Serially assessed bisphenol A and phthalate exposure and association with kidney function in children with chronic kidney disease in the US and Canada: A longitudinal cohort study


Autoři: Melanie H. Jacobson aff001;  Yinxiang Wu aff002;  Mengling Liu aff002;  Teresa M. Attina aff001;  Mrudula Naidu aff001;  Rajendiran Karthikraj aff004;  Kurunthachalam Kannan aff001;  Bradley A. Warady aff006;  Susan Furth aff007;  Suzanne Vento aff008;  Howard Trachtman aff008;  Leonardo Trasande aff001
Působiště autorů: Division of Environmental Pediatrics, Department of Pediatrics, NYU Langone Medical Center, New York, New York, United States of America aff001;  Department of Population Health, NYU Langone Medical Center, New York, New York, United States of America aff002;  Department of Environmental Medicine, NYU Langone Medical Center, New York, New York, United States of America aff003;  Wadsworth Center, New York State Department of Health, Albany, New York, United States of America aff004;  Department of Environmental Health Sciences, School of Public Health, State University of New York at Albany, Albany, New York, United States of America aff005;  Division of Nephrology, Department of Pediatrics, Children’s Mercy Kansas City, Kansas City, Missouri, United States of America aff006;  Division of Nephrology, Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America aff007;  Division of Nephrology, Department of Pediatrics, NYU Langone Medical Center, New York, New York, United States of America aff008;  Wagner Graduate School of Public Service, New York University, New York, New York, United States of America aff009;  School of Global Public Health, New York University, New York, New York, United States of America aff010
Vyšlo v časopise: Serially assessed bisphenol A and phthalate exposure and association with kidney function in children with chronic kidney disease in the US and Canada: A longitudinal cohort study. PLoS Med 17(10): e32767. doi:10.1371/journal.pmed.1003384
Kategorie: Research Article
doi: 10.1371/journal.pmed.1003384

Souhrn

Background

Exposure to environmental chemicals may be a modifiable risk factor for progression of chronic kidney disease (CKD). The purpose of this study was to examine the impact of serially assessed exposure to bisphenol A (BPA) and phthalates on measures of kidney function, tubular injury, and oxidative stress over time in a cohort of children with CKD.

Methods and findings

Samples were collected between 2005 and 2015 from 618 children and adolescents enrolled in the Chronic Kidney Disease in Children study, an observational cohort study of pediatric CKD patients from the US and Canada. Most study participants were male (63.8%) and white (58.3%), and participants had a median age of 11.0 years (interquartile range 7.6 to 14.6) at the baseline visit. In urine samples collected serially over an average of 3.0 years (standard deviation [SD] 1.6), concentrations of BPA, phthalic acid (PA), and phthalate metabolites were measured as well as biomarkers of tubular injury (kidney injury molecule-1 [KIM-1] and neutrophil gelatinase-associated lipocalin [NGAL]) and oxidative stress (8-hydroxy-2′-deoxyguanosine [8-OHdG] and F2-isoprostane). Clinical renal function measures included estimated glomerular filtration rate (eGFR), proteinuria, and blood pressure. Linear mixed models were fit to estimate the associations between urinary concentrations of 6 chemical exposure measures (i.e., BPA, PA, and 4 phthalate metabolite groups) and clinical renal outcomes and urinary concentrations of KIM-1, NGAL, 8-OHdG, and F2-isoprostane controlling for sex, age, race/ethnicity, glomerular status, birth weight, premature birth, angiotensin-converting enzyme inhibitor use, angiotensin receptor blocker use, BMI z-score for age and sex, and urinary creatinine. Urinary concentrations of BPA, PA, and phthalate metabolites were positively associated with urinary KIM-1, NGAL, 8-OHdG, and F2-isoprostane levels over time. For example, a 1-SD increase in ∑di-n-octyl phthalate metabolites was associated with increases in NGAL (β = 0.13 [95% CI: 0.05, 0.21], p = 0.001), KIM-1 (β = 0.30 [95% CI: 0.21, 0.40], p < 0.001), 8-OHdG (β = 0.10 [95% CI: 0.06, 0.13], p < 0.001), and F2-isoprostane (β = 0.13 [95% CI: 0.01, 0.25], p = 0.04) over time. BPA and phthalate metabolites were not associated with eGFR, proteinuria, or blood pressure, but PA was associated with lower eGFR over time. For a 1-SD increase in ln-transformed PA, there was an average decrease in eGFR of 0.38 ml/min/1.73 m2 (95% CI: −0.75, −0.01; p = 0.04). Limitations of this study included utilization of spot urine samples for exposure assessment of non-persistent compounds and lack of specific information on potential sources of exposure.

Conclusions

Although BPA and phthalate metabolites were not associated with clinical renal endpoints such as eGFR or proteinuria, there was a consistent pattern of increased tubular injury and oxidative stress over time, which have been shown to affect renal function in the long term. This raises concerns about the potential for clinically significant changes in renal function in relation to exposure to common environmental toxicants at current levels.

Klíčová slova:

Biomarkers – Chronic kidney disease – Kidneys – Metabolites – Oxidative stress – Phthalates – Renal system – Urinary biomarkers


Zdroje

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