Switch from calcineurin inhibitors to sirolimus-induced renal recovery in heart transplant recipients in the midterm follow-up.
BACKGROUND
Calcineurin inhibitor (CI)-based immunosuppression has prolonged the survival of heart transplant recipients. However, CI-induced renal injury remains as a major problem in these patients. Sirolimus is an immunosuppressant with no significant impact on renal function. A limited number of recent papers have showed that the switch from CI to sirolimus improved renal function in late follow-up of heart transplant patients with CI-related nephrotoxicity.


METHODS
Ten heart transplant recipients with CI-induced nephrotoxicity (creatinine 3.9+/-1.8 mg/dl) at a median of 701 (465 to 1325) days posttransplant had CI switched to sirolimus (target though levels 10 to 14 ng/ml) while mycophenolate mofetil (MMF, 3g/day) was maintained and adjusted according to white blood cell count.


RESULTS
This maneuver caused a marked decrease in serum creatinine (P<0.00001) at 30 (1.2+/-0.4 mg/dl), 90 (1.3+/-0.4 mg/dl) and 180 (1.3+/-0.4 mg/dl) days post-conversion and a significant decrease in serum potassium levels (5.1+/-0.5 at baseline vs. 3.9+/-0.3 at 180 days, P<0.00005). After the drugs switch no changes in hemoglobin levels, white blood cell count, platelets count, blood glucose and glutamic oxaloacetic transaminase plasma levels were observed. Total cholesterol increased from 242+/-28 to 290+/-117 mg/dl (P>0.05) after 90 days and decreased to 216+/-58 mg/dl at day 180 (P>0.05) after statins dose adjustment. Rejection and infection rates were not modified by sirolimus.


CONCLUSIONS
Conversion to a sirolimus-based immunosuppression regimen associated with MMF allowed striking renal function recovery in heart transplant recipients with calcineurin inhibitor-induced renal impairment at midterm follow-up.
Division of Cardiology, São José do Rio Preto Medical School, Brazil. rbestetti@netsite.com.br
Reinaldo
R
Bestetti
Tatiana A D
TA
Theodoropoulos
Emmanuel A
EA
Burdmann
Mário Abbud
MA
Filho
José A
JA
Cordeiro
Daniel
D
Villafanha
D000328:Adult; D001219:Aspartate Aminotransferases / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D065095:Calcineurin Inhibitors; D002784:Cholesterol / Q000097:blood; D003404:Creatinine / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000517:prevention & control*; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D051437:Renal Insufficiency / Q000139:chemically induced* / Q000188:drug therapy / Q000201:enzymology; D020123:Sirolimus / Q000627:therapeutic use*
D001786:Blood Glucose; D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D002784:Cholesterol; D003404:Creatinine; D001219:Aspartate Aminotransferases; D009173:Mycophenolic Acid; D020123:Sirolimus