Management of patients with hypertension and chronic kidney disease referred to Hypertension Excellence Centres among 27 countries. On behalf of the European Society of Hypertension Working Group on Hypertension and the Kidney.

Objective Real-life management of patients with hypertension and chronic kidney disease (CKD) among European Society of Hypertension Excellence Centres (ESH-ECs) is unclear : we aimed to investigate it. Methods A survey was conducted in 2023. The questionnaire contained 64 questions asking ESH-ECs representatives to estimate how patients with CKD are managed. Results Overall, 88 ESH-ECS representatives from 27 countries participated. According to the responders, renin-angiotensin system (RAS) blockers, calcium-channel blockers and thiazides were often added when these medications were lacking in CKD patients, but physicians were more prone to initiate RAS blockers (90% [interquartile range: 70-95%]) than MRA (20% [10-30%]), SGLT2i (30% [20-50%]) or (GLP1-RA (10% [5-15%]). Despite treatment optimisation, 30% of responders indicated that hypertension remained uncontrolled (30% (15-40%) vs 18% [10%-25%]) in CKD and CKD patients, respectively). Hyperkalemia was the most frequent barrier to initiate RAS blockers, and dosage reduction was considered in 45% of responders when kalaemia was 5.5-5.9 mmol/L. Conclusions RAS blockers are initiated in most ESH-ECS in CKD patients, but MRA and SGLT2i initiations are less frequent. Hyperkalemia was the main barrier for initiation or adequate dosing of RAS blockade, and RAS blockers' dosage reduction was the usual management.

What is the context? Hypertension is a strong independent risk factor for development of chronic kidney disease (CKD) and progression of CKD to ESKD. Improved adherence to the guidelines in the treatment of CKD is believed to provide further reduction of cardiorenal events. European Society of Hypertension Excellence Centres (ESH-ECs) have been developed in Europe to provide excellency regarding management of patients with hypertension and implement guidelines. Numerous deficits regarding general practitioner CKD screening, use of nephroprotective drugs and referral to nephrologists prior to referral to ESH-ECs have been reported. In contrast, real-life management of these patients among ESH-ECs is unknown. Before implementation of strategies to improve guideline adherence in Europe, we aimed to investigate how patients with CKD are managed among the ESH-ECs.What is the study about? In this study, a survey was conducted in 2023 by the ESH to assess management of CKD patients referred to ESH-ECs. The questionnaire contained 64 questions asking ESH-ECs representatives to estimate how patients with CKD are managed among their centres.What are the results? RAAS blockers are initiated in 90% of ESH-ECs in CKD patients, but the initiation of MRA and SGLT2i is less frequently done. Hyperkalemia is the main barrier for initiation or adequate dosing of RAAS blockade, and its most reported management was RAAS blockers dosage reduction. These findings will be crucial to implement strategies in order to improve management of patients with CKD and guideline adherence among ESH-ECs.

Glycosuria amount in response to hyperglycaemia and risk for diabetic kidney disease and related events in Type 1 diabetic patients.

BACKGROUND: Hyperglycaemia impairs tubulo-glomerular feedback. We tested whether variable tubulo-glomerular feedback during hyperglycaemia contributes to renal risk heterogeneity seen in Type 1 diabetes. METHODS: During the period 1990-92, we studied the tubulo-glomerular feedback in Type 1 diabetic patients at high or low renal risk [21 of 54 with glomerular hyperfiltration and/or microalbuminuria against 11 of 55 with normal glomerular filtration rate (GFR) and urinary albumin despite uncontrolled diabetes]. The GFR, effective renal plasma flow, mean arterial pressure and fractional reabsorptions of glucose, osmols, sodium and lithium were measured sequentially during normo- and hyperglycaemia. All patients were followed up until 2016 for incident proteinuria, estimated GFR <60 mL/min/1.73 m2, doubling of serum creatinine, end-stage renal disease or all-cause death. RESULTS: Glycaemia increased from 6.1 ± 1.3 to 15.1 ± 1.9 mmol/L in both high-risk and low-risk patients. Glycosuria was lower in the high- versus low-risk patients: 0.34 ± 0.25 versus 0.64 ± 0.44 mmol/min (P = 0.03). Both groups displayed similar kidney function during normoglycaemia. Hyperglycaemia increased more importantly GFR and fractional reabsorptions, and pre-glomerular vasodilatation in the high- than in the low-risk patients (all P < 0.05). Over 21 years, 31.5% high- versus 12.7% low-risk patients developed endpoints (adjusted P = 0.006). In a multi-adjusted survival analysis of patients having undergone renal tests, each 0.10 mmol/min glycosuria during hyperglycaemia reduced the outcome risk by 0.72 (95% confidence interval 0.49-0.97, P = 0.03). CONCLUSIONS: Reduced tubulo-glomerular feedback and glycosuria during hyperglycaemia indicate high renal risk for Type 1 diabetic patients. Inter-individual variability in tubulo-glomerular feedback activity determines renal risk in Type 1 diabetes.

Breast cancer and spironolactone: an observational postmarketing study.

INTRODUCTION: Recent studies have discussed the risk of breast cancer with antihypertensive drugs. For spironolactone, data are conflicting. The present paper investigates this potential signal in VigiBase®, the World Health Organization Global Individual Case Safety Report (ICSR) database. METHODS: In VigiBase®, we performed a case/non-case study using data registered from 1981 (spironolactone's marketing authorization) to December 31, 2017. Among women ≥ 50 years, we measured the risk of reporting "Breast malignant tumors" compared with all other adverse drug reactions (as a crude and adjusted (a) reporting odds ratio (ROR 95% CI)) for spironolactone compared with first, all other drugs and second, pseudo aldosterone antagonists (amiloride, triamterene). ROR were adjusted for age, year of report, continent of report, number of drug prescribed, and completeness score. Sensitivity analyses were performed after exclusion of drug competitors (i.e., drugs like estroprogestative therapy and progestogens that could mask a putative signal) and reports from health professionals. RESULTS: During the study period, 125 ICSRs reported spironolactone exposure and breast malignant cancer in women ≥ 50 years. We failed to find a positive association between spironolactone exposure and breast cancer in comparison with exposure to other drugs (aROR = 0.63 95% CI [0.52-0.75]) or pseudo aldosterone antagonists (amiloride, triamterene) (0.56 [0.44-0.72]). Similar trends were found after exclusion of drug competitors and/or reports from health professionals. CONCLUSION: This study did not find evidence for breast cancer associated with spironolactone.

Screening obstructive sleep apnea-hypopnea syndrome in hypertensive patients: a comparative study of the efficiency of the Epworth sleepiness scale.

BACKGROUND: Untreated Obstructive Sleep Apnea Hypnopnea Syndrome (OSAHS) is a known factor contributing to resistant hypertension (HT). Continuous Positive Airways Pressure (CPAP) is effective to decrease blood pressure (BP) in severe OSAHS. In our clinical practice, hypertensive patients seem less symptomatic with regard to severe OSAHS than normotensive patients, leading to a risk of underdiagnosis when OSAHS is screened with Epworth Sleepiness Scale (ESS). We aimed to confirm that severe OSAHS is less symptomatic in HT patients than normotensive patients using ESS. METHODS: We retrospectively compared two age, gender-matched groups - 100 hypertensive patients and 100 normotensive patients - with severe OSAHS defined as an AHI (Apnea Hypopnea Index) ≥30. OSAHS was considered symptomatic when ESS > 10. RESULTS: The two groups of patients did not differ significantly with respect to main characteristics including Body Mass Index (BMI), AHI and ODI (Oxygen Desaturation Index). Systolic and Diastolic BP were higher in HT patients (p < 0.01). HT patients were less symptomatic with regard to severe OSAHS with a lower ESS (10.0 vs 11.9, p < 0.01), and a lower number of patients with an ESS > 10 (30% vs 58%, p < 0.01). In multivariable analysis adjusted on age, gender, Obesity, Systolic BP, Diastolic BP, AHI and ADO, normotension was significantly associated with symptomatic OSAHS (OR = 2.83, [1.298-6.192], p < 0.01). CONCLUSIONS: In our study on patients with severe OSAHS, ESS score was lower in hypertensive patients than in normotensive patients. This discrepancy may lead to an underestimation of severe OSAHS in hypertensive patients.

Screening and management of hypertensive patients with chronic kidney disease referred to Hypertension Excellence Centres among 27 countries. A pilot survey based on questionnaire.

OBJECTIVE: Real-life management of hypertensive patients with chronic kidney disease (CKD) is unclear. METHODS: A survey was conducted in 2023 by the European Society of Hypertension (ESH) to assess management of CKD patients referred to ESH-Hypertension Excellence Centres (ESH-ECs) at first referral visit. The questionnaire contained 64 questions with which ESH-ECs representatives were asked to estimate preexisting CKD management quality. RESULTS: Overall, 88 ESH-ECs from 27 countries participated (fully completed surveys: 66/88 [75.0%]). ESH-ECs reported that 28% (median, interquartile range: 15-50%) had preexisting CKD, with 10% of them (5-30%) previously referred to a nephrologist, while 30% (15-40%) had resistant hypertension. The reported rate of previous recent (<6 months) estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR) testing were 80% (50-95%) and 30% (15-50%), respectively. The reported use of renin-angiotensin system blockers was 80% (70-90%). When a nephrologist was part of the ESH-EC teams the reported rates SGLT2 inhibitors (27.5% [20-40%] vs. 15% [10-25], P = 0.003), GLP1-RA (10% [10-20%] vs. 5% [5-10%], P = 0.003) and mineralocorticoid receptor antagonists (20% [10-30%] vs. 15% [10-20%], P = 0.05) use were greater as compared to ESH-ECs without nephrologist participation. The rate of reported resistant hypertension, recent eGFR and UACR results and management of CKD patients prior to referral varied widely across countries. CONCLUSIONS: Our estimation indicates deficits regarding CKD screening, use of nephroprotective drugs and referral to nephrologists before referral to ESH-ECs but results varied widely across countries. This information can be used to build specific programs to improve care in hypertensives with CKD.

Cost Analysis of Radiofrequency Ablation for Adrenal Adenoma in Patients with Primary Aldosteronism and Hypertension: Results from the ADERADHTA Pilot Study and Comparison with Surgical Adrenalectomy.

PURPOSE: Primary Aldosteronism (PA) is increasingly considered as a common disease affecting up to 10% of the hypertensive population. Standard of care comprises laparoscopic total adrenalectomy but innovative treatment such as RadioFrequency Ablation (RFA) constitutes an emerging promising alternative to surgery. The main aim of this study is to analyse the cost of RFA versus surgery on aldosterone-producing adenoma patient from the French National Health Insurance (FNHI) perspective. METHODS: The ADERADHTA study was a prospective pilot study aiming to evaluate both safety and efficacy of the novel use of adrenal RFA on the patients with PA. This study conducted on two French sites and enrolled adult patients, between 2016 and 2018, presenting hypertension and underwent the RFA procedure. Direct medical (inpatient and outpatient) and non-medical (transportation, daily allowance) costs were calculated over a 6-month follow-up period. Moreover, the procedure costs for the RFA were calculated from the hospital perspective. Descriptive statistics were implemented. RESULTS: Analysis was done on 21 patients in RFA groups and 27 patients in the surgery group. The difference in hospital costs between the RFA and surgery groups was €3774 (RFA: €1923; Surgery: €5697 p < 0.001) in favour of RFA. Inpatient and outpatient costs over the 6-month follow-up period were estimated at €3,48 for patients who underwent RFA. The production cost of implementing the RFA procedure was estimated at €1539 from the hospital perspective. CONCLUSION: Our study was the first to show that RFA is 2 to 3 times less costly than surgery. The trial is registered at ClinicalTrials.gov under the number NCT02756754.

Prevention of risks associated with inappropriate use/unnecessary consumption of medicines.

In the code of public health, misuse is defined as intentional and inappropriate use of a medicine or product, which is not in accordance with the terms of the marketing authorisation or the registration as well as with good practice recommendations. Very often this involves an individual or the interaction of several individuals including the patient, his/her carers, prescriber(s) and/or dispensers. Misuse is common; it is the source of medicinal adverse effects for which a significant part is avoidable. Medicines initially prescribed or dispensed in the context of their marketing authorization (MA) can also be the subject of primary dependency and misappropriation. Companies which develop medicines nationally make declarations to the ANSM (French National Agency for the Safety of Medicines and Health Products) and implement measures to limit non-compliant use of their products. Recently, the coronavirus disease-2019 (COVID-19) pandemic has highlighted the influence and societal impact of drug misuse. The finding of the existence of systemic misuse, the impossibility of proposing simple solutions leads us to propose two main areas for improved information and the training of users and health professionals in medicines in the context of multi-faceted interventions: prevention of misuse on the one hand and its identification and treatment on the other hand.

Hypertension in Children and Adolescents: A Position Statement From a Panel of Multidisciplinary Experts Coordinated by the French Society of Hypertension.

Hypertension is much less common in children than in adults. The group of experts decided to perform a review of the literature to draw up a position statement that could be used in everyday practice. The group rated recommendations using the GRADE approach. All children over the age of 3 years should have their blood pressure measured annually. Due to the lack of data on cardiovascular morbidity and mortality associated with blood pressure values, the definition of hypertension in children is a statistical value based on the normal distribution of blood pressure in the paediatric population, and children and adolescents are considered as having hypertension when their blood pressure is greater than or equal to the 95th percentile. Nevertheless, it is recommended to use normative blood pressure tables developed according to age, height and gender, to define hypertension. Measuring blood pressure in children can be technically challenging and several measurement methods are listed here. Regardless of the age of the child, it is recommended to carefully check for a secondary cause of hypertension as in 2/3 of cases it has a renal or cardiac origin. The care pathway and principles of the therapeutic strategy are described here.

Radiofrequency ablation for adenoma in patients with primary aldosteronism and hypertension: ADERADHTA, a pilot study.

OBJECTIVE: To evaluate the efficacy and the feasibility of radiofrequency ablation to treat aldosterone-producing adenomas. METHODS: In an open prospective bicentric pilot study, patients with hypertension on ambulatory blood pressure measurement, a primary aldosteronism, an adenoma measuring less than 4 cm, and confirmation of lateralization by adrenal venous sampling were recruited. The primary endpoint, based on ABPM performed at 6 months after the radiofrequency ablation, was a daytime SBP/DBP less than 135/85 mmHg without any antihypertensive drugs or a reduction of at least 20 mmHg for SBP or 10 mmHg for DBP. RESULTS: Thirty patients have been included (mean age = 51 ±â€Š11 years; 50% women). Mean baseline daytime SBP and DBP were 144 ±â€Š19 / 95 ±â€Š15 mmHg and 80% received at least two antihypertensive drugs. At 6 months: 47% (95% CI 28-66) of patients reached the primary endpoint, mean daytime SBP and DBP were 131 ±â€Š14 (101-154)/87 ±â€Š10 (71-107) mmHg; 43% of them did not take any antihypertensive drug and 70% of them did not take potassium supplements. Few complications were recorded: four cases of back pain at day 1 postablation; three limited pneumothoraxes, which resolved spontaneously; one lesion of a polar renal artery. CONCLUSION: Radiofrequency ablation for hypertensive patients with aldosterone-producing adenomas seems to be an emerging promising alternative to surgery. Its efficacy and its feasibility have to be confirmed in a larger sample of patients.

[Diabetes and COVID-19]. / Diabète et COVID-19.

According to previous reports, diabetes seems to be associated with serious clinical events due to COVID-19. But is diabetes per se a risk factor of being infected by the virus? We discuss these points. Data about the antidiabetic drugs are scarce. Dipeptidylpeptidase-4 (DPP-4) is found as both a cell surface protein ubiquitously expressed in many tissues and as a soluble molecule found in serum/plasma, fluids. DPP-4 is involved in infection of cells by some viruses. We relate data about the use of DPP-4 inhibitors in diabetic patients. We conclude relating French and international recommendations in people with diabetes.

Diabetes and COVID-19.

According to previous reports, diabetes seems to be a risk factor which worsens the serious clinical events caused by COVID-19. But is diabetes per se a risk factor that increases the probability of getting the virus? This paper will discuss this point. There are not many research data on antidiabetic drugs in this context. The potential influence of glucose-lowering agents on the severity of COVID-19 has not been described yet. Dipeptidylpeptidase-4 (DPP-4) is a cell surface protein ubiquitously expressed in many tissues and it is also a soluble molecule found in serum/plasma fluids. DPP-4 is involved in infection of cells by some viruses. This paper reviews data about the use of DPP-4 inhibitors and others diabetes drugs on COVID-19 patients. As such, no available evidence has yet suggested that glucose-lowering drugs - including those targeting DPP4-related pathways - produce any significant harm or benefit in the context of human infections. However, insulin must remain the first-choice agent in the management of critically ill-hospitalized patients, while it is recommended to suspend other agents in unstable patients. This paper provides related French and international recommendations for people with diabetes who got infected by COVID-19 and upholds that infections may alter glucose control and may require additional vigilance.

Renin-angiotensin-aldosterone system and COVID-19 infection.

With the multiplication of COVID-19 severe acute respiratory syndrome cases due to SARS-COV2, some concerns about angiotensin-converting enzyme 1 (ACE1) inhibitors (ACEi) and angiotensin II type 1 receptor blockers (ARB) have emerged. Since the ACE2 (angiotensin-converting enzyme 2) enzyme is the receptor that allows SARS COV2 entry into cells, the fear was that pre-existing treatment with ACEi or ARB might increase the risk of developing severe or fatal severe acute respiratory syndrome in case of COVID-19 infection. The present article discusses these concerns. ACE2 is a membrane-bound enzyme (carboxypeptidase) that contributes to the inactivation of angiotensin II and therefore physiologically counters angiotensin II effects. ACEis do not inhibit ACE2. Although ARBs have been shown to up-regulate ACE2 tissue expression in experimental animals, evidence was not always consistent in human studies. Moreover, to date there is no evidence that ACEi or ARB administration facilitates SARS-COV2 cell entry by increasing ACE2 tissue expression in either animal or human studies. Finally, some studies support the hypothesis that elevated ACE2 membrane expression and tissue activity by administration of ARB and/or infusion of soluble ACE2 could confer protective properties against inflammatory tissue damage in COVID-19 infection. In summary, based on the currently available evidence and as advocated by many medical societies, ACEi or ARB should not be discontinued because of concerns with COVID-19 infection, except when the hemodynamic situation is precarious and case-by-case adjustment is required.

Drugs acting on renin angiotensin system and use in ill patients with COVID-19.

Some concerns about the prescription of drugs acting on the renin-angiotensin system (angiotensin-converting enzyme 1 (ACE1) inhibitors, ACEi; angiotensin II type 1 receptor blockers, ARB) have emerged due to SARS COV2 and COVID-19 pandemic. These very legitimate questions are directly the consequence of the recent recognition of the fundamental role of ACE2 (angiotensin-converting enzyme 2) in COVID-19 infection. Indeed, SARS COV2 utilizes ACE2 as a membrane receptor to enter target cells. Consequently, the putative impact of drugs modulating the renin-angiotensin system on the risk of developing severe or fatal severe acute respiratory syndrome in case of COVID-19 infection emerged. As a membrane-bound enzyme (carboxypeptidase), ACE2 inactivates angiotensin II and therefore physiologically counters its effects. Due to a different structure compared with ACE1, ACE2 is insensitive to ACEIs. In vitro, both ARBs and ACEi appear able to upregulate ACE2 tissue expression and activity but these results were not confirmed in Humans. The exact impact of both ARBs and ACEis on COVID-19 infection is definitively known and preliminary results are even in favor of a protective role confers by these drugs. Due to the crucial role of ACE2, some groups support the hypothesis that a modulation of ACE2 expression could represent a valuable therapeutic target could confer protective properties against inflammatory tissue damage in COVID-19 infection. So, studies are currently ongoing to test the impact of elevated ACE2 membrane expression, administration of ARB and infusion of soluble ACE2. In summary, based on the currently available evidences and as recommended by several medical societies, ACEi or ARB should not be systematically discontinued because to date no safety signal was raised with the use of these drugs.

Impact of cone beam - CT on adrenal vein sampling in primary aldosteronism.

PURPOSE: The aim of this study in a group of patients with primary aldosteronism was to evaluate the contribution of CB-CT (cone beam CT) to the overall success rate of adrenal vein sampling (AVS), and in particular to the selective cannulation of the right adrenal vein (RAV). METHOD: This was a retrospective single-center study including 91 AVS procedures performed by our consultant radiologist between March 2011 and January 2017. Fifty cases were performed with CB-CT and 50 were performed without. Angiography with CB-CT was carried out after RAV cannulation to check the accurate catheter position. For each patient, we collected technical and biochemical success rates, as well as irradiation data. RESULTS: The overall success rate of AVS with CB-CT was 80 %, vs. 44 % without (p = 0.00046), with right-sided selectivity of 88 % vs. 49 % (p < 0.0001). There was no significant increase in radiation exposure with CB-CT (p = 0.8206). Fluoroscopy time and quantity of iodine injected were significantly lower with CB-CT than without (p = 0.0039 and p < 0.0001). CONCLUSION: CB-CT allows a better evaluation of the selectivity of right-sided adrenal catheterization and greatly increases the overall success rate of AVS.

Genesis of an emergency public drug information website by the French Society of Pharmacology and Therapeutics during the COVID-19 pandemic.

On March 16, 2020, the French Society of Pharmacology and Therapeutics put online a national Question and Answer (Q&A) website, https://sfpt-fr.org/covid19 on the proper use of drugs during the COVID-19 pandemic. The working group 'Drugs and COVID-19' was composed of a scientific council, an editorial team, and experts in the field. The first questions were posted online during the first evening of home-confinement in France, March 17, 2020. Six weeks later, 140 Q&As have been posted. Questions on the controversial use of hydroxychloroquine and to a lesser extent concerning azithromycin have been the most consulted Q&As. Q&As have been consulted 226 014 times in 41 days. This large visibility was obtained through an early communication on Twitter, Facebook, traditional print, and web media. In addition, an early communication through the French Ministry of Health and the French National Agency for Medicines and Health Products Safety ANSM had a large impact in terms of daily number of views. There is a pressing need to sustain a public drug information service combining the expertise of scholarly pharmacology societies, pharmacovigilance network, and the Ministry of Health to quickly provide understandable, clear, expert answers to the general population's concerns regarding COVID-19 and drug use and to counter fake news.

[Assessment for antihypertensive drug intake in France in 2019 and adherence]. / Dosage des médicaments antihypertenseurs en France en 2019 et observance.

Non-adherence to antihypertensive treatment is one of the critical contributors to sub-optimal blood pressure control. The French Society of Hypertension remembered that urine and serum biochemical detection of antihypertensive drugs could be useful in a patient with resistant hypertension. Talking to a patient with biochemically confirmed non-adherence to blood pressure-lowering therapy and repeating them improved adherence to drugs. Despite its usefulness, biochemical detection of antihypertensive drugs is not routinely effective in France as they are not reimbursed by French Medical Care, except in patients attending hospitals. The list of blood pressure-lowering drugs able to be biochemically detected in France and their modalities are recorded here.

[Assessment for antihypertensive drug intake: How, where and when?] / Pourquoi, comment et où dose-t-on les antihypertenseurs en 2019 ?

AIM: Hypertension is a public health problem managed according to therapeutic strategies published in France by the Hauteautoritéde santé (HAS - French Health Authorities). For patients with resistant hypertension, related or not to a non-adherence, prescribers need to be sure the exposure is high enough to achieve the tensional target. Quantitative analysis of antihypertensive drugs in different biological matrices (blood/urine) is one possible solution. However, this involves determining the concentrations observed at standard doses and knowing how to interpret the measured concentrations. It is also necessary to identify medical laboratories that can assay antihypertensive drugs. This was the aim of our work. METHODS: The main antihypertensive drugs recommended by the HAS have been listed. For each of them, we looked for published steady-state plasma/serum concentrations and quantities excreted in the urine at usual dosages. In addition, the elimination half-life and linear pharmacokinetic profile were specified for each antihypertensive agent measured in plasma/serum. Pharmacology-Toxicology laboratories in France likely to carry out assays were identified. The time taken to report the result and the cost of the analysis were also specified. RESULTS: All of the afore-mentioned information has been collected and presented in a table. This can then be used to compare the plasma/serum concentration or the quantity measured in a patient's urine with the values reported in the literature. In cases where the blood sampling times differ between those of the patient and the published data, the patient's measured value is compared to the estimated value based on the published concentrations and pharmacokinetics. CONCLUSION: Interpretation of the plasma/serum/urinary value measured or estimated for an antihypertensive drug is a particularly interesting approach to determine if drug exposure is enough and a possible non-adherence. However, this activity is mostly carried out in hospital centres.