A longitudinal panel study exploring associations of urinary phthalate metabolites mixture with renal function in Chinese children

• MBP was dose-responsive associated with eGFR CysC reduction, which was the strongest at lag 0. • MBP was the major contributor in mPAEs mixture to early kidney damage. • Thyroid hormones modified the association of MBP and beta-2-microglobulin. • The effect of MBP on early kidney damage was more prominent in boys and primary school children. Evidence from longitudinal studies examining the associations between urinary phthalate metabolites (mPAEs) and early kidney damage in children has been limited, and the underlying mechanisms still remain unclear. We carried out a longitudinal panel study involving up to 3 repeated visits, and each visit across 4 consecutive days, with 142 children aged 4-12 years from Guangzhou. mPAEs were determined in morning urine of each day and early kidney damage indicators were detected on the 4 th day. We employed linear mixed-effect models (LMEs), and Bayesian kernel machine regression (BKMR) models to evaluate associations of mPAEs as individual and mixture with early kidney damage, and the interaction of thyroid hormones with mPAEs in such associations. We found that each 1-fold increment of mono-n-butyl phthalate (MBP) at health examination day (Lag0) was significantly associated with 4.734% (95% confidence interval: 1.313%, 8.155%) reduction of Cystatin-C (CysC)-based estimated glomerular filtration rate (eGFR CysC ) (FDR< 0.05) and such relationships were in dose-response manner. Meanwhile, BKMR models showed the relations of mPAEs mixture with increased CysC and Beta-2-microglobulin (β2MG), and reduced eGFR CysC were dominated by MBP. Moreover, thyroid hormones were linked to early kidney damage, and free thyroxin (FT4) modified the associations of MBP and β2MG, which was more obvious in children with low level of FT4. Interactions of age group and gender with MBP were significant, the effect of MBP on early kidney damage was stronger in primary school children and boys. In summary, our findings indicated that urinary mPAEs as individual and mixture were associated with early kidney damage indicators, which contributed to MBP were modified by FT4.