Abstract
Neonicotinoids are systemic insecticides used since the 1990’s , that possess renal tubular toxicity. We conducted a field-based descriptive study in the North Central Dry-zone of Sri Lanka, where chronic kidney disease (CKD) of unknown etiology has been increasing since the 1990’s. To elucidate the relationship between renal tubular dysfunctions and urinary neonicotinoids concentrations, we collected spot urine samples from15 CKD patients, 15 family members, and 62 neighbors in 2015, analyzed two renal tubular biomarkers, Cystatin-C and L-FABP, quantified seven neonicotinoids and a metabolite N-desmethyl-acetamiprid by LC–MS/MS; and we investigated their symptoms using a questionnaire. Cystatin-C and L-FABP had a positive correlation (p < 0.001). N-Desmethyl-acetamiprid was detected in 92.4% of the urine samples, followed by dinotefuran (17.4%), thiamethoxam (17.4%), clothianidin (9.8%), thiacloprid and imidacloprid. Dinotefuran and thiacloprid have never been registered in Sri Lanka. In High Cystatin-C group (> 70 μg/gCre, n = 7), higher urinary concentration of dinotefuran (p = 0.009), and in Zero Cystatin-C group (< LOQ, n = 7), higher N-desmethyl-acetamiprid (p = 0.013), dinotefuran (p = 0.049), and thiacloprid (p = 0.035), and more complaints of chest pains, stomachache, skin eruption and diarrhea (p < 0.05) were found than in Normal Cystatin-C group (n = 78). Urinary neonicotinoids may be one of the potential risk factors for renal tubular dysfunction in this area.
Highlights
Chronic kidney disease (CKD) is a global health issue[1]
After obtaining written informed consent from the participants, in May 2015, approx. 50 ml of spot urine samples were collected from 33 residents in Wilgamuwa and Anuradhapura, and in December 2015, 59 residents in Anuradhapura, including CKD patients, and the families lived in the CKD of unknown/uncertain etiology (CKDu) affected area, and others
No remarkable difference between 15 CKD patients and 77 healthy participants was observed in urinary blood detection (40%, 52.9%, p = 0.41, Chi-square test); acidic dominant pH (5.7 ± 0.3, 5.7 ± 0.6, p = 0.51, Chi-square test); low urinary creatinine concentration no more than 0.5 g/L (33.3%, 29.9%, p = 0.92, Chi-square test); low gravity less than 1.005 (55.6%, 20.8%, p = 0.31, only performed in May); and urine albumin to creatinine ratio (UACR), creatinine adjusted albumin no less than 30 mg/g Cre (33.3%, 3.6%, p = 0.06, Chi-square test)
Summary
Chronic kidney disease (CKD) is a global health issue[1]. The causes of CKD, such as diabetes mellitus, hypertension, chronic nephritis, acute kidney injury and nephrotoxins, caused by arsenic and fluoride, have been discussed. As urinary biomarkers of renal tubule condition, albumin and low molecular proteins, which is constantly secreted from glomerulus and absorbed by normal renal tubules have been used, e.g. urine albumin to creatinine ratio (UACR)[10,11,12,13,14,15]. L-FABP 14–15 kDa, protein Liver Proximal tubules under ischemia and oxidative stress Glomerulus, pathological proximal tubules Normal proximal tubules ≦8.4 μg/g Cre. Dyspnea or tachypnea; cough; cyanosis; respiratory arrest Nausea; vomiting; stomachache; oral-esophageal-gastric erosion Diaphoresis or anhidrosis; excessive discharge of saliva and bronchial secretion/mouth dryness Mydriasis or miosis; abnormal light reflex Fever or low body temperature Muscle weakness or spasm; high creatine kinase Metabolic acidosis; leukocytoclastic vasculitis; renal and hepatic disfunction
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