Effects of Calcineurin Inhibitors on Urinary Sodium Excretion Early after Allogenic Hematopoietic Stem Cell Transplantation

Background: Calcineurin inhibitors (CI) such as cyclosporine A (CsA) and tacrolimus often cause renal dysfunction resulting in an increase in serum creatinine (Cr), hyperkalemia, hypomagenesemia, and hyperuricemia. Electrolyte and uric acid abnormalities are considered mainly due to renal tubular impairment. However, the effects of CI on the sodium regulation have yet to be fully evaluated. In the present study, we have quantitatively evaluated the effects of CI on urinary sodium excretion in patients receiving tarolimus or CsA in the early period after allogenetic hematopoietic stem cell transplantation (HSCT).

Patients and methods: One hundred recipients of allogeneic HSCT receiving CI (CsA, n=50; tacrolimus, n=50) with the available weekly data for calculating fractional excretion of sodium (FENa) for 4-week period after transplantation were enrolled. No significant differences were observed in patient characteristics except for the type of donor between CsA and tarolimus groups. FENa was calculated according to the following formula: 100 x (Urinary sodium x Serum Cr)/(Serum sodium x Urinary Cr).

Results: Both CsA and tarolimus groups showed increase in FENa at 2nd to 4th weeks after transplantation as compared with those at 1st week (0.96±0.44 for CsA; 0.92±0.49 for tacrolimus). Among them, a significant increase was only observed at 3rd and 4th weeks in tacrolimus group, but not in CsA group. In addition, FENa was significantly higher at 4th week in tacrolimus group as compared with CsA group (1.60±1.12 vs. 1.13±0.80 :p<0.05).

Conclusion: These results suggest that urinary sodium excretion increases under the administration of CI after allogeneic HSCT probably through renal tubular impairment and that there is a significant difference in the renal tubular toxicity between tacrolimus and CsA.