Department of Pediatrics, Division of Environmental Pediatrics, NYU Langone Medical Center, New York, NY, USA.
Department of Population Health, NYU Langone Medical Center, New York, NY, USA.
Environ Int. 2021 Oct;155:106597. doi: 10.1016/j.envint.2021.106597. Epub 2021 May 2.
Growing evidence suggests that exposure to environmental chemicals, such as pesticides, impacts renal function and chronic kidney disease (CKD). However, it is not clear if pesticides may affect CKD progression and no studies exist in children.
The objective of this study was to examine associations between serially measured urinary OP pesticide metabolites and clinical and laboratory measures of kidney function over time among children with CKD.
This study used data on 618 participants enrolled in the CKD in Children study (CKiD), a cohort study of pediatric CKD patients from the US and Canada. Children were followed over an average of 3.0 years (standard deviation (SD) = 1.6) between 2005 and 2015. In serially collected urine samples over time, six nonspecific dialkyl phosphate (DAP) metabolites of OP pesticides were measured. Biomarkers of tubular injury (kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL)) and oxidant stress (8-hydroxy-2'-deoxyguanosine (8-OHdG) and F-isoprostane) were determined in the same specimens. Estimated glomerular filtration rate (eGFR), proteinuria, and blood pressure were assessed annually.
DAPs were associated with increased KIM-1 and 8-OHdG throughout follow-up. A standard deviation increase in ∑diethyl metabolites was associated with increases of 11.9% (95% Confidence Interval (CI): 4.8%, 19.4%) and 13.2% (95% CI: 9.3%, 17.2%) in KIM-1 and 8-OHdG over time, respectively. DAPs were associated with lower eGFR at baseline and higher eGFR over subsequent years.
These findings provide preliminary evidence suggesting that urinary DAP metabolites are associated with subclinical kidney injury among children with CKD, which may signal the potential for clinical events to manifest in the future. The results from this study are significant from both a clinical and public health perspective, given that OP pesticide exposure is a modifiable risk factor.
越来越多的证据表明，接触环境化学物质，如杀虫剂，会影响肾功能和慢性肾脏病（CKD）。然而，目前尚不清楚杀虫剂是否会影响 CKD 的进展，而且在儿童中也没有相关研究。
本研究旨在探讨在患有 CKD 的儿童中，随着时间的推移，连续测量的尿液有机磷（OP）农药代谢物与临床和实验室肾功能指标之间的关联。
本研究使用了美国和加拿大的 CKiD 研究（一项儿科 CKD 患者的队列研究）中 618 名参与者的数据。在 2005 年至 2015 年期间，这些儿童的平均随访时间为 3.0 年（标准差为 1.6 年）。在随时间采集的尿液样本中，检测了六种非特异性二烷基磷酸盐（DAP）OP 农药代谢物。在同一标本中测定了肾小管损伤的生物标志物（肾损伤分子 1（KIM-1）和中性粒细胞明胶酶相关脂质运载蛋白（NGAL））和氧化应激的生物标志物（8-羟基-2'-脱氧鸟苷（8-OHdG）和 F-异前列烷）。每年评估估算肾小球滤过率（eGFR）、蛋白尿和血压。
DAP 与随访期间 KIM-1 和 8-OHdG 的增加有关。∑二乙基代谢物的标准偏差增加与 KIM-1 和 8-OHdG 分别增加 11.9%（95%置信区间：4.8%，19.4%）和 13.2%（95%置信区间：9.3%，17.2%）有关。DAP 与基线时 eGFR 较低和随后几年 eGFR 较高有关。
这些发现提供了初步证据，表明 CKD 儿童尿液中 DAP 代谢物与亚临床肾脏损伤有关，这可能预示着未来可能会出现临床事件。鉴于有机磷农药暴露是一个可改变的风险因素，因此从临床和公共卫生的角度来看，这项研究的结果意义重大。
