How do kidney function and mycotoxins interact?

Kidney function and mycotoxin exposure may interact in two directions: impaired renal handling can affect toxin disposition, while ochratoxin A (OTA) and citrinin have experimentally demonstrated tubular toxicity.

Renal elimination and accumulation

• OTA renal handling is complex: only unbound, albumin-free OTA is filtered, while proximal-tubule transport involves basolateral OAT1/OAT3 uptake, apical secretion (including MRP2, BCRP, and NPT4), and reabsorption through OAT4 and pH-dependent passive diffusion. Reabsorption can prolong urinary elimination and increase tubular exposure.
• In observational human data, OTA concentrations were higher in severe renal disease: one hemodialysis study reported mean blood concentrations of 2.1 ng/mL versus 0.4 ng/mL in healthy controls. Dialysis did not appear to remove OTA efficiently in an end-stage renal disease cohort.
• Citrinin is converted mainly to dihydrocitrinone; both are recovered in urine after oral exposure, supporting renal elimination. However, renal-impairment pharmacokinetics for citrinin have not been defined.

Experimental tubular toxicity

• OTA preferentially damages the S3 proximal-tubule segment in rodents, causing degeneration, apoptosis/cell death, karyomegaly, and architectural disruption. In male F344 rats, renal pathology occurred at 70 and 210 μg/kg/day over up to 90 days, whereas 21 μg/kg/day caused no renal effects in that study.
• OTA injury is biologically consistent with oxidative stress, mitochondrial dysfunction, and apoptosis.
• Citrinin causes tubular degeneration and necrosis in animals. In a 28-day rat study, histopathology occurred at 100 μg/kg/day, not 25 μg/kg/day; the reported NOAEL was 20 μg/kg/day.

Bottom line

• Kidney dysfunction is a credible modifier of OTA elimination, and both OTA and citrinin can directly injure renal tubules experimentally. These findings do not establish equivalent injury at typical human exposures, but they support caution when interpreting urinary mycotoxin biomarkers or exposure in people with reduced kidney function.