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1.
Eur J Endocrinol ; 188(1)2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36651157

RESUMO

OBJECTIVES: The saline suppression test (SST) serves to confirm the diagnosis of primary aldosteronism (PA), while adrenal vein sampling (AVS) is used to subtype PA as unilateral or bilateral. Criteria that can accurately identify those with bilateral PA based on SST results could reduce the need for AVS. We previously demonstrated that a combination of plasma aldosterone concentration (PAC) < 300 pmol L-1 and a reduction in aldosterone-to-renin ratio (ARR) following recumbent SST had high specificity for predicting bilateral PA in an Australian cohort of 92 patients with PA who have undergone AVS. We sought to validate our predictive criteria in larger, independent cohorts of patients with PA. DESIGN: An international, multi-centre cohort study. METHODS: Data from 55 patients at Monash Health, Victoria, Australia, 106 patients from the First Affiliated Hospital of Chongqing Medical University, China, and 105 patients from Nihon University Itabashi Hospital, Japan were analysed. RESULTS: A combination of PAC <300 pmol L-1 and a reduction in ARR following recumbent SST predicted bilateral PA with specificities of 88.2%, 97.0%, and 100.0% in Australian, Chinese, and Japanese cohorts, respectively. This criterion could allow 22%-38% of patients with PA to bypass AVS and proceed directly to medical treatment. CONCLUSION: In patients undergoing the recumbent SST, a post-saline PAC <300 pmol L-1 together with a reduction in ARR can predict bilateral PA with high specificity and may allow targeted treatment to be commenced without AVS in up to a third of patients.


Assuntos
Aldosterona , Hiperaldosteronismo , Humanos , Estudos de Coortes , Austrália , Solução Salina , Estudos Retrospectivos , Glândulas Suprarrenais/irrigação sanguínea
2.
Eur J Med Res ; 28(1): 26, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36639782

RESUMO

BACKGROUND: Aldosterone relieves transcriptional repression of epithelial sodium channel (ENaC) by inhibiting Dot1a and Af9 expression and their interaction with ENaC promoter in various tissues. Expressions of ENaC and Af9 in inner ear have been identified. However, it is not known how Dot1l is regulated by aldosterone in inner ear. METHODS: Twenty-eight adult guinea pigs were randomly divided into the control group and treatment group. Aldosterone 1 mg/kg/d was injected intraperitoneally in the treatment group and saline in the control group for 7 days. Animals were killed 1 month later following auditory brainstem response examination. Histomorphology of cochlea was detected with hematoxylin-eosin staining, and Dot1l expression was examined with immunohistochemistry and Western blot. RESULTS: There was no significant difference in ABR thresholds before and after injection of aldosterone or saline in either group. Endolymphatic hydrops was found in 75% of animals in the treatment group. Dot1l was found in both groups in the stria vascularis, Reissner's membrane, spiral limbus, organ of Corti and spiral ligament. Dot1l expression in the treatment group was decreased by aldosterone. CONCLUSIONS: Dot1l in guinea pig cochlea is inhibited by aldosterone with induction of endolymphatic hydrops. Dot1l may be closely related to endolymph regulation by aldosterone and to pathogenesis of Meniere's disease.


Assuntos
Hidropisia Endolinfática , Doença de Meniere , Cobaias , Animais , Aldosterona/farmacologia , Aldosterona/metabolismo , Cóclea/metabolismo , Cóclea/patologia , Hidropisia Endolinfática/etiologia , Hidropisia Endolinfática/metabolismo , Hidropisia Endolinfática/patologia , Doença de Meniere/complicações , Doença de Meniere/metabolismo , Doença de Meniere/patologia
3.
J Am Coll Cardiol ; 81(4): 321-331, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36697132

RESUMO

BACKGROUND: Data on angioedema risk among sacubitril-valsartan (SV) users in real-world settings are limited. OBJECTIVES: We sought to evaluate the risk of angioedema among SV new users compared with angiotensin-converting enzyme (ACE) inhibitor and angiotensin-receptor-blocker (ARB) new users separately. METHODS: We conducted a propensity score-matched cohort study, comparing SV new users (no use of SV, ACE inhibitor, ARB 6 months before) and SV new users with prior use (within 183 or 14 days) of ACE inhibitor or ARB (ACE inhibitor-SV and ARB-SV users; recent ACE inhibitor-SV and recent ARB-SV users, respectively) vs ACE inhibitor and ARB new users separately. RESULTS: Compared with ACE inhibitor, SV new (HR: 0.18; 95% CI: 0.11-0.29) and ACE inhibitor-SV users (HR: 0.31; 95% CI: 0.23-0.43) showed lower risk of angioedema. On the other hand, there was no difference in angioedema risk when SV new users (HR: 0.59; 95% CI: 0.35-1.01) or ARB-SV users (HR: 0.85; 95% CI: 0.58-1.26) were compared with ARB new users. Compared with SV new users, ACE inhibitor-SV users (HR: 1.62; 95% CI: 0.91-2.89) trended toward higher angioedema risk, which intensified when the ACE inhibitor to SV switch occurred within 14 days (recent ACE inhibitor-SV) (HR: 1.98; 95% CI: 1.11-3.53). Similarly, ARB-SV users (HR: 2.03; 95% CI: 1.16-3.54) experienced an increased risk compared with SV new users, which intensified for the more recent switchers (recent ARB-SV) (HR: 2.45; 95% CI: 1.36-4.43). CONCLUSIONS: We did not observe an increased risk of angioedema among SV new users compared with ACE inhibitor or ARB users. However, there was an increased risk of angioedema among SV users who recently switched from ACE inhibitor or ARB compared with SV new users.


Assuntos
Angioedema , Inibidores da Enzima Conversora de Angiotensina , Humanos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Renina , Aldosterona , Angiotensinas , Antagonistas de Receptores de Angiotensina/efeitos adversos , Estudos de Coortes , Inibidores de Proteases/efeitos adversos , Angioedema/induzido quimicamente , Angioedema/epidemiologia
4.
BMC Nephrol ; 24(1): 18, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36658531

RESUMO

BACKGROUND: Hyperkalemia (HK) is a barrier to optimization of renin-angiotensin-aldosterone system inhibitor (RAASi) therapy in heart failure (HF) and chronic kidney disease (CKD). We investigated cardiorenal risk associated with changes in RAASi regimen after an episode of HK in patients with HF and/or CKD. METHODS: This observational study utilized data from hospital records, claims, and health registers from the US (Optum's de-identified Market Clarity Data) and Japan (Medical Data Vision). Included patients had an index episode of HK between July 2019 and September 2021 (US), or May 2020 and September 2021 (Japan), with prior diagnosis of HF or CKD (stage 3 or 4), and RAASi use. Risk of a cardiorenal composite outcome (HF emergency visit, HF hospitalization, or progression to end-stage kidney disease) was determined in patients who discontinued RAASi, down-titrated their dose by > 25%, or maintained or up-titrated their dose following the HK episode. RESULTS: A total of 15,488 and 6020 patients were included from the US and Japan, respectively. Prior to the episode of HK, 59% (US) and 27% (Japan) of patients had achieved > 50% target RAASi dose. Following the episode of HK, 33% (US) and 32% (Japan) of patients did not fill a new RAASi prescription. Risk of the cardiorenal outcome at 6 months was higher in patients who discontinued or down-titrated versus maintained or up-titrated RAASi treatment both in the US (17.5, 18.3, and 10.6%; p <  0.001) and in Japan (19.7, 20.0, and 15.1%; p <  0.001). CONCLUSION: HK-related RAASi discontinuation or down-titration was associated with higher risk of cardiorenal events versus maintained or up-titrated RAASi.


Assuntos
Inibidores da Enzima Conversora de Angiotensina , Insuficiência Cardíaca , Hiperpotassemia , Insuficiência Renal Crônica , Humanos , Aldosterona , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Anti-Hipertensivos/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/tratamento farmacológico , Hiperpotassemia/induzido quimicamente , Hiperpotassemia/tratamento farmacológico , Potássio/uso terapêutico , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Sistema Renina-Angiotensina
5.
Laeknabladid ; 109(1): 18-21, 2023 Jan.
Artigo em Islandês | MEDLINE | ID: mdl-36541908

RESUMO

The Neonatal weight loss is a common problem which most physicians who take care of newborns should recognise. The most common reason is insufficient dietary intake. However the reason can also be an underlying disease. Aldosterone insufficiency in neonates is a rare disease and if not treated correctly can be life threatening. It presents with serious electrolytes abnormalities and metabolic acidosis. It is therefore important to distinguish between serious and benign causes of weight loss in neonates.


Assuntos
Hipoaldosteronismo , Humanos , Recém-Nascido , Hipoaldosteronismo/diagnóstico , Hipoaldosteronismo/terapia , Hipoaldosteronismo/etiologia , Aldosterona
6.
Int J Mol Med ; 51(2)2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36524378

RESUMO

Renal tubulointerstitial fibrosis (TIF) is a hallmark in the continuous progression of chronic kidney disease (CKD), in which excessive activation of the renin­angiotensin­-aldosterone system serves a crucial role. Currently, there are no targeted therapies for the progression of TIF. microRNA (miR)­26a may be an ideal anti­fibrosis candidate molecule; however, the effect of miR­26 on aldosterone (ALD)­induced TIF remains unclear. This study aimed to elucidate the role of miR­26a in ALD­induced TIF. In the present study, we hypothesized that delivery of miR­26a by exosomes could attenuate ALD­induced TIF. miR­26a expression was downregulated in the kidney of ALD­induced mice compared with the mice in the sham group. Exosome­encapsulated miR­26a (Exo­miR­26a) was manufactured and injected into ALD­treated mice through the tail vein. In vivo experiments showed that Exo­miR­26a alleviated the downregulated miR­26a expression in the kidney, tubular injury and ALD­induced TIF, which was determined using Masson's trichrome staining and assessment of lipocalin 2, α­smooth muscle actin, collagen I and fibronectin expression. Moreover, in vitro experiments revealed that Exo­miR­26a inhibited epithelial­mesenchymal transition and extracellular matrix deposition in mouse tubular epithelial cells. Mechanistically, overexpressing miR­26a led to decreased expression levels of connective tissue growth factor by directly binding to its 3'­UTR and inhibiting the activation of SMAD3. These findings demonstrated that the exosomal delivery of miR­26a may alleviate ALD­induced TIF, which may provide new insights into the treatment of CKD.


Assuntos
Exossomos , MicroRNAs , Insuficiência Renal Crônica , Animais , Camundongos , Regiões 3' não Traduzidas , Aldosterona/metabolismo , Aldosterona/farmacologia , Fator de Crescimento do Tecido Conjuntivo/genética , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Exossomos/genética , Exossomos/metabolismo , Fibrose , Rim/patologia , MicroRNAs/metabolismo , MicroRNAs/farmacologia , Insuficiência Renal Crônica/metabolismo , Insuficiência Renal Crônica/patologia , Transdução de Sinais , Proteína Smad3/genética , Proteína Smad3/metabolismo
7.
Peptides ; 160: 170925, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36549423

RESUMO

The renal kallikrein-kinin system (RKKS) has been related to blood pressure control and sodium and water balance. We have previously shown that female spontaneously hypertensive rats (SHR) have high urinary kallikrein activity (UKa) and lower blood pressure (BP) than males whereas ovariectomy stimulates UKa and diminishes BP. We also showed that high K+ intake and prepuberal gonadectomy (Gx) diminish BP with a concomitant increase in UKa and plasma aldosterone levels. Since kallikrein co-localize in the same distal nephron segments of aldosterone effectors, we explored the effect of pharmacological blockage of aldosterone receptor, epithelial Na+ (ENaC) and the rectifying outer medulla K+ (ROMK) channels in different gonad contexts on the gene expression, renal tissue content and urine release of kallikrein. Klk1 gene expression was determined by real-time PCR and enzymatic activity of kallikrein by the amidolytic method. We found that the inhibition of the aldosterone receptor by spironolactone increases kallikrein renal tissue storage and decreases its urinary activity, especially in Gx rats. Moreover, ENaC blockade by benzamil increases the renal content of kallikrein without affecting synthesis or excretion, especially in females and Gx animals, while the inhibition of ROMK by glibenclamide increases the synthesis and renal content of kallikrein only in intact male animals. We concluded that RKKS regulation showed sexual dimorphism and seemed to be modulated by sex hormones throughout a process involving aldosterone and the aldosterone-sensitive ion channels..


Assuntos
Aldosterona , Hipertensão , Masculino , Ratos , Feminino , Animais , Aldosterona/metabolismo , Ratos Endogâmicos SHR , Receptores de Mineralocorticoides/metabolismo , Hipertensão/metabolismo , Calicreínas/genética , Calicreínas/metabolismo , Rim/metabolismo , Néfrons/metabolismo , Sódio/metabolismo , Canais Iônicos/metabolismo , Canais Epiteliais de Sódio/genética , Canais Epiteliais de Sódio/metabolismo
8.
Mol Cell Endocrinol ; 561: 111836, 2023 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-36549461

RESUMO

Primary hyperaldosteronism is a major cause of secondary hypertension and carries additional cardiovascular risks beyond that of the elevated blood pressure. Primary hyperaldosteronism is more prevalent in obese people, and weight loss reduces aldosterone levels. It needs to be determined whether obesity related factors directly contribute to the pathogenesis of primary hyperaldosteronism. Here we show that the non-esterified fatty acids (NEFA) palmitic acid, and to a lesser extent, linoleic acid significantly stimulated aldosterone production and steroid enzyme induction in adrenocortical HAC15 cells of human origin. Palmitic acid, linoleic acid, and to a much lesser extent, oleic acid induced the expression of aldosterone synthase. Induction of the Steroidogenic Acute Regulatory Protein (StAR) was modest. Increased aldosterone secretion was independent of fatty acid beta-oxidation in the mitochondria but may involve free fatty acid receptor 1 (FFAR1/GPR40) and endoplasmic reticulum (ER) stress. Palmitic acid and linoleic acid induced the expression of C/EBP Homologous Protein (CHOP), a marker of ER stress, correlating with their ability to induce aldosterone synthase gene expression. Palmitic acid, but not linoleic acid decreased mitochondrial potentials and induced uncoupling protein 2 (UCP2). Palmitic acid enhanced, while docosahexaenoic acid (DHA) suppressed aldosterone response to angiotensin II (Ang-II). Our study provides evidence that NEFAs modulate aldosterone production, and further suggests that hyperaldosteronism shares similar pathogenesis with other obesity-related disorders such as metabolic syndrome.


Assuntos
Hiperaldosteronismo , Hipertensão , Humanos , Aldosterona/farmacologia , Aldosterona/metabolismo , Ácidos Graxos/metabolismo , Citocromo P-450 CYP11B2/genética , Hiperaldosteronismo/genética , Ácido Palmítico/farmacologia
9.
Clin Epigenetics ; 14(1): 159, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36457109

RESUMO

BACKGROUND: The epigenetic regulation of the renin-angiotensin-aldosterone system (RAAS) potentially plays a role in the pathophysiology underlying the high burden of hypertension in sub-Saharan Africans (SSA). Here we report the first epigenome-wide association study (EWAS) of plasma renin and aldosterone concentrations and the aldosterone-to-renin ratio (ARR). METHODS: Epigenome-wide DNA methylation was measured using the Illumina 450K array on whole blood samples of 68 Ghanaians. Differentially methylated positions (DMPs) were assessed for plasma renin concentration, aldosterone, and ARR using linear regression models adjusted for age, sex, body mass index, diabetes mellitus, hypertension, and technical covariates. Additionally, we extracted methylation loci previously associated with hypertension, kidney function, or that were annotated to RAAS-related genes and associated these with renin and aldosterone concentration. RESULTS: We identified one DMP for renin, ten DMPs for aldosterone, and one DMP associated with ARR. Top DMPs were annotated to the PTPRN2, SKIL, and KCNT1 genes, which have been reported in relation to cardiometabolic risk factors, atherosclerosis, and sodium-potassium handling. Moreover, EWAS loci previously associated with hypertension, kidney function, or RAAS-related genes were also associated with renin, aldosterone, and ARR. CONCLUSION: In this first EWAS on RAAS hormones, we identified DMPs associated with renin, aldosterone, and ARR in a SSA population. These findings are a first step in understanding the role of DNA methylation in regulation of the RAAS in general and in a SSA population specifically. Replication and translational studies are needed to establish the role of these DMPs in the hypertension burden in SSA populations.


Assuntos
Aldosterona , Hipertensão , Renina , Humanos , Aldosterona/sangue , Metilação de DNA , Epigênese Genética , Epigenoma , Gana , Hipertensão/genética , Proteínas do Tecido Nervoso , Canais de Potássio Ativados por Sódio , Renina/sangue
10.
Medicine (Baltimore) ; 101(47): e31403, 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36451378

RESUMO

RATIONALE: Adrenal mixed corticomedullary tumors (MCMTs) are single tumor masses composed of an intimately admixed population of both adrenal cortical cells and medullary components. Most medullary tumor components are pheochromocytomas; however, MCMTs composed of ganglioneuroma and adrenal cortical adenoma are extremely rare. The current case is a rare case of adrenal MCMT composed of ganglioneuroma and adrenal cortical adenoma with primary aldosteronism. PATIENT CONCERNS: A 49-year-old male was admitted because of hypokalemia and an adrenal mass. He was diagnosed with hypertension in his 20s and was taking blood pressure medications. DIAGNOSIS: Plasma aldosterone concentration 376.5 pg/dL (normal 37.8~233.0 pg/mL) and potassium 2.8 mmol/L (normal 3.4~4.9 mmol/L) were detected. The aldosterone-to-renin ratio [the ratio of plasma aldosterone concentration (ng/dL) to PRA (ng/mL/hour)] was 38. The saline loading test showed that serum aldosterone (49.4 ng/dL) was not suppressed, compared with the basal level (28.4 ng/dL). The adrenal venous sampling test showed that the aldosterone level markedly increased to 1521.2 pg/mL. Abdominal computed tomography revealed an enlarged relatively well-circumscribed multinodular mass (35 × 13 × 30 mm) in the right adrenal gland. INTERVENTIONS: Laparoscopic right adrenalectomy was performed under the clinical diagnosis of a functioning adrenal cortical adenoma. OUTCOMES: After laparoscopic right adrenalectomy, the serum aldosterone and renin levels returned to normal. The patient maintained a normal aldosterone level without recurrence for 16 months. LESSONS: Adrenal MCMTs of the ganglioneuroma and cortical adenomas in the ipsilateral adrenal gland are extremely rare. Adrenal MCMTs exhibit benign clinical behavior, with no metastasis or death due to the tumor. With the development of diagnostic imaging technology, it is possible to identify mixed tumors. However, surgical resection of adrenal gland is a common treatment and a final diagnosis should be made based on the pathological results after surgery. Because this is to rule out the occurrence of rare malignant tumors and confirm the pattern of mixed tumors.


Assuntos
Adenoma Pleomorfo , Neoplasias das Glândulas Suprarrenais , Adenoma Adrenocortical , Ganglioneuroma , Masculino , Humanos , Pessoa de Meia-Idade , Adenoma Adrenocortical/diagnóstico , Adenoma Adrenocortical/cirurgia , Ganglioneuroma/diagnóstico , Ganglioneuroma/cirurgia , Aldosterona , Renina , Glândulas Suprarrenais , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/cirurgia
11.
BMC Endocr Disord ; 22(1): 300, 2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36461073

RESUMO

BACKGROUND: 17α-hydroxylase deficiency (17OHD) is a rare autosomal recessive disorder. Aldosterone levels are usually low in patients with 17OHD. However, among the approximately 150 cases of 17OHD reported to date, aldosterone levels were not low in all cases. Therefore, some 17OHD cases may have been misdiagnosed as primary aldosteronism (PA) cases. Often before puberty, 17OHD is diagnosed because of abnormal genital morphology and menstrual irregularities. However, we report a very rare case of 17OHD in an elderly patient with a high aldosterone/renin ratio (ARR) similar to that in PA. CASE PRESENTATION: A 63-year-old Japanese woman was transferred to our medical facility for the evaluation of bilateral adrenal hypertrophy, which was incidentally discovered during an abdominal examination after cholecystectomy. The patient had hypokalemia and a high aldosterone/renin ratio. Her medical history included hypertension and right intracerebral capsular hemorrhage at the age of 30 years. Additional testing revealed low cortisol, high adrenocorticotropic hormone, and low testosterone and dehydroepiandrosterone sulfate, indicating congenital adrenal hyperplasia. Genetic analysis revealed a mutation in the CYP17A1 gene and a karyotype of 46, XY; hence, she was diagnosed with 17OHD. CONCLUSION: 17OHD can resemble PA. The combination of a high ARR and low cortisol level should trigger the consideration of 17OHD.


Assuntos
Hiperaldosteronismo , Doenças Metabólicas , Humanos , Idoso , Feminino , Adulto , Pessoa de Meia-Idade , Aldosterona , Hidrocortisona , Renina , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/genética , Oxigenases de Função Mista , Erros de Diagnóstico
12.
Int Immunopharmacol ; 113(Pt A): 109396, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36461595

RESUMO

Cardiovascular complications are the leading causes of death in patients with chronic kidney disease (CKD), accounting for approximately 50% of deaths. Despite significant advances in the understanding of cardiac disease due to CKD, the underlying mechanisms involved in many pathological changes have not been fully elucidated. In our previous study, we observed severe fibrosis in the contralateral kidney of a 6-month-old rat UUO model. In the present experiment, we also observed severe fibrosis in the hearts of rats subjected to UUO and the macrophage-to-myofibroblast transition (MMT). These effects were inhibited by the mineralocorticoid receptor (MR) blocker eplerenone. Notably, in vitro, aldosterone-activated MR induced the MMT and subsequently promoted the secretion of CTGF, the target of MR, from macrophages; these changes were inhibited by eplerenone. The CTGF also induced the MMT and both the aldosterone and CTGF-induced MMT could be alleviated by the CTGF blocker. In conclusion, our results suggest that targeting the MR/CTGF pathway to inhibit the MMT may be an effective therapeutic strategy for the treatment of cardiac fibrosis.


Assuntos
Síndrome Cardiorrenal , Cardiopatias , Insuficiência Renal Crônica , Ratos , Animais , Eplerenona/farmacologia , Eplerenona/uso terapêutico , Receptores de Mineralocorticoides , Síndrome Cardiorrenal/tratamento farmacológico , Miofibroblastos , Aldosterona , Macrófagos , Fibrose
13.
Can Vet J ; 63(12): 1226-1235, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36467377

RESUMO

This study investigated the plasma aldosterone concentration (PAC) in cats with chronic kidney disease (CKD) and retrospectively evaluated the survival of cats with high PAC. Furthermore, this study prospectively examined eplerenone's effect on survival time in CKD cats with high PAC. The PAC was measured retrospectively in blood samples obtained from 156 client-owned cats that visited a veterinary hospital. The cats were designated into 2 groups: clinically healthy (n = 101) and those with CKD (n = 55). The PAC was measured by solid-phase radioimmunoassay; median (minimum-maximum) PAC in healthy cats was 97 pg/mL (range: 10 to 416 pg/mL) and the upper limit (95th percentile) was 243 pg/mL. In the CKD group, PAC [126 pg/mL (range: 10 to 981 pg/mL)] was higher (P < 0.01) than in the clinically healthy group. In cats with CKD, the survival time of those with high PAC (n = 16) (> 243 pg/mL) was shorter (P = 0.019) than that of those (n = 39) with normal PAC. Administering an aldosterone antagonist, eplerenone, at 2.5 to 5 mg/kg body weight prolonged survival (P = 0.005) in CKD cats with high PAC (n = 8). In conclusion, PAC could be a prognostic marker of CKD in cats and eplerenone may prolong survival in cats with CKD and a high PAC.


Effets de la concentration plasmatique d'aldostérone et du traitement à l'éplérénone sur la survie des chats atteints d'insuffisance rénale chronique. Cette étude a examiné la concentration plasmatique d'aldostérone (PAC) chez les chats atteints d'insuffisance rénale chronique (IRC) et a évalué rétrospectivement la survie des chats ayant une PAC élevée. De plus, cette étude a examiné de manière prospective l'effet de l'éplérénone sur le temps de survie chez les chats IRC avec une PAC élevée. La PAC a été mesurée rétrospectivement dans des échantillons de sang prélevés sur 156 chats appartenant à des clients ayant visité un hôpital vétérinaire. Les chats ont été répartis en 2 groupes : cliniquement sains (n = 101) et ceux atteints d'IRC (n = 55). La PAC a été mesurée par radio-immunodosage en phase solide; la PAC médiane (minimale-maximale) chez les chats sains était de 97 pg/mL (plage : 10 à 416 pg/mL) et la limite supérieure (95e centile) était de 243 pg/mL. Dans le groupe IRC, la PAC [126 pg/mL (plage : 10 à 981 pg/mL)] était plus élevée (P < 0,01) que dans le groupe cliniquement sain. Chez les chats atteints d'IRC, le temps de survie de ceux avec une PAC élevée (n = 16) (> 243 pg/mL) était plus court (P = 0,019) que celui de ceux (n = 39) avec une PAC normale. L'administration d'un antagoniste de l'aldostérone, l'éplérénone, à raison de 2,5 à 5 mg/kg de poids corporel a prolongé la survie (P = 0,005) chez les chats atteints d'IRC avec une PAC élevée (n = 8). En conclusion, la PAC pourrait être un marqueur pronostique de l'IRC chez le chat et l'éplérénone pourrait prolonger la survie des chats atteints d'IRC et d'une PAC élevée.(Traduit par Dr Serge Messier).


Assuntos
Doenças do Gato , Insuficiência Renal Crônica , Gatos , Animais , Eplerenona/uso terapêutico , Aldosterona , Estudos Retrospectivos , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/veterinária , Anti-Hipertensivos , Doenças do Gato/tratamento farmacológico
14.
Cells ; 11(24)2022 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-36552716

RESUMO

Metabolic effects of physical activity may be reno-protective in the context of hypertension, although exercise stresses kidneys. Aldosterone participates in renal disease in hypertension, but exercise affects the plasma concentration of aldosterone. This study was designed to evaluate whether physical activity and pharmacological treatment by aldosterone have additive effects on renal protection in hypertensive rats. Female spontaneously hypertensive rats (SHR) or normotensive Wistar rats performed voluntary running wheel activity alone or in combination with aldosterone blockade (spironolactone). The following groups were studied: young and pre-hypertensive SHR (n = 5 sedentary; n = 10 running wheels, mean body weight 129 g), 10-month-old Wistar rats (n = 6 sedentary; n = 6 running wheels, mean body weight 263 g), 10-month-old SHRs (n = 18 sedentary, mean body weight 224 g; n = 6 running wheels, mean body weight 272 g; n = 6 aldosterone, mean body weight 219 g; n = 6 aldosterone and running wheels, mean body weight 265 g). Another group of SHRs had free access to running wheels for 6 months and kept sedentary for the last 3 months (n = 6, mean body weight 240 g). Aldosterone was given for the last 4 months. SHRs from the running groups had free access to running wheels beginning at the age of 6 weeks. Renal function was analyzed by microalbuminuria (Alb/Cre), urinary secretion of kidney injury molecule-1 (uKim-1), and plasma blood urea nitrogen (BUN) concentration. Molecular adaptation of the kidney to hypertension and its modification by spironolactone and/or exercise were analyzed by real-time PCR, immunoblots, and histology. After six months of hypertension, rats had increased Alb/Cre and BUN but normal uKim-1. Voluntary free running activity normalized BUN but not Alb/Cre, whereas spironolactone reduced Alb/Cre but not BUN. Exercise constitutively increased renal expression of proprotein convertase subtilisin/kexin type 9 (PCSK9; mRNA and protein) and arginase-2 (mRNA). Spironolactone reduced these effects. uKim-1 increased in rats performing voluntary running wheel activity exercise irrespectively of blood pressure and aldosterone blockade. We observed independent but no additive effects of aldosterone blockade and physical activity on renal function and on molecules potentially affecting renal lipid metabolism.


Assuntos
Hipertensão , Pró-Proteína Convertase 9 , Animais , Feminino , Ratos , Aldosterona , Peso Corporal , Hipertensão/tratamento farmacológico , Rim/metabolismo , Ratos Endogâmicos SHR , Ratos Wistar , RNA Mensageiro/metabolismo , Espironolactona/farmacologia , Atividade Motora/fisiologia
15.
Front Endocrinol (Lausanne) ; 13: 1005934, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36506080

RESUMO

Introduction: Unilateral primary aldosteronism (UPA) and bilateral primary aldosteronism (BPA) are the two subtypes of PA. Discriminating UPA from BPA is of great significance. Although adrenal venous sampling (AVS) is the gold standard for diagnosis, it has shortcomings. Thus, improved methods are needed. Methods: The original data were extracted from the public database "Dryad". Ten parameters were included to develop prediction models for PA subtype diagnosis using machine learning technology. Moreover, the optimal model was chose and validated in an external dataset. Results: In the modeling dataset, 165 patients (71 UPA, 94 BPA) were included, while in the external dataset, 43 consecutive patients (20 UPA, 23 BPA) were included. The ten parameters utilized in the prediction model include age, sex, systolic and diastolic blood pressure, aldosterone to renin ratio (ARR), serum potassium, ARR after 50 mg captopril challenge test (CCT), primary aldosterone concentration (PAC) after saline infusion test (SIT), PAC reduction rate after SIT, and number of types of antihypertensive agents at diagnosis. The accuracy, sensitivity, specificity, F1 score, and AUC for the optimal model using the random forest classifier were 90.0%, 81.8%, 96.4%, 0.878, and 0.938, respectively, in the testing dataset and 81.4%, 90.0%, 73.9%, 0.818 and 0.887, respectively, in the validating external dataset. The most important variables contributing to the prediction model were PAC after SIT, ARR, and ARR after CCT. Discussion: We developed a machine learning-based predictive model for PA subtype diagnosis based on ten clinical parameters without CT imaging. In the future, artificial intelligence-based prediction models might become a robust prediction tool for PA subtype diagnosis, thereby, might reducing at least some of the requests for CT or AVS and assisting clinical decision-making.


Assuntos
Hiperaldosteronismo , Humanos , Hiperaldosteronismo/diagnóstico , Inteligência Artificial , Aldosterona , Captopril , Aprendizado de Máquina
17.
Kidney360 ; 3(11): 1909-1923, 2022 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-36514401

RESUMO

Background: Elevated abundance of sodium-chloride cotransporter (NCC) and phosphorylated NCC (pNCC) are potential markers of primary aldosteronism (PA), but these effects may be driven by hypokalemia. Methods: We measured plasma potassium in patients with PA. If potassium was <4.0 mmol/L, patients were given sufficient oral potassium chloride (KCl) over 24 hours to achieve as close to 4.0 mmol/L as possible. Clinical chemistries were assessed, and urinary extracellular vesicles (uEVs) were examined to investigate effects on NCC. Results: Among 21 patients with PA who received a median total dose of 6.0 g (2.4-16.8 g) of KCl, increases were observed in plasma potassium (from 3.4 to 4.0 mmol/L; P<0.001), aldosterone (from 305 to 558 pmol/L; P=0.01), and renin (from 1.2 to 2.5 mIU/L; P<0.001), whereas decreases were detected in uEV levels of NCC (median fold change(post/basal) [FC]=0.71 [0.09-1.99]; P=0.02), pT60-NCC (FC=0.84 [0.06-1.66]; P=0.05), and pT55/60-NCC (FC=0.67 [0.08-2.42]; P=0.02). By contrast, in 10 patients with PA who did not receive KCl, there were no apparent changes in plasma potassium, NCC abundance, and phosphorylation status, but increases were observed in plasma aldosterone (from 178 to 418 pmol/L; P=0.006) and renin (from 2.0 to 3.0 mU/L; P=0.009). Plasma potassium correlated inversely with uEV levels of NCC (R 2=0.11; P=0.01), pT60-NCC (R 2=0.11; P=0.01), and pT55/60-NCC (R 2=0.11; P=0.01). Conclusions: Acute oral KCl loading replenished plasma potassium in patients with PA and suppressed NCC abundance and phosphorylation, despite a significant rise in plasma aldosterone. This supports the view that potassium supplementation in humans with PA overrides the aldosterone stimulatory effect on NCC. The increased plasma aldosterone in patients with PA without KCl supplementation may be due to aldosterone response to posture challenge.


Assuntos
Hiperaldosteronismo , Simportadores de Cloreto de Sódio , Humanos , Aldosterona , Cloreto de Potássio/farmacologia , Renina , Fosforilação , Potássio , Hiperaldosteronismo/tratamento farmacológico , Suplementos Nutricionais
18.
PLoS Comput Biol ; 18(12): e1010607, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36538563

RESUMO

Maintaining normal potassium (K+) concentrations in the extra- and intracellular fluid is critical for cell function. K+ homeostasis is achieved by ensuring proper distribution between extra- and intracellular fluid compartments and by matching K+ excretion with intake. The Na+-K+-ATPase pump facilitates K+ uptake into the skeletal muscle, where most K+ is stored. Na+-K+-ATPase activity is stimulated by insulin and aldosterone. The kidneys regulate long term K+ homeostasis by controlling the amount of K+ excreted through urine. Renal handling of K+ is mediated by a number of regulatory mechanisms, including an aldosterone-mediated feedback control, in which high extracellular K+ concentration stimulates aldosterone secretion, which enhances urine K+ excretion, and a gastrointestinal feedforward control mechanism, in which dietary K+ intake increases K+ excretion. Recently, a muscle-kidney cross talk signal has been hypothesized, where the K+ concentration in skeletal muscle cells directly affects urine K+ excretion without changes in extracellular K+ concentration. To understand how these mechanisms coordinate under different K+ challenges, we have developed a compartmental model of whole-body K+ regulation. The model represents the intra- and extracellular fluid compartments in a human (male) as well as a detailed kidney compartment. We included (i) the gastrointestinal feedforward control mechanism, (ii) the effect of insulin and (iii) aldosterone on Na+-K+-ATPase K+ uptake, and (iv) aldosterone stimulation of renal K+ secretion. We used this model to investigate the impact of regulatory mechanisms on K+ homeostasis. Model predictions showed how the regulatory mechanisms synthesize to ensure that the extra- and intracelluller fluid K+ concentrations remain in normal range in times of K+ loading and fasting. Additionally, we predict that without the hypothesized muscle-kidney cross talk signal, the model was unable to predict a return to normal extracellular K+ concentration after a period of high K+ loading or depletion.


Assuntos
Aldosterona , Potássio , Masculino , Humanos , Potássio/metabolismo , Retroalimentação , Rim/metabolismo , Homeostase/fisiologia , Insulina , Modelos Teóricos , Adenosina Trifosfatases , ATPase Trocadora de Sódio-Potássio/metabolismo
19.
Int J Mol Sci ; 23(23)2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36499387

RESUMO

Both aldosterone and arginine vasopressin (AVP) are produced in the heart and may participate in cardiac fibrosis. However, their relationship remains unknown. This study aims to demonstrate the regulation and role of AVP in aldosterone synthesis in the heart. Rats were subjected to a sham operation or myocardial infarction (MI) by ligating the coronary artery. Cardiac function and fibrosis were assessed using echocardiography and immunohistochemical staining, respectively. In addition, the effects of AVP stimulation on cardiac microvascular endothelial cells (CMECs) were studied using ELISA, real-time PCR, and Western blotting. Compared with the rats having undergone a sham operation, the MI rats had an increased LVMI, type I collagen composition, and concentrations of aldosterone and AVP in the heart but decreased cardiac function. As the MI rats aged, the LVMI, type I collagen, aldosterone, and AVP increased, while the LVMI decreased. Furthermore, AVP time-dependently induced aldosterone secretion and CYP11B2 mRNA expression in CMECs. The p-CREB levels were significantly increased by AVP. Nevertheless, these effects were completely blocked by SR49059 or partially inhibited by KN93. This study demonstrated that AVP could induce the secretion of local cardiac aldosterone, which may involve CaMK and CREB phosphorylation and CYP11B2 upregulation through V1 receptor activation.


Assuntos
Arginina Vasopressina , Infarto do Miocárdio , Ratos , Animais , Arginina Vasopressina/farmacologia , Arginina Vasopressina/metabolismo , Colágeno Tipo I , Células Endoteliais/metabolismo , Coração , Aldosterona/metabolismo , Fibrose
20.
PLoS One ; 17(12): e0279552, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36584085

RESUMO

PURPOSE: Adrenal vein sampling (AVS) is the reference standard for evaluation of lateralized hormone production in primary aldosteronism. We aimed to investigate the impact of pre-interventional right renal vein (RRV) to right adrenal vein (RAV) distance measurement on fluoroscopy time, contrast agent exposure and radiation dose during AVS. MATERIALS AND METHODS: Forty-five patients with primary aldosteronism undergoing AVS were enrolled in our retrospective study and divided into three groups. In the group "ruler" (n = 14), RRV-RAV-distances were determined pre-interventionally by cross-sectional imaging (CT/MRI) and AVS was performed by one interventional radiologist with limited experience in AVS. CT/MRI-derived and fluoroscopy-derived RRV-RAV-distances were correlated for aimed cannulation of the RAV. Patients in group "no ruler" (n = 24, three interventional radiologists with limited experience in AVS) and in group "expert", (n = 7, one expert interventional radiologist) underwent AVS without pre-interventional estimation of RRV-RAV-distances. Procedure parameters (fluoroscopy time, contrast agent volume, radiation dose) of group "ruler" were compared to both other groups by Kruskal-Wallis rank-sum test. RESULTS: Correlation of CT/MRI-derived and fluoroscopy-derived RRV-RAV-distances was good (r = 0.74;p = 0.003). The median RRV-RAV-distance was 4.5cm at CT/MRI (95%-CI:4.2-5.0cm) and 4.0cm at fluoroscopy (95%-CI:3.8-4.5cm). Fluoroscopy time (p<0.0001), contrast agent exposure (p = 0.0003) and radiation dose (air kerma and dose area product both p = 0.038) were significantly lower in group "ruler" compared to group "no ruler" (all p<0.05), and similar to group "expert" (all p>0.05). CONCLUSIONS: CT/MRI-derived pre-interventional renal-adrenal vein distance measurements correlate well with angiographic distance measurements. Pre-interventional estimation of the RRV-RAV-distance allows for aimed cannulation of the RAV with potential reduction of fluoroscopy time, contrast agent exposure and radiation-dose during AVS.


Assuntos
Meios de Contraste , Hiperaldosteronismo , Humanos , Estudos Retrospectivos , Glândulas Suprarrenais/diagnóstico por imagem , Doses de Radiação , Aldosterona
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