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Investigation of a targeted panel of gut microbiome-derived toxins in children with chronic kidney disease.
Pediatr Nephrol
January 2025
for the CKiD Study Investigators and the NIDDK CKD Biomarkers Consortium, 3500 Civic Center Boulevard, Philadelphia, PA, 19041, USA.
Background: The gut-kidney axis is implicated in chronic kidney disease (CKD) morbidity. We describe how a panel of gut microbiome-derived toxins relates to kidney function and neurocognitive outcomes in children with CKD, consisting of indoleacetate, 3-indoxylsulfate, p-cresol glucuronide, p-cresol sulfate, and phenylacetylglutamine.
Methods: The Chronic Kidney Disease in Children (CKiD) cohort is a North American multicenter prospective cohort that enrolled children aged 6 months to 16 years with estimated glomerular filtration rate (eGFR) 30-89 ml/min/1.
Metabolomics Signatures of serotonin reuptake inhibitor (Escitalopram), serotonin norepinephrine reuptake inhibitor (Duloxetine) and Cognitive Behavior Therapy on Key Neurotransmitter Pathways in Major Depressive Disorder.
medRxiv
April 2024
Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, United States.
Metabolomics provides powerful tools that can inform about heterogeneity in disease and response to treatments. In this study, we employed an electrochemistry-based targeted metabolomics platform to assess the metabolic effects of three randomly-assigned treatments: escitalopram, duloxetine, and Cognitive Behavior Therapy (CBT) in 163 treatment-naïve outpatients with major depressive disorder. Serum samples from baseline and 12 weeks post-treatment were analyzed using targeted liquid chromatography-electrochemistry for metabolites related to tryptophan, tyrosine metabolism and related pathways.
View Article and Find Full Text PDFImpact of Chronic Kidney Disease on Brain Structure and Function.
Front Neurol
February 2022
Division of Nephrology, Dialysis, and Transplantation, University of Iowa Stead Family Children's Hospital, Iowa City, IA, United States.
Chronic kidney disease (CKD) affects more than 37 million American adults. Adult-onset CKD is typically attributed to acquired comorbidities such as aging, type II diabetes, and cardiovascular disease. Conversely, congenital abnormalities of the kidney and urinary tract are the most common cause of CKD in children.
View Article and Find Full Text PDFIndoxyl sulfate, a gut microbiome-derived uremic toxin, is associated with psychic anxiety and its functional magnetic resonance imaging-based neurologic signature.
Sci Rep
October 2021
Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA.
It is unknown whether indoles, metabolites of tryptophan that are derived entirely from bacterial metabolism in the gut, are associated with symptoms of depression and anxiety. Serum samples (baseline, 12 weeks) were drawn from participants (n = 196) randomized to treatment with cognitive behavioral therapy (CBT), escitalopram, or duloxetine for major depressive disorder. Baseline indoxyl sulfate abundance was positively correlated with severity of psychic anxiety and total anxiety and with resting state functional connectivity to a network that processes aversive stimuli (which includes the subcallosal cingulate cortex (SCC-FC), bilateral anterior insula, right anterior midcingulate cortex, and the right premotor areas).
View Article and Find Full Text PDFGut-derived uremic toxin handling in vivo requires OAT-mediated tubular secretion in chronic kidney disease.
JCI Insight
April 2020
Department of Pediatrics, University of California, San Diego, La Jolla, California, USA.
The role of the renal organic anion transporters OAT1 (also known as SLC22A6, originally identified as NKT) and OAT3 (also known as SLC22A8) in chronic kidney disease (CKD) remains poorly understood. This is particularly so from the viewpoint of residual proximal tubular secretion, a key adaptive mechanism to deal with protein-bound uremic toxins in CKD. Using the subtotal nephrectomy (STN) model, plasma metabolites accumulating in STN rats treated with and without the OAT inhibitor, probenecid, were identified.
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