Mechanistically, magnesium mitigates cisplatin-induced hypomagnesemia (exacerbated by CRT-related gastrointestinal losses) and preserves tubular transport by maintaining TRPM6/epidermal growth factor–dependent magnesium handling in the distal nephron; experimental data indicate that magnesium deficiency increases renal platinum accumulation and down-regulates efflux transporters (MRP2/MRP4/MRP6), whereas repletion restores transporter abundance and attenuates injury [27,35]. This evidence concerns the gene ABCC4 and familial primary hypomagnesemia.