Title
Magnesium loss in cyclosporine-treated patients is related to renal epidermal growth factor downregulation Magnesium loss in cyclosporine-treated patients is related to renal epidermal growth factor downregulation
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Publication type
article
Publication
Berlin ,
Subject
Human medicine
Source (journal)
Nephrology, dialysis, transplantation. - Berlin
Volume/pages
29(2014) :5 , p. 1097-1102
ISSN
0931-0509
ISI
000336093900024
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
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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