Ortega Bernardo, Dey Jason M, Gardella Allison R, Proano Jacob, Vaneerde Deanna
Department of Biology, The College at Brockport State University of New York, Brockport, New York
Department of Biology, The College at Brockport State University of New York, Brockport, New York.
Physiol Rep. 2017 Mar;5(5). doi: 10.14814/phy2.13176.
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 balance in patients and only have a mild effect on Mg homeostasis in rodents at elevated doses. EGF has also been shown to affect phosphate (P) transport in rat and rabbit proximal convoluted tubules (PCT), but evidence from studies targeting EGFR and looking at P excretion in whole animals is still missing. Thus, the role of EGF in regulating reabsorption of Mg and/or P 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 and mild hypomagnesemia, but no changes in P or Mg excretion. In contrast, a single injection of ME-1 resulted in hyperphosphatemia and a significant reduction in P excretion 2 days after treatment, while no changes in serum Mg or Mg excretion were observed. Dietary Mg deprivation is known to trigger a rapid Mg 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 deprivation. These data show that EGFR plays a significant role in regulating P reabsorption in the kidney PCT, but suggest only a minor role in long-term regulation of Mg transport in the distal convoluted tubule.
针对表皮生长因子受体（EGFR）的单克隆抗体疗法常常会导致人类患者出现低镁血症。相比之下，EGFR酪氨酸激酶抑制剂不会影响患者的镁平衡，且只有在高剂量时才会对啮齿动物的镁稳态产生轻微影响。表皮生长因子（EGF）也已被证明会影响大鼠和兔子近端肾小管（PCT）中的磷酸盐（P）转运，但针对EGFR并观察全动物磷排泄情况的研究证据仍然缺失。因此，EGF在调节肾脏中镁和/或磷的重吸收方面的作用仍存在争议。在此，我们给小鼠注射抗EGFR单克隆抗体ME-1，持续2周，观察到血清磷显著升高和轻度低镁血症，但磷或镁的排泄没有变化。相比之下，单次注射ME-1会导致高磷血症，并在治疗后2天使磷排泄显著减少，而血清镁或镁排泄没有变化。已知饮食中缺镁除了会引发高磷血症和高磷尿症外，还会触发快速的镁保留反应。有趣的是，一剂ME-1并没有显著改变小鼠对2天缺镁的反应。这些数据表明，EGFR在调节肾脏近端肾小管的磷重吸收中起重要作用，但在远端肾小管镁转运的长期调节中仅起次要作用。
