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

Abstract

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.