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Concentrations of representative uraemic toxins in a healthy versus non-dialysis chronic kidney disease paediatric population

Evelien Snauwaert (UGent) , Wim Van Biesen (UGent) , Ann Raes (UGent) , Griet Glorieux (UGent) , VALERIE VAN BOGAERT (UGent) , Koen Van Hoeck, Marc Coppens (UGent) , Sanne Roels (UGent) , Johan Vande Walle (UGent) and Sunny Eloot (UGent)
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Abstract
Background. Chronic kidney disease (CKD) in childhood is poorly explained by routine markers (e.g. urea and creatinine) and is better depicted in adults by other uraemic toxins. This study describes concentrations of representative uraemic toxins in non-dialysis CKD versus healthy children. Methods. In 50 healthy children and 57 children with CKD Stages 1-5 [median estimated glomerular filtration rate 48 (25th-75th percentile 24-71) mL/min/1.73 m(2); none on dialysis], serum concentrations of small solutes [symmetric and asymmetric dimethyl-arginine (SDMA and ADMA, respectively)], middle molecules [beta 2-microglobuline (beta 2M), complement factor D (CfD)] and protein-bound solutes [p-cresylglucuronide (pCG), hippuric acid (HA), indoleacetic acid (IAA), indoxyl sulphate (IxS), p-cresyl sulphate (pCS) and 3-carboxy-4-methyl-5-propyl-furanpropionic acid (CMPF)] were measured. Concentrations in the CKD group were expressed as z-score relative to controls andmatched for age and gender. Results. SDMA, CfD, b2M, IxS, pCS, IAA, CMPF and HA concentrations were higher in the overall CKD group compared with controls, ranging from 1.7 standard deviations (SD) for IAA and HA to 11.1 SD for SDMA. SDMA, CfD, b2M, IxS and CMPF in CKD Stages 1-2 with concentrations 4.8, 2.8, 4.5, 1.9 and 1.6 SD higher, respectively. In contrast, pCS, pCG and IAA concentrations were only higher than controls from CKD Stages 3-4 onwards, but only in CKD Stage 5 for ADMA and HA (z-score 2.6 and 20.2, respectively). Conclusions. This is the first study to establish reference values for a wide range of uraemic toxins in non-dialysis CKD and healthy children. We observed an accumulation of multiple uraemic toxins, each with a particular retention profile according to the different CKD stages.
Keywords
child, chronic kidney disease, reference values, uraemic toxins, ASYMMETRIC DIMETHYLARGININE ADMA, GLOMERULAR-FILTRATION-RATE, TANDEM MASS-SPECTROMETRY, STAGE RENAL-DISEASE, COMPLEMENT FACTOR-D, P-CRESYL SULFATE, CYSTATIN-C, SYMMETRIC DIMETHYLARGININE, CARDIOVASCULAR RISK, VEGETABLE CONSUMPTION

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Chicago
Snauwaert, Evelien, Wim Van Biesen, Ann Raes, Griet Glorieux, VALERIE VAN BOGAERT, Koen Van Hoeck, Marc Coppens, Sanne Roels, Johan Vande Walle, and Sunny Eloot. 2018. “Concentrations of Representative Uraemic Toxins in a Healthy Versus Non-dialysis Chronic Kidney Disease Paediatric Population.” Nephrology Dialysis Transplantation 33 (6): 978–986.
APA
Snauwaert, Evelien, Van Biesen, W., Raes, A., Glorieux, G., VAN BOGAERT, V., Van Hoeck, K., Coppens, M., et al. (2018). Concentrations of representative uraemic toxins in a healthy versus non-dialysis chronic kidney disease paediatric population. NEPHROLOGY DIALYSIS TRANSPLANTATION, 33(6), 978–986.
Vancouver
1.
Snauwaert E, Van Biesen W, Raes A, Glorieux G, VAN BOGAERT V, Van Hoeck K, et al. Concentrations of representative uraemic toxins in a healthy versus non-dialysis chronic kidney disease paediatric population. NEPHROLOGY DIALYSIS TRANSPLANTATION. 2018;33(6):978–86.
MLA
Snauwaert, Evelien, Wim Van Biesen, Ann Raes, et al. “Concentrations of Representative Uraemic Toxins in a Healthy Versus Non-dialysis Chronic Kidney Disease Paediatric Population.” NEPHROLOGY DIALYSIS TRANSPLANTATION 33.6 (2018): 978–986. Print.
@article{8527933,
  abstract     = {Background. Chronic kidney disease (CKD) in childhood is poorly explained by routine markers (e.g. urea and creatinine) and is better depicted in adults by other uraemic toxins. This study describes concentrations of representative uraemic toxins in non-dialysis CKD versus healthy children. 
Methods. In 50 healthy children and 57 children with CKD Stages 1-5 [median estimated glomerular filtration rate 48 (25th-75th percentile 24-71) mL/min/1.73 m(2); none on dialysis], serum concentrations of small solutes [symmetric and asymmetric dimethyl-arginine (SDMA and ADMA, respectively)], middle molecules [beta 2-microglobuline (beta 2M), complement factor D (CfD)] and protein-bound solutes [p-cresylglucuronide (pCG), hippuric acid (HA), indoleacetic acid (IAA), indoxyl sulphate (IxS), p-cresyl sulphate (pCS) and 3-carboxy-4-methyl-5-propyl-furanpropionic acid (CMPF)] were measured. Concentrations in the CKD group were expressed as z-score relative to controls andmatched for age and gender. 
Results. SDMA, CfD, b2M, IxS, pCS, IAA, CMPF and HA concentrations were higher in the overall CKD group compared with controls, ranging from 1.7 standard deviations (SD) for IAA and HA to 11.1 SD for SDMA. SDMA, CfD, b2M, IxS and CMPF in CKD Stages 1-2 with concentrations 4.8, 2.8, 4.5, 1.9 and 1.6 SD higher, respectively. In contrast, pCS, pCG and IAA concentrations were only higher than controls from CKD Stages 3-4 onwards, but only in CKD Stage 5 for ADMA and HA (z-score 2.6 and 20.2, respectively). 
Conclusions. This is the first study to establish reference values for a wide range of uraemic toxins in non-dialysis CKD and healthy children. We observed an accumulation of multiple uraemic toxins, each with a particular retention profile according to the different CKD stages.},
  author       = {Snauwaert, Evelien and Van Biesen, Wim and Raes, Ann and Glorieux, Griet and VAN BOGAERT, VALERIE and Van Hoeck, Koen and Coppens, Marc and Roels, Sanne and Vande Walle, Johan and Eloot, Sunny},
  issn         = {0931-0509},
  journal      = {NEPHROLOGY DIALYSIS TRANSPLANTATION},
  keyword      = {child,chronic kidney disease,reference values,uraemic toxins,ASYMMETRIC DIMETHYLARGININE ADMA,GLOMERULAR-FILTRATION-RATE,TANDEM MASS-SPECTROMETRY,STAGE RENAL-DISEASE,COMPLEMENT FACTOR-D,P-CRESYL SULFATE,CYSTATIN-C,SYMMETRIC DIMETHYLARGININE,CARDIOVASCULAR RISK,VEGETABLE CONSUMPTION},
  language     = {eng},
  number       = {6},
  pages        = {978--986},
  title        = {Concentrations of representative uraemic toxins in a healthy versus non-dialysis chronic kidney disease paediatric population},
  url          = {http://dx.doi.org/10.1093/ndt/gfx224},
  volume       = {33},
  year         = {2018},
}

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