Search

Background: Membranoproliferative glomerulonephritis (MPGN) can be divided into immune-complex MPGN (IC-MPGN) and C3 glomerulopathy (C3G), which includes dense deposit disease (DDD) and C3 glomerulonephritis (C3GN). These conditions result from abnormalities in different complement pathways and may lead to different prognoses. However, there are limited studies describing the respective clinical courses. Methods: In this study, Japanese pediatric patients diagnosed with MPGN based on kidney biopsies conducted between February 2002 and December 2022 were reclassified as having IC-MPGN or C3G (DDD or C3GN). We retrospectively analyzed the clinical characteristics and outcomes of these patients. Results: Out of 25 patients with MPGN, three (12.0%) were diagnosed with DDD, 20 (80.0%) with C3GN, and two (8.0%) with IC-MPGN. There were 13 (65.0%) patients and one (33.3%) patient in remission after treatment for C3GN and DDD, respectively, and no patients with IC-MPGN achieved remission. The median follow-up period was 5.3 (2.5–8.9) years, and none of the patients in either group progressed to an estimated glomerular filtration rate < 15 ml/min/1.73 m2. Patients with C3GN presenting mild to moderate proteinuria (n = 8) received a renin-angiotensin system inhibitor (RAS-I) alone, and these patients exhibited a significant decrease in the urinary protein creatinine ratio and a notable increase in serum C3 levels at the last follow-up. Conclusions: Most patients with MPGN were diagnosed with C3GN. The remission rate for C3GN was high, and no patients developed kidney failure during the approximately 5-year follow-up. Additionally, patients with C3GN with mild to moderate proteinuria had good outcomes with RAS-I alone, but continued vigilance is necessary to determine long-term prognosis. [ABSTRACT FROM AUTHOR]

In the quest to uncover biological cues that help explain organic changes brought on by an external stimulus, like stress, new technologies have become necessary. The Laser Speckle Contrast Analysis (LASCA) approach is one of these technologies that may be used to analyze biological data, including respiratory rate (RR) intervals, and then use the results to determine heart rate variability (HRV Thus, to evaluate the stress brought on by physical activity, this study used the LASCA approach. A stress induction procedure involving physical exertion was employed, and the results were compared to other established techniques (cortisol analysis and ECG signal) to verify the LASCA methodology as a tool for measuring HRV and stress. The study sample comprised 27 willing participants. The technique involving LASCA allowed for the non-invasive (non-contact) acquisition of HRV and the study of stress. Furthermore, it made it possible to gather pertinent data, such as recognizing modifications to the thermoregulation, peripheral vasomotor tonus, and renin-angiotensin-aldosterone systems that were brought on by elevated stress and, as a result, variations in HRV readings. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is a highly aggressive and incurable disease accounting for about 10,000 deaths in the USA each year. Despite the current treatment approach which includes surgery with chemotherapy and radiation therapy, there remains a high prevalence of recurrence. Notable improvements have been observed in persons receiving concurrent antihypertensive drugs such as renin angiotensin inhibitors (RAS) or the antidiabetic drug metformin with standard therapy. Anti-tumoral effects of RAS inhibitors and metformin have been observed in in vitro and in vivo studies. Although clinical trials have shown mixed results, the potential for the use of RAS inhibitors and metformin as adjuvant GBM therapy remains promising. Nevertheless, evidence suggest that these drugs exert multimodal antitumor actions; by particularly targeting several cancer hallmarks. In this review, we highlight the results of clinical studies using multidrug cocktails containing RAS inhibitors and or metformin added to standard therapy for GBM. In addition, we highlight the possible molecular mechanisms by which these repurposed drugs with an excellent safety profile might elicit their anti-tumoral effects. RAS inhibition elicits anti-inflammatory, anti-angiogenic, and immune sensitivity effects in GBM. However, metformin promotes anti-migratory, anti-proliferative and pro-apoptotic effects mainly through the activation of AMP-activated protein kinase. Also, we discussed metformin's potential in targeting both GBM cells as well as GBM associated-stem cells. Finally, we summarize a few drug interactions that may cause an additive or antagonistic effect that may lead to adverse effects and influence treatment outcome. [ABSTRACT FROM AUTHOR]

Recent years have seen a resurgence of interest for the renin–angiotensin–aldosterone system in critically ill patients. Emerging data suggest that this vital homeostatic system, which plays a crucial role in maintaining systemic and renal hemodynamics during stressful conditions, is altered in septic shock, ultimately leading to impaired angiotensin II—angiotensin II type 1 receptor signaling. Indeed, available evidence from both experimental models and human studies indicates that alterations in the renin–angiotensin–aldosterone system during septic shock can occur at three distinct levels: 1. Impaired generation of angiotensin II, possibly attributable to defects in angiotensin-converting enzyme activity; 2. Enhanced degradation of angiotensin II by peptidases; and/or 3. Unavailability of angiotensin II type 1 receptor due to internalization or reduced synthesis. These alterations can occur either independently or in combination, ultimately leading to an uncoupling between the renin–angiotensin–aldosterone system input and downstream angiotensin II type 1 receptor signaling. It remains unclear whether exogenous angiotensin II infusion can adequately address all these mechanisms, and additional interventions may be required. These observations open a new avenue of research and offer the potential for novel therapeutic strategies to improve patient prognosis. In the near future, a deeper understanding of renin–angiotensin–aldosterone system alterations in septic shock should help to decipher patients' phenotypes and to implement targeted interventions. [ABSTRACT FROM AUTHOR]

Background: Dipeptidyl peptidase 3 (DPP3) is a ubiquitous cytosolic enzyme released into the bloodstream after tissue injury, that can degrade angiotensin II. High concentrations of circulating DPP3 (cDPP3) have been associated with worse outcomes during sepsis. The aim of this study was to assess the effect of Procizumab (PCZ), a monoclonal antibody that neutralizes cDPP3, in an experimental model of septic shock. Methods: In this randomized, open-label, controlled study, 16 anesthetized and mechanically ventilated pigs with peritonitis were randomized to receive PCZ or standard treatment when the mean arterial pressure (MAP) dropped below 50 mmHg. Resuscitation with fluids, antimicrobial therapy, peritoneal lavage, and norepinephrine was initiated one hour later to maintain MAP between 65–75 mmHg for 12 h. Hemodynamic variables, tissue oxygenation indices, and measures of organ failure and myocardial injury were collected. Organ blood flow was assessed using isotopic assessment (99mtechnetium albumin). cDPP3 activity, equilibrium analysis of the renin–angiotensin system and circulating catecholamines were measured. Tissue mRNA expression of interleukin-6 and downregulation of adrenergic and angiotensin receptors were assessed on vascular and myocardial samples. Results: PCZ-treated animals had reduced cDPP3 levels and required less norepinephrine and fluid than septic control animals for similar organ perfusion and regional blood flow. PCZ-treated animals had less myocardial injury, and higher PaO2/FiO2 ratios. PCZ was associated with lower circulating catecholamine levels; higher circulating angiotensin II and higher angiotensin II receptor type 1 myocardial protein expression, and with lower myocardial and radial artery mRNA interleukin-6 expression. Conclusions: In an experimental model of septic shock, PCZ administration was associated with reduced fluid and catecholamine requirements, less myocardial injury and cardiovascular inflammation, along with preserved angiotensin II signaling. [ABSTRACT FROM AUTHOR]

Diabetes mellitus, a disease that affects hundreds of millions of people worldwide, is increasing in prevalence in all age groups, including children and adolescents. Much of the morbidity and mortality associated with diabetes is closely related to hypertension, often coincident with diabetes. Comorbid hypertension and diabetes often worsen the outcomes of each other, likely rooted in some overlapping pathogenic mechanisms. In this educational review, we will discuss the shared pathophysiology of diabetes and hypertension, particularly in regard to inflammation and oxidative stress, the sympathetic nervous system, vascular remodeling, and the renin–angiotensin–aldosterone system (RAAS). We will also review current hypertension diagnosis and management guidelines from many international jurisdictions for both adult and paediatric populations in the setting of diabetes. Many of these guidelines highlight the use and utility of RAAS blockers in this clinical scenario; however, on review of the evidence for their use, several meta-analyses and systematic reviews fail to demonstrate superiority of RAAS blockers over other anti-hypertensive medications. Finally, we discuss several new anti-hypertensive medications, review their mechanisms of action, and highlight some of the evidence for their use in the setting of hypertension and diabetes. [ABSTRACT FROM AUTHOR]

Obesity has emerged as a significant public health challenge. With the ongoing increase in life expectancy, the prevalence of obesity is steadily growing, particularly among older age demographics. The extension of life expectancy frequently results in additional years of vulnerability to chronic health issues associated with obesity in the elderly. The concept of SARS-CoV-2 directly infecting adipose tissue stems from the fact that both adipocytes and stromal vascular fraction cells express ACE2, the primary receptor facilitating SARS-CoV-2 entry. It is noteworthy that adipose tissue demonstrates ACE2 expression levels similar to those found in the lungs within the same individual. Additionally, ACE2 expression in the adipose tissue of obese individuals surpasses that in non-obese counterparts. Viral attachment to ACE2 has the potential to disturb the equilibrium of renin-angiotensin system homeostasis, leading to an exacerbated inflammatory response. Consequently, adipose tissue has been investigated as a potential site for active SARS-CoV-2 infection, suggesting its plausible role in virus persistence and contribution to both acute and long-term consequences associated with COVID-19. This review is dedicated to presenting current evidence concerning the presence of SARS-CoV-2 in the adipose tissue of elderly individuals infected with the virus. Both obesity and aging are circumstances that contribute to severe health challenges, heightening the risk of disease and mortality. We will particularly focus on examining the mechanisms implicated in the long-term consequences, with the intention of providing insights into potential strategies for mitigating the aftermath of the disease. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this systematic review was to compare the clinical outcomes of dental implants in users of antihypertensive medication with those of nonusers. Methods: This systematic review followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and was registered in the International Prospective Register of Systematic Reviews under the number CRD42022319336. The electronic databases Medline (PubMed) and Central Cochrane were searched for relevant scientific literature published in English through May 2022. The focused question was, "Do patients taking antihypertensive medications have a similar impact on the clinical outcome and survival of dental implants compared with nonusers?". Results: A total of 49 articles were found, of which 3 articles were finally selected for a qualitative synthesis. The three studies included 959 patients. In all three studies, the commonly used medication was renin-angiotensin system (RAS) inhibitors. Two studies mentioned implant survival rate, which was 99.4% in antihypertensive medication users and 96.1% in the nonusers. One study found a higher implant stability quotient (ISQ) in patients taking antihypertensive medication (75.7 ± 5.9) compared with patients not taking antihypertensive medication (73.7 ± 8.1). Conclusions: The limited available evidence showed that patient taking antihypertensive medications had comparable success rate and implant stability to patients not taking medications. The studies included patients taking different antihypertensive medications, so a drug-specific conclusion regarding the clinical outcome of dental implants is not possible. Further studies are needed, including patients taking certain antihypertensive medications, to determine their effects on dental implants. [ABSTRACT FROM AUTHOR]

The renin-angiotensin system (RAS) constitutes one of the principal mechanisms to maintain hemodynamic and fluid homeostasis. However, most research until now on RAS primarily focuses on its relationship with hypertension and its role in critically ill hypotensive populations is not well understood. With the approval of angiotensin II (Ang II) in the United States and Europe, following a phase 3 randomized controlled trial showing efficacy in catecholamine-resistant vasodilatory shock, there is growing interest in RAS in critically ill patients. Among the fundamental components of RAS, renin acts as the initial stimulus for the entire system. In the context of hypotension, its release increases in response to low blood pressure sensed by renal baroreceptors and attenuated negative Ang II feedback loop. Thus, elevated renin could reflect disease severity and predict poor outcomes. Studies investigating this hypothesis have validated the prognostic accuracy of renin in various critically ill populations, with several reports indicating its superiority to lactate for mortality prediction. Accordingly, renin reduction has been used to assess the effectiveness of Ang II administration. Furthermore, renin holds potential to identify patients who might benefit from Ang II treatment, potentially paving the way for personalized vasopressor management. Despite these promising data, most available evidence is derived from retrospective analysis and necessitates prospective confirmation. The absence of a rapid, point-of-care and reliable renin assay presents another hurdle to its integration into routine clinical practice. This narrative review aims to describe the current understanding and future directions of renin as a biomarker during resuscitation of critically ill patients. [ABSTRACT FROM AUTHOR]

In this review, we will cover (i) the proteolytic cascade of the RAAS, (ii) its regulation by multiple feedback-controlled parameters, and (iii) the major effects of the RAAS. For the effects of the RAAS, we focus on the role of the RAAS in the regulation of volume homeostasis and vascular tone, as major determinants of arterial blood pressure. [ABSTRACT FROM AUTHOR]

Background: It is well known that kidney injury is vital organ damage in Fabry disease (FD). Renin–angiotensin system (RAS) inhibitors are known to reduce proteinuria in patients with chronic kidney disease (CKD) by dilating the glomerular export arteries and reducing intraglomerular pressure. This improvement in intraglomerular pressure, although lowering the glomerular filtration rate, is thought to prevent renal damage and be renoprotective in the long term. RAS inhibitors may be effective in FD patients with proteinuria to prevent the progression of kidney disease, however, the degree to which they are used in clinical practice is unknown. Methods: The J-CKD-DB-Ex is a comprehensive multicenter database that automatically extracts medical data on CKD patients. J-CKD-DB-Ex contains data on 187,398 patients in five medical centers. FD patients were identified by ICD-10. Clinical data and prescriptions of FD patients between January 1 of 2014, and December 31 of 2020 were used for the analysis. Results: We identified 39 patients with FD from the J-CKD-DB-Ex including those with suspected FD. We confirmed 22 patients as FD. Half of the patients received RAS inhibitors. RAS inhibitors tended to be used in CKD patients with more severe renal impairment. Conclusions: This case series revealed the actual clinical practice of FD patients with CKD. In particular, we found cases in which patients had proteinuria, but were not treated with RAS inhibitors. The database was shown to be useful in assessing the clinical patterns of patients with rare diseases. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is a pervasive clinical challenge characterized by compromised cardiac function and reduced quality of life. The kinin-kallikrein system (KSS), a multifaceted peptide cascade, has garnered substantial attention due to its potential role in HF. Through activation of B1 and/or B2 receptors and downstream signaling, kinins modulate various physiological processes, including inflammation, coagulation, pain, blood pressure control, and vascular permeability. Notably, aberrations in KKS components have been linked to HF risk. The elevation of vasodilatory bradykinin (BK) due to kallikrein activity reduces preload and afterload, while concurrently fostering sodium reabsorption inhibition. However, kallikrein's conversion of prorenin to renin leads to angiotensinsII upregulation, resulting in vasoconstriction and fluid retention, alongside increased immune cell activity that fuels inflammation and cardiac remodeling. Importantly, prolonged KKS activation resulting from volume overload and tissue stretch contributes to cardiac collagen loss. The conventional renin-angiotensin-aldosterone system (RAAS) inhibitors used in HF management may inadvertently intensify KKS activity, exacerbating collagen depletion and cardiac remodeling. It is crucial to balance the KKS's role in acute cardiac damage, which may temporarily enhance function and metabolic parameters against its detrimental long-term effects. Thus, KKS blockade emerges as a promising strategy to impede HF progression. By attenuating the link between immune system function and tissue damage, KKS inhibition can potentially reduce cardiac remodeling and alleviate HF symptoms. However, the nuanced roles of BK in various acute conditions necessitate further investigation into the sustained benefits of kallikrein inhibitors in patients with chronic HF. [ABSTRACT FROM AUTHOR]

The study presented here aims at assessing the effects of hypobaric hypoxia on RAAS pathway and its components along with mitigation of anomalies with quercetin prophylaxis. One hour prior to hypobaric hypoxia exposure, male SD rats were orally supplemented with quercetin (50 mg/kg BW) and acetazolamide (50 mg/kg BW) and exposed them to 25,000 ft. (7,620 m) in a simulated environmental chamber for 12 h at 25 ± 2 °C. Different biochemical parameters like renin activity, aldosterone, angiotensin I, ACE 2 were determined in plasma. As a conventional response to low oxygen conditions, oxidative stress parameters (ROS and MDA) were elevated along with suppressed antioxidant system (GPx and catalase) in plasma of rats. Quercetin prophylaxis significantly down regulated the hypoxia induced oxidative stress by reducing plasma ROS & MDA levels with efficient enhancement of antioxidants (GPx and Catalase). Further, hypoxia mediated regulation of renin and ACE 2 proves the outstanding efficacy of quercetin in repudiating altercations in RAAS cascade due to hypobaric hypoxia. Furthermore, differential protein expression of HIF-1α, NFκB, IL-18 and endothelin-1 analyzed by western blotting approves the biochemical outcomes and showed that quercetin significantly aids in the reduction of inflammation under hypoxia. Studies conducted with Surface Plasmon Resonance demonstrated a binding among quercetin and ACE 2 that indicates that this flavonoid might regulate RAAS pathway via ACE 2. Henceforth, the study promotes the prophylaxis of quercetin for the better adaptability under hypobaric hypoxic conditions via modulating the RAAS pathway. [ABSTRACT FROM AUTHOR]

Clinical outcomes after catheter ablation in patients with reduced left ventricular (LV) ejection fraction (EF) and atrial fibrillation (AF) remain unclear. This study aimed to explore the clinical outcomes of patients with arrhythmia-induced cardiomyopathy (AIC) and the influence of pharmacological treatment on clinical outcomes in patients with AIC after the procedure. Ninety-six patients with AF with a reduced LVEF (LVEF < 50%, 66.7 ± 10.9 years; 72 males) underwent AF ablation. AIC was defined as patients whose LVEF recovered ≥ 50% after catheter ablation (n = 67) and patients whose LVEF remained reduced were defined as non-AIC (n = 29). During a median follow-up of 25 (13–40) months, Kaplan–Meier analysis demonstrated that patients with AIC were associated with less frequent cardiovascular death (p = 0.025) and hospitalization for worsening heart failure (p < 0.001) than those without AIC. Freedom from AF recurrence was similar between the two groups (p = 0.47). In multivariate analysis, the LV end-diastolic diameter (p = 0.0002) and the CHA2DS2-VASc scores (p = 0.0062) were independent predictors of AIC. Among the 67 patients with AIC, no significant differences in baseline characteristics, except for LV chamber size and cryoballoon use, were observed between patients with AIC with (n = 31) and without renin–angiotensin system (RAS) inhibitors (n = 36). In the Kaplan–Meier analysis, cardiovascular death, hospitalization for worsening heart failure, and AF recurrence after catheter ablation did not differ between patients treated with and without RAS inhibitors (all p > 0.05). Catheter ablation in patients with AIC due to AF is associated with a good post-procedural prognosis. IRB information The study was approved by the Research Ethics Committee of the University of Fukui (No. 20220151) and clinical trial registration (UMIN000050391). [ABSTRACT FROM AUTHOR]

The article discusses the underutilization of ambulatory blood pressure monitoring (ABPM) in patients with childhood-onset systemic lupus erythematosus (SLE). ABPM has been shown to have advantages over clinic blood pressure measurements, but its use in patients with childhood-onset SLE is low, despite the known cardiovascular risk associated with the condition. The article presents data from a nationally representative sample and a single-center cohort, highlighting the discrepancy between the prevalence of potential ABPM indications and the actual utilization of ABPM in patients with childhood-onset SLE. The authors emphasize the need for multidisciplinary approaches to improve cardiovascular outcomes in this population and call for further research on the optimal timing and frequency of ABPM. They also highlight the importance of understanding barriers to the uptake of ABPM in order to effectively improve cardiovascular health in this population. [Extracted from the article]

During the early stages of the development of the living multiorgan systems, genome modifications other than sequence variation occur that guide cell differentiation and organogenesis. These modifications are known to operate as a fetal programming code during this period, and recent research indicates that there are some tissue-specific codes in organogenesis whose effects may persist after birth until adulthood. Consequently, the events that disrupt the pre-established epigenetic pattern could induce shifts in organ physiology, with implications on health from birth or later in adult life. Chronic kidney disease (CKD) is one of the main causes of mortality worldwide; its etiology is multifactorial, but diabetes, obesity, and hypertension are the main causes of CKD in adults, although there are other risk factors that are mainly associated with an individual's lifestyle. Recent studies suggest that fetal reprogramming in the developing kidney could be implicated in the susceptibility to kidney disease in both childhood and adulthood. Some epigenetic modifications, such as genome methylation status, dysregulation of miRNA, and histone coding alterations in genes related to the regulation of the renin-angiotensin axis, a common denominator in CKD, may have originated during fetal development. This review focuses on epigenetic changes during nephrogenesis and their repercussions on kidney health and disease. In addition, the focus is on the influence of environmental factors during pregnancy, such as maternal metabolic diseases and dietary and metabolic conditions, as well as some sex differences in fetal kidney reprogramming during which dysregulation of the renin-angiotensin system is involved. [ABSTRACT FROM AUTHOR]

Resistant hypertension (RHT) is characterized by persistently high blood pressure (BP) levels above the widely recommended therapeutic targets of less than 140/90 mmHg office BP, despite life-style measures and optimal medical therapies, including at least three antihypertensive drug classes at maximum tolerated dose (one should be a diuretic). This condition is strongly related to hypertension-mediated organ damage and, mostly, high risk of hospitalization due to hypertension emergencies or acute cardiovascular events. Hypertension guidelines proposed a triple combination therapy based on renin angiotensin system blocking agent, a thiazide or thiazide-like diuretic, and a dihydropyridinic calcium-channel blocker, to almost all patients with RHT, who should also receive either a beta-blocker or a mineralocorticoid receptor antagonist, or both, depending on concomitant conditions and contraindications. Several other drugs may be attempted, when elevated BP levels persist in these RHT patients, although their added efficacy in lowering BP levels on top of optimal medical therapy is uncertain. Also, renal denervation has demonstrated to be a valid therapeutic alternative in RHT patients. More recently, novel drug classes and molecules have been tested in phase 2 randomised controlled clinical trials in patients with RHT on top of optimal medical therapy with at least 2–3 antihypertensive drugs. These novel drugs, which are orally administered and are able to antagonize different pathophysiological pathways, are represented by non-steroid mineralocorticorticoid receptor antagonists, selective aldosterone synthase inhibitors, and dual endothelin receptor antagonists, all of which have proven to reduce seated office and 24-h ambulatory systolic/diastolic BP levels. The main findings of randomized clinical trials performed with these drugs as well as their potential indications for the clinical management of RHT patients are summarised in this systematic review article. [ABSTRACT FROM AUTHOR]

Several attempts have been made, by the scientific community, to develop a unifying hypothesis that explains the clinical syndrome of heart failure (HF). The currently widely accepted neurohormonal model has substituted the cardiorenal and the cardiocirculatory models, which focused on salt-water retention and low cardiac output/peripheral vasoconstriction, respectively. According to the neurohormonal model, HF with eccentric left ventricular (LV) hypertrophy (LVH) (systolic HF or HF with reduced LV ejection fraction [LVEF] or HFrEF) develops and progresses because endogenous neurohormonal systems, predominantly the sympathetic nervous system (SNS) and the renin–angiotensin–aldosterone system (RAAS), exhibit prolonged activation following the initial heart injury exerting deleterious hemodynamic and direct nonhemodynamic cardiovascular effects. However, there is evidence to suggest that SNS overactivity often preexists HF development due to its association with HF risk factors, is also present in HF with preserved LVEF (diastolic HF or HFpEF), and that it is linked to immune/inflammatory factors. Furthermore, SNS activity in HF may be augmented by coexisting noncardiac morbidities and modified by genetic factors and demographics. The purpose of this paper is to provide a contemporary overview of the complex associations between SNS overactivity and the development and progression of HF, summarize the underlying mechanisms, and discuss the clinical implications as they relate to therapeutic interventions mitigating SNS overactivity. [ABSTRACT FROM AUTHOR]

Patients with septic shock who experience refractory hypotension despite adequate fluid resuscitation and high-dose noradrenaline have high mortality rates. To improve outcomes, evidence-based guidelines recommend starting a second vasopressor, such as vasopressin, if noradrenaline doses exceed 0.5 µg/kg/min. Recently, promising results have been observed in treating refractory hypotension with angiotensin II, which has been shown to increase mean arterial pressure and has been associated with improved outcomes. This narrative review aims to provide an overview of the pathophysiology of the renin-angiotensin system and the role of endogenous angiotensin II in vasodilatory shock with a focus on how angiotensin II treatment impacts clinical outcomes and on identifying the population that may benefit most from its use. [ABSTRACT FROM AUTHOR]

Background: Several risk factors are associated with the chronic evolution of migraine. Clinical and preclinical studies have provided data about the role of hypertension (HT) as one of the potential modifiable risk factors of chronic migraine (CM). This review is focused on the biological and clinical evidence supporting common mechanisms underlying HT and migraine and the potential role of HT in the transition from episodic to chronic migraine. Methods: We conducted a narrative review from a literature search covering the available evidence from studies investigating: i) the role of HT in the transition to CM in clinical practice; ii) the biological mechanisms potentially underpinning the association between HT and evolution to CM; iii) the role of antihypertensive medications in migraine prophylaxis. Results: HT proved to be at the base of multiple mechanisms underlying migraine and migraine chronicization. Endothelial dysfunction, blood–brain barrier alterations, calcitonin gene-related peptide signaling, and renin–angiotensin–aldosterone system dysregulation are involved in the worsening effect of HT on migraine frequency, and the role of HT in the transition to CM is supported by clinical observations. Conclusions: The observed evidence supports HT contribution to CM evolution due to shared pathophysiologic mechanisms. While a bidirectional influence appears to be ascertained, data are still lacking about the one-way role of HT as direct risk factor for CM transition. Further research is needed to confirm a causal role of HT in this process. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) poses a significant health risk in contemporary society. Current CKD treatments primarily involve renin-angiotensin-aldosterone system inhibitors and mineralocorticoid receptor antagonists, albeit associated with hyperkalemia risks. A novel selective mineralocorticoid receptor antagonist, finerenone, offers a promising, safer alternative for CKD therapy. Summary: This review comprehensively assesses the role and efficacy of finerenone in CKD treatment by analyzing clinical and animal studies. Emerging evidence consistently supports finerenone's ability to effectively slow the progression of CKD. By targeting the mineralocorticoid receptor, finerenone not only mitigates renal damage but also exhibits a favorable safety profile, minimizing hyperkalemia concerns. Conclusion: Finerenone emerges as a valuable addition to CKD therapy, demonstrating potential benefits in delaying CKD progression while minimizing side effects. Nevertheless, further clinical trials are necessary to provide a comprehensive understanding of its safety and efficacy. [ABSTRACT FROM AUTHOR]

Kidney fibrosis is one of the complications of chronic kidney disease (CKD (and contributes to end-stage renal disease which requires dialysis and kidney transplantation. Several signaling pathways such as renin–angiotensin system (RAS), microRNAs (miRNAs) and transforming growth factor-β1 (TGF-β1)/Smad have a prominent role in pathophysiology and progression of renal fibrosis. Activation of classical RAS, the elevation of angiotensin II (Ang II) production and overexpression of AT1R, develop renal fibrosis via TGF-β/Smad pathway. While the non-classical RAS arm, Ang 1–7/AT2R, MasR reveals an anti-fibrotic effect via antagonizing Ang II. This review focused on studies illustrating the interaction of RAS with sexual female hormone estradiol and miRNAs in the progression of renal fibrosis with more emphasis on the TGF-β signaling pathway. MiRNAs, especially miRNA-21 and miRNA-29 showed regulatory effects in renal fibrosis. Also, 17β-estradiol (E2) is a renoprotective hormone that improved renal fibrosis. Beneficial effects of ACE inhibitors and ARBs are reported in the prevention of renal fibrosis in patients. Future studies are also merited to delineate the new therapy strategies such as miRNAs targeting, combination therapy of E2 or HRT, ACEis, and ARBs with miRNAs mimics and antagomirs in CKD to provide a new therapeutic approach for kidney patients. [ABSTRACT FROM AUTHOR]

Background: IgA nephropathy (IgAN) is one of the most prevalent primary glomerular diseases in children and adolescents. In 2021, The Kidney Disease: Improving Global Outcomes (KDIGO) released Clinical Practice Guidelines for the Management of Glomerular Diseases as an update to the 2012 guidelines. However, the lack of available evidence for the treatment of IgAN in children has led to an absence of treatment recommendations. Clinical Case: We present the case of a 19-year-old male with IgAN who was lost to follow-up after an appointment at a children's hospital 3 years prior. He presents for care at an adult hospital after running out of his medications for many months. He is found to have an elevated blood pressure of 152/97 and an elevated creatinine at 0.8 mg/dL. Discussion: There is not only a need for treatment guidelines for IgAN in pediatric patients, but also a need for guidelines for adolescent patients with IgAN as they transition from pediatric to adult care. Therefore, we review the KDIGO treatment guidelines for adults with IgAN and the treatment evidence for children with IgAN and discuss the management dilemma that exists for adolescents and young adults (AYA) with IgAN. Specifically, we propose renin-angiotensin-aldosterone blockade (RASB) treatment, irrespective of blood pressure, for AYA with proteinuria >0.5 g/day. We also propose treatment with corticosteroids for patients with proteinuria >1 g/day and/or mesangial hypercellularity. Conclusion: The formation of treatment guidelines for patients transitioning from pediatric to adult nephrology care is paramount. [ABSTRACT FROM AUTHOR]

Background: MYH9-related disease (MYH9-RD) is characterized by congenital macrothrombocytopenia, Döhle body-like granulocyte inclusions, and nephropathy, which may progress to end-stage kidney disease (ESKD). However, information on the effects of renin-angiotensin system (RAS) inhibitors on kidney survival is currently lacking and the outcomes of kidney replacement therapy (KRT) in MYH9-RD are largely unknown. Methods: We conducted a cross-sectional nationwide survey by sending questionnaires to 145 institutions in Japan and analyzed data for 49 patients. Results: The median patient age was 27 years. Genetic analysis was performed in 37 (76%) patients. Twenty-four patients (65%) had MYH9 variants affecting the motor domain of non-muscle myosin heavy chain-IIA, and these patients had poorer kidney survival than those with variants affecting the tail domain (P = 0.02). There was no significant difference in kidney survival between patients treated with and without RAS inhibitors. Hemodialysis and peritoneal dialysis were performed in 16 and 7 patients, respectively. There were no major bleeding complications during the perioperative period or during follow-up, except for one patient. Most of the 11 patients who underwent kidney transplantation required perioperative red cell concentrate transfusions, but there was no graft loss during the median posttransplant observational period of 2.0 (interquartile range, 1.3–6.8) years. Conclusion: Our study demonstrated no beneficial effect of RAS inhibitors on kidney function in patients with MYH9-RD, indicating the need for further studies with more patients. All modalities of KRT are feasible options for MYH9-RD patients who progress to ESKD, with adequate attention to bleeding complications. [ABSTRACT FROM AUTHOR]

Copyright of Die Urologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The article focuses on a treatment option for Japanese children with severe nephrotic IgA vasculitis with nephritis, suggesting initial treatment with tonsillectomy combined with intravenous methylprednisolone pulse, aiming to prevent proteinuria recurrence and contribute to the prevention of chronic kidney disease. Topics include the clinical outcomes of children who received this treatment, comparisons between different initial treatments, and the importance of aiming for clinical remission.

Background: Although a range of renin-angiotensin-aldosterone system (RAAS) modulators are available for blood pressure lowering, the optimal choice within this class remains unclear. We aimed to compare the efficacy and safety of RAAS modulators in the adult hypertensive population.A systematic literature search was performed in PubMed, CENTRAL, and Embase. The primary efficacy outcome was all-cause mortality and the secondary efficacy outcome was cardiovascular mortality. Tolerability outcome was discontinuation due to adverse events. Safety outcomes included the occurrence of cough, dizziness, edema, hyperkalemia, and hypotension. Network meta-analyses were performed utilizing a random-effects model within a frequentist framework.We finally identified 51 articles from 49 randomized controlled trials. When compared to placebo, mineralocorticoid receptor antagonists (MRAs) significantly reduced the risk of all-cause mortality (odds ratio (OR) 0.83; 95% confidence interval (CI) 0.74–0.92) and cardiovascular mortality (OR 0.79; 95% CI 0.68–0.93), while none of other RAAS modulators significantly lowered the risk of all-cause or cardiovascular mortality. Individual comparisons indicated that MRAs were associated with a significantly lower risk of all-cause mortality than the other RAAS modulators (reduction: 16% compared with angiotensin-converting enzyme inhibitors (ACEIs), 14% compared with angiotensin receptor blockers (ARBs), and 22% compared with direct renin inhibitors (DRIs)). No difference in discontinuation due to adverse events was found in a comparison of RAAS modulators with placebo. With regard to safety outcomes, ACEIs have a higher risk of cough (OR 4.68; 95% CI 1.61–13.60), ARBs have a higher risk of dizziness (OR 1.42; 95% CI 1.06–1.91), hypotension (OR 2.10; 95% CI 1.02–4.34), and hyperkalemia (OR 1.99; 95% CI 1.17–3.41), and MRAs had a higher risk of hyperkalemia (OR 2.68; 95% CI 1.99–3.62) when compared to placebo.MRAs were the only RAAS modulators with a survival benefit in adults with hypertension, although they carried a higher risk of hyperkalemia. Our data challenge current hypertension guidelines which recommend MRAs as fourth-line therapy, and suggest that MRAs should be prescribed earlier and more widely.PROSPERO identifier number CRD42023405714.Methods: Although a range of renin-angiotensin-aldosterone system (RAAS) modulators are available for blood pressure lowering, the optimal choice within this class remains unclear. We aimed to compare the efficacy and safety of RAAS modulators in the adult hypertensive population.A systematic literature search was performed in PubMed, CENTRAL, and Embase. The primary efficacy outcome was all-cause mortality and the secondary efficacy outcome was cardiovascular mortality. Tolerability outcome was discontinuation due to adverse events. Safety outcomes included the occurrence of cough, dizziness, edema, hyperkalemia, and hypotension. Network meta-analyses were performed utilizing a random-effects model within a frequentist framework.We finally identified 51 articles from 49 randomized controlled trials. When compared to placebo, mineralocorticoid receptor antagonists (MRAs) significantly reduced the risk of all-cause mortality (odds ratio (OR) 0.83; 95% confidence interval (CI) 0.74–0.92) and cardiovascular mortality (OR 0.79; 95% CI 0.68–0.93), while none of other RAAS modulators significantly lowered the risk of all-cause or cardiovascular mortality. Individual comparisons indicated that MRAs were associated with a significantly lower risk of all-cause mortality than the other RAAS modulators (reduction: 16% compared with angiotensin-converting enzyme inhibitors (ACEIs), 14% compared with angiotensin receptor blockers (ARBs), and 22% compared with direct renin inhibitors (DRIs)). No difference in discontinuation due to adverse events was found in a comparison of RAAS modulators with placebo. With regard to safety outcomes, ACEIs have a higher risk of cough (OR 4.68; 95% CI 1.61–13.60), ARBs have a higher risk of dizziness (OR 1.42; 95% CI 1.06–1.91), hypotension (OR 2.10; 95% CI 1.02–4.34), and hyperkalemia (OR 1.99; 95% CI 1.17–3.41), and MRAs had a higher risk of hyperkalemia (OR 2.68; 95% CI 1.99–3.62) when compared to placebo.MRAs were the only RAAS modulators with a survival benefit in adults with hypertension, although they carried a higher risk of hyperkalemia. Our data challenge current hypertension guidelines which recommend MRAs as fourth-line therapy, and suggest that MRAs should be prescribed earlier and more widely.PROSPERO identifier number CRD42023405714.Results: Although a range of renin-angiotensin-aldosterone system (RAAS) modulators are available for blood pressure lowering, the optimal choice within this class remains unclear. We aimed to compare the efficacy and safety of RAAS modulators in the adult hypertensive population.A systematic literature search was performed in PubMed, CENTRAL, and Embase. The primary efficacy outcome was all-cause mortality and the secondary efficacy outcome was cardiovascular mortality. Tolerability outcome was discontinuation due to adverse events. Safety outcomes included the occurrence of cough, dizziness, edema, hyperkalemia, and hypotension. Network meta-analyses were performed utilizing a random-effects model within a frequentist framework.We finally identified 51 articles from 49 randomized controlled trials. When compared to placebo, mineralocorticoid receptor antagonists (MRAs) significantly reduced the risk of all-cause mortality (odds ratio (OR) 0.83; 95% confidence interval (CI) 0.74–0.92) and cardiovascular mortality (OR 0.79; 95% CI 0.68–0.93), while none of other RAAS modulators significantly lowered the risk of all-cause or cardiovascular mortality. Individual comparisons indicated that MRAs were associated with a significantly lower risk of all-cause mortality than the other RAAS modulators (reduction: 16% compared with angiotensin-converting enzyme inhibitors (ACEIs), 14% compared with angiotensin receptor blockers (ARBs), and 22% compared with direct renin inhibitors (DRIs)). No difference in discontinuation due to adverse events was found in a comparison of RAAS modulators with placebo. With regard to safety outcomes, ACEIs have a higher risk of cough (OR 4.68; 95% CI 1.61–13.60), ARBs have a higher risk of dizziness (OR 1.42; 95% CI 1.06–1.91), hypotension (OR 2.10; 95% CI 1.02–4.34), and hyperkalemia (OR 1.99; 95% CI 1.17–3.41), and MRAs had a higher risk of hyperkalemia (OR 2.68; 95% CI 1.99–3.62) when compared to placebo.MRAs were the only RAAS modulators with a survival benefit in adults with hypertension, although they carried a higher risk of hyperkalemia. Our data challenge current hypertension guidelines which recommend MRAs as fourth-line therapy, and suggest that MRAs should be prescribed earlier and more widely.PROSPERO identifier number CRD42023405714.Conclusions: Although a range of renin-angiotensin-aldosterone system (RAAS) modulators are available for blood pressure lowering, the optimal choice within this class remains unclear. We aimed to compare the efficacy and safety of RAAS modulators in the adult hypertensive population.A systematic literature search was performed in PubMed, CENTRAL, and Embase. The primary efficacy outcome was all-cause mortality and the secondary efficacy outcome was cardiovascular mortality. Tolerability outcome was discontinuation due to adverse events. Safety outcomes included the occurrence of cough, dizziness, edema, hyperkalemia, and hypotension. Network meta-analyses were performed utilizing a random-effects model within a frequentist framework.We finally identified 51 articles from 49 randomized controlled trials. When compared to placebo, mineralocorticoid receptor antagonists (MRAs) significantly reduced the risk of all-cause mortality (odds ratio (OR) 0.83; 95% confidence interval (CI) 0.74–0.92) and cardiovascular mortality (OR 0.79; 95% CI 0.68–0.93), while none of other RAAS modulators significantly lowered the risk of all-cause or cardiovascular mortality. Individual comparisons indicated that MRAs were associated with a significantly lower risk of all-cause mortality than the other RAAS modulators (reduction: 16% compared with angiotensin-converting enzyme inhibitors (ACEIs), 14% compared with angiotensin receptor blockers (ARBs), and 22% compared with direct renin inhibitors (DRIs)). No difference in discontinuation due to adverse events was found in a comparison of RAAS modulators with placebo. With regard to safety outcomes, ACEIs have a higher risk of cough (OR 4.68; 95% CI 1.61–13.60), ARBs have a higher risk of dizziness (OR 1.42; 95% CI 1.06–1.91), hypotension (OR 2.10; 95% CI 1.02–4.34), and hyperkalemia (OR 1.99; 95% CI 1.17–3.41), and MRAs had a higher risk of hyperkalemia (OR 2.68; 95% CI 1.99–3.62) when compared to placebo.MRAs were the only RAAS modulators with a survival benefit in adults with hypertension, although they carried a higher risk of hyperkalemia. Our data challenge current hypertension guidelines which recommend MRAs as fourth-line therapy, and suggest that MRAs should be prescribed earlier and more widely.PROSPERO identifier number CRD42023405714.Registration: Although a range of renin-angiotensin-aldosterone system (RAAS) modulators are available for blood pressure lowering, the optimal choice within this class remains unclear. We aimed to compare the efficacy and safety of RAAS modulators in the adult hypertensive population.A systematic literature search was performed in PubMed, CENTRAL, and Embase. The primary efficacy outcome was all-cause mortality and the secondary efficacy outcome was cardiovascular mortality. Tolerability outcome was discontinuation due to adverse events. Safety outcomes included the occurrence of cough, dizziness, edema, hyperkalemia, and hypotension. Network meta-analyses were performed utilizing a random-effects model within a frequentist framework.We finally identified 51 articles from 49 randomized controlled trials. When compared to placebo, mineralocorticoid receptor antagonists (MRAs) significantly reduced the risk of all-cause mortality (odds ratio (OR) 0.83; 95% confidence interval (CI) 0.74–0.92) and cardiovascular mortality (OR 0.79; 95% CI 0.68–0.93), while none of other RAAS modulators significantly lowered the risk of all-cause or cardiovascular mortality. Individual comparisons indicated that MRAs were associated with a significantly lower risk of all-cause mortality than the other RAAS modulators (reduction: 16% compared with angiotensin-converting enzyme inhibitors (ACEIs), 14% compared with angiotensin receptor blockers (ARBs), and 22% compared with direct renin inhibitors (DRIs)). No difference in discontinuation due to adverse events was found in a comparison of RAAS modulators with placebo. With regard to safety outcomes, ACEIs have a higher risk of cough (OR 4.68; 95% CI 1.61–13.60), ARBs have a higher risk of dizziness (OR 1.42; 95% CI 1.06–1.91), hypotension (OR 2.10; 95% CI 1.02–4.34), and hyperkalemia (OR 1.99; 95% CI 1.17–3.41), and MRAs had a higher risk of hyperkalemia (OR 2.68; 95% CI 1.99–3.62) when compared to placebo.MRAs were the only RAAS modulators with a survival benefit in adults with hypertension, although they carried a higher risk of hyperkalemia. Our data challenge current hypertension guidelines which recommend MRAs as fourth-line therapy, and suggest that MRAs should be prescribed earlier and more widely.PROSPERO identifier number CRD42023405714. [ABSTRACT FROM AUTHOR]

COVID-19 patients experience a complex interplay involving ACE2, thrombin, D-dimer, and lipid profile, yet its full understanding remains elusive. ACE2, a pivotal regulator of the renin-angiotensin system and the primary receptor for SARS-CoV-2 undergoes downregulation upon viral binding, potentially leading to severe cases with acute respiratory distress syndrome (ARDS). A specific ACE2 gene polymorphism (rs2285666) may be associated with COVID-19 susceptibility, with the A allele potentially increasing infection risk. COVID-19 disease progression is linked to coagulation abnormalities, but the exact connection with thrombin and D-dimer remains uncertain. A study examining coagulation parameters in COVID-19 patients admitted to Al-Diwania Educational Hospital from February to May 2022 found that thrombin and D-dimer levels were directly related to disease severity. Severe cases exhibited significantly altered coagulation function compared to mild and recovered cases, with notably higher D-dimer levels and elevated thrombin serum concentrations. Moreover, dyslipidemia, particularly low HDL cholesterol, is a prevalent comorbidity in COVID-19 patients and may be linked to worse outcomes. In conclusion, COVID-19 is associated with a prothrombotic state and dysregulation of the renin-angiotensin system due to ACE2 downregulation following viral binding. The intricate interplay between ACE2, thrombin, D-dimer, and lipid profile necessitates further investigation. The multifaceted nature of the disease demands continued research to unravel its pathogenesis and identify potential therapeutic targets. [ABSTRACT FROM AUTHOR]

Despite the remarkable and progressive advances made in the prevention and management of cardiovascular diseases, the recurrence of cardiovascular events remains unacceptably elevated with a notable size of the residual risk. Indeed, in patients who suffered from myocardial infarction or who underwent percutaneous or surgical myocardial revascularization, life-style changes and optimized pharmacological therapy with antiplatelet drugs, lipid lowering agents, beta-blockers, renin angiotensin system inhibitors and antidiabetic drugs, when appropriate, are systematically prescribed but they might be insufficient to protect from further events. In such a context, an increasing body of evidence supports the benefits of cardiac rehabilitation (CR) in the setting of secondary cardiovascular prevention, consisting in the reduction of myocardial oxygen demands, in the inhibition of atherosclerotic plaque progression and in an improvement of exercise performance, quality of life and survival. However, prescription and implementation of CR programs is still not sufficiently considered.The aim of this position paper of the Italian Society of Cardiovascular Prevention (SIPREC) and of the Italian Heart Failure Association (ITAHFA) is to examine the reasons of the insufficient use of this strategy in clinical practice and to propose some feasible solutions to overcome this clinical gap. [ABSTRACT FROM AUTHOR]

Nephrotic syndrome is a common condition characterized by filtration of large amounts of protein, hypoalbuminemia, reduced plasma oncotic pressure, sodium retention, and edema. The mechanism responsible for sodium retention in this condition is still controversial. Two different pathophysiological pathways have been proposed to explain edema formation: activation of neurohumoral effector mechanisms, including the renin–angiotensin–aldosterone system, or abnormal intrinsic/primary renal sodium retention. A 5-year-old boy with X-linked adrenoleukodystrophy presented with bilateral leg swelling, massive proteinuria, and hypoalbuminemia. Minimal change disease was diagnosed. The patient was initially treated with corticosteroids and experienced several relapses. The progression of fractional excretion of sodium correlated with proteinuria and undetectable aldosterone levels. This unusual finding suggests that the mechanism of tubular sodium avidity in this child with mineralocorticoid insufficiency was independent of the renin–angiotensin–aldosterone system. [ABSTRACT FROM AUTHOR]

Infection by the recent SARS-CoV-2 virus causes the COVID-19 disease with variable clinical manifestations ranging from asymptomatic or mild respiratory symptoms to severe respiratory distress and multiorgan failure. The renin-angiotensin system, responsible for maintaining homeostasis and governing several critical processes, has been considered the main system involved in the pathogenesis and progression of COVID-19. Here, we aimed to assess the possible association between variants in the RAS-related genes and COVID-19 susceptibility and severity in a sample of the Moroccan population. A total of 325 individuals were recruited in this study, with 102 outpatients, 105 hospitalized patients, and 118 healthy controls negative for SARS-CoV-2 infection, and subjected to NGS gene panel sequencing containing eleven RAS pathway genes. A total of 65 functional variants were identified, including 63 missenses, 1 splice, and 1 INDEL. Most of them were rare, with 47 (72%) found in a single individual. According to the common disease/common variant hypothesis, five common candidate variants with MAF > 10% were identified (ACE2 rs2285666, TMPRSS2 rs12329760, AGT rs699 genes, ACE rs4341, and ACE rs4343). Statistical analysis showed that the ACE rs4343 AA genotype was associated with a 2.5-fold increased risk of severe COVID-19 (p = 0.026), and the T genotype of the ACE2 rs2285666 variant showed a borderline association with susceptibility to SARS-CoV-2 in males (p = 0.097). In conclusion, our results showed that the RAS pathway genes are highly conserved among Moroccans, and most of the identified variants are rare. Among the common variants, the ACE rs4343 polymorphism would lead to a genetic predisposition for severe COVID-19. [ABSTRACT FROM AUTHOR]

Basal cell carcinoma (BCC) is the most prevalent human neoplasm, with constantly increasing annual incidence. Despite its slow growth, BCC is locally invasive and, if left untreated, can cause severe complications, including metastasis and death. The renin-angiotensin system (RAS) plays a key role in electrolyte balance, atrial pressure, tissue development, homeostasis, and inflammation, but also in cancer development. After binding to its type 1 receptor (AT1R), angiotensin II (ANGII), the system's principal hormonal effector, regulates cancer pathways spanning from the formation of the initial cancer cell to the construction and nutrition of the tumor microenvironment, angiogenesis, proliferation, and metastasis. Although the role of RAS in the development of skin pathologies has not been widely researched, RAS-targeting antihypertensive medications have been shown to have a chemoprotective effect against BCC. Based on those findings, our group conducted a series of genetic association studies to investigate the association between common functional variations in key genes related to ANGII production (AGT, ACE, ACE2, AT1R, AT2R, and CMA1) and the risk of BCC occurrence. This review provides a summary of the current understanding of the ANGII involvement in BCC development. The reliable and easily assessed pool of genetic biomarkers may be used for predictive testing and prevention purposes in high-risk individuals. [ABSTRACT FROM AUTHOR]