Improvement of renal dysfunction by conversion from calcineurin inhibitors to sirolimus after heart transplantation.
BACKGROUND
Chronic renal dysfunction is a common occurrence after heart transplantation in patients treated with calcineurin inhibitors (CIs). We evaluated the renal-sparing effects of converting stable heart transplant patients with renal dysfunction from a CI to sirolimus.


METHODS
Beginning in 2000, heart transplant patients with renal dysfunction were converted from a CI to sirolimus. CI was abruptly discontinued and sirolimus added at 5 mg twice a day for 2 days and then 2 mg daily. The treatment goal was a 24-hour level of 6 to 12 ng/ml. All patients were also managed with mycophenolate mofetil (MMF) at 1,000 mg twice daily.


RESULTS
Eighty from a total of 235 cardiac transplant patients were converted to sirolimus. The average time post-transplant for conversion was 4.78 years (range 3 days to 16 years). The average age at transplant was 55.43 years (range 15 to 70). At a mean of 304 days post-conversion, the mean serum creatinine (sCr) decreased from 2.04 +/- 0.57 mg/dl pre-conversion to 1.64 +/- 0.48 mg/dl (p < 0.001). In patients whose sCr was <2.5 mg/dl before conversion, the mean SCr level decreased from 1.81 +/- 0.39 to 1.62 +/- 0.5 mg/dl post-conversion (p = 0.01), with no patient developing end-stage renal disease (ESRD). Four patients with sCr > or =2.5 developed ESRD requiring dialysis despite conversion. In the remaining 15 patients with sCr > or =2.5 mg/dl, the sCr decreased from 2.85 +/- 0.29 to 1.73 +/- 0.43 mg/dl (p = 0.001).


CONCLUSIONS
Conversion to sirolimus from CI is safe and has a renal-sparing effect in the management of heart transplant patients with chronic renal dysfunction. Based on these results, sirolimus has a role as a first-line immunosuppressive agent in heart transplant patients with renal dysfunction.
Hunt
Judson
J
Transplant Center, Medical City Hospital, Dallas, Texas, USA.
Lerman
Mark
M
Magee
Mitchell J
MJ
Dewey
Todd M
TM
Herbert
Morley
M
Mack
Michael J
MJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D065095:Calcineurin Inhibitors; D003404:Creatinine / Q000097:blood; D018450:Disease Progression; D005260:Female; D016027:Heart Transplantation / Q000009:adverse effects* / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000627:therapeutic use*; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D020123:Sirolimus / Q000097:blood / Q000627:therapeutic use*; D013997:Time Factors
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D003404:Creatinine; D020123:Sirolimus