Mina Ebrahimi, Stephen R Hooper, Mark M Mitsnefes, Ramachandran S Vasan, Paul L Kimmel, Bradley A Warady, Susan L Furth, Erum A Hartung, Michelle R Denburg, Arthur M Lee
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引用次数: 0
Abstract
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/1.73 m2. Data from the 2-year study visit were used for this analysis. Toxin quantification (Metabolon Inc., Durham, NC) was performed with ultra-high performance liquid chromatography/tandem mass spectrometry. Executive function and echocardiograms were assessed. Regression analysis examined the association of toxin levels with eGFR, CKD etiology, and neurocognitive and cardiac assessments (adjusted for age, sex, and urine protein:creatinine [UPCR]).
Results: There were 150 CKiD participants included in this study. All toxins levels were significantly inversely correlated with eGFR (Spearman's rho - 0.45 to - 0.69). Children with non-glomerular CKD had significantly higher levels of 3-indoxylsulfate, phenylacetylglutamine, and p-cresol glucuronide. The toxin levels did not associate with neurocognitive outcomes. P-cresol glucuronide and phenylacetylglutamine negatively associated with left ventricular mass index z score, but did not associate with left ventricular hypertrophy.
Conclusions: Children with CKD have high levels of circulating gut microbiome-derived toxins. The levels of these toxins are strongly correlated with eGFR. There appear to be differences in toxin level based on glomerular versus non-glomerular etiology, even when accounting for the differences in eGFR between these two subgroups. In this sample, we did not detect any associations between these toxin levels and neurocognitive or cardiac outcomes.
期刊介绍：
International Pediatric Nephrology Association
Pediatric Nephrology publishes original clinical research related to acute and chronic diseases that affect renal function, blood pressure, and fluid and electrolyte disorders in children. Studies may involve medical, surgical, nutritional, physiologic, biochemical, genetic, pathologic or immunologic aspects of disease, imaging techniques or consequences of acute or chronic kidney disease. There are 12 issues per year that contain Editorial Commentaries, Reviews, Educational Reviews, Original Articles, Brief Reports, Rapid Communications, Clinical Quizzes, and Letters to the Editors.
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