Indoxyl sulfate associates with cardiovascular phenotype in children with chronic kidney disease
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Date
2019
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Abstract
Background: Cardiovascular disease is the leading cause of death in children with chronic kidney disease (CKD). Serum levels of gut-derived uremic toxins increase with deterioration of kidney function and are associated with cardiac comorbidities in adult CKD patients. Methods: Indoxyl sulfate (IS) and p-cresyl sulfate (pCS) were measured by high-performance liquid chromatography in serum of children participating in the Cardiovascular Comorbidity in Children with CKD (4C) Study. Results were correlated with measurements of the carotid intima-media thickness (cIMT), central pulse wave velocity (PWV), and left ventricular mass index (LVMI) in children aged 6–17 years with initial eGFR of 10–60 ml/min per 1.73 m2. Results: The median serum levels of total IS and of pCS, measured in 609 patients, were 5.3 μmol/l (8.7) and 17.0 μmol/l (21.6), respectively. In a multivariable regression model, IS and pCS showed significant positive associations with urea and negative associations with eGFR and uric acid. Furthermore, positive associations of pCS with age, serum albumin, and non-Mediterranean residency and a negative association with glomerular disease were observed. By multivariable regression analysis, only IS was significantly associated with a higher cIMT SDS at baseline and progression of PWV SDS within 12 months, independent of other risk factors. Conclusions: Serum levels of gut-derived uremic toxins IS and pCS correlated inversely with eGFR in children. Only IS was significantly associated with surrogate markers of cardiovascular disease in this large pediatric CKD cohort. © 2019, IPNA.
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Adolescent , Biomarkers , Cardiovascular Diseases , Child , Cresols , Disease Progression , Female , Glomerular Filtration Rate , Humans , Indican , Male , Phenotype , Renal Insufficiency, Chronic , Sulfuric Acid Esters , 4 cresyl sulfate , albumin , indican , sulfate , unclassified drug , urea , uric acid , 4-cresol sulfate , biological marker , cresol , indican , sulfate , adolescent , age distribution , albumin blood level , arterial wall thickness , Article , blood level , cardiovascular disease , child , chronic kidney failure , cohort analysis , comorbidity , controlled study , estimated glomerular filtration rate , European , female , glomerulopathy , heart left ventricle mass , high performance liquid chromatography , human , major clinical study , male , observational study , phenotype , priority journal , pulse wave , risk factor , urea blood level , uremia , uric acid blood level , blood , cardiovascular disease , chronic kidney failure , complication , disease exacerbation , glomerulus filtration rate , phenotype