Urinary phthalate metabolites mixture, serum cytokines and renal function in children: A panel study

Epidemiological evidence regarded the relations of phthalates with children's renal function and its underlying mechanism were largely unknown. We conducted a panel study using 287 paired urine-blood samples by repeated measurements of 103 children (4-13 years) across 3 seasons to explore effects of urinary phthalate metabolites on estimated glomerular filtration rate (eGFR) and the potential role of multiple cytokines. We found that mono-ethyl phthalate (MEP), monobutyl phthalate (MBP), mono-benzyl phthalate (MBzP) and mono-n-octyl phthalate (MOP) were significantly associated with eGFR reduction. Compared with the lowest quartile, MBP, MBzP and MEP in the third and fourth quartiles exhibited a graded decrease in eGFR. Meanwhile, weighted quantile sum regression analyses showed an inverse association of metabolites mixture with eGFR, to which MEP, MBzP, MOP were the major contributors. MEP also remained robust in multiple-phthalate model. Age and weight status might modify such relationships with significant interactions. Furthermore, eGFR related phthalate metabolites were associated with increased multiple cytokines, and CCL27, CXCL1 might be potential mediators between MEP and eGFR with mild mediated proportions. Accordingly, urinary phthalate metabolites were related to eGFR reduction in dose-response manner and multiple cytokines elevation, of which CCL27 and CXCL1 might partly mediate phthalate-associated decreased renal function among children.