Serum indoxyl sulfate concentrations associate with progression of chronic kidney disease in children

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dc.contributor.authorHolle, Johannes
dc.contributor.authorKirchner, Marietta
dc.contributor.authorOkun, Juergen
dc.contributor.authorBayazit, Aysun K.
dc.contributor.authorObrycki, Lukasz
dc.contributor.authorCanpolat, Nur
dc.contributor.authorDrozdz, Dorota
dc.date.accessioned2020-12-01T11:57:49Z
dc.date.available2020-12-01T11:57:49Z
dc.date.issued2020
dc.departmentEge Üniversitesien_US
dc.description.abstractThe 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_US
dc.description.sponsorshipEuropean Renal Association - European Dialysis and Transplant Association; KfH Foundation for Preventive Medicine; German Federal Ministry of Education and ResearchFederal Ministry of Education & Research (BMBF) [01EO0802]en_US
dc.description.sponsorshipSupport for this study was received from the European Renal Association - European Dialysis and Transplant Association, the KfH Foundation for Preventive Medicine, and the German Federal Ministry of Education and Research (reference number: 01EO0802). the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en_US
dc.identifier.doi10.1371/journal.pone.0240446en_US
dc.identifier.issn1932-6203
dc.identifier.issue10en_US
dc.identifier.pmid33108385en_US
dc.identifier.scopus2-s2.0-85094839832en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org/10.1371/journal.pone.0240446
dc.identifier.urihttps://hdl.handle.net/11454/61820
dc.identifier.volume15en_US
dc.identifier.wosWOS:000588372400029en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherPublic Library Scienceen_US
dc.relation.ispartofPlos Oneen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.titleSerum indoxyl sulfate concentrations associate with progression of chronic kidney disease in childrenen_US
dc.typeArticleen_US

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