Safety and efficacy of once-daily dexfadrostat phosphate in patients with primary aldosteronism: a randomised, parallel group, multicentre, phase 2 trial.

Background: Primary aldosteronism (PA) is caused by autonomous aldosterone overproduction and characterised by uncontrolled hypertension. There are currently no treatments that target aldosterone synthesis. We evaluated the safety and efficacy of a novel aldosterone synthase inhibitor, dexfadrostat phosphate, in patients with PA. Methods: This multi-centre, randomised, phase 2 trial was conducted between November 2019 and May 2022 (NCT04007406; EudraCT code 2019-000919-85). Adults with PA and an office systolic blood pressure of 145-190 mmHg were included. After a 2-week single-blind placebo run-in period, participants were randomised 1:1:1 to receive oral dexfadrostat phosphate 4, 8, or 12 mg once daily for an 8-week double-blind treatment period, followed by a 2-week single-blind placebo withdrawal period. Randomisation was conducted centrally and stratified by centre and sex. At the beginning and end of the treatment period, 24 h ambulatory systolic blood pressure (aSBP) was recorded. Blood samples were taken every 2 weeks. Primary endpoints were the change in aldosterone-to-renin ratio (ARR) and mean 24 h aSBP from baseline to the end of the treatment period in the combined dose group of all participants receiving any dose of dexfadrostat phosphate. Safety endpoints were the occurrence of treatment-emergent adverse events (TEAEs) and serious adverse events over the entire study in all randomised participants who received at least one dose of dexfadrostat phosphate. Findings: In total, 35 participants received dexfadrostat phosphate and all participants completed the study. Twenty-six participants (74.3%) were male, the mean age was 51.9 years (SD 8.7), and most were White (n = 32, 91.4%). The median ARR and the mean 24 h aSBP significantly decreased from the beginning to the end of the treatment period in the combined dose group (ARR: 15.3 vs 0.6, least-squares mean [LSM] change in log-normal values -2.5, p < 0.0001; aSBP: 142.6 vs 131.9 mmHg, LSM change -10.7 mmHg, p < 0.0001). There were no safety concerns; all TEAEs were mild or moderate and there were no serious TEAEs. Interpretation: Dexfadrostat phosphate corrected the ARR and aSBP and was well tolerated in patients with PA, demonstrating the benefit of pharmacologically targeting the source of hyperaldosteronism. Funding: DAMIAN Pharma AG.

Association of serum copeptin and urinary uromodulin with kidney function, blood pressure and albuminuria at 6 weeks post-partum in pre-eclampsia.

Background: Preeclampsia (PE) is associated with subsequent higher risk of cardiovascular and kidney disease. Serum copeptin, as a proxy for vasopressin, and urinary uromodulin, were associated with PE physiopathology and kidney functional mass respectively. We describe concentrations of these proteins in the post-partum period and characterize their association with persistent hypertension (HTN) or albuminuria. Methods: Patients with PE and healthy controls with uncomplicated pregnancy were prospectively included at two teaching hospitals in Switzerland. Clinical parameters along with serum copeptin and urinary uromodulin were measured at 6 weeks post-partum. PE patients were further characterized based on presence of HTN (defined as either systolic BP (SBP) ≥140 mmHg or diastolic (BP) ≥90 mmHg) or albuminuria [defined as urinary albumin to creatinine ratio (ACR) ≥3 mg/mmol]. Results: We included 226 patients with 35 controls, 120 (62.8%) PE with persistent HTN/albuminuria and 71 (37.1%) PE without persistent HTN/albuminuria. Median serum copeptin concentration was 4.27 (2.9-6.2) pmol/L without differences between study groups (p > 0.05). Higher copeptin levels were associated with higher SBP in controls (p = 0.039), but not in PE (p > 0.05). Median urinary uromodulin concentration was 17.5 (7.8-28.7) mg/g with lower levels in PE patients as compared to healthy controls (p < 0.001), but comparable levels between PE patients with or without HTN/albuminuria (p > 0.05). Higher uromodulin levels were associated with lower albuminuria in PE as well as control patients (p = 0.040). Conclusion: Serum copeptin levels at 6 weeks post-partum are similar between PE patients and healthy controls and cannot distinguish between PE with or without residual kidney damage. This would argue against a significant pathophysiological role of the vasopressin pathway in mediating organ damage in the post-partum period. On the opposite, post-partum urinary uromodulin levels are markedly lower in PE patients as compared to healthy controls, potentially reflecting an increased susceptibility to vascular and kidney damage that could associate with adverse long-term cardiovascular and kidney outcomes.

Quantification of endogenous Angiotensin 1-10, 1-9, 1-8, 1-7, and 1-5 in human plasma using micro-UHPLC-MS/MS: Outlining the importance of the pre-analytics for reliable results.

Angiotensin peptides (ANGs) play a central role in the renin-angiotensin-aldosterone system, rendering them interesting biomarkers associated with hypertension. Precise quantification of circulating ANGs holds the potential to assess the activity of angiotensin-converting enzyme (ACE), a key protease targeted by widely prescribed drugs, namely ACE inhibitors. This ability could pave the way for personalised medicine, offering insights into the prescription of inhibitors targeting either the proteases or the receptors within the system. Despite recent developments in liquid chromatography-mass spectrometry (LC-MS) methods for measuring circulating ANG concentrations, comprehensive stability studies of ANGs in human plasma are absent in the literature, raising concerns about the reliability of measured concentrations and their link to clinical conditions. To address this critical gap, we conducted an exhaustive evaluation of the pre-analytical stability of ANG1-10, ANG1-9, ANG1-8, ANG1-7, and ANG1-5. By employing surfactants to mitigate non-specific adsorption and a dedicated mix of protease inhibitors to limit protease activity, we established an MS-based assay for these five peptides. We used this method to quantify circulating concentrations of ANGs in the plasma of 11 healthy donors and 3 patients under kidney dialysis. Our findings revealed that ANG1-10 and ANG1-8 circulate at concentrations ranging from 1 to 10 pM in healthy subjects and exhibit a high degree of correlation. Notably, ANG1-9, ANG1-7, and ANG1-5 were undetectable in any of the 14 patients, despite a sub-picomolar limit of detection. This strikingly contrasts with the reference concentrations reported in the literature, which typically fall within the picomolar range. In light of these discrepancies, we strongly advocate for rigorous pre-analytical considerations and comprehensive stability studies to ensure reliable results. We emphasise the pivotal role of heightened pre-analytical awareness within the clinical chemistry community, and we hope for continued growth in this critical area.

[Thiazid diuretics : some useful considerations in clinical practice]. / Diurétiques thiazidiques. Quelques considérations utiles en pratique clinique.

Thiazide diuretics are an essential part of the treatment of hypertension, which affects nearly a third of the world's population. Hydrochlorothiazide is the most widely used member of this class, due to its long availability on the market and the many combinations available with other substances. Other analogues of this class exist, with notable advantages from a clinical point of view, recognized under the name of thiazide-like. This article reviews some of the considerations in clinical practice concerning the different types of thiazides currently available in Switzerland.

Les diurétiques thiazidiques font partie des traitements de premier choix dans la prise en charge de l'hypertension artérielle, touchant près d'un tiers de la population mondiale. L'hydrochlorothiazide est le représentant de cette classe médicamenteuse le plus utilisé dans les combinaisons antihypertensives en Suisse. D'autres analogues de cette classe existent sur le marché, avec des avantages notables du point de vue clinique, reconnus sous la dénomination de thiazides-like. Le choix de l'utilisation d'un diurétique thiazidique repose avant tout sur les indications et les contre-indications relatives à cette classe. Cet article propose une revue de quelques considérations en pratique clinique sur les différents types de thiazides actuellement disponibles en Suisse.

[Hypertension: what's new in 2023]. / Hypertension artérielle : ce qui a changé en 2023.

Highlights for 2023 include the confirmation of hypertension as a cardiovascular risk factor and the standard procedure for measuring blood pressure. Transdermal oestrogens do not appear to be associated with an increased risk of hypertension unlike oestrogen given orally. The usefulness of blood pressure measured in hospital in elderly patients and the risks of intensive treatment are reviewed. A new study suggests that we are not all equal when it comes to recommended treatments. Finally, RNA interference technology has enabled the synthesis of a new antihypertensive treatment administered every 6 months that inhibits the production of hepatic angiotensinogen with a good effect on blood pressure.

Le survol de l'année 2023 met l'accent sur l'hypertension artérielle (HTA) comme facteur de risque cardiovasculaire et sur les conditions de mesure de la pression artérielle. Du côté hormonal, les œstrogènes en application transdermique ne semblent pas être associés à un risque augmenté d'HTA, contrairement à ceux administrés par voie orale. L'utilité de la pression artérielle mesurée en milieu hospitalier chez des patients âgés et les risques de son traitement intensif sont également discutés. Une nouvelle étude suggère que nous ne sommes pas tous égaux face aux traitements recommandés. Enfin, la technologie des ARN interférents a permis la synthèse d'un nouveau traitement antihypertenseur administré aux 6 mois inhibant la production d'angiotensinogène hépatique avec un bon effet sur la pression artérielle.

The differential impact of a 6-versus 12-month pharmacist-led interprofessional medication adherence program on medication adherence in patients with diabetic kidney disease: the randomized PANDIA-IRIS study.

Background: For every 100 patients with diabetes, 40 will develop diabetic kidney disease (DKD) over time. This diabetes complication may be partly due to poor adherence to their prescribed medications. In this study, we aimed to evaluate the differential impact of a 6- versus 12-month pharmacist-led interprofessional medication adherence program (IMAP) on the components of adherence (i.e., implementation and discontinuation) in patients with DKD, during and after the intervention. Methods: All included patients benefited from the IMAP, which consists in face-to-face regular motivational interviews between the patient and the pharmacist based on the adherence feedback from electronic monitors (EMs), in which the prescribed treatments were delivered. Adherence reports were available to prescribers during the intervention period. Patients were randomized 1:1 into two parallel arms: a 12-month IMAP intervention in group A versus a 6-month intervention in group B. Adherence was monitored continuously for 24 months post-inclusion during the consecutive intervention and follow-up phases. In the follow-up phase post-intervention, EM data were blinded. Blood pressure was measured by the pharmacist at each visit. The repeated measures of daily patient medication intake outcomes (1/0) to antidiabetics, antihypertensive drugs, and statins were modeled longitudinally using the generalized estimated equation in both groups and in both the intervention and the follow-up phases. Results: EM data of 72 patients were analyzed (34 in group A and 38 in group B). Patient implementation to antidiabetics and antihypertensive drugs increased during the IMAP intervention phase and decreased progressively during the follow-up period. At 12 months, implementation to antidiabetics was statistically higher in group A versus group B (93.8% versus 86.8%; Δ 7.0%, 95% CI: 5.7%; 8.3%); implementation to antihypertensive drugs was also higher in group A versus B (97.9% versus 92.1%; Δ 5.8%, 95% CI: 4.8%; 6.7%). At 24 months, implementation to antidiabetics and antihypertensive drugs remained higher in group A versus B (for antidiabetics: 88.6% versus 85.6%; Δ 3.0%, 95% CI: 1.7%; 4.4% and for antihypertensive drugs: 94.4% versus 85.9%; Δ 8.5%, 95% CI: 6.6%; 10.7%). No difference in pharmacy-based blood pressure was observed between groups. Implementation to statins was comparable at each time point between groups. Three patients discontinued at least one treatment; they were all in group B. In total, 46% (16/35) of patients in the 12-month intervention versus 37% (14/38) of patients in the 6-month intervention left the study during the intervention phase, mainly due to personal reasons. Conclusion: The IMAP improves adherence to chronic medications in patients with DKD. The longer the patients benefit from the intervention, the more the implementation increases over time, and the more the effect lasts after the end of the intervention. These data suggest that a 12-month rather than a 6-month program should be provided as a standard of care to support medication adherence in this population. The impact on clinical outcomes needs to be demonstrated. Clinical Trial Registration: Clinicaltrials.gov, identifier NCT04190251_PANDIA IRIS.

Contrast-enhanced ultrasonography reveals a lower cortical perfusion and a decreased renal flow reserve in hypertensive patients.

BACKGROUND: Microvascular structural alteration and dysfunction is a hallmark of arterial hypertension. So far, the visualization and the quantification of renal microcirculation in humans has been hampered by the lack of non-nephrotoxic and non-invasive radiologic techniques. Contrast-enhanced ultrasonography (CEUS) is an appealing method to investigate renal microcirculation and has not been investigated in this setting. We aimed to compare renal microcirculation in normotensive (NT) and hypertensive (HT) participants using CEUS at rest and during a sympathetic stress test. METHODS: We measured the renal perfusion index (PI, primary outcome), the renal resistive index (RRI), beat-to-beat systemic hemodynamics and plasma catecholamines before and during a 2-min cold pressor test (CPT) in NT and HT participants. Linear mixed model analysis was used to compare the effect of the CPT on the variables of interest. RESULTS: Seventy-three participants (32 HT) with normal kidney function were included. HT participants had a lower baseline PI compared with NT participants [median (interquartile range) 1476 (959-2155) arbitrary units (a.u.) vs 2062 (1438-3318) a.u., P < .001]. The CPT increased blood pressure, heart rate and catecholamines in all participants. The increase in PI observed in NT during the CPT was blunted in HT [+504 (117-920) a.u. vs +1159 (678-2352) a.u in NT, interaction P = .013]. Age, sex and body mass index did not modify these results. CONCLUSIONS: HT patients had a lower basal renal cortical perfusion. During the cold pressor test, HT participants had a smaller increase in the PI, suggesting that renal cortical flow reserve is impaired.

Performance of the Aktiia optical blood pressure measurement device in the elderly: a comparison with double blinded auscultation in different body positions.

BACKGROUND: Accurate blood pressure (BP) measurement is essential for the correct diagnosis and management of hypertension (HTN) especially in the elderly population. As with of all BP devices, the accuracy of cuffless devices must be verified. This study (NCT04027777) aimed to evaluate the performance of a wrist cuffless optical BP device in an elderly population cohort in different body positions with auscultation as the reference measurement. DESIGN AND METHODS: Patients aged 65-85 years with different BP categories but without diabetes were recruited. After an initial calibration based on auscultatory measurements, BP estimation from the Aktiia Bracelet (Aktiia SA, Switzerland) were compared to reference double-blinded auscultatory measurements in sitting, standing and lying positions on four separate visits distributed over one month. In the absence of a universal standard for cuffless BP device at the time of the study, modified ISO81060-2 criteria were used for performance analysis. RESULTS: Thirty-five participants were included in the analysis fulfilling the inclusion requirements of ISO 81060-2. A total of 469 paired measurements were obtained with overall 83% acceptance rate. Differences (mean ± SD)   between Aktiia Bracelet and auscultation for systolic BP were -0.26 ± 9.96 mmHg for all body positions aggregated (sitting 1.23 ± 7.88 mmHg, standing -1.81 ± 11.11 mmHg, lying -1.8 ± 9.96 mmHg). Similarly, differences for diastolic BP were -0.75 ± 7.0 mmHg (0.2 ± 5.55 mmHg, -5.35 ± 7.75 mmHg and -0.94 ± 7.47 mmHg, respectively). Standard deviation of the averaged differences per subject for systolic/diastolic BP was 3.8/2.5 mmHg in sitting and 4.4/3.7 mmHg for all body positions aggregated. CONCLUSIONS: Overall, this study demonstrates a similar performance of the Aktiia Bracelet compared to auscultation in an elderly population in body positions representative of daily activities. The use of more comfortable, non-invasive, and non-occlusive BP monitors during long periods may facilitate e-health and may contribute to better management of HTN, including diagnosis and treatment of HTN, in the elderly.

Accuracy of blood pressure measurements is essential in the diagnosis and the follow-up of patients with high blood pressure. As with any blood pressure measuring device, a validation is necessary. In this study including a elderly population, we compared values obtained by the cuffless Aktiia Bracelet (Aktiia SA, Switzerland) after an initial calibration with the reference auscultatory method during four separate study days distributed over one month. We show that the accuracy of the Aktiia Bracelet is similar to auscultation. The accuracy varies depending on the position in which the measurement is performed. Overall, the accuracy is not modified by a higher age category. The use of a cuffless device in the elderly population characterized by high prevalence of hypertension may facilitate the follow-up of blood pressure with more comfort and minimal constraints.

[Hyperkaliemia in hypertensive patients : more than a coincidence?] / Hyperkaliémie chez le patient hypertendu : plus qu'une coïncidence ?

Hyperkaliemia is a relatively common electrolyte disorder whose manifestations and consequences can be serious if severe hyperkalemia is not treated. In the context of hypertension, it is important to look for co-morbidities and conditions favoring hyperkaliemia, to review the drugs prescribed that could contribute to potassium elevation and to bear in mind that when the common causes have been excluded, a genetic origin may be present. In this article, the focus is on the association of hypertension and hyperkaliemia, in the context of the marketing of new cardiovascular and renal drugs that may induce this electrolyte disorder.

L'hyperkaliémie représente un trouble électrolytique relativement fréquent dont les manifestations et conséquences peuvent être graves si l'hyperkaliémie sévère n'est pas corrigée. Dans le contexte d'une hypertension, il faut rechercher les comorbidités et les conditions favorisant l'hyperkaliémie, revoir les médicaments prescrits qui pourraient contribuer à l'élévation du potassium et garder en mémoire que lorsque les causes fréquentes ont été exclues, une origine génétique peut être présente. Dans cet article, l'accent est mis sur l'association de l'hypertension et l'hyperkaliémie, dans le contexte de la mise sur le marché de nouveaux médicaments dans les domaines cardiovasculaire et rénal qui pourraient favoriser la survenue de ce trouble électrolytique.

[Management of hypertension in athletes]. / Prise en charge de l'hypertension artérielle chez les athlètes.

Hypertension is the leading cardiovascular disease in athletes and requires special attention. Some sports-related habits may predispose certain athletes to its development specially the tall athletes and those who train primarily for strength may be at greater risk. Potential side effects and legal restrictions on the use of certain antihypertensive drugs in sport must be taken into account when choosing antihypertensive treatment in athletes.

L'hypertension est la principale maladie cardiovasculaire chez les athlètes et doit faire l'objet d'une attention particulière. Quelques habitudes associées au sport peuvent prédisposer certains athlètes au développement de l'hypertension, notamment ceux de grande taille et/ou ceux qui pratiquent principalement un entraînement de force. Les éventuels effets secondaires et la possible limitation réglementaire à l'usage de certains traitements antihypertenseurs doivent être pris en compte lors du choix du traitement de l'hypertension chez les athlètes.

Blood pressure and vascular determinants of glomerular filtration rate decline in diabetic kidney disease.

Objective: In patients with type 2 diabetes and diabetic kidney disease (DKD), explore the relationship between estimated glomerular filtration rate decline (eGFR-d) and simultaneously assessed vascular risk markers including office, ambulatory or central blood pressure, pulse pressure, carotid-femoral pulse wave velocity (PWV), carotid intima-media thickness (IMT) and renal resistive indexes (RRI). Research design and methods: At baseline, vascular risk markers were measured in addition to the routine clinical workup. The eGFR-d was based on 2000-2019 creatinine values. Parameters were compared by eGFR-d quartiles. Regression models of eGFR-d and vascular markers were assessed. Results: In total, 135 patients were included. Mean age was 63.8 ± 10.8y, baseline eGFR 60.2 ± 26.4 ml/min/1.73 m2 and urine albumin-creatinine ratio (ACR) 49 ± 108 mg/mmol. Mean eGFR-d was based on 43 ± 39 creatinine values within a time span of 7.0 ± 1.9y. The average yearly eGFR decline was -1.8 ± 3.0 ml/min/1.73 m2 ranging from -5.8 ± 2.3 in the first quartile to +1.4 ± 1.7 in the fourth quartile. Mean 24 h systolic (SBP) and diastolic (DBP) blood pressure were 126 ± 17 and 74 ± 9 mmHg. Mean PWV was 11.8 ± 2.8 m/s, RRI 0.76 ± 0.07 and IMT 0.77 ± 0.21 mm. SBP and pulse pressure correlated with eGFR-d but not DBP. 24 h SBP stood out as a stronger predictor of eGFR-d than office or central SBP. PWV and RRI correlated with eGFR decline in univariate, but not multivariate regression models including 24 SBP and ACR. Conclusions: In this study, eGFR decline was highly variable in patients with type 2 diabetes and DKD. Twenty-four hour SBP provided an added value to the routine measurement of ACR in predicting eGFR decline, whereas PWV and RRI did not.

Determinants of Renal Micro-Perfusion as Assessed with Contrast-Enhanced Ultrasound in Healthy Males and Females.

(1) Background: The renal microcirculation is essential to maintain the renal function, but its determinants in humans have been poorly studied. Contrast-enhanced ultrasound (CEUS) allows the non-invasive quantification of the cortical micro-perfusion at the bedside using the perfusion index (PI). The aims of this study were to assess whether differences exist in PI between healthy males and females and to identify clinical determinants associated with cortical micro-perfusion. (2) Methods: Healthy, normotensive volunteers (eGFR > 60 mL/min/1.73 m2, no albuminuria) underwent CEUS under standardized conditions with the destruction-reperfusion (DR) technique. The mean PI of four DR sequences was reported as the primary outcome measure (3) Results: A total of 115 subjects (77 females and 38 males) completed the study; the mean ± SD age was, respectively, 37.1 ± 12.2 and 37.1 ± 12.7 years in females and males, and the mean eGFR was 105.9 ± 15.1 and 91.0 ± 17.4 mL/min/1.73 m2. The PI (median) was higher in females than in males, i.e., 2705 (IQR 1641-3777) vs. 1965 (IQR 1294-3346) arbitrary units (a.u), p = 0.02). A correlation analysis showed positive associations between PI and eGFR, female sex, heart rate, plasma renin activity (PRA) and plasma aldosterone concentrations (PAC), negative associations with potassium, bicarbonate and systolic blood pressure, and no associations with age, body mass index and renal resistive index (RRI). In a multivariate linear regression analysis, only PRA remained significantly associated with PI. (4) Conclusions: Although the PI was higher among females, this association was no longer significant after adjustment for covariates. There was no difference in females tested during the follicular or the luteal phases. In conclusion, the PI was only weakly influenced by classic clinical variables, but was positively associated with PRA, suggesting that the renin-angiotensin system plays a role in the regulation of the cortical micro-perfusion in humans. Identifying which other factors contribute to the large variations in micro-perfusion across individuals needs further study.

Differences in the Food Consumption Between Kidney Stone Formers and Nonformers in the Swiss Kidney Stone Cohort.

OBJECTIVE: Diet has a major influence on the formation and management of kidney stones. However, kidney stone formers' diet is difficult to capture in a large population. Our objective was to describe the dietary intake of kidney stone formers in Switzerland and to compare it to nonstone formers. METHODS: We used data from the Swiss Kidney Stone Cohort (n = 261), a multicentric cohort of recurrent or incident kidney stone formers with additional risk factors, and a control group of computed tomography-scan proven nonstone formers (n = 197). Dieticians conducted two consecutive 24-h dietary recalls, using structured interviews and validated software (GloboDiet). We took the mean consumption per participant of the two 24-h dietary recalls to describe the dietary intake and used two-part models to compare the two groups. RESULTS: The dietary intake was overall similar between stone and nonstone formers. However, we identified that kidney stone formers had a higher probability of consuming cakes and biscuits (odds ratio (OR) [95% CI] = 1.56[1.03; 2.37]) and soft drinks (OR = 1.66[1.08; 2.55]). Kidney stone formers had a lower probability of consuming nuts and seeds (OR = 0.53[0.35; 0.82]), fresh cheese (OR = 0.54[0.30; 0.96]), teas (OR = 0.50[0.3; 0.84]), and alcoholic beverages (OR = 0.35[0.23; 0.54]), especially wine (OR = 0.42[0.27; 0.65]). Furthermore, among consumers, stone formers reported smaller quantities of vegetables (ß coeff[95% CI] = - 0.23[- 0.41; - 0.06]), coffee (ß coeff = - 0.21[- 0.37; - 0.05]), teas (ß coeff = - 0.52[- 0.92; - 0.11]) and alcoholic beverages (ß coeff = - 0.34[- 0.63; - 0.06]). CONCLUSION: Stone formers reported lower intakes of vegetables, tea, coffee, and alcoholic beverages, more specifically wine, but reported drinking more frequently soft drinks than nonstone formers. For the other food groups, stone formers and nonformers reported similar dietary intakes. Further research is needed to better understand the links between diet and kidney stone formation and develop dietary recommendations adapted to the local settings and cultural habits.

[Hypertension: what's new in 2022]. / Hypertension artérielle : ce qui a changé en 2022.

Our article summarizing the most important studies of the past year emphasizes the difficulty of controlling blood pressure (BP) in hypertensive patients. In addition, it discusses factors such as temperature and sodium that may influence BP, proposes new targets in pregnant hypertensive patients, and challenges the usefulness of taking an antihypertensive drug nightly. Finally, a strategy targeting endothelin blockade in resistant hypertension is presented.

Notre article résumant les études marquantes de l'année écoulée met l'accent sur la difficulté à contrôler la pression artérielle (PA) chez les hypertendus. De plus, il aborde certains facteurs comme la température et le sodium pouvant influencer la PA, les cibles chez les patientes hypertendues enceintes et l'utilité d'une prise vespérale d'un antihypertenseur. Finalement, une stratégie visant le blocage de l'endothéline est présentée dans l'hypertension résistante.

The Swiss Kidney Stone Cohort: A Longitudinal, Multicentric, Observational Cohort to Study Course and Causes of Kidney Stone Disease in Switzerland.

BACKGROUND: Kidney stone disease has a high prevalence worldwide of approximately 10% of the population and is characterized by a high recurrence rate. Kidney stone disease results from a combination of genetic, environmental, and lifestyle risk factors, and the dissection of these factors is complex. METHODS: The Swiss Kidney Stone Cohort (SKSC) is an investigator-initiated prospective, multicentric longitudinal, observational study in patients with kidney stones followed with regular visits over a period of 3 years after inclusion. Ongoing follow-ups by biannual telephone interviews will provide long-term outcome data. SKSC comprises 782 adult patients (age >18 years) with either recurrent stones or a single stone event with at least one risk factor for recurrence. In addition, a control cohort of 207 individuals without kidney stone history and absence of kidney stones on a low-dose CT scan at enrolment has also been recruited. SKSC includes extensive collections of clinical data, biochemical data in blood and 24-h urine samples, and genetic data. Biosamples are stored at a dedicated biobank. Information on diet and dietary habits was collected through food frequency questionnaires and standardized recall interviews by trained dieticians with the Globodiet software. CONCLUSION: SKSC provides a unique opportunity and resource to further study cause and course of kidney disease in a large population with data and samples collected of a homogeneous collective of patients throughout the whole Swiss population.

Glomerular diseases in pregnancy: pragmatic recommendations for clinical management.

Our understanding of the various aspects of pregnancy in women with kidney diseases has significantly improved in the last decades. Nevertheless, little is known about specific kidney diseases. Glomerular diseases are not only a frequent cause of chronic kidney disease in young women, but combine many challenges in pregnancy: immunologic diseases, hypertension, proteinuria, and kidney tissue damage. An international working group undertook the review of available current literature and elicited expert opinions on glomerular diseases in pregnancy with the aim to provide pragmatic information for nephrologists according to the present state-of-the-art knowledge. This work also highlights areas of clinical uncertainty and emphasizes the need for further collaborative studies to improve maternal and fetal health.

Saxagliptin: A potential doping agent? A randomized, double-blinded, placebo-controlled, and crossover pilot study in young active men.

Neuropeptide Ys (NPYs) contribute to sympathetic-adreno stimulation: NPY1-36 potentiates the effects of catecholamines (CATs), whereas NPY3-36 inhibits CAT release. We sought to investigate whether inhibiting dipeptidyl-peptidase-4 (DPP4), cleaving NPY1-36 into NPY3-36, leads to increased NPY1-36 potentiating effects and reduced NPY3-36 inhibitory effects on CATs, thereby improving endurance performance. Seven male participants (age 27 ± 3 years, BMI 23.1 ± 2.4 kg/m2 ) performed time-to-exhaustion cycling exercise at 95% of peak power output with either placebo, or saxagliptin, a DPP4 inhibitor. Oxygen consumption (V̇O2 ), heart rate variability, NPY1-36, NPY3-36, catecholamines, and lactate were measured at several time points before, during, and after exercise. With saxagliptin, DPP4 activity (12.7 ± 1.6 vs. 0.2 ± 0.3 U/L, p = 0.001; d = 10.7) was decreased at rest, while NPY3-36 (1.94 ± 0.88 vs. 0.73 ± 0.22 pm; p < 0.001; d = 2.04) decreased and NPY1-36 increased during exercise (2.64 ± 2.22 vs. 4.59 ± 2.98 pm; p < 0.01; d = 0.19). CATs were unchanged. Time-to-exhaustion was 32% higher with saxagliptin. The difference in time-to-exhaustion between placebo and saxagliptin was correlated with NPY1-36 differences (R = 0.78, p < 0.05). Peak V̇O2 and other cardio-respiratory values were not different, whereas peak NPY concentrations were higher with saxagliptin. DPP4 blockade improved performance, increased NPY1-36, and decreased NPY3-36 concentrations which may have potentiating effects on the influences of CATs. However, DPP4 is involved in many different actions, thus NPYs are one group of factors that may underly its performance-enhancing effects; further studies are required to determine the exact mechanisms.

Accuracy of blood pressure measurement across BMI categories using the OptiBP™ mobile application.

PURPOSE: Obesity is a clear risk factor for hypertension. Blood pressure (BP) measurement in obese patients may be biased by cuff size and upper arm shape which may affect the accuracy of measurements. This study aimed to assess the accuracy of the OptiBP smartphone application for three different body mass index (BMI) categories (normal, overweight and obese). MATERIALS AND METHODS: Participants with a wide range of BP and BMI were recruited at Lausanne University Hospital's hypertension clinic in Switzerland. OptiBP estimated BP by recording an optical signal reflecting light from the participants' fingertips into a smartphone camera. Age, sex and BP distribution were collected to fulfil the AAMI/ESH/ISO universal standards. Both auscultatory BP references and OptiBP BP were measured and compared using the simultaneous opposite arms method, as described in the 81060-2:2018 ISO norm. Subgroup analyses were performed for each BMI category. RESULTS: We analyzed 414 recordings from 95 patients: 34 were overweight and 15 were obese. The OptiBP application had a performance acceptance rate of 82%. The mean and standard deviation (SD) differences between the optical BP estimations and the auscultatory reference rates (criterion 1) were respected in all subgroups: SBP mean value was 2.08 (SD 7.58); 1.32 (6.44); -2.29 (5.62) respectively in obese, overweight and normal weight subgroup. For criterion 2, which investigates the precision errors on an individual level, the threshold for systolic BP in the obese group was slightly above the requirement for this criterion. CONCLUSION: This study demonstrated that the OptiBP application is easily applicable to overweight and obese participants. Differences between the reference measure and the OptiBP estimation were within ISO limits (criterion 1). In obese participants, the SD of mean error was outside criterion 2 limits. Whether auscultatory measurement, due to arm morphology or the OptiBP is associated with increasing bias in obese still needs to be studied.

What is the context? • Hypertension and obesity have a major impact on population health and costs. • Obesity is a chronic disease characterized by abnormal or excessive fat accumulation. • Obesity, in combination with other diseases like hypertension, is a major risk factor for cardiovascular and total death. • In Europe, the obesity rate is 21.5% for men and 24.5% for women. • Hypertension, which continues to increase in the population, is a factor that can be modified when well managed. • Blood pressure measurement by the usual method may be complicated in obese patients due to fat accumulation and the shape of the arm and can lead to measurement errors. In addition, the non-invasive blood pressure measurement can be constraining and uncomfortable.What is new? • Smartphone apps are gradually appearing and allow the measurement of blood pressure without a pressure cuff using photoplethysmography. • OptiBP is a smartphone application that provides an estimate of blood pressure that has been evaluated in the general population. • The objective of this study is to assess whether OptiBP is equally effective in obese and overweight patients.What is the impact? • The use of smartphones to estimate BP in overweight and obese patients may be a solution to the known bias associated with cuff measurement. • The acquisition of more and more data with a larger number of patients will allow the continuous improvement of the application's algorithm.

May Measurement Month 2017-2019: results from Switzerland.

May Measurement Month (MMM) is an international screening campaign for arterial hypertension initiated by the International Society of Hypertension and endorsed by the World Hypertension League. Its aim is to raise the awareness of elevated blood pressure (BP) in the population worldwide. The goal of the present analyses is to assess the results obtained during three years of this campaign in Switzerland. Swiss data from MMM17 to MMM19 campaigns were used. BP and a questionnaire for basic demographic and clinical information were recorded for each participant. BP measurements and definition of arterial hypertension followed the standard MMM protocol. To assess BP control, European Society of Hypertension 2018 thresholds of <140/90 mmHg were used. Overall, 3635 participants had their BP measured, including 2423 women (66.7%) and 1212 (33.3%) men. More than half of the data came from pharmacies during MMM18 and MMM 19 campaigns. The difference in BP between pharmacies and other screenings sites was small. Overall, prevalence and awareness rates were 32.7% and 72.3%, respectively. Of those on medication, 60.9% were controlled, and of all hypertensive patients, 39.4% had controlled BP. In Switzerland, the prevalence of hypertension based on a 3-year awareness campaign was similar to previous epidemiological data within the country. One third of the population screened had hypertension, two thirds were aware of it, and less than half had controlled BP.