Preservation of renal function after heart transplantation: initial single-center experience with sirolimus.
BACKGROUND
Long-term survivors of heart transplantation are often confronted with chronic kidney disease, by definition related to the intake of calcineurin-inhibitors. Sirolimus is increasingly proposed as an alternative immunosuppressive agent due to its absence of nephrotoxicity.


METHODS
Between November 2002 and November 2003, 9 adult heart transplant candidates with moderate to severe chronic renal disease were switched from cyclosporine to sirolimus. The conversion scheme consisted of an immediate stop of cyclosporine and an 8-mg loading dose of sirolimus, followed by 3 mg/d; after 1 week, the sirolimus dose was adjusted to maintain trough levels between 5 and 15 microg/L. The majority of patients were on corticosteroids, and on either azathioprine or mycophenolate mofetil. At conversion, the mean serum creatinine level was 2.11 (+/-0.4) mg/dL and the mean glomerular filtration rate (GFR) was 32 (+/-7) mL/min/1.73 m(2). Prior to conversion, the renal dysfunction was predominantly stable.


RESULTS
After conversion, there were 7 dropouts (75%) due to several side effects related to sirolimus: edema (n = 2), general discomfort (n = 2), delayed wound healing (n = 1), cardiac thrombus (n = 1), and diarrhea (n = 1). The median treatment time with Sirolimus, therefore, was only 4.0 months. While on sirolimus, the renal function of all patients remained unchanged or showed even some improvement. Retrospective nephrological review revealed severe renal artery stenoses in 2 patients and serious generalized abdominal and renal atheromatosis in 7 patients. No cardiac dysfunction was seen.


CONCLUSIONS
Conversion from cyclosporine to sirolimus was problematic due to sirolimus side effects, occurring at any time after the switch. One should also question whether chronic kidney disease after heart transplantation is routinely caused by the administration of calcineurin-inhibitors, in view of the generalized renal and abdominal atheromatosis.
De Meester
J M J
JM
Department of Nephrology, Dialysis & Hypertension, Onze Lieve Vrouw Ziekenhuis Aalst, Aalst, Belgium. johan.de.meester@olvz-aalst.be
Van Vlem
B
B
Walravens
M
M
Vanderheyden
M
M
Verstreken
S
S
Goethals
M
M
Kerre
N
N
Wellens
F
F
D000368:Aged; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D005919:Glomerular Filtration Rate; D016027:Heart Transplantation / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007668:Kidney / Q000502:physiology*; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D020123:Sirolimus / Q000493:pharmacokinetics / Q000627:therapeutic use*
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D020123:Sirolimus