A side-effect of the immunosuppressive drug FK506 (Prograf; tacrolimus) is hypomagnesaemia. We have investigated the effects of short-term (7-day) treatment of rats with FK506, using a protocol designed to indicate whether there are modifications in the renal tubular handling of magnesium and other electrolytes, or in the tissue deposition of magnesium, which may account for the hypomagnesaemia. We have also investigated whether parathyroid hormone has a role in the observed hypomagnesaemia. Two studies have been performed; in the first we administered FK506 (0.5 mgċkg-1 body weightċday-1) or vehicle by intraperitoneal injection for 7 days, and then housed the rats in metabolic cages for the 24 h collection of urine. At the end of the metabolic cage period, the animals were anaesthetized, and blood and tissue samples were taken for analysis. In the second set of experiments the dosage regime was identical, but at the end of the treatment period the animals were anaesthetized for implantation of arterial and venous cannulae, and then received a saline (plus inulin) infusion for 6 h, during which time blood and urine samples were collected. The dose of FK506 employed did not decrease the glomerular filtration rate. FK506 elicited hypomagnesaemia in both sets of experiments, accompanied by inappropriately high fractional excretion of magnesium. There was also evidence of disruption of the normal renal reabsorption of calcium, but this did not result in hypocalcaemia. Plasma parathyroid hormone activity was not significantly different between the two groups, and there was no evidence of altered tissue content of magnesium in kidney, liver, heart, skeletal muscle or bone. The study confirms that hypomagnesaemia is a significant side-effect of FK506, even at a relatively low dose which did not decrease the glomerular filtration rate. The effect is not due to a decrease in parathyroid hormone release, or to translocation of magnesium from plasma to tissues, but does reflect decreased renal tubular magnesium (and calcium) reabsorption.
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August 31 2000
The hypomagnesaemic action of FK506: urinary excretion of magnesium and calcium and the role of parathyroid hormone
Christopher J. LOTE;
1Division of Medical Sciences, Medical School, University of Birmingham, Birmingham B15 2TT, U.K.
Correspondence: Professor C. J. Lote (e-mail [email protected]).
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Andrew THEWLES;
Andrew THEWLES
1Division of Medical Sciences, Medical School, University of Birmingham, Birmingham B15 2TT, U.K.
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Jeanne A. WOOD;
Jeanne A. WOOD
1Division of Medical Sciences, Medical School, University of Birmingham, Birmingham B15 2TT, U.K.
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Tariq ZAFAR
Tariq ZAFAR
1Division of Medical Sciences, Medical School, University of Birmingham, Birmingham B15 2TT, U.K.
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Publisher: Portland Press Ltd
Received:
March 17 2000
Revision Received:
May 17 2000
Accepted:
June 06 2000
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society and the Medical Research Society © 2000
2000
Clin Sci (Lond) (2000) 99 (4): 285–292.
Article history
Received:
March 17 2000
Revision Received:
May 17 2000
Accepted:
June 06 2000
Citation
Christopher J. LOTE, Andrew THEWLES, Jeanne A. WOOD, Tariq ZAFAR; The hypomagnesaemic action of FK506: urinary excretion of magnesium and calcium and the role of parathyroid hormone. Clin Sci (Lond) 1 October 2000; 99 (4): 285–292. doi: https://doi.org/10.1042/cs0990285
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