The independent and interactive effects of phthalates exposure and hypertension on the indicators of early renal injury in US adults: Evidence from NHANES 2001–2004

The association between phthalates and early renal injury is largely unknown in adults. We aim to explore the associations of phthalates and hypertension with early renal injury, and the interactive effects of phthalate and hypertension on the early renal injury. This study enrolled 3283 U.S. adults from NHANES 2001-2004. We detected nine phthalate metabolites in spot urine. We also measured the multiple indicators of early renal injury, including albumin-to-creatinine (Cr) ratio (ACR), β2-microglobulin (B2M), cystatin C (CYST), and calculated the estimated glomerular filtration rate (eGFR), including Cr-based eGFR, CYST-based eGFR, and Cr-CYST-based eGFR. Multiple linear regression and multivariable logistic regression were used to explore the associations among urinary phthalate metabolites, hypertension, and the indicators of early renal injury. The results showed that monobenzyl phthalate (MBzP), mono (3-carboxypropyl) phthalate (MCPP), and mono (2-ethylhexyl) phthalate (MEHP) were positively associated with ACR, B2M, CYST and negatively associated with three eGFR. Mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) was positively associated with ACR, with a β value of 0.099 (95% CI: 0.046, 0.152). Meanwhile, MEHP was associated with a higher risk of ACR abnormality, with an OR value of 1.258 (95% CI: 1.067, 1.482). MBzP, MCPP, and MEOHP increased the risks of ACR, B2M, CYST, and eGFR abnormality. Hypertension was positively associated with ACR, with a β value of 0.460 (95% CI: 0.360, 0.561). We also found interactive effects of monoethyl phthalate (MEP), MCPP, MBzP, monobutyl phthalate (MnBP), and hypertension on B2M, CYST, and three kinds of eGFR. Our results indicated that certain phthalate metabolites might contribute to increased risks of early renal injury. The hypertension population may be more sensitive to the early renal injury caused by phthalates exposure than the non-hypertension population.