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Pediatric Nephrology
Published in: Pediatric Nephrology 12/2019

01-12-2019 | Chronic Kidney Disease | Original Article

Indoxyl sulfate associates with cardiovascular phenotype in children with chronic kidney disease

Authors: Johannes Holle, Uwe Querfeld, Marietta Kirchner, Alexandros Anninos, Jürgen Okun, Daniela Thurn-Valsassina, Aysun Bayazit, Ana Niemirska, Nur Canpolat, Ipek Kaplan Bulut, Ali Duzova, Ali Anarat, Rukshana Shroff, Yelda Bilginer, Salim Caliskan, Cengiz Candan, Jerome Harambat, Zeynep Birsin Özcakar, Oguz Soylemezoglu, Sibylle Tschumi, Sandra Habbig, Ebru Yilmaz, Ayse Balat, Aleksandra Zurowska, Nilgun Cakar, Birgitta Kranz, Pelin Ertan, Anette Melk, Karolis Azukaitis, Franz Schaefer

Published in: Pediatric Nephrology | Issue 12/2019

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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.
Appendix
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Metadata
Title
Indoxyl sulfate associates with cardiovascular phenotype in children with chronic kidney disease
Authors
Johannes Holle
Uwe Querfeld
Marietta Kirchner
Alexandros Anninos
Jürgen Okun
Daniela Thurn-Valsassina
Aysun Bayazit
Ana Niemirska
Nur Canpolat
Ipek Kaplan Bulut
Ali Duzova
Ali Anarat
Rukshana Shroff
Yelda Bilginer
Salim Caliskan
Cengiz Candan
Jerome Harambat
Zeynep Birsin Özcakar
Oguz Soylemezoglu
Sibylle Tschumi
Sandra Habbig
Ebru Yilmaz
Ayse Balat
Aleksandra Zurowska
Nilgun Cakar
Birgitta Kranz
Pelin Ertan
Anette Melk
Karolis Azukaitis
Franz Schaefer
Publication date
01-12-2019
Publisher
Springer Berlin Heidelberg
Published in
Pediatric Nephrology / Issue 12/2019
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-019-04331-6

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