Interaction of cyclosporine and FK506 with diuretics in transplant patients.
BACKGROUND
The calcineurin inhibitors cyclosporine and FK506 are widely used for immunosuppression in solid organ transplantation. One of the side effects of these agents is renal magnesium wasting. The site of action and molecular mechanism of this effect are not known. We hypothesized that agents such as diuretics that cause renal magnesium wasting through a similar action would not have an additive effect on magnesium deficiency with calcineurin inhibitors.


METHODS
The records of 50 heart transplant patients on calcineurin inhibitors were reviewed to determine levels of serum magnesium and required replacement dose of magnesium, diuretic usage, and other laboratory values.


RESULTS
Loop diuretics did not change either the magnesium level or magnesium replacement requirements in patients on calcineurin inhibitors. In contrast, the thiazide diuretic resulted in an increase in serum magnesium and a decrease in magnesium replacement. Results were similar when the cyclosporine or FK506 groups were evaluated alone. Patients taking FK506 had lower serum magnesium values and higher requirements for magnesium replacement compared with patients taking cyclosporine.


CONCLUSIONS
We conclude that calcineurin inhibitors and loop diuretics have a similar site of action.
Arthur
J M
JM
Departments of Medicine and Biochemistry and Molecular Biology, The University of Louisville, KY 40202-1764, USA. jarthur@louisville.edu
Shamim
S
S
D000704:Analysis of Variance; D001581:Benzothiadiazines; D065095:Calcineurin Inhibitors; D016572:Cyclosporine / Q000627:therapeutic use*; D004232:Diuretics; D004347:Drug Interactions; D005260:Female; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008138:Loop of Henle / Q000187:drug effects / Q000378:metabolism; D008274:Magnesium / Q000097:blood / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011188:Potassium / Q000097:blood; D012189:Retrospective Studies; D049993:Sodium Chloride Symporter Inhibitors / Q000627:therapeutic use*; D016559:Tacrolimus / Q000627:therapeutic use*
D001581:Benzothiadiazines; D065095:Calcineurin Inhibitors; D004232:Diuretics; D007166:Immunosuppressive Agents; D049993:Sodium Chloride Symporter Inhibitors; D016572:Cyclosporine; D008274:Magnesium; D011188:Potassium; D016559:Tacrolimus