Journal article
Investigation of a targeted panel of gut microbiome-derived toxins in children with chronic kidney disease
Pediatric nephrology (Berlin, West), v 40(5), pp 1759-1770
01 May 2025
PMID: 39820505
Abstract
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.
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 m
. 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]).
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.
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.
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Details
- Title
- Investigation of a targeted panel of gut microbiome-derived toxins in children with chronic kidney disease
- Creators
- Mina Ebrahimi - Drexel UniversityStephen R Hooper - University of North Carolina at Chapel HillMark M Mitsnefes - Cincinnati Children's Hospital Medical CenterRamachandran S Vasan - The University of Texas at San AntonioPaul L Kimmel - National Institutes of HealthBradley A Warady - University of Missouri–Kansas CitySusan L Furth - Children's Hospital of PhiladelphiaErum A Hartung - Children's Hospital of PhiladelphiaMichelle R Denburg - Children's Hospital of PhiladelphiaArthur M Lee - Philadelphia Fire Department
- Publication Details
- Pediatric nephrology (Berlin, West), v 40(5), pp 1759-1770
- Publisher
- Springer Nature
- Grant note
- K38 HL169660 / NHLBI NIH HHS U01 DK106982 / NIDDK NIH HHS R38 HL143613 / NHLBI NIH HHS U01 DK066143 / NIDDK NIH HHS P50 DK114786 / NIDDK NIH HHS U24 DK137522 / NIDDK NIH HHS K26 DK138375 / NIDDK NIH HHS U24 DK066116 / NIDDK NIH HHS U01 DK066174 / NIDDK NIH HHS R21 AT009752 / NCCIH NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Medicine
- Web of Science ID
- WOS:001397104600001
- Scopus ID
- 2-s2.0-85217174357
- Other Identifier
- 991022197327904721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Pediatrics
- Urology & Nephrology