title: Antibody-mediated inhibition of EGFR reduces phosphate excretion and induces hyperphosphatemia and mild hypomagnesemia in mice.
abstract: Monoclonal antibody therapies targeting the EGF receptor (EGFR) frequently result in hypomagnesemia in human patients. In contrast, EGFR tyrosine kinase inhibitors do not affect Mg2+balance in patients and only have a mild effect on Mg2+homeostasis in rodents at elevated doses. EGF has also been shown to affect phosphate (Pi) transport in rat and rabbit proximal convoluted tubules (PCT), but evidence from studies targeting EGFR and looking at Piexcretion in whole animals is still missing. Thus, the role of EGF in regulating reabsorption of Mg2+and/or Piin 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 Piand mild hypomagnesemia, but no changes in Pior Mg2+excretion. In contrast, a single injection of ME-1 resulted in hyperphosphatemia and a significant reduction in Piexcretion 2 days after treatment, while no changes in serum Mg2+or Mg2+excretion were observed. Dietary Mg2+deprivation is known to trigger a rapid Mg2+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 Mg2+deprivation. These data show that EGFR plays a significant role in regulating Pireabsorption in the kidney PCT, but suggest only a minor role in long-term regulation of Mg2+transport in the distal convoluted tubule.
authors.affiliation: Department of Biology, The College at Brockport State University of New York, Brockport, New York bortega@brockport.edu.
authors.forename: Bernardo
authors.identifier: http://orcid.org/0000-0002-3473-7778
authors.initials: B
authors.lastname: Ortega
authors.affiliation: Department of Biology, The College at Brockport State University of New York, Brockport, New York.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Dey
authors.affiliation: Department of Biology, The College at Brockport State University of New York, Brockport, New York.
authors.forename: Allison R
authors.initials: AR
authors.lastname: Gardella
authors.affiliation: Department of Biology, The College at Brockport State University of New York, Brockport, New York.
authors.forename: Jacob
authors.initials: J
authors.lastname: Proano
authors.affiliation: Department of Biology, The College at Brockport State University of New York, Brockport, New York.
authors.forename: Deanna
authors.initials: D
authors.lastname: Vaneerde
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D066246:ErbB Receptors / Q000276:immunology*; D000089703:Fibroblast Growth Factor-23; D053565:Hypercalciuria / Q000097:blood / Q000139:chemically induced* / Q000276:immunology; D054559:Hyperphosphatemia / Q000097:blood / Q000139:chemically induced* / Q000276:immunology; D017136:Ion Transport; D007686:Kidney Tubules, Distal / Q000378:metabolism; D008274:Magnesium / Q000097:blood; D051379:Mice; D009397:Nephrocalcinosis / Q000097:blood / Q000139:chemically induced* / Q000276:immunology; D010710:Phosphates / Q000097:blood*; D015499:Renal Tubular Transport, Inborn Errors / Q000097:blood / Q000139:chemically induced* / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; C000717427:FGF23 protein, human; C000717428:Fgf23 protein, mouse; D010710:Phosphates; D000089703:Fibroblast Growth Factor-23; C541485:EGFR protein, mouse; D066246:ErbB Receptors; D008274:Magnesium
keywords: 
  EGFR
  ; 
  PTH
  ; FGF23; Klotho; magnesium deficiency; phosphate