Antibody‐mediated inhibition of EGFR reduces phosphate excretion and induces hyperphosphatemia and mild hypomagnesemia in mice

Monoclonal antibody therapies targeting the EGF receptor (EGFR) frequently result in hypomagnesemia in human patients. In contrast, EGFR tyrosine kinase inhibitors do not affect Mg(2+) balance in patients and only have a mild effect on Mg(2+) homeostasis in rodents at elevated doses. EGF has also been shown to affect phosphate (P(i)) transport in rat and rabbit proximal convoluted tubules (PCT), but evidence from studies targeting EGFR and looking at P(i) excretion in whole animals is still missing. Thus, the role of EGF in regulating reabsorption of Mg(2+) and/or P(i) in the kidney remains controversial. Here, we inject mice with the anti‐EGFR monoclonal antibody ME‐1 for 2 weeks and observe a significant increase in serum P(i) and mild hypomagnesemia, but no changes in P(i) or Mg(2+) excretion. In contrast, a single injection of ME‐1 resulted in hyperphosphatemia and a significant reduction in P(i) excretion 2 days after treatment, while no changes in serum Mg(2+) or Mg(2+) excretion were observed. Dietary Mg(2+) deprivation is known to trigger a rapid Mg(2+) conservation response in addition to hyperphosphatemia and hyperphosphaturia. Interestingly, one dose of ME‐1 did not significantly modify the response of mice to 2 days of Mg(2+) deprivation. These data show that EGFR plays a significant role in regulating P(i) reabsorption in the kidney PCT, but suggest only a minor role in long‐term regulation of Mg(2+) transport in the distal convoluted tubule.