Pesticide Levels and Other Etiopathogenetic Factors in Patients with Chronic Kidney Disease of Unknown Cause in Central India – A Case–Control Study

Abstract

Background The etiology of chronic kidney disease of unknown cause (CKDu) remains unexplained, with environmental toxins, i.e., heavy metals and pesticides. being explored for their causal role. We measured pesticide levels in blood and urine in patients with CKDu in central India. We compared them with healthy and chronic kidney disease (CKD) controls. Materials and Methods This case–control study compared patients with CKDu (n = 55), CKD (n = 53) and healthy controls (n = 50). Levels of 6 organophosphates (OPs) and 16 organochlorines were measured by GC-MS. Drinking water sources and pesticide use, and hours spent in sunlight were also evaluated. Results CKDu and CKD subjects were age and sex matched. CKDu and CKD subjects had higher median chlorpyrifos (CP) 3.69 (2.36–5.65) and 3.79 (1.9–5.53) µg/L; pesticide use 19.6% and 12.5%; and heat spent hours 3.0 (2.0, 5.0) compared to healthy subjects 1.49 (0.97–2.20) µg/L; 0%; and 1.0 (1.0, 3.0) hours, respectively (p ≤ 0.001 for all). Surface water use was higher in CKDu (49%) compared to CKD (20.7%) and healthy subjects (20%) (p<0.01). The CP (ρ −0.0532, p<0.01), and ethion (ET) (ρ 0.221, p<0.01) had inverse correlation with GFR. Urine CP and ET were significantly higher in healthy controls. On multinomial regression, CP was independently associated with CKDu (OR, 95%CI) (3.5, 2.1–5.9) and CKD (3.7, 2.2–6.1). ET was also associated with CKDu (2.2, 1.2–3.9) and CKD (1.9, 1.1–3.4). Spending 4 hours or more in sunlight was associated with CKDu (6.1, 1.7–22.3) and CKD (6.0,1.7–21.3) (P<0.01 for all) in reference to healthy subjects. Surface water was associated with CKDu (4.0, 1.3–12.7) (p<.01). Conclusion Environmental factors such as spending 4 hours or more in sunlight and higher levels of OP pesticides, namely, CP and ET, are associated with both CKDu and CKD. As higher levels of pesticides were seen in both groups of CKDu and CKD, the association of pesticides with CKDu could not be established. The higher levels could be due to low eGFR. Surface water use is independently associated with CKDu; however, larger studies are required to establish the causation.