bluuebunny/crossref_metadata_2025_split huggingface dataset:
FEATURES OF CHANGES IN THE LEVELS OF MATRIX METALLOPROTEINASES AND THEIR INHIBITORS IN DIABETIC PATIENTS WITH RESISTANT HYPERTENSION AFTER RENAL DENERVATION
Authors: Falkovskaya Alla , Mordovin V. , Pekarskiy S. , Manukyan M. , Zyubanova I. , Lichikaki V. , Tsoy E. , Vtorushina A. , Khunkhinova S. , Gusakova A. , Moiseeva A. , Caraus A. , Tsymbalyuk E. 
Published: June 2022

Objective:
The family of matrix metalloproteinases (MMPs) involved in fibrogenesis, but the effect of renal denervation (RDN) on their levels is currently insufficiently studied and highly controversial. The aim of study was to evaluate the change in MMPs and their inhibitors during 2 years after RDN in patients with resistant hypertension (RHTN) and type 2 diabetes mellitus (DM).

Design and method:
Forty three patients with RHTN and type 2 DM were included in single-arm prospective interventional studies (protocol numbers NCT01499810 and NCT02667912 on ClinicalTrials.gov) (mean age 60.6 ± 8.8 years, mean office (systolic/diastolic) blood pressure (BP) 169.7/89.1 ± 19.2/15.2mmHg, HbA1c 6.7 ± 1.4%, 17(40%) men). All patients were undergone to ambulatory 24-hour BP and assessment of lab testes (plasma concentrations of MMP-9, MMP-2, tissue inhibitor of MMP type 1 (TIMP1), TIMP-1/MMP-2 and TIMP-1/MMP-9 ratios) at baseline and at 6–12–24 months follow-up. The patients were advised not to change their medication regimen during the study.

Results:
At baseline 70%/16%/17% of patients had an elevated level of MMP-9/MMP-2/TIMP-1, respectively. At 6 months after RDN there was a significant decrease in mean 24-hour systolic/diastolic BP (SBP/DBP) (-8.8 [95%CI -1.3;-18.4]/-8.6 [95%CI -2.5;-4.7] mmHg, P < 0.05). The number of responders (patients with decrease in 24-hour SBP 10 mmHg and more) was 26 (61%). There were no significant changes in the mean levels of MMPs, TIMT1 and their ratios at 6-12-24 months follow up. At the same time, at 2 years after RDN there was a significant decrease in level of MMP-9 in responders compared with non-responders (-319.6[-2.3;-636.8] ng/mL, p = 0.04 vs 66.6 [221.4;-354.5] ng/mL, p = 0.63).

Conclusions:
Our data indicate the decrease in the MMP-9 level at 2 years after RDN only in the responders, that may be due to a decrease in the hemodynamic load and peripheral vasodilation that no longer requires the involving of proteolytic systems for an improvement in tissue blood flow.
DIAGNOSTIC PERFORMANCE OF PRE-DIALYSIS AND AMBULATORY BLOOD PRESSURE LEVELS IN MEN AND WOMEN HEMODIALYSIS PATIENTS
Authors: Karagiannidis Artemios , Theodorakopoulou Marieta , Alexandrou Maria-Eleni , Faitatzidou Danai , Baksiova Afroditi , Giamalis Panagiotis , Papagianni Aikaterini , Sarafidis Pantelis 
Published: June 2022

Objective:
Ambulatory-blood-pressure (BP) control is worse in men than in women with chronic kidney disease or kidney transplantation. So far no study assessed in parallel possible effects of sex differences on the prevalence, control, and BP phenotypes according to pre-dialysis and 48-h ABPM in hemodialysis patients. Further, no study has evaluated the diagnostic accuracy of pre-dialysis BP in men and women hemodialysis patients.

Design and method:
129 male and 91 female hemodialysis patients that underwent 48-h ABPM with Mobil-O-Graph-NG were included in this analysis. Hypertension was defined as follows: (1)pre-dialysis BP greater than or equal to 140/90mmHg or use of antihypertensive agents, (2)48-h BP greater than or equal to 130/80mmHg or use of antihypertensive agents.

Results:
The prevalence of hypertension was not different between men and women with the use of pre-dialysis BP (92.2% vs 92.3%, p = 0.987, respectively) or 48-h ABPM (92.2% vs 89%, p = 0.411). With the use of pre-dialysis BP men had significantly lower control rates than women (18.5% vs 32.1%, p = 0.025); a similar pattern of worse control in men was apparent with ABPM, but the difference was not statistically significant (22.7% vs 28.4%, p = 0.360). The rate of patients with concordant lack of control by pre-dialysis and ABPM was significantly higher in men than women (65.3% vs 49.4%, p = 0.023); white-coat (14.9% vs 17.6%, p = 0.593) and masked hypertension (10.7% vs 18.8%, p = 0.101) did not differ between-groups. However, the misclassifation rate with the use of pre-dialysis BP was lower in men than women. There was moderate or at best fair agreement between pre-dialysis and ABPM with regards to the prevalence (men: kappa-statistics = 0.39, p < 0.001 and women: 0.27, p = 0.011) and control rates (kappa-statistics = 0.25, p = 0.005 and 0.17, p = 0.124, respectively). Pre-dialysis BP greater than or equal to 140/90mmHg had sensitivity/specificity of 85.9%/51.4% in men and 72.4%/54.5% in women for the diagnosis of elevated 48-h BP. Receiver-operating-curve analyses confirmed this poor diagnostic performance.

Conclusions:
The prevalence of hypertension is similar between men and women hemodialysis patients but men have worse rates of office BP control. The diagnostic accuracy of pre-dialysis BP was equally poor in men and women hemodialysis patients.
DIRECT COMPARISON OF INTERSECTING-TANGENTS VERSUS SECOND DERIVATIVE FOR DETERMINATION OF PULSE TRANSIT TIME AND PULSE WAVE VELOCITY
Authors: Tairi Amira , Obeid Hasan , Fortier Catherine , Paré Mathilde , Côté Nadège , Philibert Emy , Garneau Charles-Antoine , Duval Karine , Groupil Rémi , Agharazii Mohsen 
Published: June 2022

Objective:
Arterial stiffness is a non-traditional risk factor for cardiovascular disease. Aortic stiffness is assessed by determination of pulse wave velocity using pulse transit time and the distance between carotid and femoral arteries. Transit time is obtained by using the foot-to-foot method to define the transit time through intersecting tangents algorithm or the point of maximal upstroke during systole (2nd derivative). Millasseau et al have proposed a formula for converting transit time between methods using SphygmoCor (intersecting tangents) and the Complior Analyse (2nd derivative). Based on a mathematical modeling of the proposed formula, there is discrepancy between values of pulse wave velocities, especially in subjects with higher aortic stiffness. The objective of this study is to directly compare the two methods using the same pressure waveforms obtained by the newer generation of Complior Analyse and using Millasseau’s formula.

Design and method:
In a cross-sectional study of heterogeneous subjects, aortic stiffness was assessed by the Complior Analyse device which uses 2nd derivative. The pulse waveforms were extracted and used for the analysis by custom MATLAB algorithm for intersecting tangents, and the results were compared to the formula proposed by Millasseau.

Results:
The preliminary results of the first 24 patients (men: 71%; mean age: 61 ± 18 years) show that Millasseau’s formula underestimates the transit times values by about 19% in comparison with the transit times obtained by the intersecting tangents method using MATLAB software (49,8 ± 18,8 ms vs 61,6 ± 18,6 ms; P < 0,001). This results in an overestimation of the pulse wave velocities values by about 30% (13,8 ± 3,8 m/s vs 10,6 ± 2,7 m/s; P < 0,001).

Conclusions:
Our preliminary results allow us to conclude that the values of pulse wave velocities obtained with Millasseau’s formula are overestimated values when comparing with values obtained by using the intersecting tangents method. Increasing the number of subjects will allow us to examine the possibility of a more reliable formula for converting transit times from one method to the other.
RENIN, ERYTHROPOIETIN AND VITAMIN D RELEASE FROM HUMAN DONOR KIDNEYS DURING NORMOTHERMIC MACHINE PERFUSION: PREDICTORS OF POST-TRANSPLANTATION OUTCOME?
Authors: Lin Hui , Du Zhaoyu , Bouari Dafsy , Rijkse Elsaline , Jan Danser A.H. , Minnee Robert , Hoogduijn Martin 
Published: June 2022

Objective:
Normothermic (37C) machine perfusion (NMP) is a potential alternative to currently used hypothermic (4C) machine perfusion (HMP) for donor kidney preservation before transplantation. NMP allows for metabolic activity and for functional assessment of donor kidneys. The kidneys are key producers of hormones and we investigated the release of prorenin/renin, erythropoietin (EPO), and vitamin D by kidneys on machine perfusion.

Design and method:
Ten donor kidneys were subjected to HMP followed by 2 h of oxygenated NMP before transplantation. NMP perfusate was collected at three time points (0 h, 1 h, 2 h). Ten HMP perfusate samples were collected for the same measurements.

Results:
Median release rates of prorenin (196 [i.q.r 28–266] ng/hour) and renin (228 [94–302] ng/hour) in the first hour of NMP were 83- and 37-fold higher than that in HMP perfusates respectively (p = 0.0009 and p < 0.0001). Median renin release rate showed a 3.2-fold downregulation during the second hour of NMP compared to the first hour. Median EPO release rate (14 [i.q.r 8–48] mIU/min) during the first hour of NMP was 2.9-fold higher than that in HMP perfusates (p = 0.035), while it remained stable in the second hour of NMP. Active vitamin D was undetectable in HMP perfusate samples, while there was a median vitamin D secretion of 56 (i.q.r 30–83) and 28 (8–50) pmol/hour in the first and second hour of NMP respectively (p = 0.0001 and p = 0.003). We then investigated whether there were correlations between the hormone releasing capacity and donor kidney status. Prorenin release rate in the second hour of NMP was lower as cold ischemia time (CIT) until NMP of donor kidneys increased (r = -0.605; p = 0.049). EPO release showed no correlation with donor age or CIT. Donor age and vitamin D release rate during two hours of NMP are highly correlated (r = 0.652; p = 0.034). Interestingly, donation after brain death (DBD) kidneys significantly released more vitamin D than donation after circulatory death (DCD) kidneys during the first and second hour of NMP (p = 0.024 and p = 0.012).

Conclusions:
These data shows that NMP increases the hormone release capacity of transplant kidneys. Hormone release may represent a tool to assess kidney function during NMP.
UPREGULATION OF NADH/NADPH OXIDASE 4 BY ANGIOTENSIN II INDUCES PODOCYTE APOPTOSIS
Authors: Ha Tae Sun , Ha Dong Soo 
Published: June 2022

Objective:
Angiotensin II induces glomerular and podocyte injury via systemic and local vasoconstrictive or non-hemodynamic effects including oxidative stress. The release of free radicals from podocytes may participate in the development of glomerular injury and proteinuria. We studied the pathophysiologic roles of oxidative stress in angiotensin II-induced podocyte apoptosis.

Design and method:
Mouse podocytes were incubated in media containing various concentrations of angiotensin II and at different incubation times and transfected by Nox4 or AT1R siRNAs or negative control scrambled siRNA for 24 h. The changes of podocyte oxidative stress and apoptosis were observed by confocal imaging, western blotting, realtime PCR, FACS and TUNEL assay according to the presence of angiotensin II.

Results:
Angiotensin II increased the generation of mitochondrial superoxide anions and reactive oxygen species levels but suppressed superoxide dismutase activity that was reversed by probucol, an antioxidant. Angiotensin II also increased NADH/NADPH oxidase 4 protein and expression in a transcriptional mechanism that was also reversed by probucol. In addition, the suppression of NADH/NADPH oxidase 4 by siRNA reduced the oxidative stress induced by angiotensin II. Furthermore, angiotensin II promoted podocyte apoptosis that was reduced significantly by probucol and NADH/NADPH oxidase 4 siRNA, and also recovered by angiotensin II type 1 receptor siRNA. In sum, angiotensin II induced podocyte oxidative stress and apoptosis through NADH/NADPH oxidase 4 and angiotensin II type 1 receptor.

Conclusions:
These findings suggest that angiotensin II promoted podocyte mitochondrial oxidative stress resulting in apoptosis via the upregulation of NADH/NADPH oxidase 4 and angiotensin II type 1 receptor and, which could be prevented by NADH/NADPH oxidase 4 inhibition and/or antagonizing angiotensin II type 1 receptor as well as antioxidants.
THE CHRONIC KIDNEY DISEASE IN AFRICA (CKD-AFRICA) COLLABORATION: A NEW PAN-AFRICAN NETWORK
Authors: George Cindy , Okpechi Ikechi G. , Woodward Mark , Kengne Andre P. 
Published: June 2022

Objective:
Evidence points to an increasing prevalence of chronic kidney disease (CKD) across Africa, particularly in high-risk groups, like those with hypertension, diabetes, and HIV. However, there has not been a concerted, Africa-wide, effort to provide estimates to inform health services planning and policy development to address CKD. The CKD-Africa Collaboration seeks to fill this gap by collating data, at individual participant data (IPD) level, from African studies. The main aims of this platform are, (1) to utilize the available data from relevant prevalence studies of CKD, to provide updated and comprehensive syntheses on the burden of CKD in Africa, and (2) to link investigators in the field of CKD epidemiology and prevention, by providing a platform to plan future observational and interventional studies on CKD in Africa.

Design and method:
Establishing the CKD-Africa Collaboration followed a stepwise approach, through the identification of data sources, developing the database platform, and acquiring and processing participant-level data. Inclusion criteria: 1) observational study with primary data; 2) ethical approval; 3) minimum sample size of 300 participants and 4) participants of African descent residing in Africa.

Results:
To date, we have curated data from 42 studies conducted in 12 African countries, with a total of 37,842 participants (Fig.). The sample sizes ranges between 300 and 2,543 per study, with adults aged 18 to 100 years. In 36% of the studies data collection took place before 2010, with the remaining 64% sampled between 2010 and 2017. Overall, 74.6% of the IPD were sampled from the general population, with CKD prevalence estimates ranging from 1% to 22%. The remaining IPD were from high-risk populations, including people with hypertension, diabetes, HIV, and first-degree relatives of people with CKD. All studies used serum creatinine to estimate glomerular filtration rate, with 85.7% of these studies employing the Jaffe method. fx155

Conclusions:
This network has far-reaching potential for Africa, as it is in an ideal position to test hypotheses and compare findings across geographical and national boundaries, and to generate a new understanding of CKD progression and its complications in this under-researched context.
ASSESSMENT OF RENAL SYMPATHETIC CONTROL USING INVASIVE PRESSURE AND FLOW VELOCITY MEASUREMENTS IN HUMANS
Authors: Collard Didier , Velde Lennart Van De , Stegehuis Valérie , Delewi Ronak , Beijk Marcel , Zijlstra Ijsbrand , Winter Rob De , Vogt Liffert , Born Bert-Jan Van Den 
Published: June 2022

Objective:
Renal sympathetic innervation is important in the control of renal and systemic hemodynamics and a target for pharmacological and catheter-based therapies. The effect of a physiological sympathetic stimulus using static handgrip exercise on renal hemodynamics and intraglomerular pressure in humans is unknown.

Design and method:
We recorded renal arterial pressure and flow velocity in patients with a clinical indication for coronary or peripheral angiography using a sensor-equipped guidewire during baseline, handgrip, resting, and hyperemia following intrarenal dopamine (30 ug/kg). Changes in perfusion pressure were expressed as delta mean arterial pressure, changes in flow velocity as percentage with respect to baseline. Intraglomerular pressure was estimated using a Windkessel model.

Results:
We included 18 patients with median age 57 years (range 27–85), 61% male in the final analysis. An overview of the hemodynamic responses is given in Figure 1. During static handgrip mean renal arterial pressure increased by 15.2 mmHg (range 4.2–53.0), while flow decreased by 11.2%, but with large variation between individuals (range -13.4–49.8%). Intraglomerular pressure increased with 4.2 mmHg (range -3.9–22.1). Flow velocity under resting conditions remained stable with median 100.6% (range 82.3–114.6) compared to baseline. During hyperemia, maximal flow was 180% (range 111–281), while intraglomerular pressure decreased to 33.0 mmHg [IQR 26.7–39.8]. Changes in renal pressure and flow during handgrip exercise were correlated (rho = -0.68; p = 0.002).

Conclusions:
We show that there are significant variations in the response to sympathetic stimulation following static handgrip exercise using invasive renal arterial measurements. These results demonstrate that intra-arterial renal hemodynamic measurements can be used to determine the renal effect of systemic sympathetic stimulus and allows identification of patients with higher and lower sympathetic control of renal perfusion. This may be useful in determining the response to therapeutic interventions aimed at altering renal sympathetic control.
AGING AND HYPERTENSION IN KIDNEY FUNCTION DECLINE: A 10-YEAR POPULATION-BASED STUDY
Authors: Jaques David A. , Vollenweider Peter , Bochud Murielle , Ponte Belen 
Published: June 2022

Objective:
Aging is associated with a physiological decline in kidney function (KFD). In this study, we aimed to describe the impact of age on the rate of KFD and its interplay with risk factors for chronic kidney disease (CKD) in the general population.

Design and method:
Participants of European descent, aged 35 to 75, were recruited from a populational cohort in Lausanne, Switzerland. Participants with a 10-year follow-up were selected. KFD was defined as the difference in estimated glomerular filtration rate (eGFR) between baseline and follow-up, divided by the observation period. Multivariate linear regressions were used with KFD as the outcome and age as the main predictor. Hypertension (HT) was tested as a modifying factor.

Results:
We included 4’163 participants with mean age 52.2 +/- 10.4, 44.7% men, 31.9% HT and 5.0% diabetics. Mean baseline eGFR was 85.9 +/- 14.6 mL/min/1.73m2. Mean KFD was -0.49 +/- 1.08 mL/min/1.73m2 per year with 70% of participants decreasing their eGFR during follow-up. The relationship between age and KFD was non-linear and age was divided in tertiles. Old participants had faster rates of KFD as compared to young and middle-age participants (p < 0.001). A significant interaction was found between age and HT on KFD prediction (p < 0.001). In HT participants, KFD was significantly different across tertiles of age (p < 0.001). On contrary, KFD was not different across tertiles of age in non-HT participants.

Conclusions:
A physiological KFD is present over time in the general population. Age contributes non-linearly to the rate of this decline with older subjects declining the fastest. The presence of HT is a major contributing factor in this setting as KFD worsened with age only in hypertensive participants. Thus, HT represents an important pathological factor aggravating the age-related physiological decline in eGFR in the general population.
WHITE-COAT HYPERTENSION: SIZE OF THE WHITE-COAT EFFECT IS STRONGLY ASSOCIATED WITH CENTRAL ARTERIAL STIFFNESS
Authors: Mcdermott Eugene Ace , Mensah Ekow Adom , Fantin Francesco , Okorie Michael , Zamboni Mauro , Rajkumar Chakravarthi 
Published: June 2022

Objective:
To explore the relationship between the systolic/diastolic white-coat effect (sWCE and dWCE), defined by the difference between clinic BP and mean daytime ambulatory BP, and central arterial stiffness.

Design and method:
The Brighton and Verona Seniors Study (BRAVES) recruited 184 healthy older adults aged 65–85 from primary care. Participants were not eligible for recruitment if they had known: cardiovascular disease, chronic kidney disease, diabetes, malignancy, smoking, statin therapy, or hormone therapy. Each participant was evaluated for office BP, anthropometrics, and cardiovascular risk factors. 24-hour ambulatory BP was measured using Diasys Integra II (Novacor, France). Carotid-femoral pulse wave velocity (cfPWV) and carotid-radial pulse wave velocity (crPWV) was measured using Complior (Alam Medical, France). 101 participants, not on antihypertensive therapy and with complete ambulatory readings, were selected for analysis. Participants were grouped by BP phenotype: normotension (NT), white-coat hypertension (WCH), masked hypertension (MH), and sustained hypertension (SH).

Results:
The 101 participants (mean age ± standard deviation: 72 ± 5 years) consisted of 32 NT, 34 WCH, 9 MH, and 26 SH. A positive correlation was seen between both sWCE (r = 0.21; p = 0.03) and dWCE (r = 0.34; p < 0.001) with cfPWV. The WCH subgroup analysis (n = 34) revealed a stronger association between sWCE (r = 0.44; p = 0.01) and dWCE (r = 0.74; p < 0.001) with cfPWV. There was no association in the other BP phenotypes. There was no association of crPWV with either sWCE or dWCE. Multivariable linear regression was conducted on sWCE and dWCE as dependent variables and age, gender, BMI and cfPWV as independent variables (sWCE model: R2 = 0.19; p = 0.23; dWCE model: R2 = 0.61, p < 0.001). After adjustment, a significant association remained between cfPWV and sWCE (B = 2.72, 95% CI 0.32–5.13, p = 0.03) and cfPWV and dWCE (B = 2.70, 95% CI 1.60–3.79, p < 0.001).

Conclusions:
In healthy older adults with WCH, sWCE and dWCE are independently associated with central arterial stiffness. Central arterial stiffness accounts for a greater proportion of the overall variance of dWCE than sWCE. The WCE is not associated with peripheral arterial stiffness. In WCH, a large WCE may identify individuals at a higher risk of cardiovascular events.