Magnesium loss in cyclosporine-treated patients is related to renal epidermal growth factor downregulation

Nephrol Dial Transplant. 2014 May;29(5):1097-102. doi: 10.1093/ndt/gft498. Epub 2013 Dec 18.


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.

Keywords: cyclosporine; epidermal growth factor; fractional excretion; magnesium; sodium.

Publication types

  • Comparative Study

MeSH terms

  • Biomarkers / analysis*
  • Case-Control Studies
  • Creatinine / blood
  • Cyclosporine / blood
  • Cyclosporine / therapeutic use*
  • Down-Regulation
  • Epidermal Growth Factor / urine*
  • Female
  • Humans
  • Immunosuppressive Agents / blood
  • Immunosuppressive Agents / therapeutic use*
  • Kidney Transplantation
  • Magnesium / blood*
  • Male
  • Middle Aged
  • Renal Insufficiency, Chronic / blood
  • Renal Insufficiency, Chronic / drug therapy*
  • Renal Insufficiency, Chronic / urine
  • Sodium / blood


  • Biomarkers
  • Immunosuppressive Agents
  • Epidermal Growth Factor
  • Cyclosporine
  • Sodium
  • Creatinine
  • Magnesium