Table 1.
An overview of divalent metal ions linked to nephrotoxicity.
| Metal (Most Common Oxidation State) | Primary Locations of Accumulation | Receptors Suggested to Be Involved in Renal Accumulation |
|---|---|---|
| Cadmium (Cd2+) | Kidneys and liver [72] | Cd2+: DMT1 [52,73], ZIP8 1 [52,74,75], ZIP14 [52] Cd2+- protein complexes: megalin–cubulin, lipocalin 2/NGAL/24p3 receptor [68,71,76] |
| Lead (Pb2+) | Bones [77] | Pb2+: Ca2+ channels [62] |
| Nickel (Ni2+) | Respiratory tract [78,79] | Ni2+: Ca2+ channels [64] |
| Manganese (Mn2+, Mn4+, and Mn7+) | Brain [80] | Mn2+: DMT1 [52], ZIP8 [36,52,81], ZIP14 [52] |
| Cobalt (Co2+ and Co3+) | Kidneys and liver [82] | Co2+: ZIP8 [61] |
| Mercury (Hg+ and Hg2+) | Kidneys [27] | Hg2+: OAT1 (basolateral) [65,66] |
1 ZIP8 knockout in mice actually increased kidney cadmium levels, which was hypothesized to occur due to less storage of cadmium in the liver and, thus, more exposure to the kidney [83].