1. Interaction of cyclosporine and FK506 with diuretics in transplant patients 
John M. Arthur, M.D.Ph.D., Shazia Shamim 
Kidney International 
Volume 58, Issue 1, Pages (July 2000)
DOI: /j x
Copyright © 2000 International Society of Nephrology Terms and Conditions

2. Figure 1
Serum magnesium level and dose of magnesium in patients on calcineurin inhibitors. Patients on FK506 had significantly lower serum magnesium and were on a higher dose of magnesium oxide compared with patients on cyclosporine (*P < 0.01). Symbols are: () cyclosporine; (▪) FK506.
Kidney International  , DOI: ( /j x)
Copyright © 2000 International Society of Nephrology Terms and Conditions

3. Figure 1
Serum magnesium level and dose of magnesium in patients on calcineurin inhibitors. Patients on FK506 had significantly lower serum magnesium and were on a higher dose of magnesium oxide compared with patients on cyclosporine (*P < 0.01). Symbols are: () cyclosporine; (▪) FK506.
Kidney International  , DOI: ( /j x)
Copyright © 2000 International Society of Nephrology Terms and Conditions

4. Figure 2
Comparison of serum magnesium level and dose of magnesium for patients on calcineurin inhibitors. Patients on either cyclosporine or FK506 were included in the analysis. Patients on loop diuretics did not differ from those on no diuretics. Patients on thiazide diuretics had a significantly higher serum magnesium concentration and were on a lower dose of magnesium replacement than those on no diuretics (*P < 0.05). Symbols are: (▪) control; () loop diuretic; () thiazide diuretic; () loop and thiazide diuretics; () thiazide and potassium-sparing diuretics; () loop, thiazide and potassium-sparing diuretics.
Kidney International  , DOI: ( /j x)
Copyright © 2000 International Society of Nephrology Terms and Conditions

5. Figure 2
Comparison of serum magnesium level and dose of magnesium for patients on calcineurin inhibitors. Patients on either cyclosporine or FK506 were included in the analysis. Patients on loop diuretics did not differ from those on no diuretics. Patients on thiazide diuretics had a significantly higher serum magnesium concentration and were on a lower dose of magnesium replacement than those on no diuretics (*P < 0.05). Symbols are: (▪) control; () loop diuretic; () thiazide diuretic; () loop and thiazide diuretics; () thiazide and potassium-sparing diuretics; () loop, thiazide and potassium-sparing diuretics.
Kidney International  , DOI: ( /j x)
Copyright © 2000 International Society of Nephrology Terms and Conditions

6. Figure 2
Comparison of serum magnesium level and dose of magnesium for patients on calcineurin inhibitors. Patients on either cyclosporine or FK506 were included in the analysis. Patients on loop diuretics did not differ from those on no diuretics. Patients on thiazide diuretics had a significantly higher serum magnesium concentration and were on a lower dose of magnesium replacement than those on no diuretics (*P < 0.05). Symbols are: (▪) control; () loop diuretic; () thiazide diuretic; () loop and thiazide diuretics; () thiazide and potassium-sparing diuretics; () loop, thiazide and potassium-sparing diuretics.
Kidney International  , DOI: ( /j x)
Copyright © 2000 International Society of Nephrology Terms and Conditions

7. Figure 2
Comparison of serum magnesium level and dose of magnesium for patients on calcineurin inhibitors. Patients on either cyclosporine or FK506 were included in the analysis. Patients on loop diuretics did not differ from those on no diuretics. Patients on thiazide diuretics had a significantly higher serum magnesium concentration and were on a lower dose of magnesium replacement than those on no diuretics (*P < 0.05). Symbols are: (▪) control; () loop diuretic; () thiazide diuretic; () loop and thiazide diuretics; () thiazide and potassium-sparing diuretics; () loop, thiazide and potassium-sparing diuretics.
Kidney International  , DOI: ( /j x)
Copyright © 2000 International Society of Nephrology Terms and Conditions

8. Figure 2
Comparison of serum magnesium level and dose of magnesium for patients on calcineurin inhibitors. Patients on either cyclosporine or FK506 were included in the analysis. Patients on loop diuretics did not differ from those on no diuretics. Patients on thiazide diuretics had a significantly higher serum magnesium concentration and were on a lower dose of magnesium replacement than those on no diuretics (*P < 0.05). Symbols are: (▪) control; () loop diuretic; () thiazide diuretic; () loop and thiazide diuretics; () thiazide and potassium-sparing diuretics; () loop, thiazide and potassium-sparing diuretics.
Kidney International  , DOI: ( /j x)
Copyright © 2000 International Society of Nephrology Terms and Conditions

9. Figure 2
Comparison of serum magnesium level and dose of magnesium for patients on calcineurin inhibitors. Patients on either cyclosporine or FK506 were included in the analysis. Patients on loop diuretics did not differ from those on no diuretics. Patients on thiazide diuretics had a significantly higher serum magnesium concentration and were on a lower dose of magnesium replacement than those on no diuretics (*P < 0.05). Symbols are: (▪) control; () loop diuretic; () thiazide diuretic; () loop and thiazide diuretics; () thiazide and potassium-sparing diuretics; () loop, thiazide and potassium-sparing diuretics.
Kidney International  , DOI: ( /j x)
Copyright © 2000 International Society of Nephrology Terms and Conditions

10. Figure 3
Schematic representation of thick ascending limb transport mechanisms responsible for magnesium reabsorption. Electroneutral movement of Na+, K+, and Cl- across the apical membrane followed by leak of K+ back into the lumen generates the lumen-positive gradient that is responsible for paracellular magnesium reabsorption. Inhibition of any of the proteins responsible for generation of this gradient interferes with reabsorption of magnesium. The hypothesized mechanism of action of calcineurin inhibitors to decrease magnesium reabsorption is shown. Normally, calcineurin inhibits protein kinase C (PKC) and prevents it from inhibiting the Na+,K+-ATPase. However, when cyclosporine or FK506 inhibits calcineurin, PKC is free to phosphorylate the Na+,K+-ATPase and decrease its activity. This results in decreased net activity of the loop that generates the lumen-positive gradient. Loop diuretics inhibit the NKCC cotransporter, which also results in a decrease in the lumen-positive gradient. Thus, both loop diuretics and calcineurin inhibitors act through the same pathway to inhibit magnesium reabsorption. Abbreviations are: ClCNKB, chloride channel; ROMK, K+ channel; NKCC, Na+/K+/2 Cl cotransporter.
Kidney International  , DOI: ( /j x)
Copyright © 2000 International Society of Nephrology Terms and Conditions