Assuntos
Biomarcadores , Inflamação , Rim , Imageamento por Ressonância Magnética , Insuficiência Renal Crônica , Humanos , Imageamento por Ressonância Magnética/métodos , Biomarcadores/sangue , Insuficiência Renal Crônica/diagnóstico por imagem , Insuficiência Renal Crônica/complicações , Inflamação/diagnóstico por imagem , Rim/diagnóstico por imagem , Rim/fisiopatologia , Rim/patologia , Feminino , Masculino , Pessoa de Meia-Idade , AdultoAssuntos
Acidose , Hiperpotassemia , Insuficiência Renal Crônica , Silicatos , Humanos , Hiperpotassemia/tratamento farmacológico , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Acidose/induzido quimicamente , Silicatos/uso terapêutico , Silicatos/efeitos adversos , MasculinoRESUMO
Importance: The adverse effects of climate change are now apparent, disproportionately affecting marginalized and vulnerable populations and resulting in urgent worldwide calls to action. Health professionals occupy a critical position in the response to climate change, including in climate mitigation and adaptation, and their professional expertise and roles as health messengers are currently underused in the society-wide response to this crisis. Observations: Clinical and public health professionals have important roles and responsibilities, some of which are shared, that they must fill for society to successfully mitigate the root causes of climate change and build a health system that can reduce morbidity and mortality impacts from climate-related hazards. When viewed through a preventive framework, the unique and synergizing roles and responsibilities provide a blueprint for investment in climate change-related prevention (primary, secondary, and tertiary), capacity building, education, and training of the health workforce. Substantial investment in increasing the competence and collaboration of health professionals is required, which must be undertaken in an urgent, coordinated, and deliberate manner. Conclusions and Relevance: Exceptional collaboration, knowledge sharing, and workforce capacity building are essential to tackle the complex ways in which climate change threatens health. This framework serves as a guide for health system leaders, education institutions, policy planners, and others seeking to create a more resilient and just health system.
Assuntos
Mão de Obra em Saúde , HumanosRESUMO
Introduction: Disruption of gut microbiota underpins some of the metabolic alterations observed in chronic kidney disease (CKD). Methods: In a nonrandomized, open-label, 3-phase pilot trial, with repeated measures within each phase, we examined the efficacy of oligofructose-enriched inulin (p-inulin) in changing the gut microbiome and their metabolic products in 15 patients with CKD. The stability of microbiome and metabolome was studied during the pretreatment phase (8 weeks), a p-inulin treatment phase (12 weeks), and a post treatment phase (8 weeks) of the study. Results: Study participants completed 373 of the 420 expected study visits (88.8%). Adherence to p-inulin was 83.4%. 16S rRNA sequencing was performed in 368 stool samples. A total of 1085 stool, urine, and plasma samples were subjected to untargeted metabolomic studies. p-inulin administration altered the composition of the gut microbiota significantly, with an increase in abundance of Bifidobacterium and Anaerostipes. Intersubject variations in microbiome and metabolome were larger than intrasubject variation, indicating the stability of the gut microbiome within each phase of the study. Overall metabolite compositions assessed by beta diversity in urine and stool metabolic profiles were significantly different across study phases. Several specific metabolites in stool, urine, and plasma were significant at false discovery rate (FDR) ≤ 0.1 over phase. Specifically, there was significant enrichment in microbial metabolites derived from saccharolysis. Conclusion: Results from our study highlight the stability of the gut microbiome and the expansive effect of p-inulin on microbiome and host cometabolism in patients with CKD. Findings from this study will enable rigorous design of microbiome-based intervention trials.
RESUMO
SIGNIFICANCE STATEMENT: In CKD, metabolic acidosis is commonly treated with alkali in the hope that it will improve bone health. In a post hoc analysis of the Bicarbonate Administration to Stabilize eGFR Pilot Trial, we investigated whether sodium bicarbonate affects serum levels of bone turnover markers and other hormones related to bone health in individuals with CKD who have normal to slightly reduced total CO2 (20-28 mEq/L). Sodium bicarbonate increased serum levels of α-klotho but had no significant effect on other bone health markers, including intact fibroblast growth factor-23 (iFGF-23), intact parathyroid hormone (iPTH), and bone-specific alkaline phosphatase (B-SAP). Further study is needed to determine the effect of bicarbonate administration on clinical aspects of bone health. BACKGROUND: Treatment with alkali has been hypothesized to improve bone health in CKD by mitigating adverse effects of acid on bone mineral. We investigated the effect of treatment with sodium bicarbonate on bone turnover markers and other factors related to bone metabolism in CKD. METHODS: This is a post hoc analysis of the Bicarbonate Administration to Stabilize eGFR Pilot Trial in which 194 individuals with CKD and serum total CO2 20-28 mEq/L were randomly assigned to placebo or one of two doses of sodium bicarbonate (0.5 or 0.8 mEq/kg lean body weight per day) for 28 weeks. The following serum measurements were performed at baseline, week 12, and week 28: B-SAP, c-telopeptide, procollagen type I intact N-terminal propeptide, iPTH, iFGF-23, soluble klotho, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and tartrate-resistant acid phosphatase 5b. The difference (sodium bicarbonate versus placebo) in mean change of each bone biomarker from baseline was determined using linear mixed models. RESULTS: One hundred sixty-eight participants submitted samples for post hoc investigations. Mean eGFR was 37±10 ml/min per 1.73 m2 and mean total CO2 was 24±3 mEq/L at baseline. Sodium bicarbonate induced a dose-dependent increase in soluble klotho levels compared with placebo. There was no significant effect of treatment with either dose of sodium bicarbonate on any of the other bone biomarkers, including iFGF-23, iPTH, and B-SAP. Effects on bone biomarkers were similar in those with baseline serum total CO2 <24 mEq/L compared with those with total CO2 ≥24 mEq/L. CONCLUSIONS: In this pilot trial of individuals with CKD and total CO2 20-28 mEq/L, sodium bicarbonate treatment increased serum klotho levels but did not affect other bone health markers over 28 weeks. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: ClinicalTrials.gov, NCT02521181.