title: Magnesium loss in cyclosporine-treated patients is related to renal epidermal growth factor downregulation.
abstract: BACKGROUND
  Cyclosporine (CsA) treatment is associated with hypomagnesaemia due to a renal Mg(2+) leak. In animal studies a role for the Mg(2+) channel TRPM6 localized in the distal convoluted tubule and stimulated by epidermal growth factor (EGF) is suggested. We hypothesize that CsA-induced hypomagnesaemia is due to a renal magnesium leak, also in patients, resulting from a downregulation of the renal EGF production, thereby inhibiting the activation of TRPM6.
  
  
  METHODS
  Renal transplant patients treated with CsA (n = 55) and 35 chronic kidney disease (CKD) patients were included. At three time points, with an interval of at least 1 month, blood and urine samples were taken to determine creatinine, Mg(2+), sodium and EGF.
  
  
  RESULTS
  Serum Mg(2+) was significantly lower in the CsA group versus the CKD group with significantly more CsA-treated patients developing hypomagnesaemia. Although the fractional excretion (FE) Mg(2+) did not differ significantly between the two groups, subanalysis of the patients with hypomagnesaemia showed a significantly higher FE Mg(2+) in CsA-treated patients compared with CKD patients (P = 0.05). The urinary EGF excretion was significantly decreased in the CsA group and was a predictor of the FE Mg(2+) in the two groups. Serum sodium was significantly decreased in the CsA group simultaneously with an increased FE Na(+).
  
  
  CONCLUSIONS
  In CsA-treated patients, the association of a low urinary EGF excretion and a decreased renal Mg(2+) reabsorption is in accordance with in vitro and animal studies. In the whole study population, log urinary EGF excretion is an independent predictor of the FE Mg(2+), supporting the role of EGF in magnesium reabsorption.
authors.affiliation: Laboratory of Experimental Medicine and Pediatrics, University of Antwerp, Antwerp, Belgium.
authors.forename: Kristien J
authors.initials: KJ
authors.lastname: Ledeganck
authors.forename: Benedicte Y
authors.initials: BY
authors.lastname: De Winter
authors.forename: Annelies
authors.initials: A
authors.lastname: Van den Driessche
authors.forename: Angelika
authors.initials: A
authors.lastname: Jürgens
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Bosmans
authors.forename: Marie M
authors.initials: MM
authors.lastname: Couttenye
authors.forename: Gert A
authors.initials: GA
authors.lastname: Verpooten
mesh_terms: D015415:Biomarkers / Q000032:analysis*; D016022:Case-Control Studies; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000097:blood / Q000627:therapeutic use*; D015536:Down-Regulation; D004815:Epidermal Growth Factor / Q000652:urine*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000627:therapeutic use*; D016030:Kidney Transplantation; D008274:Magnesium / Q000097:blood*; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000188:drug therapy* / Q000652:urine; D012964:Sodium / Q000097:blood
chemical_list: D015415:Biomarkers; D007166:Immunosuppressive Agents; D004815:Epidermal Growth Factor; D016572:Cyclosporine; D012964:Sodium; D003404:Creatinine; D008274:Magnesium
keywords: cyclosporine; epidermal growth factor; fractional excretion; magnesium; sodium