Serum indoxyl sulfate concentrations associate with progression of chronic kidney disease in children
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Serum indoxyl sulfate concentrations associate with progression of chronic kidney disease in children. / Holle, Johannes; Kirchner, Marietta; Okun, Jürgen; Bayazit, Aysun K; Obrycki, Lukasz; Canpolat, Nur; Bulut, Ipek Kaplan; Azukaitis, Karolis; Duzova, Ali; Ranchin, Bruno; Shroff, Rukshana; Candan, Cengiz; Oh, Jun; Klaus, Günter; Lugani, Francesca; Gimpel, Charlotte; Büscher, Rainer; Yilmaz, Alev; Baskin, Esra; Erdogan, Hakan; Zaloszyc, Ariane; Özcelik, Gül; Drozdz, Dorota; Jankauskiene, Augustina; Nobili, Francois; Melk, Anette; Querfeld, Uwe; Schaefer, Franz; 4C Study Consortium.
In: PLOS ONE, Vol. 15, No. 10, 2020, p. e0240446.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Serum indoxyl sulfate concentrations associate with progression of chronic kidney disease in children
AU - Holle, Johannes
AU - Kirchner, Marietta
AU - Okun, Jürgen
AU - Bayazit, Aysun K
AU - Obrycki, Lukasz
AU - Canpolat, Nur
AU - Bulut, Ipek Kaplan
AU - Azukaitis, Karolis
AU - Duzova, Ali
AU - Ranchin, Bruno
AU - Shroff, Rukshana
AU - Candan, Cengiz
AU - Oh, Jun
AU - Klaus, Günter
AU - Lugani, Francesca
AU - Gimpel, Charlotte
AU - Büscher, Rainer
AU - Yilmaz, Alev
AU - Baskin, Esra
AU - Erdogan, Hakan
AU - Zaloszyc, Ariane
AU - Özcelik, Gül
AU - Drozdz, Dorota
AU - Jankauskiene, Augustina
AU - Nobili, Francois
AU - Melk, Anette
AU - Querfeld, Uwe
AU - Schaefer, Franz
AU - 4C Study Consortium
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
U2 - 10.1371/journal.pone.0240446
DO - 10.1371/journal.pone.0240446
M3 - SCORING: Journal article
C2 - 33108385
VL - 15
SP - e0240446
JO - PLOS ONE
JF - PLOS ONE
SN - 1932-6203
IS - 10
ER -
