Accumulation of uraemic toxins is reflected only partially by estimated GFR in paediatric patients with chronic kidney disease.

BACKGROUND: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.