Background

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.

Objectives

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.

Methods

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 F₂-isoprostane) were determined in the same specimens. Estimated glomerular filtration rate (eGFR), proteinuria, and blood pressure were assessed annually.

Results

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.

Conclusions

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.

中文翻译：

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有机磷农药与儿童慢性肾脏病的进展：一项前瞻性队列研究

背景

越来越多的证据表明，接触杀虫剂等环境化学物质会影响肾功能和慢性肾病 (CKD)。然而，尚不清楚农药是否会影响 CKD 的进展，也没有针对儿童的研究。

目标

本研究的目的是探讨 CKD 儿童随时间推移连续测量的尿 OP 农药代谢物与临床和实验室肾功能测量值之间的关联。

方法

本研究使用了 618 名儿童 CKD 研究 (CKiD) 参与者的数据，这是一项针对美国和加拿大儿童 CKD 患者的队列研究。2005 年至 2015 年间，对儿童进行了平均 3.0 年的随访（标准差 (SD) = 1.6）。在一段时间内连续收集的尿液样本中，测量了 OP 农药的六种非特异性磷酸二烷基酯 (DAP) 代谢物。确定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（8-羟基-2'-脱氧鸟苷 (8-OHdG) 和 F 2 -异前列腺素_）在同一个标​​本中。每年评估估计肾小球滤过率（eGFR）、蛋白尿和血压。

结果

在整个随访过程中，DAP 与 KIM-1 和 8-OHdG 的增加相关。KIM-1 和 8 中 Σ二乙基代谢物的标准差增加与 11.9%（95% 置信区间 (CI)：4.8%、19.4%）和 13.2%（95% CI：9.3%、17.2%）的增加相关-OHdG 分别随时间变化。DAP 与基线时较低的 eGFR 和随后几年较高的 eGFR 相关。

结论

这些发现提供了初步证据，表明尿 DAP 代谢物与 CKD 儿童的亚临床肾损伤有关，这可能预示着未来出现临床事件的可能性。鉴于有机磷农药暴露是一个可改变的风险因素，这项研究的结果从临床和公共卫生的角度来看都具有重要意义。