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Epidermal growth factor (EGF) stimulates cell proliferation and differentiation after binding to its receptor. Next to its role in magnesium homeostasis, EGF disturbances have been described in oncology, diabetes and autism spectrum disorders. The aim of this study was to determine EGF serum and urine values for both healthy children and adults. Next, we investigated the relation between several variables and urinary and serum EGF concentrations. Both healthy adults (n = 50) and children (n = 78) were included. Serum and urinary EGF concentrations were measured with ELISA technology. Serum EGF was inversely correlated with age (r = -0.873; p<0.001) and positively correlated with serum magnesium (r = 0.597; p<0.001). The urinary EGF was also inversely correlated with age (r = -0.855; p<0.001). In adults and children older than 13 years of age, the urinary EGF significantly differed between sexes (p = 0.001). Urinary EGF was positively correlated with serum magnesium (r = 0.583; p<0.001) and creatinine clearance (r = 0.524; p<0.001) and negatively correlated with the fractional excretion of magnesium (r = 0.248; p = 0.014). In a multivariate model, age and serum magnesium remained independently related to serum EGF while age, serum EGF and serum magnesium remained independently related to urinary EGF. This study provides valuable insights in urinary and serum EGF patterns in healthy subjects. By systematically correcting EGF for body surface, significant correlations with age, gender and magnesium were observed.

Background: It was shown in animal models and adults that the epidermal growth factor (EGF) is involved in the pathophysiology of calcineurin inhibitor (CNI) induced renal magnesium loss. In children, however, the exact mechanism remains unclear, which was set as the purpose of the present study. Methods: Children with nephrotic syndrome and renal transplant children treated with CNI (n = 50) and non-CNI treated children (n = 46) were included in this study. Urine and serum samples were collected at three time points to determine magnesium, creatinine, and EGF. The magnesium intake was calculated from a food frequency questionnaire. Results: Serum Mg2+ and urinary EGF/creatinine were significantly lower in the CNI treated children, with significantly more CNI-treated children developing hypomagnesaemia. In the latter patients, the fractional excretion of magnesium (FE Mg2+) was significantly higher. Urinary EGF, age, renal function, and serum magnesium were independent predictors of the FE Mg2+. Only 29% of the children reached the recommended daily intake of magnesium. The magnesium intake did not differ between hypomagnesemic and normomagnesemic patients and was not a predictor of the FE Mg2+. Conclusions: In CNI-treated children who developed hypomagnesemia, the FE Mg2+ was increased. The urinary EGF concentration, age, and renal function are independent predictors of the FE Mg2+.