Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 20.770
Filtrar
1.
Int J Mol Sci ; 25(17)2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39273497

RESUMO

The hormone renin is produced in the kidney by the juxtaglomerular cells. It is the rate-limiting factor in the circulating renin-angiotensin-aldosterone system (RAAS), which contributes to electrolyte, water, and blood pressure homeostasis. In the kidneys, the distal tubule and the collecting duct are the key target segments for RAAS. The collecting duct is important for urine production and also for salt, water, and acid-base homeostasis. The critical functional role of the collecting duct is mediated by the principal and the intercalated cells and is regulated by different hormones like aldosterone and vasopressin. The collecting duct is not only a target for hormones but also a place of hormone production. It is accepted that renin is produced in the collecting duct at a low level. Several studies have described that the cells in the collecting duct exhibit plasticity properties because the ratio of principal to intercalated cells can change under specific circumstances. This narrative review focuses on two aspects of the collecting duct that remain somehow aside from mainstream research, namely the cell plasticity and the renin expression. We discuss the link between these collecting duct features, which we see as a promising area for future research given recent findings.


Assuntos
Plasticidade Celular , Túbulos Renais Coletores , Sistema Renina-Angiotensina , Renina , Renina/metabolismo , Humanos , Animais , Túbulos Renais Coletores/metabolismo , Sistema Renina-Angiotensina/fisiologia , Vasopressinas/metabolismo
2.
Ren Fail ; 46(2): 2400541, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39248389

RESUMO

AIMS: Finerenone has been approved for treating diabetic kidney disease (DKD) with reducing cardiorenal risk. Real-world data on finerenone treatment for the management of DKD are presently lacking. This study aimed to investigate the effect of finerenone on the renal parameters of the Chinese DKD population in the real-world medical setting for the first time, especially in combination with renin-angiotensin system inhibitors (RASi) and sodium-glucose cotransporter 2 inhibitors (SGLT2i). METHODS: Forty-two DKD patients were selected and completed a 6-month finerenone treatment. Renal parameters and adverse effects were collected at every visit. RESULTS: The median urine albumin-to-creatinine ratio (UACR) was 1426.11 (755.42, 3638.23) mg/g. Among them, the proportion of patients with a UACR of 300-5000 mg/g was 76.2%, and the proportion of patients with a UACR of >5000 mg/g was 14.3%. The median estimated glomerular filtration rate (eGFR) was 54.50 (34.16, 81.73) mL/min/1.73 m2. Finerenone decreased the UACR significantly throughout the study period (p < .05). The maximal decline of UACR at month 6 was 73%. Moreover, the proportion of patients with a 30% or greater reduction in UACR was 68.42% in month 6. There was a smaller decline (9-11%) in the eGFR after initiating finerenone (p > .05). One patient each discontinued finerenone due to hyperkalemia (2.4%) and acute kidney injury (2.4%). No patient reported hypotension, breast pain, and gynecomastia. CONCLUSIONS: This study from China first demonstrated finerenone decreased UACR with manageable safety in real-world DKD treatment. A triple regimen of RASi, SGLT2i, and finerenone may be a promising treatment strategy for lowering albuminuria and reducing hyperkalemia risk in advanced DKD patients.


Assuntos
Nefropatias Diabéticas , Taxa de Filtração Glomerular , Naftiridinas , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Masculino , Feminino , Nefropatias Diabéticas/tratamento farmacológico , China , Pessoa de Meia-Idade , Idoso , Naftiridinas/uso terapêutico , Naftiridinas/efeitos adversos , Taxa de Filtração Glomerular/efeitos dos fármacos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Albuminúria/tratamento farmacológico , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Antagonistas de Receptores de Mineralocorticoides/efeitos adversos , Creatinina/sangue , Creatinina/urina , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Sistema Renina-Angiotensina/efeitos dos fármacos , Resultado do Tratamento
3.
Int J Mol Sci ; 25(17)2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39273282

RESUMO

Every individual at some point encounters the progressive biological process of aging, which is considered one of the major risk factors for common diseases. The main drivers of aging are oxidative stress, senescence, and reactive oxygen species (ROS). The renin-angiotensin-aldosterone system (RAAS) includes several systematic processes for the regulation of blood pressure, which is caused by an imbalance of electrolytes. During activation of the RAAS, binding of angiotensin II (ANG II) to angiotensin II type 1 receptor (AGTR1) activates intracellular nicotinamide adenine dinucleotide phosphate (NADPH) oxidase to generate superoxide anions and promote uncoupling of endothelial nitric oxide (NO) synthase, which in turn decreases NO availability and increases ROS production. Promoting oxidative stress and DNA damage mediated by ANG II is tightly regulated. Individuals with sodium deficiency-associated diseases such as Gitelman syndrome (GS) and Bartter syndrome (BS) show downregulation of inflammation-related processes and have reduced oxidative stress and ROS. Additionally, the histone deacetylase sirtuin-1 (SIRT1) has a significant impact on the aging process, with reduced activity with age. However, GS/BS patients generally sustain higher levels of sirtuin-1 (SIRT1) activity than age-matched healthy individuals. SIRT1 expression in GS/BS patients tends to be higher than in healthy age-matched individuals; therefore, it can be assumed that there will be a trend towards healthy aging in these patients. In this review, we highlight the importance of the hallmarks of aging, inflammation, and the RAAS system in GS/BS patients and how this might impact healthy aging. We further propose future research directions for studying the etiology of GS/BS at the molecular level using patient-derived renal stem cells and induced pluripotent stem cells.


Assuntos
Envelhecimento , Estresse Oxidativo , Sistema Renina-Angiotensina , Sirtuína 1 , Humanos , Sistema Renina-Angiotensina/fisiologia , Envelhecimento/metabolismo , Sirtuína 1/metabolismo , Sirtuína 1/genética , Espécies Reativas de Oxigênio/metabolismo , Síndrome de Gitelman/metabolismo , Síndrome de Gitelman/genética , Síndrome de Bartter/metabolismo , Síndrome de Bartter/genética , Sódio/metabolismo , Angiotensina II/metabolismo
4.
Adv Exp Med Biol ; 1460: 575-594, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39287865

RESUMO

Lipotoxicity can mediate endothelial dysfunction in obesity. Altered endothelial cell phenotype during the pathobiological course of the lipotoxicity may lead to hemostatic abnormalities, which is a hallmark of several hematological disorders. Impaired hemostasis could also be directly related to numerous metabolic diseases such as hypertension, diabetes, and atherosclerosis. On the other hand, the local hematopoietic bone marrow (BM) renin-angiotensin system (RAS) contributes to the development of atherosclerosis via acting on the lipotoxicity processes. Local BM RAS, principally an autocrine/paracrine/intracrine hematological system, is located at the crossroads of cellular regulation, molecular interactions, and lipotoxicity-mediated vascular endothelial dysfunction. The positive regulatory role of plasma LDL on AT1 receptor-mediated hematopoietic stem cell (HSC) differentiation and the production of pro-atherogenic monocytes have been described. LDL-regulated HSC function may explain in part hypercholesterolemia-induced inflammation as well as the anti-inflammatory and anti-atherosclerotic effects of AT1 receptor blockers. The role of local adipose tissue RAS is directly related to the pathogenesis of metabolic derangements in obesity. There may be a crosstalk between local BM RAS and local adipose tissue RAS at the genomics and transcriptomics levels. This chapter aims to review hematological alterations propagating the pathological influences of lipotoxicity on the vascular endothelium.


Assuntos
Doenças Hematológicas , Obesidade , Sistema Renina-Angiotensina , Humanos , Obesidade/metabolismo , Obesidade/complicações , Doenças Hematológicas/metabolismo , Doenças Hematológicas/patologia , Doenças Hematológicas/etiologia , Sistema Renina-Angiotensina/fisiologia , Animais , Endotélio Vascular/metabolismo , Endotélio Vascular/patologia , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Aterosclerose/metabolismo , Aterosclerose/patologia , Aterosclerose/etiologia
5.
Rev Med Suisse ; 20(884): 1488-1491, 2024 Aug 28.
Artigo em Francês | MEDLINE | ID: mdl-39219391

RESUMO

In addition to optimal glycemic control and management of other factors aggravating the pathology (hypertension, dyslipidemia, -obesity), the cornerstone of treatment of diabetic kidney disease (DKD) includes blockers of the renin-angiotensin system, sodium-glucose cotransporter 2 inhibitors or nonsteroidal antagonists of the mineralocorticoid receptor (finerenone). Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are recommended in the treatment of high-risk patients with type 2 diabetes (T2DM) to reduce cardiovascular (CV) risk. Data from CV studies indicate a nephroprotective effect of certain GLP-1 RAs in T2DM patients with DKD. The FLOW study published in May 2024, analyzing the impact of semaglutide vs placebo on renal events as primary outcome, confirms this renal protection of GLP-1 RAs.


Outre le contrôle glycémique et la prise en charge d'autres ­facteurs d'aggravation de la pathologie, la pierre angulaire du traitement de la maladie rénale diabétique (MRD) comprend les bloqueurs du système rénine-angiotensine, les inhibiteurs du cotransporteur sodium-glucose de type 2 ou encore la finérénone (antagoniste de l'aldostérone). Les agonistes du récepteur du glucagon-like peptide-1 (ARGLP-1) sont recommandés dans le traitement des patients avec un diabète de type 2 (DT2) à haut risque afin de réduire le risque cardiovasculaire (CV). Les ­données provenant des études CV indiquent un effet néphro­protecteur de certains ARGLP-1 chez les patients DT2 avec MRD. L'étude FLOW, publiée fin mai 2024 et analysant l'impact du sémaglutide sur les événements rénaux comme critère principal, confirme cette protection rénale des ARGLP-1.


Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Receptor do Peptídeo Semelhante ao Glucagon 1 , Humanos , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Nefropatias Diabéticas/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/farmacologia , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Peptídeos Semelhantes ao Glucagon/farmacologia , Doenças Cardiovasculares/prevenção & controle , Sistema Renina-Angiotensina/efeitos dos fármacos , Sistema Renina-Angiotensina/fisiologia , Agonistas do Receptor do Peptídeo 1 Semelhante ao Glucagon
6.
Am J Reprod Immunol ; 92(2): e13915, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39132825

RESUMO

The emergence of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to the global COVID-19 pandemic, significantly impacting the health of pregnant women. Obstetric populations, already vulnerable, face increased morbidity and mortality related to COVID-19, aggravated by preexisting comorbidities. Recent studies have shed light on the potential correlation between COVID-19 and preeclampsia (PE), a leading cause of maternal and perinatal morbidity worldwide, emphasizing the significance of exploring the relationship between these two conditions. Here, we review the pathophysiological similarities that PE shares with COVID-19, with a particular focus on severe COVID-19 cases and in PE-like syndrome cases related with SARS-CoV-2 infection. We highlight cellular and molecular mechanistic inter-connectivity between these two conditions, for example, regulation of renin-angiotensin system, tight junction and barrier integrity, and the complement system. Finally, we discuss how COVID-19 pandemic dynamics, including the emergence of variants and vaccination efforts, has shaped the clinical scenario and influenced the severity and management of both COVID-19 and PE. Continued research on the mechanisms of SARS-CoV-2 infection during pregnancy and the potential risk of developing PE from previous infections is warranted to delineate the complexities of COVID-19 and PE interactions and to improve clinical management of both conditions.


Assuntos
COVID-19 , Pré-Eclâmpsia , Complicações Infecciosas na Gravidez , SARS-CoV-2 , Humanos , COVID-19/fisiopatologia , COVID-19/imunologia , Gravidez , Feminino , Pré-Eclâmpsia/fisiopatologia , Pré-Eclâmpsia/epidemiologia , Pré-Eclâmpsia/imunologia , SARS-CoV-2/fisiologia , Complicações Infecciosas na Gravidez/imunologia , Complicações Infecciosas na Gravidez/virologia , Sistema Renina-Angiotensina
7.
CMAJ ; 196(27): E931-E939, 2024 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-39134317

RESUMO

BACKGROUND: Hepatitis B virus (HBV) infection is a common cause of liver-related morbidity and mortality. Evidence suggests that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) decrease liver fibrosis, an intermediate step between liver injury and hepatocellular carcinoma (HCC). Our aim was to investigate the association between the use of ACEIs and ARBs on incident HCC and liver-related mortality among patients with HBV infection. METHODS: We conducted a population-based study on a new-user cohort of patients seen at 24 hospitals across China. We included adult patients with HBV infection who started ACEIs or ARBs (ACEIs/ARBs), or calcium channel blockers or thiazide diuretics (CCBs/THZs) from January 2012 to December 2022. The primary outcome was incident HCC; secondary outcomes were liver-related mortality and new-onset cirrhosis. We used propensity score matching and Cox proportional hazards regression to estimate the hazard ratio (HR) and 95% confidence intervals (CIs) of study outcomes. RESULTS: Among 32 692 eligible patients (median age 58 [interquartile range (IQR) 48-68] yr, and 18 804 male [57.5%]), we matched 9946 pairs of patients starting ACEIs/ARBs or CCBs/THZs. During a mean follow-up of 2.3 years, the incidence rate of HCC per 1000 person-years was 4.11 and 5.94 among patients who started ACEIs/ARBs and CCBs/THZs, respectively, in the matched cohort. Use of ACEIs/ARBs was associated with lower risks of incident HCC (HR 0.66, 95% CI 0.50-0.86), liver-related mortality (HR 0.77, 95% CI 0.64-0.93), and new-onset cirrhosis (HR 0.81, 95% CI 0.70-0.94). INTERPRETATION: In this cohort of patients with HBV infection, new users of ACEIs/ARBs had a lower risk of incident HCC, liver-related mortality, and new-onset cirrhosis than new users of CCBs/THZs.


Assuntos
Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/epidemiologia , Masculino , Neoplasias Hepáticas/epidemiologia , Feminino , Pessoa de Meia-Idade , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Idoso , Antagonistas de Receptores de Angiotensina/uso terapêutico , Antagonistas de Receptores de Angiotensina/efeitos adversos , China/epidemiologia , Hepatite B/complicações , Cirrose Hepática , Incidência , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Pontuação de Propensão , Modelos de Riscos Proporcionais , Fatores de Risco , Sistema Renina-Angiotensina/efeitos dos fármacos
8.
Curr Opin Nephrol Hypertens ; 33(6): 551-556, 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-39137040

RESUMO

PURPOSE OF REVIEW: After decades of relying on the control of hypertension and treatment with renin angiotensin system inhibitors as the only evidence-based interventions to slow the progression of chronic kidney disease (CKD), we have entered an era when multiple effective treatment options are available. This review considers the mechanisms and benefits of these novel treatments as well as the challenges associated with achieving optimal combination therapy. RECENT FINDINGS: Over the past 5 years, large clinical trials have provided robust evidence that, when added to renin angiotensin system inhibitors, treatment with sodium glucose cotransporter 2 inhibitors reduces the rate of CKD progression and the risk of cardiovascular events in people with CKD with or without diabetes and with or without albuminuria; nonsteroidal mineralocorticoid antagonists and glucagon-like peptide-1 receptor agonists afford similar benefits in people with type 2 diabetes and CKD. The mechanisms of actions of these novel therapies suggest that combination therapy will produce additive benefits, though specific evidence is sparse. SUMMARY: Further trials are warranted to investigate the benefits of combination therapy with novel treatments in people with CKD. Clinical implementation of optimal combination therapy will require reorganization of services to ensure that patients receive adequate education, support and monitoring.


Assuntos
Doenças Cardiovasculares , Insuficiência Renal Crônica , Sistema Renina-Angiotensina , Humanos , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/tratamento farmacológico , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/complicações , Sistema Renina-Angiotensina/efeitos dos fármacos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Quimioterapia Combinada , Anti-Hipertensivos/uso terapêutico , Rim/efeitos dos fármacos , Rim/fisiopatologia , Rim/metabolismo , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Resultado do Tratamento , Progressão da Doença , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico
9.
Inflammopharmacology ; 32(5): 3037-3056, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39164607

RESUMO

Mammalian zinc ectopeptidases have significant functions in deactivating neurological and hormonal peptide signals on the cell surface. The identification of Opiorphin, a physiological inhibitor of zinc ectopeptidases that inactivate enkephalin, has revealed its strong analgesic effects in both chemical and mechanical pain models. Opiorphin achieves this by increasing the transmission of endogenous opioids, which are dependent on the body's own opioid system. The function of opiorphin is closely linked to the rat sialorphin peptide, which inhibits pain perception by enhancing the activity of naturally occurring enkephalinergic pathways that depend on µ- and δ-opioid receptors. Opiorphin is highly intriguing in terms of its physiological implications within the endogenous opioidergic pathways, particularly in its ability to regulate mood-related states and pain perception. Opiorphin can induce antidepressant-like effects by influencing the levels of naturally occurring enkephalin, which are released in response to specific physical and/or psychological stimuli. This effect is achieved through the modulation of delta-opioid receptor-dependent pathways. Furthermore, research has demonstrated that opiorphin's impact on the cardiovascular system is facilitated by the renin-angiotensin system (RAS), sympathetic ganglia, and adrenal medulla, rather than the opioid system. Hence, opiorphin shows great potential as a solitary candidate for the treatment of several illnesses such as neurodegeneration, pain, and mood disorders.


Assuntos
Oligopeptídeos , Proteínas e Peptídeos Salivares , Humanos , Animais , Oligopeptídeos/farmacologia , Proteínas e Peptídeos Salivares/metabolismo , Proteínas e Peptídeos Salivares/farmacologia , Dor/metabolismo , Dor/tratamento farmacológico , Antidepressivos/farmacologia , Sistema Renina-Angiotensina/fisiologia , Sistema Renina-Angiotensina/efeitos dos fármacos , Analgésicos Opioides/farmacologia , Receptores Opioides/metabolismo
10.
Hypertension ; 81(10): 2152-2161, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39171392

RESUMO

BACKGROUND: Although the concept of the intrarenal renin-angiotensin system (RAS) in renal disease is well-described in the literature, the precise pathogenic role and mechanism of this local system have not been directly assessed in the absence of confounding influence from the systemic RAS. The present study used novel mouse models of collecting duct (CD)-specific deletion of (pro)renin receptor (PRR) or renin together with pharmacological inhibition of soluble PRR production to unravel the precise contribution of the intrarenal RAS to renal injury induced by unilateral ureteral obstruction. METHODS: We examined the impact of CD-specific deletion of PRR, CD-specific deletion of renin, and S1P (site-1 protease) inhibitor PF429242 treatment on renal fibrosis and inflammation and the indices of the intrarenal RAS in a mouse model of unilateral ureteral obstruction. RESULTS: After 3 days of unilateral ureteral obstruction, the indices of the intrarenal RAS including the renal medullary renin content, activity and mRNA expression, and Ang (angiotensin) II content in obstructed kidneys of floxed mice were all increased. That effect was reversed with CD-specific deletion of PRR, CD-specific deletion of renin, and PF429242 treatment, accompanied by consistent improvement in renal fibrosis and inflammation. On the other hand, renal cortical renin levels were unaffected by unilateral ureteral obstruction, irrespective of the genotype. Similar results were obtained via pharmacological inhibition of S1P, the key protease for the generation of soluble PRR. CONCLUSIONS: Our results reveal that PRR-dependent/soluble PRR-dependent activation of CD renin represents a key determinant of the intrarenal RAS and, thus, obstruction-induced renal inflammation and fibrosis.


Assuntos
Túbulos Renais Coletores , Receptores de Superfície Celular , Sistema Renina-Angiotensina , Obstrução Ureteral , Animais , Obstrução Ureteral/complicações , Camundongos , Sistema Renina-Angiotensina/fisiologia , Receptores de Superfície Celular/metabolismo , Receptores de Superfície Celular/genética , Túbulos Renais Coletores/metabolismo , Túbulos Renais Coletores/patologia , Modelos Animais de Doenças , Renina/metabolismo , Renina/genética , Receptor de Pró-Renina , Masculino , Fibrose/metabolismo , Rim/patologia , Rim/metabolismo
11.
Hypertension ; 81(10): 2082-2090, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39087321

RESUMO

BACKGROUND: In contrast to proteinuric chronic kidney disease (CKD), the relative cardioprotective benefits of antihypertensive medications in nonproteinuric CKD are unknown. We examined long-term cardiovascular outcomes and mortality in patients with nonproteinuric CKD treated with renin-angiotensin system inhibitors (RASIs) versus other antihypertensive medications. METHODS: Among participants of the CRIC study (Chronic Renal Insufficiency Cohort) without proteinuria, we used intention-to-treat analyses with inverse probability of treatment weighting and Cox proportional hazards modeling to determine the association of RASIs versus other antihypertensive medications with a composite cardiovascular outcome (myocardial infarction, stroke, heart failure hospitalization, and death) and mortality. Secondary analyses included per-protocol analyses accounting for continuous adherence and time-updated analyses accounting for the proportion of time using RASIs during follow-up. RESULTS: A total of 2806 participants met the inclusion criteria. In the intention-to-treat analyses, RASIs versus other antihypertensive medications were not associated with an appreciable difference in cardiovascular events (adjusted hazard ratio [aHR], 0.94 [95% CI, 0.80-1.11]) or mortality (aHR, 1.06 [95% CI, 0.88-1.28]). In the per-protocol analyses, RASIs were associated with a lower risk of adverse cardiovascular events (aHR, 0.78 [95% CI, 0.63-0.97]) and mortality (aHR, 0.64 [95% CI, 0.48-0.85]). Similarly, in the time-updated analyses, a higher proportion of RASI use over time was associated with a lower mortality risk (aHR, 0.33 [95% CI, 0.14-0.86]). CONCLUSIONS: Among individuals with nonproteinuric CKD, after accounting for time-updated use, RASIs are associated with fewer cardiovascular events and a lower mortality risk compared with other antihypertensive medications. Patients with nonproteinuric CKD may benefit from prioritizing RASIs for hypertension management.


Assuntos
Inibidores da Enzima Conversora de Angiotensina , Anti-Hipertensivos , Insuficiência Renal Crônica , Sistema Renina-Angiotensina , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/mortalidade , Insuficiência Renal Crônica/complicações , Sistema Renina-Angiotensina/efeitos dos fármacos , Anti-Hipertensivos/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Idoso , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/tratamento farmacológico , Modelos de Riscos Proporcionais , Adulto , Antagonistas de Receptores de Angiotensina/uso terapêutico
12.
Front Endocrinol (Lausanne) ; 15: 1424207, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39140032

RESUMO

Background: Prior research has highlighted the association between uric acid (UA) and the activation of the renin-angiotensin-aldosterone system (RAAS). However, the specific relationship between aldosterone, the RAAS's end product, and UA-related diseases remains poorly understood. This study aims to clarify the impact of aldosterone on the development and progression of hyperuricemia and gout in hypertensive patients. Methods: Our study involved 34534 hypertensive participants, assessing plasma aldosterone concentration (PAC)'s role in UA-related diseases, mainly hyperuricemia and gout. We applied multiple logistic regression to investigate the impact of PAC and used restricted cubic splines (RCS) for examining the dose-response relationship between PAC and these diseases. To gain deeper insights, we conducted threshold analyses, further clarifying the nature of this relationship. Finally, we undertook subgroup analyses to evaluate PAC's effects across diverse conditions and among different subgroups. Results: Multivariate logistic regression analysis revealed a significant correlation between the occurrence of hyperuricemia and gout and the elevation of PAC levels. Compared to the first quartile (Q1) group, groups Q2, Q3, and Q4 all exhibited a significantly increased risk of occurrence. Moreover, the conducted RCS analysis demonstrated a significant nonlinear dose-response relationship, especially when PAC was greater than 14 ng/dL, with a further increased risk of hyperuricemia and gout. Finally, comprehensive subgroup analyses consistently reinforced these findings. Conclusion: This study demonstrates a close association between elevated PAC levels and the development of UA-related diseases, namely hyperuricemia and gout, in hypertensive patients. Further prospective studies are warranted to confirm and validate this relationship.


Assuntos
Aldosterona , Gota , Hipertensão , Hiperuricemia , Humanos , Hiperuricemia/sangue , Hiperuricemia/complicações , Gota/sangue , Gota/epidemiologia , Gota/complicações , Masculino , Aldosterona/sangue , Hipertensão/sangue , Hipertensão/complicações , Pessoa de Meia-Idade , Feminino , Idoso , Ácido Úrico/sangue , Sistema Renina-Angiotensina/fisiologia , Adulto
13.
J Biochem Mol Toxicol ; 38(8): e23795, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39132761

RESUMO

Renal fibrosis (RF) is one of the underlying pathological conditions leading to progressive loss of renal function and end-stage renal disease (ESRD). Over the years, various therapeutic approaches have been explored to combat RF and prevent ESRD. Despite significant advances in understanding the underlying molecular mechanism(s), effective therapeutic interventions for RF are limited. Current therapeutic strategies primarily target these underlying mechanisms to halt or reverse fibrotic progression. Inhibition of transforming growth factor-ß (TGF-ß) signaling, a pivotal mediator of RF has emerged as a central strategy to manage RF. Small molecules, peptides, and monoclonal antibodies that target TGF-ß receptors or downstream effectors have demonstrated potential in preclinical models. Modulating the renin-angiotensin system and targeting the endothelin system also provide established approaches for controlling fibrosis-related hemodynamic changes. Complementary to pharmacological strategies, lifestyle modifications, and dietary interventions contribute to holistic management. This comprehensive review aims to summarize the underlying mechanisms of RF and provide an overview of the therapeutic strategies and novel antifibrotic agents that hold promise in its treatment.


Assuntos
Antifibróticos , Fibrose , Humanos , Fibrose/tratamento farmacológico , Antifibróticos/uso terapêutico , Antifibróticos/farmacologia , Nefropatias/tratamento farmacológico , Nefropatias/patologia , Animais , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta/antagonistas & inibidores , Rim/patologia , Rim/efeitos dos fármacos , Rim/metabolismo , Sistema Renina-Angiotensina/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
14.
Rev Med Virol ; 34(5): e2577, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39215460

RESUMO

Dengue is a disease caused by a flavivirus (DENV) and transmitted by the bite of a mosquito, primarily the Aedes aegypti and Aedes albopictus species. Previous studies have demonstrated a relationship between the host gut microbiota and the evolution of dengue. It seems to be a bidirectional relationship, in which the DENV can affect the microbiota by inducing alterations related to intestinal permeability, leading to the release of molecules from microbiota dysbiosis that can influence the evolution of dengue. The role of angiotensin II (Ang II) in the microbiota/dengue relationship is not well understood, but it is known that the renin-angiotensin system (RAS) is present in the intestinal tract and interacts with the gut microbiota. The possible effect of Ang II on the microbiota/Ang II/dengue relationship can be summarised as follows: the presence of Ang II induced hypertension, the increase in angiotensinogen, chymase, and microRNAs during the disease, the induction of vascular dysfunction, the production of trimethylamine N-oxide and the brain/microbiota relationship, all of which are elements present in dengue that could be part of the microbiota/Ang II/dengue interactions. These findings suggest the potential use of Ang II synthesis blockers and the use of AT1 receptor antagonists as therapeutic drugs in dengue.


Assuntos
Dengue , Microbioma Gastrointestinal , Humanos , Microbioma Gastrointestinal/efeitos dos fármacos , Dengue/virologia , Animais , Disbiose/microbiologia , Angiotensina II/metabolismo , Vírus da Dengue/fisiologia , Sistema Renina-Angiotensina/efeitos dos fármacos , Aedes/microbiologia , Aedes/virologia
15.
Nutrients ; 16(16)2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39203744

RESUMO

Lactoferrin, a glycoprotein derived from breastmilk, is recognized for its health benefits in infants and children; however, its protective effects when administered during gestation and lactation against offspring hypertension remain unclear. This study aimed to investigate whether maternal lactoferrin supplementation could prevent hypertension in offspring born to mothers with chronic kidney disease (CKD), with a focus on nitric oxide (NO), renin-angiotensin system (RAS) regulation, and alterations in gut microbiota and short-chain fatty acids (SCFAs). Prior to pregnancy, female rats were subjected to a 0.5% adenine diet for 3 weeks to induce CKD. During pregnancy and lactation, pregnant rats received one of four diets: normal chow, 0.5% adenine diet, 10% lactoferrin diet, or adenine diet supplemented with lactoferrin. Male offspring were euthanized at 12 weeks of age (n = 8 per group). Supplementation with lactoferrin during gestation and lactation prevented hypertension in adult offspring induced by a maternal adenine diet. The maternal adenine diet caused a decrease in the index of NO availability, which was restored by 67% with maternal LF supplementation. Additionally, LF was related to the regulation of the RAS, as evidenced by a reduced renal expression of renin and the angiotensin II type 1 receptor. Combined maternal adenine and LF diets altered beta diversity, shifted the offspring's gut microbiota, decreased propionate levels, and reduced the renal expression of SCFA receptors. The beneficial effects of lactoferrin are likely mediated through enhanced NO availability, rebalancing the RAS, and alterations in gut microbiota composition and SCFAs. Our findings suggest that maternal lactoferrin supplementation improves hypertension in offspring in a model of adenine-induced CKD, bringing us closer to potentially translating lactoferrin supplementation clinically for children born to mothers with CKD.


Assuntos
Adenina , Suplementos Nutricionais , Microbioma Gastrointestinal , Hipertensão , Lactação , Lactoferrina , Fenômenos Fisiológicos da Nutrição Materna , Sistema Renina-Angiotensina , Animais , Lactoferrina/administração & dosagem , Lactoferrina/farmacologia , Feminino , Gravidez , Masculino , Hipertensão/prevenção & controle , Hipertensão/induzido quimicamente , Hipertensão/etiologia , Ratos , Sistema Renina-Angiotensina/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal/prevenção & controle , Óxido Nítrico/metabolismo , Insuficiência Renal Crônica/prevenção & controle , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/induzido quimicamente , Ácidos Graxos Voláteis/metabolismo , Ratos Sprague-Dawley , Dieta
16.
Cell Signal ; 122: 111335, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39117253

RESUMO

Sodium glucose cotransporter 2 inhibitors (SGLT2is) are a newly developed class of anti-diabetics which exert potent hypoglycemic effects in the diabetic milieu. However, the evidence suggests that they also have extra-glycemic effects. The renin-angiotensin-aldosterone system (RAAS) is a hormonal system widely distributed in the body that is important for water and electrolyte homeostasis as well as renal and cardiovascular function. Therefore, modulating RAAS activity is a main goal in patients, notably diabetic patients, which are at higher risk of complications involving these organ systems. Some studies have suggested that SGLT2is have modulatory effects on RAAS activity in addition to their hypoglycemic effects and, thus, these drugs can be considered as promising therapeutic agents for renal and cardiovascular disorders. However, the exact molecular interactions between SGLT2 inhibition and RAAS activity are not clearly understood. Therefore, in the current study we surveyed the literature for possible molecular mechanisms by which SGLT2is modulate RAAS activity.


Assuntos
Sistema Renina-Angiotensina , Inibidores do Transportador 2 de Sódio-Glicose , Animais , Humanos , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/farmacologia , Sistema Renina-Angiotensina/efeitos dos fármacos , Transportador 2 de Glucose-Sódio/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia
17.
Cell Signal ; 122: 111343, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39127136

RESUMO

Glaucoma, a leading cause of blindness worldwide, encompasses a group of pathological conditions affecting the optic nerve and is characterized by progressive retinal ganglion cell loss, cupping of the optic nerve head, and distinct visual field defects. While elevated intraocular pressure (IOP) is the main risk factor for glaucoma, many patients do not have elevated IOP. Consequently, other risk factors, such as ocular blood flow abnormalities and immunological factors, have been implicated in its pathophysiology. Traditional therapeutic strategies primarily aim to reduce IOP, but there is growing interest in developing novel treatment approaches to improve disease management and reduce the high rates of severe visual impairment. In this context, targeting the ocular renin-angiotensin-aldosterone system (RAAS) has been found as a potential curative strategy. The RAAS contributes to glaucoma development through key effectors such as prorenin, angiotensin II, and aldosterone. Recent evidence has highlighted the potential of using RAAS modulators to combat glaucoma, yielding encouraging results. Our study aims to explore the molecular pathways linking the ocular RAAS and glaucoma, summarizing recent advances that elucidate the role of the RAAS in triggering oxidative stress, inflammation, and remodelling in the pathogenesis of glaucoma. Additionally, we will present emerging therapeutic approaches that utilize RAAS modulators and antioxidants to slow the progression of glaucoma.


Assuntos
Glaucoma , Sistema Renina-Angiotensina , Animais , Humanos , Glaucoma/metabolismo , Glaucoma/terapia , Pressão Intraocular , Estresse Oxidativo , Transdução de Sinais , Aldosterona/metabolismo
18.
Int J Mol Sci ; 25(16)2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39201324

RESUMO

Premenopausal women generally exhibit lower blood pressure and a lower prevalence of hypertension than men of the same age, but these differences reverse postmenopause due to estrogen withdrawal. Sexual dimorphism has been described in different components of kidney physiology and pathophysiology, including the renin-angiotensin-aldosterone system, endothelin system, and tubular transporters. This review explores the sex-specific differences in kidney function and blood pressure regulation. Understanding these differences provides insights into potential therapeutic targets for managing hypertension and kidney diseases, considering the patient's sex and hormonal status.


Assuntos
Pressão Sanguínea , Hipertensão , Rim , Sistema Renina-Angiotensina , Caracteres Sexuais , Humanos , Pressão Sanguínea/fisiologia , Rim/metabolismo , Sistema Renina-Angiotensina/fisiologia , Feminino , Hipertensão/fisiopatologia , Hipertensão/metabolismo , Masculino , Animais , Fatores Sexuais
19.
BMC Nephrol ; 25(1): 268, 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39179976

RESUMO

BACKGROUND: Urinary Dickkopf 3 (DKK3) excretion is a recently established biomarker of renal functional development. Its excretion into the peritoneal cavity has not been reported. We here studied DKK3 in peritoneal dialysis. METHODS: DKK3 was assessed in serum, urine and dialysate in a prevalent adult peritoneal dialysis cohort and its concentration analyzed in relation to creatinine and clinical characteristics. RESULTS: Highest DKK3 concentrations were found in serum, followed by urine. Dialysate concentrations were significantly lower. Dialysate DKK3 correlated with both other compartments. Serum, dialysate and urine values were stable during three months of follow-up. Continuous ambulatory dialysis (CAPD) but not cycler-assisted peritoneal dialysis (CCPD) volume-dependently increased peritoneal DKK3 in relation to creatinine. RAAS blockade significantly decreased urinary, but not serum or peritoneal DKK3. CONCLUSION: Our data provide a detailed characterization of DKK3 in peritoneal dialysis. They support the notion that the RAAS system is essential for renal DKK3 handling.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Diálise Peritoneal , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Quimiocinas/sangue , Quimiocinas/metabolismo , Idoso , Adulto , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Falência Renal Crônica/terapia , Falência Renal Crônica/metabolismo , Biomarcadores/sangue , Soluções para Diálise/metabolismo , Rim/metabolismo , Peritônio/metabolismo , Diálise Peritoneal Ambulatorial Contínua , Sistema Renina-Angiotensina/fisiologia , Creatinina/urina , Creatinina/sangue , Creatinina/metabolismo
20.
Crit Care Explor ; 6(8): e1134, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39110074

RESUMO

IMPORTANCE: Pediatric acute kidney injury (AKI) is a prevalent and morbid complication of shock. Its pathogenesis and early identification remain elusive. OBJECTIVES: We aim to determine whether renal blood flow (RBF) measurements by point-of-care ultrasound (POCUS) and renin-angiotensin-aldosterone system (RAAS) hormones in pediatric shock associate with vasoactive requirements and AKI. DESIGN, SETTING, AND PARTICIPANTS: This is a single-center prospective, noninterventional observational cohort study in one tertiary PICU in North American from 2020 to 2022 that enrolled children younger than 18 years with shock without preexisting end-stage renal disease. MAIN OUTCOMES AND MEASURES: RBF was measured by POCUS on hospital days 1 and 3 and plasma RAAS hormone levels were measured on day 1. The primary outcome was the presence of AKI by Kidney Disease Improving Global Outcomes criteria at first ultrasound with key secondary outcomes of creatinine, blood urea nitrogen (BUN), Vasoactive-Inotrope Score (VIS), and norepinephrine equivalent dosing (NED) 48 hours after first ultrasound. RESULTS: Fifty patients were recruited (20 with AKI, mean age 10.5 yr, 48% female). POCUS RBF showed lower qualitative blood flow (power Doppler ultrasound [PDU] score) and higher regional vascular resistance (renal resistive index [RRI]) in children with AKI (p = 0.017 and p = 0.0007). Renin and aldosterone levels were higher in the AKI cohort (p = 0.003 and p = 0.007). Admission RRI and PDU associated with higher day 3 VIS and NED after adjusting for age, day 1 VIS, and RAAS hormones. Admission renin associated with higher day 3 creatinine and BUN after adjusting for age, day 1 VIS, and the ultrasound parameters. CONCLUSIONS AND RELEVANCE: In pediatric shock, kidney blood flow was abnormal and renin and aldosterone were elevated in those with AKI. Kidney blood flow abnormalities are independently associated with future cardiovascular dysfunction; renin elevations are independently associated with future kidney dysfunction. Kidney blood flow by POCUS may identify children who will have persistent as opposed to resolving AKI. RAAS perturbations may drive AKI in pediatric shock.


Assuntos
Injúria Renal Aguda , Circulação Renal , Sistema Renina-Angiotensina , Humanos , Feminino , Criança , Masculino , Estudos Prospectivos , Injúria Renal Aguda/sangue , Injúria Renal Aguda/fisiopatologia , Injúria Renal Aguda/etiologia , Sistema Renina-Angiotensina/fisiologia , Adolescente , Choque/sangue , Choque/fisiopatologia , Pré-Escolar , Estudos de Coortes , Lactente , Rim/fisiopatologia , Rim/irrigação sanguínea , Rim/diagnóstico por imagem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA