Ethylene glycol poisoning induces nephrolithiasis including complement-fibrinogen-related renal tubular injury in rats.

Renal tubular damage is one of the hallmarks of ethylene glycol (EG) poisoning and is associated with calcium oxalate crystals in the kidney. We firstly conducted transcriptome analysis to search novel mechanisms of renal toxicity during EG intoxication (8 g/kg body weight, orally, 2 and 5 days) in rat kidney. Biochemical parameters in urine as well as blood plasma showed transient kidney injury that peaked at 2 days and recovered by 5 days after the administration of EG. Transcriptome analysis indicated the inductions of all fibrinogen genes (Fga, Fgb, and Fgg) and several complement components on day 2 and 5, respectively, suggesting the possible involvement of complement-fibrinogen in renal tubular injury. Immunostaining showed C3c and fibrinogen to be increased in renal tubules on day 2 of EG intoxication, confirming that the complement-fibrinogen axis may play a role in EG-related nephrolithiasis. Transmission electron microscopy (TEM) of proximal tubules showed fluid accumulations that may include EG metabolite oxalate, as well as autophagosomes containing ribosomes on days 2-5 of EG administration. TEM also indicated brush border injury in the proximal tubules, confirming renal injury after EG administration. These results revealed that the increase of complement components and fibrinogen results in aberrant deposition of these products. These findings should be beneficial for understanding the pathogenesis of EG-induced nephrolithiasis.