• Phthalate exposure is common in patients with chronic kidney disease. • Phthalate exposure has potential renal tubular toxicity. • Phthalate-associated oxidative damage can mediate its nephrotoxicity. Phthalate exposure can cause health hazards, including nephrotoxicity. However, the daily intake and adverse renal effects of phthalate exposure in patients with chronic kidney disease (CKD) remain unclear. Participants with non-dialysis-dependent CKD (i.e., not requiring long-term hemodialysis or peritoneal dialysis) stages 3–5 were enrolled in this one-year longitudinal investigation. We calculated the estimated daily intakes (EDIs) of five main phthalate compounds from their urinary biomonitoring data to evaluate the impact of phthalate exposure on urinary renal biomarkers reflecting oxidative damage and renal tubular injury. The overall urinary phthalate detection rate was 100% among 112 male and 57 female participants. Our analyses demonstrated that EDIs of di-(2-ethylhexyl) phthalate, diethyl phthalate (DEP), and dibutyl phthalate (DBP) independently correlated with the increases in kidney injury molecule-1 (β (95% confidence interval (CI)), 0.352 (0.193–0.512), 0.240 (0.135–0.345), and 0.312 (0.193–0.431) log ng/g creatinine per log ng/kg body weight/day of corresponding EDIs; p <0.001). Furthermore, the EDIs of DEP, dimethyl phthalate, and DBP were independently associated with the elevations in 8-hydroxy-2’-deoxyguanosine (β (95% CI), 0.278 (0.206–0.350), 0.509 (0.361–0.658), and 0.319 (0.215–0.423) log μg/g creatinine per log ng/kg body weight/day, respectively; p <0.001). The mediating role of oxidative damage in phthalate-associated renal tubular injury was also identified. Our study highlights the nephrotoxicity of phthalate exposure in patients with CKD and suggests that renal tubular injury and oxidative damage play crucial roles in phthalate-associated nephrotoxicity, which is underestimated using traditional renal surrogates.
Hsiao et al. (Sun,) studied this question.