摘要：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 F 2 -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.
关键词：Pesticides ; Chronic kidney disease ; Renal function ; Children ; ACEI angiotensin converting enzyme inhibitor ; ARB angiotensin receptor blocker ; AR(1) autoregressive model in the first-order ; BMI body mass index ; CI confidence interval ; CKD chronic kidney disease ; CKDu CKD of unknown etiology ; CKiD Chronic Kidney Disease in Children ; DBP diastolic blood pressure ; DAP dialkyl phosphate ; DE diethyl ; DM dimethyl ; DMP dimethylphosphate ; DEP diethylphosphate ; DMTP dimethylthiophosphate ; DETP diethylthiophosphate ; DMDTP dimethylphosphorodithidate ; DEDTP diethyldithiophosphate ; eGFR estimated glomerular filtration rate ; ESKD end-stage kidney disease ; GM geometric mean ; GSD geometric standard deviation ; ICC intraclass correlation coefficient ; IQR interquartile range ; KIM-1 kidney injury molecule-1 ; LME linear mixed-effects ; LOD limit of detection ; NGAL neutrophil gelatinase-associated lipocalin ; NHANES National Health and Nutrition Examination Survey ; 8-OHdG 8-hydroxy-2′-deoxyguanosine ; RRT renal replacement therapy ; SBP systolic blood pressure ; UPCR urinary protein to creatinine ratio
