dc.contributor.author
Holle, Johannes
dc.contributor.author
Kirchner, Marietta
dc.contributor.author
Okun, Jürgen
dc.contributor.author
Bayazit, Aysun K.
dc.contributor.author
Obrycki, Lukasz
dc.contributor.author
Canpolat, Nur
dc.contributor.author
Bulut, Ipek Kaplan
dc.contributor.author
Azukaitis, Karolis
dc.contributor.author
Duzova, Ali
dc.contributor.author
Ranchin, Bruno
dc.contributor.author
Shroff, Rukshana
dc.contributor.author
Candan, Cengiz
dc.contributor.author
Oh, Jun
dc.contributor.author
Klaus, Günter
dc.contributor.author
Lugani, Francesca
dc.contributor.author
Gimpel, Charlotte
dc.contributor.author
Büscher, Rainer
dc.contributor.author
Yilmaz, Alev
dc.contributor.author
Baskin, Esra
dc.contributor.author
Erdogan, Hakan
dc.contributor.author
Zaloszyc, Ariane
dc.contributor.author
Özcelik, Gül
dc.contributor.author
Drozdz, Dorota
dc.contributor.author
Jankauskiene, Augustina
dc.contributor.author
Nobili, Francois
dc.contributor.author
Melk, Anette
dc.contributor.author
Querfeld, Uwe
dc.contributor.author
Schaefer, Franz
dc.contributor.author
4C Study Consortium
dc.date.accessioned
2021-04-15T11:03:44Z
dc.date.available
2021-04-15T11:03:44Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/30350
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-30091
dc.description.abstract
The uremic toxins indoxyl sulfate (IS) and p-cresyl sulfate (pCS) accumulate in patients with chronic kidney disease (CKD) as a consequence of altered gut microbiota metabolism and a decline in renal excretion. Despite of solid experimental evidence for nephrotoxic effects, the impact of uremic toxins on the progression of CKD has not been investigated in representative patient cohorts. In this analysis, IS and pCS serum concentrations were measured in 604 pediatric participants (mean eGFR of 27 ± 11 ml/min/1.73m2) at enrolment into the prospective Cardiovascular Comorbidity in Children with CKD study. Associations with progression of CKD were analyzed by Kaplan-Meier analyses and Cox proportional hazard models. During a median follow up time of 2.2 years (IQR 4.3-0.8 years), the composite renal survival endpoint, defined as 50% loss of eGFR, or eGFR <10ml/min/1.73m2 or start of renal replacement therapy, was reached by 360 patients (60%). Median survival time was shorter in patients with IS and pCS levels in the highest versus lowest quartile for both IS (1.5 years, 95%CI [1.1,2.0] versus 6.0 years, 95%CI [5.0,8.4]) and pCS (1.8 years, 95%CI [1.5,2.8] versus 4.4 years, 95%CI [3.4,6.0]). Multivariable Cox regression disclosed a significant association of IS, but not pCS, with renal survival, which was independent of other risk factors including baseline eGFR, proteinuria and blood pressure. In this exploratory analysis we provide the first data showing a significant association of IS, but not pCS serum concentrations with the progression of CKD in children, independent of other known risk factors. In the absence of comorbidities, which interfere with serum levels of uremic toxins, such as diabetes, obesity and metabolic syndrome, these results highlight the important role of uremic toxins and accentuate the unmet need of effective elimination strategies to lower the uremic toxin burden and abate progression of CKD.
en
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
Kaplan-Meier Estimate
en
dc.subject
Proportional Hazards Models
en
dc.subject
Renal Insufficiency, Chronic
en
dc.subject
Sulfuric Acid Esters
en
dc.subject
Survival Analysis
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
dc.title
Serum indoxyl sulfate concentrations associate with progression of chronic kidney disease in children
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.articlenumber
e0240446
dcterms.bibliographicCitation.doi
10.1371/journal.pone.0240446
dcterms.bibliographicCitation.journaltitle
PLOS ONE
dcterms.bibliographicCitation.number
10
dcterms.bibliographicCitation.originalpublishername
Public Library of Science (PLoS)
dcterms.bibliographicCitation.volume
15
refubium.affiliation
Charité - Universitätsmedizin Berlin
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.bibliographicCitation.pmid
33108385
dcterms.isPartOf.eissn
1932-6203