15 Silica deposits in renal tissue from a chronic kidney disease of unknown etiology (CKDu) hotspot region in Mexico

Abstract Chronic kidney disease of unknown etiology (CKDu) is a worldwide epidemic. In Aguascalientes, Mexico, it disproportionately affects adolescents, presenting primarily with focal segmental glomerulosclerosis (FSGS). Our experimental and clinical studies have implicated silica particle exposure as a potential contributor to CKDu through oxidative and mitochondrial injury. Objective: Assess the presence of silica particles in renal tissue from adolescents with adaptive podocytopathy and adults with adaptive FSGS in Aguascalientes, Mexico, using single-particle inductively coupled plasma mass spectrometry (SP-ICP-MS), and to explore possible environmental sources of exposure. Methods: This case-control study included kidney biopsies from four groups (median age 30 yr, IQR 18 to 42; 50.9% female): (1) adolescents with adaptive podocytopathy (n = 15), (2) adults with adaptive FSGS (n = 19), (3) adults with other glomerulopathies (n = 10), and (4) renal tissue from trauma nephrectomy controls (n = 10). Results: Among 54 kidney biopsies were analysed, silica particles were detected in 66% of adolescents and 65% of adults with adaptive FSGS, compared with 0% and 10% in the other groups (P < 0.01). Mean silica particle density was highest in adolescents (1.7 ± 0.4 particles/mm³) and FSGS adults (1.26 ± 0.1), versus 0.23 ± 0.04 and 0.29 ± 0.12 in disease and trauma controls, respectively. Silica was also found in water from non-commercial purification plants but absent in the public water system (72,272.8 versus 0 particles/ml, P < 0.001). Conclusions: Elevated renal silica in affected individuals and water sources supports a potential environmental contribution to CKDu pathogenesis in Aguascalientes, Mexico.