ESPN 51th Annual Meeting

ESPN 2018

Indoxylsulfate associates with cardiovascular phenotype in children with chronic kidney disease
Johannes Holle 1 Marietta Kirchner 2 Daniela Thurn 3 Aysun Bayazit 4 Ana Nimierska 6 Nur Canpolat 5 Karolis Azukaitis 1 Ali Duzova 1 Ali Anarat 4 Rukshana Shroff 9 Anette Melk 3 Uwe Querfeld 1 Franz Schaefer 10

1- Clinic of Pediatric Nephrology, Charite Children’s Hospital, Berlin, Germany
2- Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany
3- Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Hannover, Germany
4- Division of Pediatric Nephrology, Cukurova University, School of Medicine, Adana, Turkey
5- Division of Pediatric Nephrology, Istanbul University Cerrahpasa Faculty of Medicine, Istanbul, Turkey
6- Department of Pediatric Nephrology, The Children’sMemorial Health Institute,Warsaw, Poland
7- Center for Pediatrics, Vilnius University , Vilnius, Lithuania
8- Division of Pediatric Nephrology, Dpt. of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey
9- Division of Pediatric Nephrology, Great Ormond Street Hospital, London, UK
10- Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, Heidelberg, Germany

Cardiovascular disease is the leading cause of death in children with chronic kidney disease (CKD). Gut-derived uremic toxins increase with deterioration of kidney function and are associated with cardiovascular morbidity and mortality in adult patients.

Material and methods:

Indoxylsulfate (IS) and p-cresylsulfate (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 and central pulse wave velocity in children aged 6 – 17 years with initial GFR of 10 – 60 ml/min per 1,73m2.


The mean serum levels of total IS and of pCS, measured in 617 patients, were 25.0 µmol/l ± 85.4 µmol/l and 20.8 ± 17.6 µmol/l, respectively. In a multivariable regression model, pCSind IS levels showed independent positive correlations with urea and negative correlations with eGFR (p<0.001) and uric acid. Further, we could observe a positive correlation of pCS with age, serum albumin and non-Mediterranean residency and a negative correlation with glomerular disease pathology. Calculated by multivariable regression analysis, IS, but not pCS, was significantly associated with a higher intima-media thickness at baseline (p=0.006) and progression of pulse wave velocity within 12 months (p=0.007), independent of other risk factors.


The gut-derived uremic toxins IS and pCS correlated inversely with eGFR in children. IS, but not pCS was significantly associated with surrogate markers of cardiovascular disease in this large pediatric CKD cohort.