Accumulation of uraemic toxins is reflected only partially by estimated GFR in paediatric patients with chronic kidney disease
Chronic kidney disease (CKD) in childhood is characterised by the accumulation of uraemic toxins resulting in a multisystem disorder that has a negative impact on quality of life. Childhood CKD is predominantly defined by a decrease in glomerular filtration rate, estimated (eGFR) by a single serum measurement of endogenous biomarkers, e.g. creatinine. The objective of this study was to evaluate how accurately eGFR predicts the concentration of uraemic toxins in a paediatric CKD cohort.
In 65 children (10.8 [5.1; 14.7] years) with CKD (eGFR 44 [20; 64] mL/min/1.73 m2), serum concentrations were determined of small solutes (uric acid [UA], urea, symmetric dimethylarginine [SDMA], asymmetric dimethylarginine [ADMA]), middle molecules (β2-microglobulin [β2M], complement factor D [CfD]) and protein-bound solutes (p-cresylglucuronide [pCG], hippuric acid, indole acetic acid, indoxyl sulphate [IxS], p-cresylsulfate [pCS] and 3-carboxy-4-methyl-5-propyl-furanpropionic acid [CMPF]). Spearman’s correlation coefficients (r) were calculated to correlate uraemic toxin concentrations with three different eGFR equations, based on either serum creatinine or β2M.
Updated Schwartz eGFR was correlated reasonably well with concentrations of creatinine (r = −0.98), urea (rs = −0.84), SDMA (r = −0.82) and middle molecules CfD and β2M (both rs = −0.90). In contrast, poor correlation coefficients were found for CMPF (rs = −0.32), UA (rs = −0.45), ADMA (rs = −0.47) and pCG (rs = −0.48). The other toxins, all protein-bound, had rs between −0.75 and −0.57. Comparable correlations were found between the three evaluated eGFR equations and uraemic toxin concentrations.
This study demonstrates that eGFR poorly predicts concentrations of protein-bound uraemic toxins, UA and ADMA in childhood CKD. Therefore, eGFR only partially reflects the complexity of the accumulation pattern of uraemic toxins in childhood CKD.
KeywordsChronic kidney disease Child Uremic toxins Glomerular filtration rate
This study was funded by the Agency for Innovation by Science and Technology (IWT), from the “Applied Biomedical Research with a Primary Societal Goal” (TBM) program in Flanders (Belgium): UToPaed project, grant number IWT-TBM 150195. The authors are indebted to our laboratory staff Sophie Lobbestael, Tom Mertens and Maria Van Landschoot, and to Sofie Vermeiren, Sofie Eerens, Kimi Lambregts, Imelda Hamels, Ariadne Van Hulle and Julia Versavau for their support.
Compliance with ethical standards
The study protocol was approved by the Ethics Committee and written informed consent was obtained from all individual participants included in the study.
Conflicts of interest
Evelien Snauwaert, Maria Van Dyck, Koen Van Hoeck, Nathalie Godefroid, Raymond Vanholder and Sanne Roels: no conflicts of interest.
Wim Van Biesen: lecture fees, travel and grant support from Fresenius Medical Care, Baxter Gambro, Leo Pharma and Astellas.
Ann Raes: lecture fees and travel support from Ferring Pharmaceuticals.
Griet Glorieux: lecture fees from Fresenius Medical Care and Baxter. Travel support from Baxter.
Johan Vande Walle: paid advisory boards of Alexion, Astellas and Ferring Pharmaceuticals for the last 2 years; lecture fees from Alexion, Astellas and Ferring Pharmaceuticals.
Sunny Eloot: lecture fees and travel support from Fresenius Medical Care.
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