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BACKGROUND AND AIMS: In the FLOW trial, semaglutide reduced the risks of kidney and cardiovascular (CV) outcomes and death in participants with type 2 diabetes mellitus (T2D) and chronic kidney disease (CKD). These prespecified analyses assessed the effects of semaglutide on CV outcomes and death by CKD severity. METHODS: Participants were randomised to subcutaneous semaglutide 1â mg or placebo weekly. The main outcome was a composite of CV death, non-fatal myocardial infarction (MI) ornon-fatal stroke (CV death/MI/stroke) as well as death due to any cause by baseline CKD severity. CKD was categorised by eGFR < or ≥60â mL/min/1.73â m2, UACR < or ≥300â mg/g or KDIGO risk classification. RESULTS: 3533 participants were randomised with a median follow-up of 3.4 years. Low/moderate KDIGO risk was present in 242 (6.9%), while 878 (24.9%) had high and 2412 (68.3%) had very high KDIGO risk. Semaglutide reduced CV death/MI/stroke by 18% (HR 0.82 [95% CI 0.68-0.98]; P = .03), with consistency across eGFR categories, UACR levels and KDIGO risk classification (all P-interaction >.13). Death due to any cause was reduced by 20% (HR 0.80 [0.67-0.95]; P = .01), with consistency across eGFR categories and KDIGO risk class (P-interaction .21 and .23, respectively). The P-interaction treatment effect for death due to any cause by UACR was .01 (<300â mg/g HR 1.17 [0.83-1.65]; ≥300â mg/g HR 0.70 [0.57-0.85]). CONCLUSIONS: Semaglutide significantly reduced the risk of CV death/MI/stroke regardless of baseline CKD severity in participants with T2D.
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RATIONALE & OBJECTIVE: Keratin-based hair-straightening treatment is a popular hair-styling method. The majority of keratin-based hair-straightening products in Israel contain glycolic acid derivatives, which are considered safe when used topically. Systemic absorption of these products is possible, and anecdotal reports have described kidney toxicity associated with their use. We report a series of cases of severe acute kidney injury (AKI) following use of hair-straightening treatment in Israel during the past several years. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: We retrospectively identified 26 patients from 14 medical centers in Israel who experienced severe AKI and reported prior treatment with hair-straightening products in 2019-2022. FINDINGS: The 26 patients described had a median age of 28.5 (range, 14-58) years and experienced severe AKI following a hair-straightening procedure. The most common symptoms at presentation were nausea, vomiting, and abdominal pain. Scalp rash was noted in 10 (38%) patients. Two patients experienced a recurrent episode of AKI following a repeat hair-straightening treatment. Seven patients underwent kidney biopsies, which demonstrated intratubular calcium oxalate deposition in 6 and microcalcification in tubular cells in 1. In all biopsies, signs of acute tubular injury were present, and an interstitial infiltrate was noted in 4 cases. Three patients required temporary dialysis. LIMITATIONS: Retrospective uncontrolled study, small number of kidney biopsies. CONCLUSIONS: This series describes cases of AKI with prior exposure to hair-straightening treatments. Acute oxalate nephropathy was the dominant finding on kidney biopsies, which may be related to absorption of glycolic acid derivatives and their metabolism to oxalate. This case series suggests a potential underrecognized cause of AKI in the young healthy population. Further studies are needed to confirm this association and to assess the extent of this phenomenon as well as its pathogenesis.
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Injúria Renal Aguda , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Estudos Retrospectivos , Injúria Renal Aguda/etiologia , Glicolatos , Oxalato de Cálcio , Rim/patologiaRESUMO
BACKGROUND: Diabetes mellitus (DM) is an important predictor of neointimal hyperplasia (NIH) and adverse clinical outcomes after percutaneous coronary intervention (PCI). LABR-312, a novel intravenous formulation of liposomal alendronate, has been shown in animal models to decrease NIH at vascular injury sites and around stent struts. The aim of the Biorest Liposomal Alendronate Administration for Diabetic Patients Undergoing Drug-Eluting Stent Percutaneous Coronary Intervention trial was to assess the safety, effectiveness, and dose response of LABR-312 administered intravenously at the time of PCI withDES in reducing NIH as measured by optical coherence tomography postprocedure in patients with DM. METHODS: Patients with DM were randomized to a bolus infusion of LABR-312 vs placebo at the time of PCI. Dose escalation of LABR-312 in the study arm was given: 0.01 mg, 0.03 mg, and 0.08 mg. The primary endpoint was the in-stent %NIH volume at 9 months as measured by optical coherence tomography. RESULTS: From September 2016 to December 2017, 271 patients with DM undergoing PCI were enrolled; 136 patients were randomized to LABR-312 infusion and 135 patients were randomized to placebo. At 9-month follow-up, no difference was seen in the primary endpoint of %NIH between LABR-312 and placebo (13.3% ± 9.2 vs 14.6% ± 8.5, P = .35). No differences were present with the varying LABR-312 doses. Clinical outcomes at 9 months were similar between groups. CONCLUSIONS: Among patients with DM undergoing PCI with drug-eluting stents, a bolus of LABR-312 injected systematically at the time of intervention did not result in a lower rate in-stent %NIH volume at 9-month follow-up.
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Doença da Artéria Coronariana , Diabetes Mellitus , Stents Farmacológicos , Intervenção Coronária Percutânea , Alendronato , Angiografia Coronária/métodos , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/cirurgia , Humanos , Neointima/etiologia , Intervenção Coronária Percutânea/métodos , Tomografia de Coerência Óptica , Resultado do TratamentoRESUMO
Bartonella henselae endocarditis mimicking systemic vasculitis has been reported in patients with valvulopathy. Herein, we describe a patient with B. henselae endocarditis involving a prosthetic pulmonic valve with positive anti-dsDNA antibodies misdiagnosed with systemic lupus erythematosus (SLE) based on the revised classification SLE criteria.
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Anticorpos Antinucleares/sangue , Bartonella henselae/crescimento & desenvolvimento , Doença da Arranhadura de Gato/diagnóstico , Endocardite Bacteriana/diagnóstico , Infecções Relacionadas à Prótese/diagnóstico , Animais , Bartonella henselae/isolamento & purificação , Doença da Arranhadura de Gato/microbiologia , Gatos , Diagnóstico Diferencial , Endocardite Bacteriana/microbiologia , Reações Falso-Positivas , Humanos , Lúpus Eritematoso Sistêmico , Masculino , Infecções Relacionadas à Prótese/microbiologia , Estenose da Valva Pulmonar/congênito , Estenose da Valva Pulmonar/cirurgia , Lobos , Adulto JovemRESUMO
BACKGROUND: Chronic kidney disease (CKD) is associated with poorer outcomes following percutaneous coronary intervention (PCI) with drug-eluting stents. Drug-eluting balloons are used for in-stent restenosis and selected cases of de-novo coronary lesions. Little is known regarding the outcomes of individuals with CKD who undergo PCI with drug-eluting balloons. The goal of this study was to assess outcomes of PCI with drug-eluting balloons in individuals with CKD. METHODS: In a retrospective analysis, outcomes of PCI with drug-eluting balloons were compared between 101 patients with CKD and 261 without CKD. CKD was defined as estimated glomerular filtration rate < 60 ml/min/1.73m2. We compared demographics, procedure data and clinical outcomes in the first and second years following the procedure. RESULTS: Rates of major adverse cardiac events (MACE) and myocardial infarction were higher in patients with than without CKD: 23.8% vs. 13.8%, P < 0.005 and 15.9% vs. 3.8%, P < 0.001, respectively. Rates of target lesion revascularization were similar, 14.9 and 11.5%, respectively, P = 0.4. Shorter duration of dual anti-platelet therapy was observed among patients with than without CKD (10.0 + 3.4 vs. 10.9 + 3.7 months, P < 0.05). First-year hemorrhage episodes were similar in the two groups (0.08 ± 0.4 and 0.03 ± 0.2, respectively, P = 0.2). In a multivariate regression analysis, CKD was associated with increased risks of first year MACE (OR 2.1; 95% confidence interval 1.0-4.3, P < 0.001). CONCLUSIONS: PCI with drug-eluting balloons was associated with increased cardiovascular morbidity and mortality in patients with than without CKD. However, rates of target lesion revascularization were similar in the two groups. Shorter duration of dual anti-platelet therapy was observed in the CKD group.
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Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/cirurgia , Stents Farmacológicos/efeitos adversos , Intervenção Coronária Percutânea/efeitos adversos , Insuficiência Renal Crônica/complicações , Idoso , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/uso terapêutico , Complicações Pós-Operatórias , Análise de Regressão , Estudos Retrospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND: Chronic kidney disease (CKD) is associated with an increased risk of adverse cardiovascular outcomes, in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). However, most studies used bare-metal stents or first-generation drug-eluting stents, and less guideline-directed therapy to reduce cardiovascular risk was reported in CKD patients. This study investigates the impact of moderate-CKD on patients undergoing PCI in the current era. METHODS: Patient level data were pooled from 2 multicenter randomized trials (BIONICS and NIREUS trials) with a near "all-comers" design, comparing PCI with ridaforolimus-eluting stents vs. zotarolimus-eluting stents in patients with CAD. Patients were classified according to the presence or absence of moderate-CKD, defined as creatinine clearance (CrCl) <60 mL/min. We compared baseline characteristics, angiographic findings, and clinical outcomes 1-year post-PCI. RESULTS: 236/2,201 (10.7%) patients had CKD, mean CrCl of 50.3 + 7.8 mL/min. These patients were generally older and more often with hypertension than non-CKD patients, but the use of guideline-directed therapy was similar between the groups. CKD was associated with an increased risk of cardiovascular death (hazard ratio [HR] 6.08; 95% CI 2.11-17.51; p < 0.001), but with a reduced occurrence of repeated revascularization, including ischemia-driven revascularization (HR 0.47; 95% CI 0.24-0.92; p < 0.05). The rate of repeated angiography per severe cardiovascular adverse event was significantly lower in the CKD than the non-CKD group (23/38 [61%] vs. 253/334 [76%], p < 0.05). CONCLUSIONS: Moderate-CKD in patients with CAD was associated with higher rates of all-cause and cardiovascular mortality, yet with a lower risk of revascularization 1-year following PCI. Lack of guideline-directed medical therapy does not explain the adverse outcome of CKD patients.
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Doença da Artéria Coronariana/cirurgia , Intervenção Coronária Percutânea/estatística & dados numéricos , Insuficiência Renal Crônica/epidemiologia , Reoperação/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Angiografia/estatística & dados numéricos , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/mortalidade , Stents Farmacológicos , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Intervenção Coronária Percutânea/instrumentação , Período Pós-Operatório , Ensaios Clínicos Controlados Aleatórios como Assunto , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico , Fatores de Risco , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND: MicroRNAs are short non-coding RNAs that regulate gene expression. The aim of this study was to gain an understanding of the possible role of the miR-106b~ 25 microRNA cluster in regulating atherosclerosis in mice. METHODS: MiR-106b~ 25 knockout mice were outcrossed into Apolipoprotein E (ApoE) knockout background to generate double knockout mice. At 36 weeks of age, lesion size was evaluated in the aortic sinus by oil-red-O staining. RESULTS: Lesion size was 2-fold smaller in double KO mice in comparison to ApoE KO mice. In addition, collagen staining showed a trend towards a stable plaque phenotype in the double KO mice. Lipid profiling of plasma samples of double KO and ApoE KO mice using FPLC revealed over 2-fold decrease in Very low density lipoprotein (VLDL) cholesterol content and a 50% decrease in low density lipoprotein (LDL) cholesterol content in double KO mice. By using target prediction software, we have identified several possible targets for the miR-106b~ 25 cluster including the VLDL and LDL receptors. We found that upon feeding miR-106b~ 25 KO mice with high fat diet, the expression of LDL and VLDL receptors was higher than in the wild-type mice, suggesting the miR-106b~ 25 cluster regulates atherosclerosis by influencing clearance of VLDL and LDL from the plasma. CONCLUSIONS: We identified the miR-106b~ 25 cluster as a novel regulator of atherosclerosis in ApoE KO mice, presumably by regulating plasma cholesterol levels.
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Apolipoproteínas E/genética , Aterosclerose/genética , MicroRNAs/genética , Placa Aterosclerótica/genética , Receptores de LDL/genética , Animais , Aorta/efeitos dos fármacos , Aorta/metabolismo , Aorta/patologia , Apolipoproteínas E/deficiência , Aterosclerose/metabolismo , Aterosclerose/patologia , Sequência de Bases , HDL-Colesterol/sangue , LDL-Colesterol/sangue , VLDL-Colesterol/sangue , Dieta Hiperlipídica/métodos , Gorduras na Dieta/administração & dosagem , Expressão Gênica , Masculino , Camundongos , Camundongos Knockout , MicroRNAs/metabolismo , Família Multigênica , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patologia , Receptores de LDL/metabolismo , Deleção de SequênciaRESUMO
BACKGROUND: Dialysate purity contributes to the inflammatory response that afflicts hemodialysis patients. OBJECTIVES: To compare the clinical and laboratory effects of using ultrapure water produced by a water treatment system including two reverse osmosis (RO) units in series, with a system that also includes an ultrapure filter (UPF). METHODS: We performed a retrospective study in 193 hemodialysis patients during two periods: period A (no UPF, 6 months) and period B (same patients, with addition of UPF, 18 months), and a historical cohort of patients treated in the same dialysis unit 2 years earlier, which served as a control group. RESULTS: Mean C-reactive protein, serum albumin and systolic blood pressure worsened in period B compared to period A and in the controls. CONCLUSIONS: A double RO system to produce ultrapure water is not inferior to the use of ultrapure filters.
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Soluções para Diálise/química , Diálise Renal/instrumentação , Ultrafiltração/instrumentação , Purificação da Água/instrumentação , Idoso , Pressão Sanguínea/fisiologia , Proteína C-Reativa/análise , Feminino , Humanos , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Osmose , Diálise Renal/métodos , Estudos Retrospectivos , Albumina Sérica/análise , Purificação da Água/métodosRESUMO
PURPOSE: To report results of renal denervation (RDN) with the first catheter-based, non-balloon occlusion ultrasonic system in patients with resistant hypertension. MATERIALS AND METHODS: In a multicenter, single-arm trial, 39 patients with resistant hypertension (defined as uncontrolled hypertension while taking ≥ 3 antihypertensive medications) were treated. The cohort consisted of 4 groups: severe resistant hypertension (office systolic blood pressure [OSBP] ≥ 160 mm Hg) treated with a unidirectional catheter (group 1; n = 14); severe resistant hypertension treated with a multidirectional catheter (group 2; n = 18); moderate resistant hypertension (OSBP 140-159 mm Hg) treated with a multidirectional catheter (group 3; n = 5); and recurrent severe resistant hypertension, after an initial response to RF RDN (group 4; n = 2). Blood pressure monitoring was performed for 6 months. RESULTS: Severe adverse events were not noted immediately after the procedure or during follow-up. Treatment time was longer with unidirectional than with multidirectional catheters (36.7 min ± 9.6 vs 11.9 min ± 5.8; P < .001). Mean reductions in office blood pressure (systolic/diastolic) at 1, 3, and 6 months were -26.1/-9.6 mm Hg, -28.0/-9.9 mm Hg, and -30.6/-14.1 mm Hg (P < .01 for all). Per-group analysis showed significant OSBP reduction for groups 1 and 2. Patients with isolated systolic hypertension had a significantly smaller reduction in OSBP after 6 months compared with patients with combined systolic/diastolic hypertension (-16.2 mm Hg ± 18.5 vs -9.9 mm Hg ± 33.4; P < .005). CONCLUSIONS: Use of the RDN system was feasible and safe in this phase I study. Significant blood pressure reductions were observed over 6 months, although less in patients with isolated systolic hypertension.
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Denervação Autônoma/métodos , Pressão Sanguínea , Ablação por Cateter , Hipertensão/cirurgia , Rim/irrigação sanguínea , Artéria Renal/inervação , Procedimentos Cirúrgicos Ultrassônicos , Idoso , Anti-Hipertensivos/uso terapêutico , Austrália , Denervação Autônoma/efeitos adversos , Denervação Autônoma/instrumentação , Pressão Sanguínea/efeitos dos fármacos , Ablação por Cateter/efeitos adversos , Ablação por Cateter/instrumentação , Catéteres , Resistência a Medicamentos , Quimioterapia Combinada , Europa (Continente) , Estudos de Viabilidade , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Israel , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Procedimentos Cirúrgicos Ultrassônicos/efeitos adversos , Procedimentos Cirúrgicos Ultrassônicos/instrumentação , Ultrassonografia de IntervençãoRESUMO
PURPOSE: To assess the safety and performance of a nonfocused and nonballooned ultrasonic (US) catheter-based renal sympathetic denervation (RDN) system in normotensive swine. MATERIALS AND METHODS: RDN with the therapeutic intravascular US catheter was evaluated in 3 experiments: (i) therapeutic intravascular US RDN vs a control group of untreated animals with follow-up of 30, 45, and 90 days (n = 6; n = 12 renal arteries for each group); (ii) therapeutic intravascular US RDN vs radiofrequency (RF) RDN in the contralateral artery in the same animal (n = 2; n = 4 renal arteries); and (iii) therapeutic intravascular US RDN in a recently stent-implanted renal artery (n = 2; n = 4 renal arteries). RESULTS: In the first experiment, therapeutic intravascular US RDN was safe, without angiographic evidence of dissection or renal artery stenosis. Neuronal tissue vacuolization, nuclei pyknosis, and perineuronal inflammation were evident after RDN, without renal artery wall damage. Norepinephrine levels were significantly lower after therapeutic intravascular US RDN after 30, 45, and 90 days compared with the control group (200.17 pg/mg ± 63.35, 184.75 pg/mg ± 44.51, and 203.43 pg/mg ± 58.54, respectively, vs 342.42 pg/mg ± 79.97). In the second experiment, deeper neuronal ablation penetrance was found with therapeutic intravascular US RDN vs RF RDN (maximal penetrance from endothelium of 7.0 mm vs 3.5 mm, respectively). There was less damage to the artery wall after therapeutic intravascular US RDN than with RF RDN, after which edema and injured endothelium were seen. In the third experiment, denervation inside the stent-implanted segments was feasible without damage to the renal artery wall or stent. CONCLUSIONS: The therapeutic intravascular US system performed safely and reduced norepinephrine levels. Deeper penetrance and better preservation of vessel wall were observed with therapeutic intravascular US RDN vs RF RDN. Neuronal ablations were observed in stent-implanted renal arteries.
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Ablação por Ultrassom Focalizado de Alta Intensidade , Rim/irrigação sanguínea , Rim/inervação , Artéria Renal/inervação , Simpatectomia/métodos , Animais , Modelos Animais , Norepinefrina/metabolismo , Stents , SuínosRESUMO
BACKGROUND: Neurofibromatosis type 1 (NF1) is a common neurocutaneous disease characterized by café-au-lait spots, axillary and inguinal freckling, neurofibromas, and optic gliomas. Increased rates of hypertension (HTN) were reported among NF1 patients, however, the prevalence of HTN and pre-HTN in pediatric NF1 patients has not been clarified. METHODS: Blood pressure (BP) measurements, weight, and renal ultrasound were assessed in 224 NF1 pediatric patients followed in a specialized NF1 clinic. RESULTS: The cohort's mean age was 9.1 ± 4.1 years. Overweight and obesity were found in 12.9 and 10.3 % of them, respectively. BP was measured averagely 2.9 times per patient on different occasions. Blood pressure was in the pre-HTN and HTN ranges in 14.9 and 16.9 % of measurements, respectively. BP >95th was detected in 20.5 % at the first measurement. Of 114 children with at least three BP measurements, 18.4 % had two values in the HTN range and 6.14 % had at least three. Overweight was not associated with HTN among children with NF1. Urinary tract ultrasonographic abnormalities were detected in 6.8 % (11/161) of cases. CONCLUSIONS: The prevalence of increased BP in pediatric NF1 is much higher than in the general pediatric population. BP has to be regularly assessed and managed in this high-risk population.
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Pressão Sanguínea , Hipertensão/epidemiologia , Neurofibromatose 1/epidemiologia , Adolescente , Fatores Etários , Índice de Massa Corporal , Criança , Pré-Escolar , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Israel/epidemiologia , Masculino , Neurofibromatose 1/diagnóstico , Prevalência , Estudos Retrospectivos , Fatores de RiscoRESUMO
Decreased generation of nitric oxide (NO) by endothelial NO synthase (eNOS) characterizes endothelial dysfunction (ECD). Delivery of arginine to eNOS by cationic amino acid transporter-1 (CAT-1) was shown to modulate eNOS activity. We found in female rats, but not in males, that CAT-1 activity is preserved with age and in chronic renal failure, two experimental models of ECD. In contrast, during pregnancy CAT-1 is inhibited. We hypothesize that female sex hormones regulate arginine transport. Arginine uptake in human umbilical vein endothelial cells (HUVEC) was determined following incubation with either 17ß-estradiol (E2) or progesterone. Exposure to E2 (50 and 100 nM) for 30 min resulted in a significant increase in arginine transport and reduction in phosphorylated CAT-1 (the inactive form) protein content. This was coupled with a decrease in phosphorylated MAPK/extracellular signal-regulated kinase (ERK) 1/2. Progesterone (1 and 100 pM for 30 min) attenuated arginine uptake and increased phosphorylated CAT-1, phosphorylated protein kinase Cα (PKCα), and phosphorylated ERK1/2 protein content. GO-6976 (PKCα inhibitor) prevented the progesterone-induced decrease in arginine transport. Coincubation with both progesterone and estrogen for 30 min resulted in attenuated arginine transport. While estradiol increases arginine transport and CAT-1 activity through modulation of constitutive signaling transduction pathways involving ERK, progesterone inhibits arginine transport and CAT-1 via both PKCα and ERK1/2 phosphorylation, an effect that predominates over estradiol.
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Arginina/metabolismo , Transportador 1 de Aminoácidos Catiônicos/agonistas , Transportador 1 de Aminoácidos Catiônicos/antagonistas & inibidores , Estradiol/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Progesterona/farmacologia , Transporte Biológico , Transportador 1 de Aminoácidos Catiônicos/metabolismo , Células Cultivadas , Relação Dose-Resposta a Droga , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Cinética , Proteína Quinase 1 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Fosforilação , Proteína Quinase C-alfa/antagonistas & inibidores , Proteína Quinase C-alfa/metabolismo , Inibidores de Proteínas Quinases/farmacologiaRESUMO
BACKGROUND: Phosphate binders are the cornerstone of hyperphosphatemia management in dialysis patients. Ferric citrate is an iron-based oral phosphate binder that effectively lowers serum phosphorus levels. STUDY DESIGN: 52-week, open-label, phase 3, randomized, controlled trial for safety-profile assessment. SETTING & PARTICIPANTS: Maintenance dialysis patients with serum phosphorus levels ≥6.0 mg/dL after washout of prior phosphate binders. INTERVENTION: 2:1 randomization to ferric citrate or active control (sevelamer carbonate and/or calcium acetate). OUTCOMES: Changes in mineral bone disease, protein-energy wasting/inflammation, and occurrence of adverse events after 1 year. MEASUREMENTS: Serum calcium, intact parathyroid hormone, phosphorus, aluminum, white blood cell count, percentage of lymphocytes, serum urea nitrogen, and bicarbonate. RESULTS: There were 292 participants randomly assigned to ferric citrate, and 149, to active control. Groups were well matched. For mean changes from baseline, phosphorus levels decreased similarly in the ferric citrate and active control groups (-2.04±1.99 [SD] vs -2.18±2.25 mg/dL, respectively; P=0.9); serum calcium levels increased similarly in the ferric citrate and active control groups (0.22±0.90 vs 0.31±0.95 mg/dL; P=0.2). Hypercalcemia occurred in 4 participants receiving calcium acetate. Parathyroid hormone levels decreased similarly in the ferric citrate and active control groups (-167.1±399.8 vs -152.7±392.1 pg/mL; P=0.8). Serum albumin, bicarbonate, serum urea nitrogen, white blood cell count and percentage of lymphocytes, and aluminum values were similar between ferric citrate and active control. Total and low-density lipoprotein cholesterol levels were lower in participants receiving sevelamer than those receiving ferric citrate and calcium acetate. Fewer participants randomly assigned to ferric citrate had serious adverse events compared with active control. LIMITATIONS: Open-label study, few peritoneal dialysis patients. CONCLUSIONS: Ferric citrate was associated with similar phosphorus control compared to active control, with similar effects on markers of bone and mineral metabolism in dialysis patients. There was no evidence of protein-energy wasting/inflammation or aluminum toxicity, and fewer participants randomly assigned to ferric citrate had serious adverse events. Ferric citrate is an effective phosphate binder with a safety profile comparable to sevelamer and calcium acetate.
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Quelantes/uso terapêutico , Compostos Férricos/uso terapêutico , Falência Renal Crônica/metabolismo , Falência Renal Crônica/terapia , Fosfatos/metabolismo , Diálise Renal , Acetatos/uso terapêutico , Idoso , Cálcio/sangue , Compostos de Cálcio/uso terapêutico , Feminino , Humanos , Hiperfosfatemia/tratamento farmacológico , Mediadores da Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Poliaminas/uso terapêutico , SevelamerRESUMO
Endothelial cell dysfunction (ECD) is a common feature of chronic renal failure (CRF). Defective nitric oxide (NO) generation due to decreased endothelial nitric oxide synthase (eNOS) activity is a crucial parameter characterizing ECD. Decreased activity of cationic amino acid transporter-1 (CAT-1), the selective arginine transporter of eNOS, has been shown to inhibit eNOS in uremia. Recently, we failed to demonstrate a decrease in glomerular arginine transport in uremic female rats (Schwartz IF, Grupper A, Soetendorp H, Hillel O, Laron I, Chernichovski T, Ingbir M, Shtabski A, Weinstein T, Chernin G, Shashar M, Hershkoviz R, Schwartz D. Am J Physiol Renal Physiol 303: F396-F404, 2012). The current experiments were designed to determine whether sexual dimorphism which characterizes glomerular arginine transport system in uremia involves the systemic vasculature as well and to assess the effect of L-arginine in such conditions. Contractile and vasodilatory responses, ultrastructural changes, and measures of the L-arginine-NO system were performed in thoracic aortas of female rats subjected to 5/6 nephrectomy. The contractile response to KCl was significantly reduced, and acetylcholine-induced vasodilation was significantly impaired in aortas from CRF dames compared with healthy rats. Both of these findings were prevented by the administration of arginine in the drinking water. The decrease in both cGMP generation, a measure of eNOS activity, and aortic eNOS and phosphorylated eNOS abundance observed in CRF rats was completely abolished by l-arginine, while arginine transport and CAT-1 protein were unchanged in all experimental groups. Arginine decreased both serum levels of advanced glycation end products and the asymmetrical dimethylarginine/arginine ratio and restored the endothelial ultrastructure in CRF rats. In conclusion. arginine administration has a profound beneficial effect on ECD, independently of cellular arginine uptake, in CRF female rats.
Assuntos
Aorta/efeitos dos fármacos , Arginina/farmacologia , Endotélio Vascular/efeitos dos fármacos , Falência Renal Crônica/fisiopatologia , Animais , Aorta/metabolismo , Aorta/fisiopatologia , Arginina/metabolismo , GMP Cíclico/metabolismo , Relação Dose-Resposta a Droga , Células Endoteliais/metabolismo , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Feminino , Rim/metabolismo , Rim/fisiopatologia , Falência Renal Crônica/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , RatosRESUMO
BACKGROUND: Little is known about iron deficiency (ID) and anemia in Chronic Obstructive Pulmonary Disease (COPD). The purposes of this study were: (i) To study the prevalence and treatment of anemia and ID in patients hospitalized with an exacerbation of COPD. (ii) to study the hematological responses and degree of dyspnea before and after correction of anemia with subcutaneous Erythropoiesis Stimulating Agents (ESAs) and intravenous (IV) iron therapy, in ambulatory anemic patients with both COPD and chronic kidney disease. METHODS: (i) We examined the hospital records of all patients with an acute exacerbation of COPD (AECOPD) to assess the investigation, prevalence, and treatment of anemia and ID. (ii) We treated 12 anemic COPD outpatients with the combination of ESAs and IV-iron, given once weekly for 5 weeks. One week later we measured the hematological response and the severity of dyspnea by Visual Analogue Scale (VAS). RESULTS: (i) Anemia and iron deficiency in hospitalized COPD patients: Of 107 consecutive patients hospitalized with an AECOPD, 47 (43.9%) were found to be anemic on admission. Two (3.3%) of the 60 non-anemic patients and 18 (38.3%) of the 47 anemic patients had serum iron, percent transferrin saturation (%Tsat) and serum ferritin measured. All 18 (100%) anemic patients had ID, yet none had oral or IV iron subscribed before or during hospitalization, or at discharge. (ii) Intervention outpatient study: ID was found in 11 (91.7%) of the 12 anemic ambulatory patients. Hemoglobin (Hb), Hematocrit (Hct) and the VAS scale scores increased significantly with the ESAs and IV-iron treatment. There was a highly significant correlation between the ∆Hb and ∆VAS; rs = 0.71 p = 0.009 and between the ∆Hct and ∆VAS; rs = 0.8 p = 0.0014. CONCLUSIONS: ID is common in COPD patients but is rarely looked for or treated. Yet correction of the ID in COPD patients with ESAs and IV iron can improve the anemia, the ID, and may improve the dyspnea.
Assuntos
Anemia/tratamento farmacológico , Anemia/epidemiologia , Deficiências Nutricionais/tratamento farmacológico , Deficiências Nutricionais/epidemiologia , Hematínicos/uso terapêutico , Deficiências de Ferro , Ferro/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/complicações , Idoso , Anemia/etiologia , Deficiências Nutricionais/etiologia , Feminino , Humanos , Injeções Intravenosas , Masculino , Prevalência , Estudos RetrospectivosRESUMO
BACKGROUND: The spectrum of cardiovascular toxicity by cyclosporine (CsA) includes hypertension, accelerated atherosclerosis, and thrombotic microangiopathy, all of which are the result of endothelial cell dysfunction. Endothelial cell dysfunction is characterized by decreased endothelial nitric oxide synthase (eNOS) activity. Cationic amino acid transporter-1 (CAT-1) is the specific arginine transporter for eNOS. CsA has been shown to attenuate nitric oxide (NO) generation. However, the mechanism remains elusive. We hypothesize that CsA inhibits eNOS activity through modulation of its selective arginine supplier CAT-1. METHODS: We studied the effect of CsA on arginine uptake, NO2/NO3 generation, and CAT-1, protein kinase Cα (PKCα), and phosphorylated PKCα protein expression in human umbilical vein endothelial cell cultures (HUVEC) in the absence and presence of L-arginine. RESULTS: CsA (0.5-2 µg/ml) significantly attenuated arginine transport in a dose- and time-dependent manner, a phenomenon which was prevented by co-incubation with L-arginine (1 mM). The aforementioned findings were accompanied by increased protein nitration, a measure for peroxynitrite accumulation. In contrast, no changes were observed in NO2/NO3 generation. CsA significantly decreased the abundance of CAT-1 protein, an effect that was attenuated by L-arginine. PKCα and phosphorylated PKCα (CAT-1 inhibitors) protein contents were not affected by CsA. CONCLUSION: CsA inhibits arginine transport and induces protein nitration in HUVEC through modulation of CAT-1.
Assuntos
Arginina/efeitos dos fármacos , Transportador 1 de Aminoácidos Catiônicos/efeitos dos fármacos , Ciclosporina/farmacologia , Células Endoteliais/efeitos dos fármacos , Imunossupressores/farmacologia , Óxido Nítrico Sintase Tipo III/antagonistas & inibidores , Arginina/metabolismo , Transporte Biológico/efeitos dos fármacos , Transportador 1 de Aminoácidos Catiônicos/metabolismo , Células Endoteliais/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Nitratos/metabolismo , Óxido Nítrico/biossíntese , Nitritos/metabolismo , Proteína Quinase C-alfa/efeitos dos fármacos , Proteína Quinase C-alfa/metabolismoRESUMO
BACKGROUND: C-reactive protein (CRP) is a recognized marker of systemic inflammation. Its association with carotid and femoral intima media thickness (surrogate measures of atherosclerosis) may explain excess cardiovascular disease risk in hemodialysis patients. OBJECTIVES: To estimate the association between CRP and both carotid and femoral IMT in hemodialysis (HD) patients; to predict CRP in these patients. METHODS: The present cross-sectional study is nested in the Sevelamer hydrochloride and ultrasound-measured femoral and carotid intima media thickness progression in end-stage renal disease (SUMMER) clinical trial. Carotid (common, internal, and bifurcation) and femoral arteries were visualized in B-mode ultrasonography. CRP was measured in serum. RESULTS: The study cohort included 144 HD patients (39.5% female, mean age 67.8 ± 11.5 years). All measures of both carotid and femoral IMT were significantly positively associated with CRP. Subjects with a history of smoking or coronary revascularization had significantly higher CRP levels, while subjects treated with sevelamer hydrochloride had significantly lower CRP. CRP was significantly positively associated with serum phosphorus, calcium, alkaline phosphatase, and PTH, and significantly inversely associated with HDL and albumin. CONCLUSIONS: CRP is significantly positively associated with both femoral and carotid IMT. Treatment with sevelamer hydrochloride is associated with lower CRP in HD patients.
Assuntos
Proteína C-Reativa/análise , Espessura Intima-Media Carotídea , Artéria Femoral/patologia , Inflamação/diagnóstico , Diálise Renal , Túnica Íntima/patologia , Túnica Média/patologia , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Poliaminas/uso terapêutico , SevelamerRESUMO
BACKGROUND: The Chimney graft (CG) procedure is one of the novel modification techniques of the endovascular aneurysm repair (EVAR) surgery to treat suprarenal and juxtarenal abdominal aortic aneurysms. Other indications for the use of CG placement include thoracic and thoracoabdominal aneurysms with supraortic branches orifice involvement and cases of common iliac artery aneurysms with or without internal iliac artery involvement. The technique is used in patients who due to aortic-neck morphology and lack of adequate fixation and/or sealing zones are not eligible for standard EVAR. In this procedure, a parallel stent-graft is placed adjacent to the main body of the aortic endograft to maintain blood supply to renovisceral or supraortic branches, once the body of the aortic stent-graft is deployed. Symptomatic occlusions of the CG with novel renovascular hypertension were not described until now. CASE PRESENTATION: A-64-year-old male patient, presented with new-onset malignant hypertension, 13 months after an EVAR operation with CG placement to the left renal artery. The patient was on preventive clopidrogel therapy, which was withheld temporarily for several days, one month before presentation. Imaging studies revealed a novel form of iatrogenic renovascular hypertension, caused by occlusion of the CG. Any attempt to recanalize the covered stent or revascularize the left kidney was rejected and conservative treatment was chosen. Seven months after presentation, blood pressure was within normal ranges with little need for antihypertensive therapy. CONCLUSIONS: Physicians should be aware that the novel emerging techniques of EVAR to overcome the limitations of the aortic-neck anatomy may still adversely influence the renal outcome with potential development of new-onset hypertension.
Assuntos
Aneurisma da Aorta Abdominal/diagnóstico por imagem , Procedimentos Endovasculares/efeitos adversos , Hipertensão Maligna/diagnóstico por imagem , Hipertensão Renovascular/diagnóstico por imagem , Complicações Pós-Operatórias/diagnóstico por imagem , Aneurisma da Aorta Abdominal/cirurgia , Humanos , Hipertensão Maligna/etiologia , Hipertensão Renovascular/etiologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Radiografia , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND AND AIMS: Diabetes-mellitus (DM) is associated with increased risk of neointimal hyperplasia (NIH) and restenosis after percutaneous coronary intervention (PCI). We examined a possible association of DM severity at the time of PCI with the development of NIH. METHODS: This post-hoc analysis from the BLADE-PCI randomized, multi-center trial included only patients with DM and baseline data of HbA1c within 14 days prior to the index PCI. All patients were treated with zotarolimus-eluting stents. The primary endpoint was percent of NIH volume at 9 months as evaluated by optical coherence tomography. This endpoint was compared between patients with uncontrolled DM (HbA1c ≥ 7.5%) and controlled DM (HbA1c <7.5%) at the index PCI. RESULTS: The mean percentages of NIH volume were 16.5% ± 9.9 and 12.75% ± 7.9 among patients with baseline HbA1c ≥ 7.5% (n = 74) and <7.5% (n = 102), respectively (p < 0.05). In multivariable analysis, HbA1c ≥ 7.5% was not associated with higher risk of NIH development [95% CI; 2.2 (-0.8, 5.3; p = 0.15)]. Higher HbA1c was not associated with increased risk of NIH at the minimum lumen area site [95% CI; 0.9 (-5.0, 6.7); p = 0.77) or percent stent strut coverage [95% CI; -0.3 (-1.3, 0.6); p = 0.45]. Secondary clinical endpoints including major adverse cardiac and cerebrovascular events, target lesion failure and death were similar between patients with worse and better DM control. CONCLUSIONS: Uncontrolled DM at the time of PCI performed with contemporary drug-eluting stents was not associated with an increased risk of NIH development.