Article ; Online: Magnesium loss in cyclosporine-treated patients is related to renal epidermal growth factor downregulation.
2014 Volume 29, Issue 5, Page(s) 1097–1102
Abstract: ... hypomagnesaemia is due to a renal magnesium leak, also in patients, resulting from a downregulation of the renal ... and stimulated by epidermal growth factor (EGF) is suggested. We hypothesize that CsA-induced ... Background: Cyclosporine (CsA) treatment is associated with hypomagnesaemia due to a renal Mg(2+ ...
| 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. |
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| MeSH term(s) | 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 | ||||||||||
| Chemical Substances | Biomarkers ; Immunosuppressive Agents ; Epidermal Growth Factor (62229-50-9) ; Cyclosporine (83HN0GTJ6D) ; Sodium (9NEZ333N27) ; Creatinine (AYI8EX34EU) ; Magnesium (I38ZP9992A) | ||||||||||
| Language | English | ||||||||||
| Publishing date | 2014-05 | ||||||||||
| Publishing country | England | ||||||||||
| Document type | Comparative Study ; Journal Article | ||||||||||
| ZDB-ID | 90594-x | ||||||||||
| ISSN | 1460-2385 ; 0931-0509 | ||||||||||
| ISSN (online) | 1460-2385 | ||||||||||
| ISSN | 0931-0509 | ||||||||||
| DOI | 10.1093/ndt/gft498 | ||||||||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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