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.

From Fibromuscular Dysplasia to Arterial Dissection and Back.

Fibromuscular dysplasia (FMD) is an idiopathic and systemic non-inflammatory and non-atherosclerotic arterial disease. Fifteen to 25% of patients with FMD present with arterial dissection in at least one arterial bed. Conversely, a substantial number of patients with renal, carotid, and visceral dissection have underlying FMD. Also, while few patients with FMD develop coronary artery dissection, lesions suggestive of multifocal FMD have been reported in 30-80% of patients with spontaneous coronary artery dissection (SCAD), and the relation between these two entities remains controversial. The frequent association of FMD with arterial dissection, both in coronary and extra-coronary arteries raises a number of practical and theoretical questions: (i) Are FMD and arterial dissections two different facets of the same disease or distinct though related entities? (ii) Is SCAD just a manifestation of coronary FMD or a different disease? (iii) What is the risk and which are predictive factors of developing arterial dissection in a patient with FMD? (iv) What proportion of patients who experienced an arterial dissection have underlying FMD, and does this finding influence the risk of subsequent arterial complications? In this review we will address these different questions using fragmentary, mostly cross-sectional evidence derived from large registries and studies from Europe and the United States, as well as arguments derived from demographics, clinical presentation, imaging, and when available histology and genetics. From there we will derive practical consequences for nosology, screening and follow-up.

[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.

Prospective flow cytometry analysis of leucocyte subsets in critically ill patients who develop sepsis: a pilot study.

PURPOSE: Sepsis in critically ill patients with injury bears a high morbidity and mortality. Extensive phenotypic monitoring of leucocyte subsets in critically ill patients at ICU admission and during sepsis development is still scarce. The main objective of this study was to identify early changes in leukocyte phenotype which would correlate with later development of sepsis. METHODS: Patients who were admitted in a tertiary ICU for organ support after severe injury (elective cardiac surgery, trauma, necessity of prolonged ventilation or stroke) were sampled on admission (T1) and 48-72 h later (T2) for phenotyping of leukocyte subsets by flow cytometry and cytokines measurements. Those who developed secondary sepsis or septic shock were sampled again on the day of sepsis diagnosis (Tx). RESULTS: Ninety-nine patients were included in the final analysis. Nineteen (19.2%) patients developed secondary sepsis or septic shock. They presented significantly higher absolute monocyte counts and CRP at T1 compared to non-septic patients (1030/µl versus 550/µl, p = 0.013 and 5.1 mg/ml versus 2.5 mg/ml, p = 0.046, respectively). They also presented elevated levels of monocytes with low expression of L-selectin (CD62Lneg monocytes) (OR[95%CI] 4.5 (1.4-14.5), p = 0.01) and higher SOFA score (p < 0.0001) at T1 and low mHLA-DR at T2 (OR[95%CI] 0.003 (0.00-0.17), p = 0.049). Stepwise logistic regression analysis showed that both monocyte markers and high SOFA score (> 8) were independently associated with nosocomial sepsis occurrence. No other leucocyte count or surface marker nor any cytokine measurement correlated with sepsis occurrence. CONCLUSION: Monocyte counts and change of phenotype are associated with secondary sepsis occurrence in critically ill patients with injury.

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.

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.

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.

[Screening and management of metabolic acidosis in patients with chronic kidney disease]. / Intérêt du dépistage et du traitement de l'acidose métabolique chez l'insuffisant rénal chronique.

Metabolic acidosis is a frequent and early biological abnormality of chronic kidney disease (CKD). Chronic metabolic acidosis affects the global homeostasis of the human body, including the metabolism of bone and muscles. Numerous studies have proved a causal relationship between metabolic acidosis and accelerated CKD progression. Hence, the measure of serum bicarbonate level should be part of the systematic follow-up of CKD patients of whom glomerular filtration rate decreases below 50 ml/min/1.73m². Both screening and treatment of metabolic acidosis are easy and cheap. Correcting metabolic acidosis, namely by the daily administration of sodium bicarbonate, helps slow down kidney decline.

L'acidose métabolique est une anomalie biologique fréquente et précoce de l'insuffisance rénale chronique (IRC). Les complications liées à cet état sont multiples et touchent notamment l'os, le muscle et le métabolisme protidique, sans parler du risque accru d'hyperkaliémie. Une causalité entre acidose métabolique et accélération du déclin rénal a été démontrée. La mesure du taux de bicarbonate sérique doit, dès lors, faire partie du suivi biologique systématique du patient en IRC dont le taux de filtration glomérulaire s'abaisse en dessous de 50 ml/min/1,73 m². Le dépistage et le traitement de l'acidose métabolique sont en effet simples et peu coûteux. La correction de l'acidose métabolique, notamment par le bicarbonate de sodium, permet de ralentir la progression de l'insuffisance rénale.

Genetic susceptibility to delayed graft function following kidney transplantation: a systematic review of the literature.

Delayed graft function (DGF) is defined as the need for dialysis within 7 days following kidney transplantation (KTx). DGF is associated with increased costs, higher risk for acute rejection and decreased long-term graft function. Renal ischaemia/reperfusion (I/R) injury plays a major role in DGF occurrence. Single nucleotide polymorphisms (SNPs) in certain genes may aggravate kidney susceptibility to I/R injury, thereby worsening post-transplant outcomes. The present article proposes an extensive review of the literature about the putative impact of donor or recipient SNPs on DGF occurrence in kidney transplant recipients (KTRs). Among 30 relevant PubMed reports, 16 articles identified an association between 18 SNPs and DGF. These polymorphisms concern 14 different well-known genes and one not-yet-identified gene located on chromosome 18. They have been categorized into five groups according to the role of the corresponding proteins in I/R cascade: (i) oxidative stress, (ii) telomere shortening, (iii) chemokines, (iv) T-cell homeostasis and (v) metabolism of anti-inflammatory molecules. The remaining 14 studies failed to demonstrate any association between the studied SNPs and the occurrence of DGF. A better understanding of the genetic susceptibility to renal I/R injury may help prevent DGF and improve clinical outcomes in KTRs.

Sepsis prediction in critically ill patients by platelet activation markers on ICU admission: a prospective pilot study.

BACKGROUND: Platelets have been involved in both immune surveillance and host defense against severe infection. To date, whether platelet phenotype or other hemostasis components could be associated with predisposition to sepsis in critical illness remains unknown. The aim of this work was to identify platelet markers that could predict sepsis occurrence in critically ill injured patients. METHODS: This single-center, prospective, observational, 7-month study was based on a cohort of 99 non-infected adult patients admitted to ICUs for elective cardiac surgery, trauma, acute brain injury, and post-operative prolonged ventilation and followed up during ICU stay. Clinical characteristics and severity score (SOFA) were recorded on admission. Platelet activation markers, including fibrinogen binding to platelets, platelet membrane P-selectin expression, plasma soluble CD40L, and platelet-leukocytes aggregates were assayed by flow cytometry at admission and 48 h later, and then at the time of sepsis diagnosis (Sepsis-3 criteria) and 7 days later for sepsis patients. Hospitalization data and outcomes were also recorded. METHODS: Of the 99 patients, 19 developed sepsis after a median time of 5 days. These patients had a higher SOFA score at admission; levels of fibrinogen binding to platelets (platelet-Fg) and of D-dimers were also significantly increased compared to the other patients. Levels 48 h after ICU admission no longer differed between the two patient groups. Platelet-Fg % was an independent predictor of sepsis (P = 0.0031). By ROC curve analysis, cutoff point for Platelet-Fg (AUC = 0.75) was 50%. In patients with a SOFA cutoff of 8, the risk of sepsis reached 87% when Platelet-Fg levels were above 50%. Patients with sepsis had longer ICU and hospital stays and higher death rate. CONCLUSIONS: Platelet-bound fibrinogen levels assayed by flow cytometry within 24 h of ICU admission help identifying critically ill patients at risk of developing sepsis.

Implications of the calcium-sensing receptor in ischemia/reperfusion.

The calcium-sensing receptor (CaSR) is a G protein-coupled receptor (GPCR) which was first isolated from bovine parathyroid glands. Its complex structure has been well characterized, which helped to better understand its function. The CaSR activity can be modulated by various ligands, either activators (also called "calcimimetics") or inhibitors (or "calcilytics"). The main role of the CaSR concerns Ca2+ homeostasis. In bone, intestine and kidney, the CaSR acts as a sensor for extracellular ionized Ca2+ concentration ([Ca2+]e) to keep it stable. Such a homeostatic function is well illustrated by human inherited diseases caused by mutations in CASR gene, characterized by Ca2+ balance disturbances. Interestingly, the CaSR is also expressed in numerous tissues which are not directly involved in Ca2+ regulation. There, the CaSR has been implicated in regulatory pathways, including cell proliferation, differentiation and apoptosis. Moreover, recent observations suggest that the CaSR may be involved in ischaemia/reperfusion (I/R) cascades. In cardiomyocytes, the expression and activation of the CaSR are significantly induced at the time of I/R, which induces apoptotic pathways. Likewise, the activation of the CaSR in I/R in brain, liver and kidney has been associated with increased cell death and aggravated structural and functional damage. The present review summarizes these observations and hypothesizes a novel therapeutic option targeting the CaSR in I/R.

IgG4-related membranous glomerulonephritis and generalized lymphadenopathy without pancreatitis: a case report.

BACKGROUND: IgG4-related disease is a recently described pathologic entity. This is the case of a patient with nephrotic syndrome and lymphadenopathy due to IgG4-related disease. Such a kidney involvement is quite peculiar and has only been described a few times recently. Renal biopsy showed a glomerular involvement with membranous glomerulonephritis in association with a tubulo-interstitial nephropathy. Moreover, the patient was not suffering from pancreatitis. CASE PRESENTATION: The patient is a middle-aged man of Moroccan origin. He has developed recurrent episodes of diffuse lymphadenopathies, renal failure and nephrotic syndrome. Renal biopsies showed membranous glomerulonephritis. DISCUSSION AND CONCLUSION: The diagnostic approach of this atypical presentation is discussed in this case report as well as diagnostic criteria, therapeutic strategies, biomarkers and pathophysiology of IgG4-related disease. IgG4-related membranous glomerulonephritis is a well-established cause of membranous glomerulonephritis. It must be sought after in every patient with a previous diagnosis of IgG4-related disease and in every patient with this histological finding on renal biopsy. Corticoids are still the first-line treatment of IgG4-related disease. New therapeutic strategies are needed to avoid glucocorticoids long term side-effects. Interestingly, the patient was prescribed cyclophosphamide in addition to glucocorticoids for an immune thrombocytopenia. This treatment had a very good impact on his IgG4-related disease.