학술논문
Indoxyl sulfate associates with cardiovascular phenotype in children with chronic kidney disease.
Document Type
Academic Journal
Author
Holle J; Department of Pediatric Pulmonology, Immunology and Intensive Care Medicine, Charité - Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany. johannes-benjamin.holle@charite.de.; Querfeld U; Department of Pediatric Nephrology, Charité - Universitätsmedizin Berlin, Berlin, Germany.; Kirchner M; Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany.; Anninos A; Department of General Pediatrics, Division of Inherited Metabolic Diseases, University Children's Hospital Heidelberg, Heidelberg, Germany.; Okun J; Department of General Pediatrics, Division of Inherited Metabolic Diseases, University Children's Hospital Heidelberg, Heidelberg, Germany.; Thurn-Valsassina D; Division of Pediatric Nephrology and Gastroenterology, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria.; Bayazit A; Department of Pediatric Nephrology, School of Medicine, Cukurova University, Adana, Turkey.; Niemirska A; Department of Nephrology and Hypertension, The Children's Memorial Health Institute, Warsaw, Poland.; Canpolat N; Division of Pediatric Nephrology, Istanbul University Cerrahpasa Faculty of Medicine, Istanbul, Turkey.; Bulut IK; Department of Pediatric Nephrology, Ege University Faculty of Medicine, Izmir, Turkey.; Duzova A; Division of Pediatric Nephrology, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey.; Anarat A; Department of Pediatric Nephrology, School of Medicine, Cukurova University, Adana, Turkey.; Shroff R; Division of Pediatric Nephrology, Great Ormond Street Hospital, London, UK.; Bilginer Y; Division of Rheumatology, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey.; Caliskan S; Division of Pediatric Nephrology, Istanbul University Cerrahpasa Faculty of Medicine, Istanbul, Turkey.; Candan C; Department of Pediatric Nephrology, Istanbul Medeniyet University, Istanbul, Turkey.; Harambat J; Pediatric Nephrology Unit, Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche, Bordeaux University Hospital, Bordeaux, France.; Özcakar ZB; Division of Pediatric Nephrology, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey.; Soylemezoglu O; Department of Pediatric Nephrology, Gazi University School of Medicine, Ankara, Turkey.; Tschumi S; Inselspital, University of Bern, Berne, Switzerland.; Habbig S; Division of Pediatric Nephrology, University Children's and Adolescent's Hospital, Cologne, Germany.; Yilmaz E; Department of Pediatric Nephrology, Sanliurfa Children's Hospital, Sanliurfa, Turkey.; Balat A; Department of Pediatric Nephrology, Istanbul Aydın University, Istanbul, Turkey.; Zurowska A; Department of Pediatric Nephrology, Medical University of Gdansk, Gdansk, Poland.; Cakar N; Department of Pediatric Nephrology, Ankara University Faculty of Medicine, Ankara, Turkey.; Kranz B; Department of General Pediatrics, Pediatric Nephrology, University Children's Hospital Muenster, Muenster, Germany.; Ertan P; Division of Pediatric Nephrology, Department of Pediatrics, Medical Faculty of Celal Bayar University, Manisa, Turkey.; Melk A; Department of Pediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Hannover, Germany.; Azukaitis K; Clinic of Pediatrics, Institute of Clinical Medicine, Vilnius University, Vilnius, Lithuania.; Schaefer F; Division of Pediatric Nephrology, Center for Pediatrics and Adolescent Medicine, University Children's Hospital Heidelberg, Heidelberg, Germany.
Source
Publisher: Springer International Country of Publication: Germany NLM ID: 8708728 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-198X (Electronic) Linking ISSN: 0931041X NLM ISO Abbreviation: Pediatr Nephrol Subsets: MEDLINE
Subject
Language
English
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.
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 m
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.