Can citrinin and ochratoxin A injure kidney tubular cells?

Citrinin and ochratoxin A (OTA) are mycotoxins with experimental evidence of renal tubular toxicity. The overall claim is plausible: oxidative stress is the more consistently supported contributor, whereas mitochondrial dysfunction is implicated but less firmly established as a causal mediator of tubular injury.

Experimental and mechanistic evidence

• Citrinin: Renal tubular models report impaired mitochondrial respiration and cellular energy production, and animal studies describe tubular structural injury and renal dysfunction. Reported oxidative effects include increased reactive oxygen species (ROS), lipid peroxidation, glutathione depletion, and reduced antioxidant defenses.
• OTA: Evidence is particularly consistent for proximal-tubule toxicity. In HK-2 renal tubular cells, OTA increases ROS and apoptosis; attenuation of these effects by N-acetylcysteine supports oxidative stress as a contributing mechanism. Rodent studies similarly report renal lipid peroxidation and diminished antioxidant defenses.
• Mitochondria: Citrinin-associated impairment of respiration and energy production supports a mitochondrial role. OTA has been associated with altered mitochondrial membrane potential, ATP production, and respiratory-chain activity, but findings vary across models, including reports of both increased and decreased ATP. Thus, no uniform mitochondrial response has been established.

Interpretation and clinical relevance

• Oxidative stress is supported as part of the injury pathway for both toxins, although it may act alongside apoptosis, impaired cellular energetics, and other toxic effects rather than as the sole mechanism.
• Direct proof that restoring mitochondrial function prevents tubular injury remains limited; mitochondrial dysfunction is therefore best considered a biologically credible, incompletely demonstrated mediator.
• Biomarker detection establishes exposure but does not establish kidney causation in people. No identified human cohort or adequately adjusted cross-sectional evidence links citrinin or OTA exposure to tubular-injury markers, eGFR decline, chronic kidney disease, or disease progression.

Bottom line

• Citrinin and OTA can injure renal tubular cells in experimental systems; oxidative stress is well supported as a contributor, while mitochondrial dysfunction is plausible but mechanistically less definitive. Human implications for chronic real-world exposure remain uncertain.