[How to manage arterial hypertension in 2024 to optimize cardiorenal protection]. / Comment prendre en charge une hypertension artérielle en 2024 pour optimiser la protection cardio-rénale.

The latest guidelines for the management of arterial hypertension, the silent killer, were published in summer 2023. They particularly emphasize again the quality of blood pressure measurement which ideally should always be automated using oscillometric device and an arm cuff already in the consulting room. They remind you how to manage the blood pressure of a patient whose hypertension has been confirmed, to stimulate drug compliance and to avoid therapeutic inertia. A holistic view of the patient with all his or her risk factors is always required. The general practitioner is the key player in the diagnosis, treatment and monitoring of the hypertensive patient whose therapeutic education has been as complete as possible with practice of self-measurement of blood pressure at home if possible. The goal is to normalize blood pressure within the first three months of treatment initiation and to reduce as much as possible the cardiovascular risk of the treated patient in the frame of preventive medicine.

Les dernières directives de prise en charge de l'hypertension artérielle, le tueur silencieux, ont été publiées à l'été 2023. Elles insistent particulièrement, à nouveau, sur la qualité de la mesure de la pression artérielle qui, idéalement, doit être automatisée toujours à l'aide d'un brassard et ce, déjà au cabinet de consultation. Elles rappellent comment gérer la pression artérielle d'un patient dont l'hypertension a bien été confirmée, comment stimuler l'adhérence au traitement et éviter l'inertie thérapeutique. Une vue globale du patient avec tous ses facteurs de risque est toujours de rigueur. Le médecin généraliste est l'acteur-clé du diagnostic, du traitement et du suivi du patient hypertendu dont l'éducation thérapeutique a été la plus complète possible avec pratique de l'automesure tensionnelle à domicile si possible. Le but est de normaliser la pression artérielle dans les trois premiers mois de la prise en charge et de réduire le plus possible le risque cardiovasculaire et rénal du patient traité dans le cadre d'une médecine préventive.

[Functional disorder and arterial hypotension]. / Les troubles fonctionnels et l'hypotension artérielle constitutionnelle.

Arterial hypotension discovery (blood pressure < 110/60 mmHg for man and < 100/60 mmHg for woman) on the occasion of medical appointments for faintness is often considered as the cause of the medical problem. That causal relationship is yet far from being always established. If a disease is identified generating arterial hypotension, the symptoms reported such as loss of energy, fatigue and/or depressive mood can of course be the consequence. However, asymptomatic chronic hypotension exists. Symptoms appearance in a hypotensive patient such as fatigue, loss of vital energy, alteration of quality of life must lead to look for another explanation than (chronic) low blood pressure. This article will discuss that point.

La découverte d'une hypotension artérielle (pression artérielle < 110/60 mmHg chez l'homme et < 100/60 mmHg chez la femme) lors de consultations pour malaise est souvent considérée comme la cause du problème médical. Cette relation causale est, cependant, loin d'être toujours établie. Si une pathologie est identifiée créant une hypotension, les symptômes rapportés comme la perte d'énergie, la fatigue et/ou l'humeur dépressive peuvent, bien sûr, en être la conséquence. Cependant une hypotension chronique asymptomatique existe. L'apparition de symptômes, chez un sujet hypotendu préalablement, tels que fatigue, perte d'élan vital, altération de la qualité de vie, doit faire rechercher une autre raison que la baisse (chronique) de la pression artérielle. Cet article va discuter cette problématique.

[Blood pressure variability : useful, trivial or potentially dangerous ?] / La variabilité tensionnelle : utile, futile ou potentiellement dangereuse ?

Usually, blood pressure variability is an adaptive physiological process allowing optimal perfusion of internal organs every time and in every clinical situation. This variability may nevertheless be excessive and then be associated with a poor cardiovascular and renal but also neurological prognosis. An excess in blood pressure variability may also be responsible for unpleasant symptoms in some patients. The different types of blood pressure variability, their causes and consequences as well as the mean to improve its control will be discussed in this article.

La variabilité tensionnelle est habituellement un processus physiologique adaptatif permettant une perfusion optimale des organes internes en tout temps et en toute situation clinique. Cette variabilité peut néanmoins être excessive, ce qui est associé à un mauvais pronostic cardiovasculaire et rénal, mais aussi neurologique. Une variabilité tensionnelle excessive peut également être responsable d'une symptomatologie gênante chez certains patients. Les différents types de variabilité tensionnelle, leurs causes et conséquences ainsi que la manière de mieux la contrôler seront discutés dans cet article.

Pathophysiology of the Nondipping Blood Pressure Pattern.

The nondipping blood pressure (BP) pattern corresponds to a disruption in the circadian BP rhythm with an insufficient decrease in BP levels during nighttime sleep as observed using 24-hour ambulatory BP monitoring. Patients with nondipping BP pattern have poorer renal and cardiovascular outcomes, independent of their average 24-hour BP levels. The pathophysiology of nondipping BP is complex and involves numerous mechanisms: perturbations of (1) the circadian rhythm, (2) the autonomic nervous system, and (3) water and sodium regulation. This review provides an outline of the pathways potentially involved in the nondipping BP profile in different conditions. A recent hypothesis is also discussed involving the role of gut microbiota in the dipping/nondipping patterns, via the fecal diet-derived short chain fatty acids.

Monitoring 25-OH and 1,25-OH vitamin D levels in hemodialysis patients after starting therapy: Does it make sense?

BACKGROUND AND AIMS: In hemodialysis patients, monitoring 25-hydroxyvitamin D (25(OH)D) levels is recommended. It is however unclear if monitoring 1,25-dihydroxyvitamin D (1,25(OH)2D) levels is interesting. MATERIALS AND METHODS: We repeatedly measured 1,25(OH)2D (DiaSorin Liaison analyser) and 25(OH)D (LCMS/MS) concentrations in patients newly treated by active or native vitamin D to study the impact of such treatments on serum concentrations. RESULTS: Ten patients were included in the native and 12 in the active vitamin D group. In the native group, a significant increase was observed between the baseline and the last 25(OH)D concentrations available (21.65[17.39;25.26] versus 33.49[28.60;40.30] ng/mL, p = 0.0059). The baseline and last available 1,25(OH)2D concentrations were not different (12.15[4.25;15.40] versus 11.35[9.72;21.85] pg/mL, p = 0.5566). In the active group, no difference was observed between the baseline and the last 25(OH)D concentrations (51.70[42.97;63.95] versus 50.89[42.02;64.49] ng/mL, p = 0.5186). The same observation was made for 1,25 (OH)2D concentrations (25.65[17.05;41.85] versus 28.70[23.36;43.73] pg/mL, p = 0.6221). Using a linear mixed model, a significant change over time was only observed in 25(OH)D serum levels for patients treated by with native vitamin D. CONCLUSION: Measuring 1,25(OH)2D levels in patients newly treated by active vitamin D does not seem useful in monitoring active vitamin D therapy.

Estimating urine albumin to creatinine ratio from protein to creatinine ratio using same day measurement: validation of equations.

OBJECTIVES: Severity of chronic kidney disease is defined by glomerular filtration rate (GFR) and albuminuria (ACR) by the KDIGO and are related to cardiovascular outcomes and end-stage-kidney-failure. However, proteinuria (PCR) is more often available than ACR in records. Recently, equations were developed to estimate ACR from PCR. We investigated their performances in our population. METHODS: In the academic medical hospital of Liège, we retrospectively analysed same day measurement of ACR and PCR and staged them according to the KDIGO A1-A2-A3 categories. Analyser Roche Cobas (R) gathered 2,633 urinalysis (May 2018-May 2019) and analyser Abbott Alinity (A) 2,386 urinalysis (May 2019-March 2020). We compared the KDIGO staging of mACR and eACR obtained from Weaver's and Sumida's equations. RESULTS: Median age was 63 [52;71]/64 [53;72] years old, 43/42% were female; 78/74% had diabetes; proportion of mACR-A1 was 65.6%/64.2%, A2 was 25.5%/25.5% and A3 was 8.8%/10.3% (Method R/A, respectively). Both equations gave similar distribution of KDIGO staging of eACR. Overall agreements were higher than 88% regardless of the analyser or of the equation. Performances in between equations were equivalent according to the multi-level AUC (multinomial logistic regression model). CONCLUSIONS: Good concordance was observed between mACR and eACR regardless of the equation or of the analyser. No patient with an A3-measured ACR was estimated within the KDIGO A1 category. Though ACR should be measured when clinically needed, it may be reasonably estimated from the PCR through these equations, for epidemiologic retrospective studies or research purposes.

The faecal abundance of short chain fatty acids is increased in men with a non-dipping blood pressure profile.

BACKGROUND AND AIMS: Gut microbiota (GM) has been involved in the pathophysiology of hypertension (HT), notably via short chain fatty acids (SCFAs). Among the clinical manifestations of HT, the absence of a significant drop in night-time blood pressure (BP) (also known as the non-dipping BP profile) has been associated with poor renal and cardiovascular outcomes. The putative link between GM-derived metabolites and BP dipping status is still unknown. METHODS: Male volunteers (n = 44) were prospectively subjected to 24-hour ambulatory blood pressure monitoring, stool sample collection and a medical questionnaire. Metabolomics analyses of stool samples were conducted using Nuclear Magnetic Resonance (NMR). RESULTS: Higher amounts of acetate, butyrate and propionate were found in the stools of non-dippers (n = 12) versus dippers (n = 26) (p = 0.0252, p = 0.0468, and p = 0.0496, respectively; n = 38 in toto). NMR spectral data were not interpretable in 5 dippers and 1 non-dipper. A similar significant association was found when including only patients without anti-HT medications (p = 0.0414, p = 0.0108, and p = 0.0602, respectively; n = 21 in toto). A not significant trend was observed when focussing only on HT patients without anti-HT medications (p = 0.0556; n = 14 in toto). CONCLUSION: Our pilot study highlights a putative link between GM-derived SCFAs and the BP dipping status, independently of the BP status itself or the anti-hypertensive medications.

Human Stool Metabolome Differs upon 24 h Blood Pressure Levels and Blood Pressure Dipping Status: A Prospective Longitudinal Study.

Dysbiosis of gut microbiota (GM) has been involved in the pathophysiology of arterial hypertension (HT), via a putative role of short chain fatty acids (SCFAs). Its role in the circadian regulation of blood pressure (BP), also called "the dipping profile", has been poorly investigated. Sixteen male volunteers and 10 female partners were subjected to 24 h ambulatory BP monitoring and were categorized in normotensive (NT) versus HT, as well as in dippers versus non-dippers. Nuclear magnetic resonance (NMR)-based metabolomics was performed on stool samples. A 5-year comparative follow-up of BP profiles and stool metabolomes was done in men. Significant correlations between stool metabolome and 24 h mean BP levels were found in both male and female cohorts and in the entire cohort (R2 = 0.72, R2 = 0.79, and R2 = 0.45, respectively). Multivariate analysis discriminated dippers versus non-dippers in both male and female cohorts and in the entire cohort (Q2 = 0.87, Q2 = 0.98, and Q2 = 0.68, respectively). Fecal amounts of acetate, propionate, and butyrate were higher in HT versus NT patients (p = 0.027; p = 0.015 and p = 0.015, respectively), as well as in non-dippers versus dippers (p = 0.027, p = 0.038, and p = 0.036, respectively) in the entire cohort. SCFA levels were significantly different in patients changing of dipping status over the 5-year follow-up. In conclusion, stool metabolome changes upon global and circadian BP profiles in both genders.

Does kidney transplantation with a standard or expanded criteria donor improve patient survival? Results from a Belgian cohort.

BACKGROUND: Changes in recipient and donor factors have reopened the question of survival benefits of kidney transplantation versus dialysis. METHODS: We analysed survival among 3808 adult Belgian patients waitlisted for a first deceased donor kidney transplant from 2000 to 2012. The primary outcome was mortality during the median waiting time plus 3 years of follow-up after transplantation or with continued dialysis. Outcomes were analysed separately for standard criteria donor (SCD) and expanded criteria donor (ECD) kidney transplants. We adjusted survival analyses for recipient age (20-44, 45-64 and ≥65 years), sex and diabetes as the primary renal disease. RESULTS: Among patients ≥65 years of age, only SCD transplantation provided a significant survival benefit compared with dialysis, with a mortality of 16.3% [95% confidence interval (CI) 13.2-19.9] with SCD transplantation, 20.5% (95% CI 16.1-24.6) with ECD transplantation and 24.6% (95% CI 19.4-29.5) with continued dialysis. Relative mortality risk was increased in the first months after transplantation compared with dialysis, with equivalent risk levels reached earlier with SCD than ECD transplantation in all age groups. CONCLUSIONS: The results of this study suggest that older patients might gain a survival benefit with SCD transplantation versus dialysis, but any survival benefit with ECD transplantation versus dialysis may be small.

A simple modification of dialysate potassium: its impact on plasma potassium concentrations and the electrocardiogram.

BACKGROUND: Sudden death is frequent in haemodialysis (HD) patients. Both hyperkalaemia and change of plasma potassium (K) concentrations induced by HD could explain this. The impact of increasing dialysate K by 1 mEq/L on plasma K concentrations and electrocardiogram (ECG) results before and after HD sessions was studied. METHODS: Patients with pre-dialysis K >5.5 mEq/L were excluded. ECG and K measurements were obtained before and after the first session of the week for 2 weeks. Then, K in the dialysate was increased (from 1 or 3 to 2 or 4 mEq/L, respectively). Blood and ECG measurements were repeated after 2 weeks of this change. RESULTS: Twenty-seven prevalent HD patients were included. As expected, a significant decrease in K concentrations was observed after the dialysis session, but this decrease was significantly lower after the switch to an increased dialysate K. The pre-dialysis K concentrations were not different after changing, but post-dialysis K concentrations were higher after switching (P < 0.0001), with a lower incidence of post-dialysis hypokalaemia. Regarding ECG, before switching, the QT interval (QT) dispersion increased during the session, whereas no difference was observed after switching. One week after switching, post-dialysis QT dispersion [38 (34-42) ms] was lower than post-dialysis QT dispersion 2 weeks and 1 week before switching [42 (38-57) ms, P = 0.0004; and 40 (35-50) ms, P = 0.0002]. CONCLUSIONS: A simple increase of 1 mEq/L of K in the dialysate is associated with a lower risk of hypokalaemia and a lower QT dispersion after the dialysis session. Further study is needed to determine if such a strategy is associated with a lower risk of sudden death.

Proteinuria in COVID-19: prevalence, characterization and prognostic role.

BACKGROUND: Proteinuria has been commonly reported in patients with COVID-19. However, only dipstick tests have been frequently used thus far. Here, the quantification and characterization of proteinuria were investigated and their association with mortality was assessed. METHODS: This retrospective, observational, single center study included 153 patients, hospitalized with COVID-19 between March 28th and April 30th, 2020, in whom total proteinuria and urinary α1-microglobulin (a marker of tubular injury) were measured. Association with mortality was evaluated, with a follow-up until May 7th, 2020. RESULTS: According to the Kidney Disease Improving Global Outcomes staging, 14% (n = 21) of the patients had category 1 proteinuria (< 150 mg/g of urine creatinine), 42% (n = 64) had category 2 (between 150 and 500 mg/g) and 44% (n = 68) had category 3 proteinuria (over 500 mg/g). Urine α1-microglobulin concentration was higher than 15 mg/g in 89% of patients. After a median follow-up of 27 [14;30] days, the mortality rate reached 18%. Total proteinuria and urinary α1-microglobulin were associated with mortality in unadjusted and adjusted models. This association was stronger in subgroups of patients with normal renal function and without a urinary catheter. CONCLUSIONS: Proteinuria is frequent in patients with COVID-19. Its characterization suggests a tubular origin, with increased urinary α1-microglobulin. Tubular proteinuria was associated with mortality in COVID-19 in our restropective, observational study.

The European/International Fibromuscular Dysplasia Registry and Initiative (FEIRI)-clinical phenotypes and their predictors based on a cohort of 1000 patients.

AIMS: Since December 2015, the European/International Fibromuscular Dysplasia (FMD) Registry enrolled 1022 patients from 22 countries. We present their characteristics according to disease subtype, age and gender, as well as predictors of widespread disease, aneurysms and dissections. METHODS AND RESULTS: All patients diagnosed with FMD (string-of-beads or focal stenosis in at least one vascular bed) based on computed tomography angiography, magnetic resonance angiography, and/or catheter-based angiography were eligible. Patients were predominantly women (82%) and Caucasians (88%). Age at diagnosis was 46 ± 16 years (12% ≥65 years old), 86% were hypertensive, 72% had multifocal, and 57% multivessel FMD. Compared to patients with multifocal FMD, patients with focal FMD were younger, more often men, had less often multivessel FMD but more revascularizations. Compared to women with FMD, men were younger, had more often focal FMD and arterial dissections. Compared to younger patients with FMD, patients ≥65 years old had more often multifocal FMD, lower estimated glomerular filtration rate and more atherosclerotic lesions. Independent predictors of multivessel FMD were age at FMD diagnosis, stroke, multifocal subtype, presence of aneurysm or dissection, and family history of FMD. Predictors of aneurysms were multivessel and multifocal FMD. Predictors of dissections were age at FMD diagnosis, male gender, stroke, and multivessel FMD. CONCLUSIONS: The European/International FMD Registry allowed large-scale characterization of distinct profiles of patients with FMD and, more importantly, identification of a unique set of independent predictors of widespread disease, aneurysms and dissections, paving the way for targeted screening, management, and follow-up of FMD.

COVID-19-associated Nephropathy Includes Tubular Necrosis and Capillary Congestion, with Evidence of SARS-CoV-2 in the Nephron.

Background: Kidney damage has been reported in patients with COVID-19. Despite numerous reports about COVID-19-associated nephropathy, the factual presence of the SARS-CoV-2 in the renal parenchyma remains controversial. Methods: We consecutively performed 16 immediate (≤3 hours) postmortem renal biopsies in patients diagnosed with COVID-19. Kidney samples from five patients who died from sepsis not related to COVID-19 were used as controls. Samples were methodically evaluated by three pathologists. Virus detection in the renal parenchyma was performed in all samples by bulk RNA RT-PCR (E and N1/N2 genes), immunostaining (2019-nCOV N-Protein), fluorescence in situ hybridization (nCoV2019-S), and electron microscopy. Results: The mean age of our COVID-19 cohort was 68.2±12.8 years, most of whom were male (69%). Proteinuria was observed in 53% of patients, whereas AKI occurred in 60% of patients. Acute tubular necrosis of variable severity was found in all patients, with no tubular or interstitial inflammation. There was no difference in acute tubular necrosis severity between the patients with COVID-19 versus controls. Congestion in glomerular and peritubular capillaries was respectively observed in 56% and 88% of patients with COVID-19, compared with 20% of controls, with no evidence of thrombi. The 2019-nCOV N-Protein was detected in proximal tubules and at the basolateral pole of scattered cells of the distal tubules in nine out of 16 patients. In situ hybridization confirmed these findings in six out of 16 patients. RT-PCR of kidney total RNA detected SARS-CoV-2 E and N1/N2 genes in one patient. Electron microscopy did not show typical viral inclusions. Conclusions: Our immediate postmortem kidney samples from patients with COVID-19 highlight a congestive pattern of AKI, with no significant glomerular or interstitial inflammation. Immunostaining and in situ hybridization suggest SARS-CoV-2 is present in various segments of the nephron.

Gut Microbiota and Fecal Levels of Short-Chain Fatty Acids Differ Upon 24-Hour Blood Pressure Levels in Men.

Gut microbiota may influence blood pressure (BP), namely via end products of carbohydrate fermentation. After informed consent, male volunteers were prospectively categorized into 3 groups upon European Society of Hypertension criteria based on 24-hour ambulatory BP measurements: (1) hypertension, (2) borderline hypertension, and (3) normotension. Stool, urine and serum samples were collected in fasting conditions. Gut microbiota was characterized by 16S amplicon sequencing. Metabolomics, including quantification of short-chain fatty acids, was conducted using nuclear magnetic resonance. Two-way ANOVA combined with Tukey post hoc test, as well as multiple permutation test and Benjamini-Hochberg-Yekutieli false discovery rate procedure, was used. The cohort included 54 males: 38 hypertensive (including 21 under treatment), 7 borderline, and 9 normotensive. No significant difference was observed between groups concerning age, body mass index, smoking habits, and weekly alcohol consumption. The genus Clostridium sensu stricto 1 positively correlated with BP levels in nontreated patients (n=33). This correlation was significant after multiple permutation tests but was not substantiated following false discovery rate adjustment. Short-chain fatty acid levels were significantly different among groups, with higher stool levels of acetate, butyrate, and propionate in hypertensive versus normotensive individuals. No difference was observed in serum and urine metabolomes. Correlation between stool metabolome and 24-hour BP levels was evidenced, with R2 reaching 0.9. Our pilot study based on 24-hour ambulatory BP measurements, 16S amplicon sequencing, and metabolomics supports an association between gut microbiota and BP homeostasis, with changes in stool abundance of short-chain fatty acids.

Performance of creatinine- or cystatin C-based equations to estimate glomerular filtration rate in sub-Saharan African populations.

Glomerular filtration rate (GFR) is the best index for kidney function; however, the applicability of GFR estimating equations in sub-Saharan African populations remains unclear. In a cross-sectional study of adults living in Kinshasa, Democratic Republic of Congo (n=210) and Abidjan, Ivory Coast (n=284), we evaluated the performance of creatinine and cystatin C-based equations using plasma clearance of iohexol as the reference standard. The race coefficient did not improve the performance of creatinine-based GFR estimates; in fact, both the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology (CKD-EPI) equations performed better without the race coefficient in participants with GFR ≥60 mL/min/1.73m2. The CKD-EPI and Full Age Spectrum (FAS) equations were unbiased and had similar precision (SD of 17.9 versus 19 mL/min/1.73 m2) and accuracy within 30% (P30, 86.7% versus 87.4%) in participants with GFR ≥60 mL/min/1.73m2. Both equations performed poorly in the subgroup with measured GFR < 60 mL/min/1.73m2 (n=80), but the FAS equation had smaller bias (-4.8 mL/min/1.73m2 versus -7.7 mL/min/1.73m2 for CKD-EPI) and higher P30 (56.3% versus 31.3% for CKD-EPI). The corresponding equations including cystatin C alone or in combination with creatinine had similar performance. In a sub-Saharan African population, adjustment for race did not improve the performance of GFR estimating equations. The creatinine-based FAS and CKD-EPI equations performed reasonably well and were comparable when GFR was ≥ 60 mL/min/1.73m2. Cystatin C did not improve performance. The FAS equation may be preferable when GFR is < 60 mL/min/1.73m2, but this should be confirmed in larger studies.

Myostatin and Insulin-Like Growth Factor 1 Are Biomarkers of Muscle Strength, Muscle Mass, and Mortality in Patients on Hemodialysis.

OBJECTIVE: Muscle strength is frequently altered in hemodialysis patients. In the present work, five potential muscle biomarkers have been studied in their ability to assess muscular strength, muscular mass and to predict mortality of hemodialysis patients: activin-A, procollagen III N-terminal peptide, follistatin, myostatin and insulin-like growth factor-1 (IGF-1). DESIGN AND METHODS: Three independent cohorts of prevalent hemodialysis patients (2 from Liège, Belgium and 1 from Marseille, France) were considered in this observational prospective study. The biomarkers were first measured in the Liege1 cohort. Two of them, myostatin and IGF-1, were then assessed in the whole population of patients (Liege1, Liege2 and Marseille). Muscle strength was assessed with handgrip strength (HGS) and muscle mass with bioimpedance analysis. One-year mortality predictive value of biomarkers was also studied in the Liège1 and Marseille cohorts. RESULTS: In the Liège1 cohort (n=67), HGS was only associated with concentrations of myostatin and IGF-1. These associations were confirmed in the whole population of 204 patients (r=0.37, P<0.001 and r=0.46, P<0.001, respectively) and remained significant (P<0.05) in multivariable models. The association between muscle mass and concentrations of myostatin and IGF-1were also significant. The ability of myostatin, IGF-1 and serum creatinine to detect a low HGS compared by Receiver Operating Characteristic curves analysis were not significantly different. Both myostatin and IGF-1 had a significant and comparable area under the curve to predict one-year mortality: 0.73 (95% CI: 0.64 to 0.83) and 0.72 (95% CI: 0.61 to 0.82), respectively. CONCLUSION: Our results suggest that myostatin and IGF-1 are two biomarkers of interest to assess muscle status of dialysis patients. Both biomarkers are associated with HGS, muscular mass, and one-year mortality.