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.
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 CKDpatients (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: Ami Mankodi; Christopher Grunseich; Martin Skov; Lisa Cook; Georg Aue; Enkhtsetseg Purev; Dara Bakar; Tanya Lehky; Karin Jurkat-Rott; Thomas H Pedersen; Richard W Childs Journal: Neuromuscul Disord Date: 2015-08-20 Impact factor: 4.296
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