechi Leonardo 
Published: June 2023

Objective:
Nonalcoholic Fatty Liver Disease (NAFLD) is reaching epidemic proportions with a prevalence in the adult population of approximately 25%. A continuum of hepatic conditions is embraced by NAFLD, from plain steatosis to liver fibrosis that can be assessed by use of surrogate clinical/biochemical scores. Recent studies have reported an association of NAFLD with chronic renal failure and its progression in the general population. Because increasing of intrarenal resistance indexes (IRI) anticipate worsening of renal function in hypertension we investigated their relationships with liver steatosis and fibrosis scores in never treated hypertensive patients.

Design and method:
In a cross-sectional study of 111 treatment-naïve, essential hypertensive patients we measured IRI and calculated scores of liver steatosis (LFS: liver fatty score; FLI: fatty liver index; HIS: hepatic steatosis index) and liver fibrosis (NFS: NAFLD fibrosis score; APRI: aminotransferase to platelet ratio index; FIB-4: fibrosis 4).

Results:
IRI were significantly and directly correlated with the LFS (r = 0.240, P = 0.025) while a borderline correlation was observed with NFS (r = 0.206, P = 0.052). No significant relationships were observed with the remaining liver steatosis and fibrosis scores. Multivariate analysis indicated an independent association of IRI and LFS (B = 0.309, P = 0.030).

Conclusions:
In treatment-naïve hypertensive patients IRI are independently associated with a score of liver steatosis suggesting that NAFLD might contribute to worsening of renal function in these patients.
RELATIONSHIP BETWEEN BMI IN ADOLESCENCE, BMI TRAJECTORIES IN ADULTHOOD AND CHRONIC KIDNEY DISEASE OUTCOMES: POPULATION-BASED COHORT STUDY
Authors: Vitkauskaite Monika , Stankevicius Rytis , Macioniene Ernesta , Miglinas Marius , Brunström Mattias 
Published: June 2023

Objective:
We aimed to investigate the association of BMI in late adolescence and BMI trajectories in adulthood with chronic kidney disease (CKD), end-stage kidney disease (ESKD) and acute kidney injury (AKI) later in life.

Design and method:
Two cohort analyses were performed, firstly evaluating the link between adolescent BMI and CKD, ESKD and AKI throughout life, secondly assessing the link between BMI change from adolescence to midlife, and the risk of CKD, ESKD and AKI thereafter. Data from the Swedish Conscription Register, the Northern Sweden Health and Disease Study, the Swedish National Patient Register and the Cause of Death Register were included. Patients were stratified into quintiles of BMI in adolescence and BMI change until midlife. Data were analysed using Cox proportional hazards model.

Results:
1 324 831 subjects met the inclusion criteria for BMI evaluation in late adolescence. The mean age at conscription was 18.3±0.8 years and the average BMI was 21.6±2.6 kg/m2. 5593 subjects developed CKD, 2358 developed ESKD and 8029 developed AKI. In the adjusted analyses, an increased risk of developing CKD and ESKD was seen from the fourth BMI quintile (HR 1.25, 95% CI 1.15-1.36 for BMI 21.9-23.6 kg/m2; HR 2.13, 95% CI 1.97-2.31 for BMI >23.6 kg/m2, for CKD), whereas the risk of AKI was increased already from the third BMI quintile (HR 1.15, 95%CI 1.15-1.24 for BMI 20.7-21.9 kg/m2). 32 221 subjects in a regional cohort had an additional BMI evaluation at mean age 42.1±8.6 years. The mean change in BMI between assessments was 4.8±3.2 kg/m2. We found that BMI increase of >7 kg/m2 from late adolescence to mid-life was associated with higher risk of CKD (HR 2.78, 95%CI 1.45-5.30) and AKI (3.49, 2.23-5.47) in non-adjusted analyses; only AKI persisted after adjustment (HR 2.60, 95%CI 1.58-4.28).

Conclusions:
To conclude, BMI in late adolescence is associated with CKD and ESKD, with increased risk from BMI levels >21.9 kg/m2. BMI increase during adulthood was only associated with an increased risk of AKI after covariate-adjustment, suggesting that adolescence is a critical period for the association between BMI and future kidney disease.
C-ATRIAL NATRIURETIC PEPTIDE (ANP)4-23 ATTENUATES RENAL FIBROSIS IN DEOXYCORTICOSTERONE-ACETATE-SALT HYPERTENSIVE MICE
Authors: Lu Yuanyuan , Li Shijin , Li Xiaodong , Gao Pingjin 
Published: June 2023

Objective:
Epithelial-mesenchymal transition (EMT) plays a critical role in hypertension-induced renal fibrosis, a final pathway that leads to end-stage renal failure. C-Atrial natriuretic peptide (ANP)4-23, a specific agonist of natriuretic peptide receptor-C (NPR-C), has been reported to have protective effects against hypertension. However, the role of C-ANP4-23 in hypertension-associated renal fibrosis has not yet been elucidated.

Design and method:
In this study, mice were randomly divided into SHAM group, DOCA-salt group, DOCA-salt + C-ANP4-23 group and C-ANP4-23 group. Renal morphology changes, renal function and fibrosis were detected. Human proximal tubular epithelial cells (HK2) stimulated by aldosterone were used for cell function and mechanism study.

Results:
The DOCA-salt treated mice exhibited hypertension, kidney fibrosis and renal dysfunction, which was attenuated by C-ANP4-23. Moreover, C-ANP4-23 inhibited DOCA-salt treatment-induced renal EMT as evidenced by decrease of the mesenchymal marker alpha-smooth muscle actin (ACTA2) and vimentin and increase of epithelial cell marker E-cadherin. In HK2 cells, aldosterone induced EMT response, which was also suppressed by C-ANP4-23. The key transcription factors (twist, snail, slug and ZEB1) involved in EMT were increased in the kidney of DOCA-salt-treated mice, which were also suppressed by C-ANP4-23. Mechanistically, C-ANP4-23 inhibited the aldosterone-induced translocation of MR from the cytosol to the nucleus without change of MR expression. Furthermore, C-ANP4-23 prevented the enhanced expression of NADPH oxidase (NOX) 4 and oxidative stress after aldosterone stimulation. Aldosterone-induced Akt and Erk1/2 activation was also suppressed by C-ANP4-23.

Conclusions:
Our data suggest that C-ANP4-23 attenuates renal fibrosis, likely through inhibition of MR activation, enhanced oxidative stress and Akt and Erk1/2 signaling pathway.
A CROSS-SECTIONAL STUDY OF SERUM OSTEOCALCIN LEVEL ASSOCIATED WITH PERIPHERAL ARTERIAL STIFFNESS BY BRACHIAL-ANKLE PULSE WAVE VELOCITY IN HYPERTENSIVE PATIENTS
Authors: Wang Yung-Hsuan , Wang Hui-Sheng , Wang Ji-Hung , Hsu Bang-Gee 
Published: June 2023

Objective:
Brachial-ankle pulse wave velocity (baPWV) is recognized as an independent risk factor for cardiovascular events, cardiovascular mortality, and all-cause mortality. Osteocalcin (OC) is associated with vascular function. The aim of this study was to evaluate the relationship between serum OC levels and peripheral arterial stiffness (PAS) in hypertensive patients measuring by baPWV.

Design and method:
Fasting blood samples were obtained from 120 hypertensive patients. Peripheral arterial stiffness was measured by baPWV device. Serum total OC levels were measured using a commercial enzyme-linked immunosorbent assay kit. Left or right brachial-ankle pulse wave velocity (baPWV) > 18.0 m/s defined the PAS group.

Results:
Twenty-four patients (20.0%) were included in the PAS group in hypertensive patients. Hypertensive patients with PAS had a significantly higher percentage of diabetes (P = 0.010), older age (P = 0.011), higher systolic blood pressure (P = 0.019), serum fasting glucose (P = 0.003), blood urea nitrogen (P = 0.024), creatinine (P = 0.004), C-reactive protein (P = 0.007), and OC level (P = 0.002), while lower estimated glomerular filtration rate (P = 0.004) than those without PAS. After multivariable logistic regression analysis, serum OC level (Odds ratio [OR]: 1.797, 95% confidence interval (CI): 1.077–3.000, P = 0.025), and age (OR: 1.076, 95% CI: 1.004–1.153, P = 0.037) are independently associated with PAS in hypertensive patients.

Conclusions:
Serum OC levels and older age are positively associated with PAS in hypertensive patients.
MUSCLE OXYGENATION AND MICROVASCULAR REACTIVITY ACROSS DIFFERENT STAGES OF CHRONIC KIDNEY DISEASE: A NEAR-INFRARED SPECTROSCOPY STUDY
Authors: Theodorakopoulou Marieta , Zafeiridis Andreas , Dipla Konstantina , Faitatzidou Danai , Koutlas Aggelos , Doumas Michael , Papagianni Aikaterini , Sarafidis Pantelis 
Published: June 2023

Objective:
Previous studies in chronic kidney disease(CKD) showed that vascular dysfunction in different circulatory beds is progressively deteriorating with CKD severity. This study evaluated muscle oxygenation and microvascular reactivity at rest, during an occlusion-reperfusion maneuver, and during exercise in patients with pre-dialysis CKD versus controls, as well as between different CKD stages

Design and method:
This observational controlled study included 90 participants (18 per CKD stage 2, 3a, 3b, 4 and 18 controls). Continuous measurement of muscle oxygenation [tissue saturation index (TSI%)] via near-infrared-spectroscopy at rest, during occlusion-reperfusion, and during a 3-min handgrip exercise(at 35% of maximal-voluntary-contraction). Aortic pulse wave velocity (PWV) and carotid intima-media thickness (cIMT) were also recorded.

Results:
Resting muscle oxygenation did not differ among the study groups (controls: 64.3±2.9 stage-2: 63.8±4.2 stage-3a: 64.1±4.1 stage-3b: 62.3±3.3 stage-4: 62.7±4.3%; p = 0.6). During occlusion, no significant differences among groups were detected in TSIocl magnitude- and occlusion-slope. However, during reperfusion, the TSImax and the hyperemic response were significantly lower in groups of patients with more advanced CKD stages (controls: 11.2±3.7 stage-2: 8.3±4.6 stage-3: 7.8±5.5 stage-3b: 7.3±4.4 stage-4: 7.2±3.3; p = 0.04). During handgrip exercise, muscle oxygenation (TSIaverage-decline) was marginally lower in CKD patients than controls, but no significant differences were detected between CKD stages.

Conclusions:
Although no differences were observed in muscle oxygenation at rest and during occlusion, the microvascular hyperemic response during reperfusion was significantly impaired in CKD and deteriorated in more advanced CKD stages. This impaired ability of microvasculature to respond to stimuli may be a crucial component of the adverse vascular profile of CKD patients and may contribute to exercise intolerance
FACTORS RELATED TO SKIN MICROVASCULAR DYSFUNCTION IN INDIVIDUALS WITH DIFFERENT RANGE OF GLUCOSE LEVELS
Authors: Lamprou Stamatina , Koletsos Nikolaos , Zografou Ioanna , Mintziori Gesthimani , Lazaridis Antonios , Doumas Michael , Gkaliagkousi Eugenia , Triantafyllou Areti 
Published: June 2023

Objective:
Existing data confirm the presence of microvascular dysfunction in hypertension and diabetes mellitus (DM). Prediabetes is recognized as a significant metabolic status, being a key factor in the occurrence of DM and there is increasing evidence concerning microvascular complications in prediabetes. Laser speckle contrast analysis (LASCA) is a non-invasive technique that can be used to evaluate skin microvascular function. The aim of our study was to assess cardiovascular factors that are possibly associated with microvascular reactivity in a population from normoglycaemia to DM.

Design and method:
Individuals with normoglycemia, prediabetes and diabetes without established cardiovascular disease were included in the study. In all participants, forearm skin blood flow was recorded under standardized conditions using a laser speckle contrast imager (PeriCam PSI NR System, Perimed). Post-occlusive reactive hyperaemia (PORH) was assessed following a standardized protocol and data were analyzed with a signal processing software (PIMSoft, Perimed). Skin microvascular reactivity was expressed as a percentage increase between baseline and peak perfusion (%). Office BP was measured in each participant according to a standard methodology and aortic blood pressure was assessed using the Sphygmocor device.

Results:
Fifty individuals (18 patients with prediabetes, 16 patients with DM and 16 controls) were included in the study. In the univariate model both glucose levels and aortic systolic blood pressure (aSBP) correlated inversely with microvascular reactivity (r = -0.382 and r = -0.349, p<0.01 for both comparisons) However, in the multivariate model only the association with aSBP remained statistically significant (beta = -0.363, p<0.05).

Conclusions:
Only central SBP, but not glucose predicted skin microvascular dysfunction in individuals with normoglycemia, prediabetes and diabetes and without established cardiovascular disease.
COMPARATIVE EFFECT OF ATENOLOL AND NEBIVOLOL ON REVERSE REMODELING OF INTRAMURAL CORONARY ARTERIOLES IN THE SPONTANEOUSLY HYPERTENSIVE RAT MODEL
Authors: Ciuceis Carolina De , Bonomini Francesca , Rosei Claudia Agabiti , Lemoli Matteo , Giugno Lorena , Rossini Claudia , Lonati Claudio , Chiarini Giulia , Malerba Paolo , Famà Francesca , Muiesan Maria Lorenza , Rizzoni Damiano , Rezzani Rita 
Published: June 2023

Objective:
Arterial hypertension is an established major risk factor for ischemic heart disease. Functional and structural abnormalities at the level of the microcirculation may play a crucial role in coronary microvascular dysfunction. Indeed, coronary flow reserve is often reduced at angiography in hypertensive patients independently on the presence of left ventricular hypertrophy (Mancini M. et al. Microcirculation 2017). The aim of this study was to assess the effect of the beta-blocker Atenolol and the selective third-generation beta1-adrenergic antagonist Nebivolol on markers of remodeling and endothelial dysfunction in coronary microvascular. Nebivolol has been demonstrated to possess direct vasodilator and antioxidant properties which may improve endothelial dysfunction and reduce smooth muscle cell proliferation.

Design and method:
For this purpose, we used three groups of SHR rats: Hypertensive untreated group (SHR); SHR plus Atenolol 50 mg/kg/day by oral gavaging for 8 weeks (SHR + ATE); SHR plus Nebivolol 20 mg/kg/day by oral gavaging for 8 weeks (SHR + NEB). Protein expression levels of vasoactive factors, oxidative stress and remodeling markers in coronary microcirculation were determined by immunohistochemical analysis of Endothelin-1 (ET-1), inducible nitric oxide synthase (iNOS) and transforming growth factor-beta1 (TGF-beta1).

Results:
No differences were observed in structural parameters of mesenteric arteries among groups. SHR + NEB showed a significant reduction in ET-1, iNOS, and TGF-beta1 staining in coronary small arteries comparing to SHR and SHR + ATE.

Conclusions:
In comparison to atenolol, nebivolol may provide additional benefit beyond blood pressure reduction and beta-receptor blockade since show greater activity in the modulation of protein involved in vasodilation and oxidative stress protection.
RETINAL ARTERIOLAR REMODELING IN PRIMARY ALDOSTERONISM: A STUDY WITH ADAPTIVE OPTICS
Authors: Rosei Claudia Agabiti , Ciuceis Carolina De , Rossini Claudia , Petelca Alina , Dusi Margherita , Chiarini Giulia , Malerba Paolo , Porteri Enzo , Salvetti Massimo , Rizzoni Damiano , Muiesan Maria Lorenza 
Published: June 2023

Objective:
Primary aldosteronism (PA) represents the most frequent form of secondary hypertension. In previous studies an hypertrophic remodeling, with smooth muscle cell growth and an increase in media to lumen ratio (MLR), has been shown in patients with primary aldosteronism (Rizzoni D et al. Hypertension 1996;28:785–790.). To date, Adaptive Optics (AO) is one of the most innovative and non-invasive methods for studying the wall-to-lumen ratio of retinal arterioles (WLR), which directly correlates with the MLR of subcutaneous small arteries (De Ciuceis C et al. J Hypertens. 2018;36(5):1154-1163.).

Design and method:
Therefore, the aim of this study was to evaluate microvascular structure of retinal arterioles by Adaptive Optics in PA patients, before and after pharmacological or surgical treatment, compared to essential hypertensive patients (EH). Eleven patients with PA before treatment have been matched with 11 patients with EH and 11 patients with treated PA in follow up. All patients underwent assessment of retinal microcirculation morphology with AO (RTX-1, Imagine Eyes; Orsay, FR) in order to calculate WLR and wall cross sectional area (WCSA).

Results:
A total of 33 patients was enrolled in the study. PA patients at the baseline showed a significant higher WLR compared to EH and to PA in follow-up (Figure 1; 0.31±0.03 vs 0.27±0.04 vs 0.275±0.03 respectively; p = 0.01). Otherwise, differences between WCSA turned out to be less relevant with no significant differences among the three groups (4500.85±879.9 vs 4195.96±553.3 vs 4278.52±836.6 respectively; p = ns).

Conclusions:
Our data confirm with a non-invasive technique the presence of a more evident retinal arterioles remodeling in PA patients compared to EH patients, as suggested by the increased WLR, and an improvement in WLR after PA surgical or pharmacological treatment. Further studies in a larger population are needed in order to confirm these data.