Open AccessAntibody‐mediated inhibition of EGFR reduces phosphate excretion and induces hyperphosphatemia and mild hypomagnesemia in mice
Author(s) -
Ortega Bernardo,
Dey Jason M.,
Gardella Allison R.,
Proano Jacob,
Vaneerde Deanna
Publication year - 2017
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.13176
Subject(s) - hyperphosphatemia , hypomagnesemia , reabsorption , medicine , excretion , endocrinology , renal physiology , homeostasis , kidney , renal function , convoluted tubule , chemistry , kidney disease , magnesium , organic chemistry
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.