Opisthorchis viverrini infection is associated with kidney injury involving excretory–secretory product-mediated inflammation, oxidative stress, and hypoxia

Abstract

Opisthorchis viverrini infection is primarily associated with hepatobiliary disease, but its renal consequences remain poorly defined. We investigated kidney injury in chronically infected Syrian golden hamsters using biochemical, histological, ultrastructural, and transcriptomic analyses. Hamsters infected nine months previously showed mild changes in conventional markers, including non-significant increases in serum creatinine and urinary protein. However, circulating complement C3 was elevated, and parasite antigen was detected in serum and renal tissue. Infected hamsters exhibited glomerular enlargement, tubular dilation, increased expression of kidney injury molecule-1, glomerular basement membrane thickening, podocyte foot-process effacement, and tubular mitochondrial swelling with disruption of cristae. Kidney transcriptomics identified injury-related responses involving hypoxia, TNFα–NF-κB, TGF-β, p53, inflammatory, apoptotic, epithelial–mesenchymal transition, and mitochondrial metabolism pathways. Direct effects of parasite-derived soluble products were also examined in human proximal tubular epithelial HK-2 cells using a non-contact co-culture system. Parasite-derived products reduced HK-2 cell viability and induced NF-κB activation, reactive oxygen species accumulation, apoptosis, and cell-cycle disturbance. These findings demonstrate subclinical glomerular and tubular injury during chronic O. viverrini infection, potentially involving systemic immune activation and parasite-derived molecules acting through inflammatory and mitochondrial stress pathways. Such early injury may increase susceptibility to severe renal disease with prolonged infection or additional comorbidities.