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George L. Bakris passed away on 15 June 2024 at the age of 72 years. This obituary aims at honouring his life and career by describing the stages in his personal and professional pathway, presenting some of his many remarkable accomplishments, and highlighting his exceptional clinical skills, mentorship, and friendship.

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.

ObjectiveIn 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 methodsAt 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.ResultsIn 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.ConclusionsIn 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.

Gout and hyperuricaemia are two clinical situations associated with an elevated risk of developing cardiovascular (heart failure, myocardial infarction, stroke) and metabolic and renal complications. One reason is probably related to the fact that the prevalence of hyperuricaemia and gout is high in clinical situations, which themselves involve a high cardiovascular risk, such as hypertension, diabetes, chronic kidney disease or obesity. However, recent studies suggest that hyperuricaemia may promote cardiovascular complications independently of other cardiovascular risk factors, by inducing chronic inflammation, oxidative stress, and endothelial dysfunction. The questions that arise today concern primarily the treatment of asymptomatic hyperuricaemia. Should it be treated to decrease the patients' cardiovascular risk and if so, starting from which level and towards which target? There are now several pieces of evidence indicating that this might be useful, but data from large studies are not unanimous. This review will discuss this issue as well as new well-tolerated treatments, such as febuxostat or SGLT2 inhibitors, which lower uric acid levels, prevent gout and lower the risk of cardio-renal events.

Diabetic kidney disease (DKD) is a major public health problem and its incidence is rising. The disease course is unpredictable with classic biomarkers, and the search for new tools to predict adverse renal outcomes is ongoing. Renal magnetic resonance imaging (MRI) now enables the quantification of metabolic and microscopic properties of the kidneys such as single-kidney, cortical and medullary blood flow, and renal tissue oxygenation and fibrosis, without the use of contrast media. A rapidly increasing number of studies show that these techniques can identify early kidney damage in patients with DKD, and possibly predict renal outcome. This review provides an overview of the currently most frequently used techniques, a summary of the results of some recent studies, and our view on their potential applications, as well as the hurdles to be overcome for the integration of these techniques into the clinical care of patients with DKD.

Growing evidence demonstrates the suitability of renal denervation in a broad population of patients; however, questions remain over its suitability and practical implementation. Given the rapidity of emerging data, this has been a challenging field for potential adopters to navigate. The purpose of this article is twofold: to provide navigation through emerging clinical data and evolving guidance; and to provide physicians with practical, evidence-based advice for identifying eligible patients and providing appropriate management in the pre- and postintervention settings. Although many of these recommendations are based on existing published guidance documents, we reflect equally on our own experiences of using this technology.

Purpose Poor adherence to drug therapy and inadequate drug regimens are two frequent factors responsible for the poor blood pressure (BP) control observed in patients with apparent resistant hypertension. We evaluated the efficacy of an antihypertensive management strategy combining a standardised therapy with three long acting drugs and electronic monitoring of drug adherence in patients with apparent resistant hypertension. Materials and Methods In this multicentric observational study, adult patients with residual hypertension on 24 h ambulatory BP monitoring (ABMP) despite the use of three or more antihypertensive drugs could be included. Olmesartan/amlodipine (40/10 mg, single pill fixed-dose combination) and chlorthalidone (25 mg) were prescribed for 3 months in two separated electronic pills boxes (EPB). The primary outcome was 24 h ambulatory systolic BP (SBP) control at 3 months, defined as mean SBP

Purpose Little is known on the beliefs, perceptions and practices of hypertension specialists in addressing non-adherence to therapy. Therefore, a survey was undertaken amongst healthcare professionals (HCPs) managing hypertension in the European Society of Hypertension (ESH) Centres of Excellence. Materials and methods Cross-sectional data were obtained between December 2020 and April 2021 using an online anonymous structured questionnaire including 26 questions/136 items, that was sent to all ESH Excellence centres. Results Overall 67 from 187 centres (37.3%) responded and 200 HCPs from 30 countries answered the questionnaire. Participants (60% men) were mainly physicians (91%) and nurses (8%) from University hospitals (77%). Among physicians, 83% had >10 years professional experience. Average time dedicated to discuss medications was 1-5 min in 48% and 6-10 min in 29% of cases. Interviews with patients about adherence were the most frequently used assessment method. Chemical detection of medications in urine was available in 36% of centres. One third of physicians involved their patients regularly in treatment decisions. The most frequent methods to improve adherence included simplification of medication therapy, more frequent visits, and home blood pressure monitoring. Conclusions The level of implementation of tools to detect and improve adherence in hypertension management by HCPs in ESH excellence centres is low. Structured educational activities focussing on adherence management and access to the newest objective measures to detect non-adherence might improve these deficits.

Introduction: The measurement of renal functional reserve (RFR) can unmask glomerular hyperfiltration in residual nephrons but its determination is time-consuming. In this study we assessed whether contrast-enhanced ultrasound (CEUS) is a valuable alternative to the gold standard inulin-clearance, and whether L-arginine or protein shakes lead to similar changes in glomerular filtration rate (GFR) as animal proteins in men and women. Methods: Changes in GFR and renal microperfusion were studied in 25 healthy subjects (8 men, 17 women) by simultaneously performing inulin clearance and CEUS (perfusion index, PI) before and 1 and 2 hours after different protein loads (L-arginine, protein shake or meat). Doppler parameters - renal resistive index (RRI) and pulsatility index (PuI) - were also measured Results: None of the oral protein loads induced significant changes in CEUS-assessed PI. Only meat increased inulin clearance (from 111.2±16.0 to 149.8±27.2 ml/min, p

Patients with chronic kidney disease on maintenance hemodialysis (HD) have a very high risk of death in the course of COVID-19. The aim of the study was to assess the effectiveness of COVID-19 vaccination to reduce the incidence of COVID-19 and the fatality rate in HD patients. A retrospective registry-based cohort study was performed in all HD adult patients in the Pomeranian Voivodeship. Vaccinations were carried out from January to April 2021 with mRNA vaccines, either BNT162b2 or mRNA-1273 with two-dose schedule. In the first analysis (2nd pandemic wave), 1,160 unvaccinated patients were included (59.7% males, 25.7% diabetic). In the second analysis (4th pandemic wave), 1,131 (59.4% male, 30.7% diabetic) individuals were included, 1,042 (92.13%) were fully vaccinated. Three hundred and fifteen HD patients (27.2%) were COVID-19 positive during the 2nd wave, and 6.9% (78/1,131) during the 4th wave. Within the fully vaccinated patients of the 4th wave, 60 were COVID-19 positive, 5.8 vs. 20.2% of unvaccinated COVID-19 positive patients in 2nd wave, respectively. COVID-19 incidence rate ratio (IRR) was 0.21 (4th wave-vaccinated vs. 2nd wave-unvaccinated) indicating a 79% reduction. The IRR between vaccinated and unvaccinated patients of the 4th wave was 0.28 in favor of vaccinated patients with 72% reduction. In the 2nd wave, 93 patients died as a result of COVID-19 (fatality rate: 29.5%). The fatality rate of fully vaccinated patients during the 4th wave was 6.7% (p = 0.004), while the fatality rate in the 4th wave within unvaccinated patients accounted for 11.1%. Significant clinical effectiveness of COVID-19 vaccination was demonstrated in a multicenter study in HD patients.

BackgroundSodium–glucose co-transport 2 inhibitors (SGLT2i) lower blood pressure (BP) in normotensive subjects and in hypertensive and normotensive diabetic and non-diabetic patients. However, the mechanisms of these BP changes are not fully understood. Therefore, we examined the clinical and biochemical determinants of the BP response to empagliflozin based on 24-h ambulatory BP monitoring.MethodsIn this post-hoc analysis of a double-blind, randomized, placebo-controlled study examining the renal effects of empagliflozin 10 mg vs. placebo in untreated normotensive non-diabetic subjects, the 1-month changes in 24 h ambulatory BP were analyzed in 39 subjects (13 placebo/26 empagliflozin) in regard to changes in biochemical and hormonal parameters.ResultsAt 1 month, empagliflozin 10 mg decreased 24-h systolic (SBP) and diastolic (DBP) BP significantly by −5 ± 7 mmHg (p < 0.001) and −2 ± 6 mmHg (p = 0.03). The effect on SBP and DBP was more pronounced during nighttime (resp. −6 ± 11 mmHg, p = 0.004; −4 ± 7 mmHg, p = 0.007). The main determinants of daytime and nighttime SBP and DBP responses were baseline BP levels (for daytime SBP: coefficient −0.5; adj. R2: 0.36; p = 0.0007; for night-time SBP: coefficient −0.6; adj. R2: 0.33; p = 0.001). Although empaglifozin induced significant biochemical changes, none correlated with blood pressure changes including urinary sodium, lithium, glucose and urate excretion and free water clearance. Plasma renin activity and plasma aldosterone levels increased significantly at 1 month suggesting plasma volume contraction, while plasma metanephrine and copeptin levels remained the same. Renal resistive indexes did not change with empagliflozin.ConclusionSGLT2 inhibition lowers daytime and nighttime ambulatory systolic and diastolic BP in normotensive non-diabetic subjects. Twenty-four jour changes are pronounced and comparable to those described in diabetic or hypertensive subjects. Baseline ambulatory BP was the only identified determinant of systolic and diastolic BP response. This suggests that still other factors than sustained glycosuria or proximal sodium excretion may contribute to the resetting to lower blood pressure levels with SGLT2 inhibition.Clinical Trial Registration:[https://www.clinicaltrials.gov], identifier [NCT03093103].

Abstract Mobile health diagnostics have been shown to be effective and scalable for chronic disease detection and management. By maximizing the smartphones’ optics and computational power, they could allow assessment of physiological information from the morphology of pulse waves and thus estimate cuffless blood pressure (BP). We trained the parameters of an existing pulse wave analysis algorithm (oBPM), previously validated in anaesthesia on pulse oximeter signals, by collecting optical signals from 51 patients fingertips via a smartphone while simultaneously acquiring BP measurements through an arterial catheter. We then compared smartphone-based measurements obtained on 50 participants in an ambulatory setting via the OptiBP app against simultaneously acquired auscultatory systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean blood pressure (MBP) measurements. Patients were normotensive (70.0% for SBP versus 61.4% for DBP), hypertensive (17.1% vs. 13.6%) or hypotensive (12.9% vs. 25.0%). The difference in BP (mean ± standard deviation) between both methods were within the ISO 81,060–2:2018 standard for SBP (− 0.7 ± 7.7 mmHg), DBP (− 0.4 ± 4.5 mmHg) and MBP (− 0.6 ± 5.2 mmHg). These results demonstrate that BP can be measured with accuracy at the finger using the OptiBP smartphone app. This may become an important tool to detect hypertension in various settings, for example in low-income countries, where the availability of smartphones is high but access to health care is low.

Background: Renal functional reserve (RFR), defined as the difference between stress and resting glomerular filtration rate (GFR), may constitute a diagnostic tool to identify patients at higher risk of developing acute kidney injury or chronic kidney disease. Blunted RFR has been demonstrated in early stages of hypertension and has been attributed to impaired vascular reactivity due to an overactive sympathetic nervous system (SNS). Objective: The purpose of this study was to investigate whether RFR correlates with other phenotypes expressing overactivity of the SNS in patients with essential hypertension and preserved renal function. Methods: Thirty-six patients with untreated essential hypertension and a GFR >60 mL/min/1.73 m2 were enrolled. The following parameters were measured: RFR, 24-h ambulatory blood pressure (BP) profile, a treadmill stress test, and an echocardiographic examination. Urine and venous samples were obtained at specific time points for the determination of clinical parameters, and both resting and stress GFR were calculated by using endogenous creatinine clearance for the measurement of RFR after an acute oral protein load (1 g/kg). Results: Twenty-one patients had a RFR

Abstract Background Men have larger kidneys than women, but it is unclear whether gender remains an independent predictor of kidney size (expressed as weight or length) after correction for body size. We analysed autopsy data to assess whether relative renal length and weight (e.g. corrected for body weight, height or body surface area (BSA)) are also larger in men. Assuming that kidney size is associated with nephron number, opposite findings could partly explain why women are less prone to the development and progression of chronic kidney disease than men. Methods All forensic autopsies performed between 2009 and 2015 at the local university hospital of Geneva in individuals of European descent aged ≥18 years without a known history of diabetes and/or kidney disease were examined. Individuals with putrefied or severely injured bodies were excluded. Relative renal weight and length were respectively defined as renal weight divided by body weight or BSA and renal length divided by body height or BSA. Results A total of 635 autopsies (68.7% men) were included in the analysis. Left kidneys were on average 8 g heavier and 2 mm longer than right kidneys (both: p

Cardiovascular calcification is a serious pathology for which effective pharmacological treatments are lacking. Here the authors show that an optimized oligo(ethylene glycol) derivative of inositol phosphate interferes with calcium phosphate crystallization and inhibits soft tissue calcification in vivo following subcutaneous injection.

Excess weight is caused by multiple factors and has increased sharply in Switzerland since the 1990s. Its consequences represent a major challenge for Switzerland, both in terms of health and the economy. Until now, there has been no cross-dataset overview study on excess weight in adults in Switzerland. Therefore, our aim was to conduct the first synthesis on excess weight in Switzerland. We included all existing nationwide Swiss studies (eight total), which included information on body mass index (BMI). Mixed multinomial logistic regression analyses were performed to assess the associations between different socio-demographic, lifestyle cofactors and the World Health Organization (WHO) categories for BMI. Along with lifestyle factors, socio-demographic factors were among the strongest determinants of BMI. In addition, self-rated health status was significantly lower for underweight, pre-obese and obese men and women than for normal weight persons. The present study is the first to synthesise all nationwide evidence on the importance of several socio-demographic and lifestyle factors as risk factors for excess weight. In particular, the highlighted importance of lifestyle factors for excess weight opens up the opportunity for further public health interventions.

AimsGlomerular damage indicated by proteinuria is a main symptom in diabetic nephropathy. Mineralocorticoid receptor (MR) antagonists (MRAs) are beneficial irrespective of aldosterone availability. Thus, we hypothesized an alternatively activated MR to promote glomerular damage in proteinuric diabetic nephropathy. Specifically, we aimed first to demonstrate the presence of steroid hormones serving as alternative MR targets in type II diabetic patients with proteinuric kidney disease, second whether MR selectivity was modified, third to characterize MR and glucocorticoid receptor (GR) expression and activity in glomerular cell types exposed to eu- and hyperglycemic conditions, fourth to characterize the pro-fibrotic potential of primary human renal mesangial cells (HRMC) upon stimulation with aldosterone and cortisol, and fifth to specify the involvement of the MR and/or GR in pro-fibrotic signaling.Materials and methodsUrinary steroid hormone profiles of patients with diabetic kidney disease were analyzed by gas chromatography-mass spectrometry and compared to an age and gender matched healthy control group taken out of a population study. In both cohorts, the activity of the MR pre-receptor enzyme 11β-hydroxysteroid dehydrogenase type 2 (HSD11B2), which inactivates cortisol to prevent it from binding to the MR, was assessed to define a change in MR selectivity. Expression of HSD11B2, MR and GR was quantified in HRMC and primary human renal glomerular endothelial cells (HRGEC). Activity of MR and GR was explored in HRMC by measuring the MR/GR down-stream signal SGK1 and the pro-fibrotic genes TGFB1, FN1 and COL1A1 in normal and high glucose conditions with the MR/GR agonists aldosterone/cortisol and the MR/GR antagonists spironolactone/RU486.ResultsPatients with diabetic kidney disease excreted more tetrahydroaldosterone than the control group reaching significance in men. The excretion of MR-agonistic steroid hormones was only increased for 18-hydroxytetrahydrocorticosterone in diabetic women. The excretion of most glucocorticoids was higher in the diabetic cohort. Higher apparent systemic HSD11B2 activity suggested less activation of the MR by cortisol in diabetic patients. Both cell types, HRMC and HRGEC, lacked expression of HSD11B2. Hyperglycemic conditions did not change MR and GR expression and activity. Stimulation with both aldosterone and cortisol promoted upregulation of pro-fibrotic genes in HRMC. This effect of MR and/or GR activation was more pronounced in high glucose conditions and partially inhibited by MRAs and GR antagonists.ConclusionsIn patients with diabetic kidney disease alternative MR activation is conceivable as cortisol and cortisone metabolites are increased. Systemic availability of active metabolites is counteracted via an increased HSD11B2 activity. As this cortisol deactivation is absent in HRMC and HRGEC, cortisol binding to the MR is enabled. Both, cortisol and aldosterone stimulation led to an increased expression of pro-fibrotic genes in HRMC. This mechanism was related to the MR as well as the GR and more marked in high glucose conditions linking the benefit of MRAs in diabetic kidney disease to these findings.

Objective: Angiotensin receptor blockers (ARB) are among the recommended first-line treatment options in patients with hypertension and chronic kidney disease (CKD). This meta-analysis evaluated the effect of ARB on blood pressure (BP) and renal function in patients with concomitant hypertension and CKD with or without diabetes. Methods: Literature search was performed in PubMed/MEDLINE, EMBASE and BIOSIS to identify parallel-group, randomized controlled trials (≥8 weeks) reporting the effects of ARB on office systolic/diastolic BP (SBP/DBP), estimated glomerular filtration rate (eGFR), serum creatinine (SCr), creatinine clearance (CrCl) or proteinuria in adults with hypertension and CKD. Mean difference (MD, generic inverse variance) with 95% confidence intervals (CIs) was used to report an outcome. Results: Among the 24 studies identified, 19 evaluated ARB as monotherapy, 4 evaluated ARB as combination therapy and one evaluated ARB both as monotherapy and combination therapy. Median (range) duration of the studies was 12 (1.84–54.0) months. ARB monotherapy significantly (p

Objective: We evaluated the effect on long term blood pressure (BP) of an interprofessional team-based care (TBC) intervention, involving nurses, pharmacists, and physicians, compared to usual care.Methods: We conducted a pragmatic randomized controlled study in ambulatory clinics and community pharmacies in Switzerland (ClinicalTrials.gov: NCT02511093). Uncontrolled treated hypertensive patients were randomized to TBC or usual care (UC). In the TBC group, nurses and pharmacists met patients every 6 weeks to measure BP, assess lifestyle, support medication adherence, and provide health education for 6 months. After each visit, they wrote a report to the physician who could adjust antihypertensive therapy. The outcome was the intention-to-treat difference in mean daytime ambulatory blood pressure measurement (ABPM) and control (

Background: Kidney perfusion and oxygenation are two important determinants of kidney graft function. In kidney transplantation, repeated graft hypoperfusion may occur during hip flexion, for example in the sitting position, due to the progressive development of fibrotic tissue around iliac arteries. The aim of this study was to assess the changes in oxygenation and perfusion of kidney grafts during hip flexion and extension using a new functional magnetic resonance imaging (fMRI) protocol.Methods: Nineteen kidney graft recipients prospectively underwent MRI on a 3T scanner including diffusion-weighted, blood oxygenation level dependent (BOLD), and arterial spin labeling sequences in hip positions 0° and >90° before and after intravenous administration of 20 mg furosemide.Results: Unexpectedly, graft perfusion values were significantly higher in flexed compared to neutral hip position. Main diffusion-derived parameters were not affected by hip position. BOLD-derived cortico-medullary R2* ratio was significantly modified during hip flexion suggesting an intrarenal redistribution of the oxygenation in favor of the medulla and to the detriment of the cortex. Furthermore, the increase in medullary oxygenation induced by furosemide was significantly blunted during hip flexion (p < 0.001).Conclusion: Hip flexion has an acute impact on perfusion and tissue oxygenation in kidney grafts. Whether these position-dependent changes affect the long-term function and outcome of kidney transplants needs further investigation.

These practice guidelines on the management of arterial hypertension are a concise summary of the more extensive ones prepared by the Task Force jointly appointed by the European Society of Hypertension and the European Society of Cardiology. These guidelines have been prepared on the basis of the best available evidence on all issues deserving recommendations; their role must be educational and not prescriptive or coercive for the management of individual subjects who may differ widely in their personal, medical and cultural characteristics. The members of the Task Force have participated independently in the preparation of these guidelines, drawing on their academic and clinical experience and by objective examination and interpretation of all available literature. A disclosure of their potential conflict of interest is reported on the websites of the ESH and the ESC.

[This corrects the article DOI: 10.1371/journal.pone.0214549.].

ObjectiveDiagnostic ratios calculated from urinary steroid hormone metabolites are used as a measure for the relative activity of steroidogenic enzymes or pathways in the clinical investigation of steroid metabolism disorders. However, population-based sex- and age-specific reference intervals and day-night differences in adults are lacking.MethodsSixty-five diagnostic ratios were calculated from steroid metabolites measured by GC-MS in day- and night-time and in 24-hour urine from 1128 adults recruited within the Swiss Kidney Project on Genes in Hypertension (SKIPOGH), a population-based, multicenter cohort study. Differences related to sex, age and day- and night-time were evaluated and reference curves in function of age and sex were modelled by multivariable linear mixed regression for diagnostic ratios and were compared to values from the literature.ResultsMost ratios had sex- and age-specific relationships. For each ratio, percentiles were plotted in function of age and sex in order to create reference curves and sex- and age-specific reference intervals derived from 2.5th and 97.5th percentiles were obtained. Most ratios reflected a higher enzyme activity during the day compared to the night.ConclusionsSex- and age-specific references for 24 hours, day and night urine steroid metabolite ratios may help distinguishing between health and disease when investigating human disorders affecting steroid synthesis and metabolism. The day-night differences observed for most of the diagnostic ratios suggest a circadian rhythm for enzymes involved in human steroid hormones metabolism.

Background The sodium/glucose cotransporter 2 inhibitor empagliflozin has cardiorenal protective properties through mechanisms beyond glucose control. In this study we assessed whether empagliflozin modifies renal oxygenation as a possible mechanism of renal protection, and determined the metabolic, renal, and hemodynamic effects of empagliflozin in nondiabetic subjects. Methods and Results In this double‐blind, randomized, placebo‐controlled study, 45 healthy volunteers underwent blood and urine sampling, renal ultrasound, and blood‐oxygenation‐level–dependent magnetic resonance imaging before and 180 minutes after administration of 10 mg empagliflozin (n=30) or placebo (n=15). These examinations were repeated after 1 month of daily intake. Cortical and medullary renal oxygenation were not affected by the acute or chronic administration of empagliflozin, as determined by 148 renal blood‐oxygenation‐level–dependent magnetic resonance imaging examinations. Empagliflozin increased glucosuria (24‐hour glucosuria at 1 month: +50.1±16.3 g). The acute decrease in proximal sodium reabsorption, as determined by endogenous fractional excretion of lithium (−34.6% versus placebo), was compensated at 1 month by a rise in plasma renin activity (+28.6%) and aldosterone (+55.7%). The 24‐hour systolic and diastolic ambulatory blood pressures decreased significantly after 1 month of empagliflozin administration (−5.1 and −2.0 mm Hg, respectively). Serum uric acid levels decreased (−28.4%), hemoglobin increased (+1.7%), and erythropoietin remained the same. Conclusions Empagliflozin has a rapid and significant effect on tubular function, with sustained glucosuria and transient natriuresis in nondiabetic normotensive subjects. These effects favor blood pressure reduction. No acute or sustained changes were found in renal cortical or medullary tissue oxygenation. It remains to be determined whether this is the case in nondiabetic or diabetic patients with congestive heart failure or kidney disease. REGISTRATION: URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT03093103.

AIM OF THE STUDY Important regional differences in uranium exposure exist because of varying uranium concentrations in soil, water and food. Comprehensive data on the exposure of the general population to uranium is, however, scarce. Based on the 24-hour urinary excretion, the uranium exposure of the adult Swiss population was assessed in relation to age, sex, place of residence, body mass index (BMI), smoking habit and type of drinking water, as well as risk factors in relation to kidney impairment and indicators of a possible renal dysfunction. METHODS Uranium was quantified in 24-hour urine from a nationwide population-based sample (n = 1393). The ratio 238U/233U was measured for isotope dilution calibration with a sector field inductively coupled plasma mass spectrometer (HR-ICP-MS). RESULTS Overall median and 95th percentile were 15 and 67 ng/24 h, respectively. The place of residence significantly influenced urinary uranium excretion. However, most of the highest urinary uranium excretion levels could not be associated to areas known for their elevated uranium concentrations in the drinking water. Sources other than the local drinking water (e.g., bottled water) might be important, too. Gender as well as albumin excretion also had a significant effect on uranium excretion. The latter was, however, strongly dependent on the presence of diabetes mellitus. No association was found for age, BMI, smoking habit or the other examined kidney related variables. CONCLUSIONS On the basis of uranium exposure, assessed via 24-hour urinary uranium excretion, and current knowledge of the toxicity of naturally occurring uranium, a substantial corresponding health risk for the general adult population is unlikely. However, as long as no specific sensitive biomarker for the biological impact of low-dose chronic uranium exposure has been identified and validated, assessing subtle health impact of such exposure will remain difficult.

Hypertension is highly prevalent after the age of 65 years affecting more than 60% of individuals in developed countries. Today, there is sufficient evidence from clinical trials that treating elderly subjects with hypertension with antihypertensive medications has a positive benefit/risk ratio even in very elderly patients (>80 years). In recent years, partial or total non-adherence has been recognized as major issues in the long-term management of hypertension in all age categories. However, whether non-adherence is more frequent in hypertensive patients older than 65 years or not is still a matter of debate and the common belief is that adherence is lower in older than in younger patients. Are clinical data supporting this belief? In this brief review, we discuss the topic of drug adherence in elderly in the context of the medical treatment of hypertension. Studies show that drug adherence is actually better in patients aged 65 to 80 years when compared to younger hypertensive patients (80 years) the prevalence of non-adherence does increase. In this patients' group, there are specific risk factors for non-adherence such as cognitive ability, depression, and health believes, in addition to classical risk factors for non-adherence. One important aspect in the elderly is the prescription of potentially inappropriate medications that will interfere with the adherence to necessary treatments. In this context, an interesting new concept was developed few years ago, i.e., the process of deprescribing. Thus, today, in addition to conventional guidelines recommendations (use of single pill combinations, individualization of treatments), the evaluation of cognitive abilities, the regular assessment of potentially inappropriate medications, and the process of deprescribing appear to be three new additional steps to improve drug adherence in the elderly and thereby ameliorate the global management of hypertension.

Background: Lowering blood pressure (BP) leads to reduced risk of stroke, myocardial infarction, and cardiovascular mortality. Single-pill combination therapies may deliver better BP control than increasing the dose of monotherapies or using more drugs separately.Objectives: The aim of the present observational study was to investigate the real-life use and the effect of first line or replacement single-pill combination therapies containing irbesartan and hydrochlorothiazide (HCTZ) on systolic BP (SBP) control rate in patients with hypertension.Methods: Overall, 780 patients with moderate or severe hypertension either untreated (289; 37%) or uncontrolled (491; 63%) with previous therapy were included in the “First Line CombinAtion Therapy in the Treatment of Stage II and III Hypertension” (FLASH) prospective Swiss national-wide cohort study. All recruited patients received single-pill antihypertensive combination therapy containing HCTZ and irbesartan. BP was measured at baseline and after 8-weeks follow-up according to guidelines.Results: Mean reductions in office systolic/diastolic BP (SBP/DBP) were 23.7 ± 13.7/11.7 ± 8.5 mmHg, with reductions of 26.9 ± 14.1/13.0 ± 8.8 mmHg or 21.8 ± 13.1/11.0 ± 8.3 mmHg when the single-pill combination of irbesartan/HCTZ was given as first line or replacement treatment, respectively (p < 0.001 for differences between first line and replacement treatment in both SBP and DBP). The guidelines-recommended goals were reached in 368 (47%), 492 (63%), and 312 (40%) patients for SBP, DBP, and SBP/DBP, respectively. The SBP control rate was higher when the combination was used as first line treatment (52 vs. 44%; p = 0.043). Overall, 145 adverse events were recorded; hypotension in 12 (1.5%) cases, hypokalaemia in 9 (1.2%), and hyperkalaemia in 3 (0.4%).Conclusions: The single-pill combination of irbesartan/HCTZ was well-tolerated and achieved substantial reductions in both systolic and diastolic BP. The SBP control rate was greater when the combination was prescribed as first line treatment as suggested by recent ESC/ESH guidelines.

Background/Aims: Despite availability of a broad spectrum of blood pressure (BP)-lowering drugs many hypertensive patients do not attain BP goals. We aimed to evaluate the influence of home blood pressure monitoring (HBPM) on patient’s awareness and attainment of BP goals under antihypertensive treatment with irbesartan alone or in combination with hydro-chlorothiazide. Methods: In total, 1,268 patients with arterial hypertension were enrolled in the Factors Influencing Results in anti-hypertenSive Treatment (FIRST) study by 348 general practitioners and internal medicine specialists across Switzerland. Patients selected for HBPM received detailed information and training on BP self-management. The study endpoints included patient’s awareness and attainment of BP goals, and the efficacy and tolerability of antihypertensive treatment at 3 months. Results: Overall, the mean age was 61±13 years and 616 (49%) were women. The mean systolic/diastolic BP was 161±17/96±11 mmHg, and 239 (19%) patients had diabetes mellitus. 758 (60%) patients were instructed to use HBPM. Both the proportion of patients aware of their BP goals (81% vs. 70%; p< 0.001) and the percentage of patients reaching their BP goal (64% vs. 57%; p=0.028) were higher in those with vs. without HBPM. The mean reduction in systolic/diastolic BP was 23.8/13.2 mmHg. Only 35 (3.0%) patients discontinued antihypertensive therapy. Conclusion: In a large Swiss cohort of patients with arterial hypertension, information and training on BP self-measurement and direct involvement of patients by using HBPM led to improvement in BP control. Treatment with irbesartan alone or in combination with hydrochlorothiazide was well tolerated and markedly reduced BP.