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

• Verfasst von: Holle, Johannes [VerfasserIn]
• Verfasst von: Kirchner, Marietta [VerfasserIn]
• Verfasst von: Okun, Jürgen G. [VerfasserIn]
• Verfasst von: Schaefer, Franz [VerfasserIn]
• Titel: Serum indoxyl sulfate concentrations associate with progression of chronic kidney disease in children
• Verf.angabe: Johannes Holle, Marietta Kirchner, Jürgen Okun, Aysun K. Bayazit, Lukasz Obrycki, Nur Canpolat, Ipek Kaplan Bulut, Karolis Azukaitis, Ali Duzova, Bruno Ranchin, Rukshana Shroff, Cengiz Candan, Jun Oh, Günter Klaus, Francesca Lugani, Charlotte Gimpel, Rainer Büscher, Alev Yilmaz, Esra Baskin, Hakan Erdogan, Ariane Zaloszyc, Gül Özcelik, Dorota Drozdz, Augustina Jankauskiene, Francois Nobili, Anette Melk, Uwe Querfeld, Franz Schaefer, on behalf of the 4C Study Consortium
• E-Jahr: 2020
• Jahr: October 27, 2020
• Umfang: 17 S.
• Fussnoten: Gesehen am 15.04.2021
• Titel Quelle: Enthalten in: PLOS ONE
• Ort Quelle: San Francisco, California, US : PLOS, 2006
• Jahr Quelle: 2020
• Band/Heft Quelle: 15(2020), 10, Artikel-ID e0240446, Seite 1-17
• ISSN Quelle: 1932-6203
• DOI: doi:10.1371/journal.pone.0240446
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Blood pressure
• Sach-SW: Chronic kidney disease
• Sach-SW: Glomerular filtration rate
• Sach-SW: Kidneys
• Sach-SW: Proteinuria
• Sach-SW: Renal analysis
• Sach-SW: Sulfates
• Sach-SW: Toxins
• K10plus-PPN: 1755016751

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.