Impact of cyclosporine A on magnesium homeostasis: clinical observation in lung transplant recipients and experimental study in mice.
BACKGROUND
Hypomagnesemia is a common finding in patients receiving cyclosporine A (CsA) therapy. The relationship between CsA-induced hypomagnesemia and nephrotoxicity and the effects of oral magnesium (Mg) supplementation remain unclear. After a retrospective analysis of the time-course of plasma Mg and creatinine levels in lung allograft recipients treated with both CsA and oral Mg supplementation, we investigated the effects of CsA treatment on Mg homeostasis in mice with normal or Mg-deficient diet and the effects of oral Mg supplementation on plasma Mg levels.


METHODS
Thirty lung-allograft recipients entered the retrospective study. One thousand two hundred twenty-eight blood samples were analyzed for blood and creatinine levels. Cyclosporine A (50 mg/kg/day by intraperitoneal injection) was administered to mice maintained on normal diet (1400 ppm) or Mg-deficient (50 ppm) diet. Magnesium levels were determined in plasma, urine, feces and femur, and creatinine levels were determined in plasma and urine.


RESULTS
Plasma Mg concentration declines from the day of transplantation in 36.7% of the patients despite Mg supplementation, without correlation with creatinine changes. In mice, CsA induced an early moderate hypomagnesemia, which could not be ameliorated by oral Mg supplementation and was aggravated by low-Mg dietary, late increase in plasma creatinine and decrease in urine creatinine without histological signs of renal injury, decrease in intestinal Mg absorption and Mg mobilization from bone.


CONCLUSIONS
Cyclosporine A treatment may induce moderate hypomagnesemia that is aggravated by inadequate Mg intake and is not ameliorated by Mg supplementation. Because of the clinical complications of hypomagnesemia, Mg should be monitored regularly in allograft recipients receiving CsA.
Sabbagh
Fadi
F
CNRS UMR 8162, IFR 13, Centre Chirurgical Marie-Lannelongue, 92350 Le Plessis-Robinson, France.
El Tawil
Zeina
Z
Lecerf
Florence
F
Hulin
Anne
A
Maurois
Pierre
P
Dartevelle
Philippe
P
Bac
Pierre
P
German-Fattal
Michèle
M
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000818:Animals; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000009:adverse effects*; D019587:Dietary Supplements; D004195:Disease Models, Animal; D005260:Female; D006706:Homeostasis; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced*; D016040:Lung Transplantation; D008274:Magnesium / Q000097:blood*; D008275:Magnesium Deficiency / Q000097:blood / Q000139:chemically induced* / Q000517:prevention & control; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D011761:Pyrrolidonecarboxylic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D012189:Retrospective Studies; D013997:Time Factors; D017211:Treatment Failure
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003404:Creatinine; D008274:Magnesium; D011761:Pyrrolidonecarboxylic Acid