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Title
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Magnesium loss in cyclosporine-treated patients is related to renal epidermal growth factor downregulation
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Author
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Abstract
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| Background Cyclosporine (CsA) treatment is associated with hypomagnesaemia due to a renal Mg2+ leak. In animal studies a role for the Mg2+ 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, Mg2+, sodium and EGF. Results Serum Mg2+ was significantly lower in the CsA group versus the CKD group with significantly more CsA-treated patients developing hypomagnesaemia. Although the fractional excretion (FE) Mg2+ did not differ significantly between the two groups, subanalysis of the patients with hypomagnesaemia showed a significantly higher FE Mg2+ 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 Mg2+ 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 Mg2+ 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 Mg2+, supporting the role of EGF in magnesium reabsorption. |
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Language
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English
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Source (journal)
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Nephrology, dialysis, transplantation. - Berlin
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Publication
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Berlin
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2014
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ISSN
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0931-0509
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DOI
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10.1093/NDT/GFT498
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Volume/pages
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29
:5
(2014)
, p. 1097-1102
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ISI
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000336093900024
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Full text (Publisher's DOI)
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