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 6.56-fold (95% confidence interval [CI]: 2.46, 17.51) significantly increased risk for CKD, displaying a dose-response relationship ( < 0.001). 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 3.88 (95% CI: 1.47, 10.28), exhibiting a dose-response relationship ( < 0.006). Furthermore, a positive additive interaction was observed between MC-LR and Cd (relative excess risk due to interaction = 1.81, 95% CI: 0.42, 3.20; attributable proportion of interaction = 0.70, 95% CI: 0.35, 1.05). 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.
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