Increasing
evidence indicates that exposure to microcystin-LR (MC-LR)
can cause kidney damage. However, the association between MC-LR exposure
and chronic kidney disease (CKD) risk in humans has not been studied.
Therefore, we conducted a population-based case–control study
involving 135 CKD cases and 135 matched controls in central China
and analyzed the effects of MC-LR alone as well as combined with the
known risk factor cadmium (Cd). Compared to the lowest quartile of
MC-LR exposure, the highest quartile had a 2.82-fold (95% confidence
interval [CI]: 1.37, 5.83) significantly increased risk for CKD, displaying
a dose–response relationship (p
trend < 0.05). Our animal study also showed that MC-LR exposure induced
kidney injury via the PI3K/AKT/mTOR signaling pathway. Comparing the
highest Cd quartile to the lowest, the adjusted odds ratio for CKD
was 3.43 (95% CI: 1.42, 8.27), exhibiting a dose–response relationship
(p
trend < 0.05). Furthermore, a positive
additive interaction was observed between MC-LR and Cd (relative excess
risk due to interaction = 2.34, 95% CI: 0.30, 4.39; attributable proportion
of interaction = 0.68, 95% CI: 0.37, 0.99). Our study firstly revealed
that MC-LR exposure is an independent risk factor for CKD and has
a synergistic relationship with Cd. MC-LR and Cd exposures are associated
with CKD risk in a dose–response manner.