title: Calcineurin inhibitor substitution with sirolimus vs. reduced-dose calcineurin inhibitor plus sirolimus is associated with improved renal dysfunction in heart transplant patients.
abstract: Heart transplant (HTx) patients are at risk of developing renal dysfunction. Sirolimus has been used as an alternative for calcineurin inhibitors (CNI) in transplant patients with renal dysfunction. Recent data suggest that the combination of sirolimus with a CNI is associated with a deterioration of renal function in renal transplant patients. The purpose of the present study was to compare the effect on the creatinine clearance (CrCl) of heart transplant (HTx) patients with renal dysfunction (RD) on CNI-based sirolimus-free regimens of conversion to either reduced-dose CNI plus sirolimus or outright substitution of CNI with sirolimus. We retrospectively identified 29 treatment switches for 26 patients with RD defined as a decline in the CrCl > 25% post-HTx. Treatment switches were divided into two groups. Group 1 included 13 switches in 13 patients (four women, nine men, age 62 +/- 10 yr) in whom sirolimus replaced CNI. Group 2 included 16 switches in 15 patients [two women, 13 men (one man underwent two such switches), age 61 +/- 9 yr] in whom CNI dose was reduced and sirolimus was added. Two men appear in both groups. Average follow-up was 10.4 +/- 3.2 months. Overall mortality, rejection, and side-effects rates were comparable between groups. At 12-months post-switch, the mean CrCl had increased from 48 +/- 15 at time of treatment switch to 56 +/- 22 mL/min in group 1 and decreased from 53 +/- 19 to 47 +/- 17 mL/min in group 2 (p = 0.02). In conclusion, substitution of CNI with sirolimus provided improved renal recovery compared with lower-dose CNI plus sirolimus in HTx patients with renal dysfunction.
authors.affiliation: Department of Medicine, Royal Victoria Hospital, McGill University Health Center, Montréal, QC, Canada.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Potter
authors.forename: Nadia
authors.initials: N
authors.lastname: Giannetti
authors.forename: Michael D deB
authors.initials: MD
authors.lastname: Edwardes
authors.forename: Renzo
authors.initials: R
authors.lastname: Cecere
authors.forename: Marcelo
authors.initials: M
authors.lastname: Cantarovich
mesh_terms: D000368:Aged; D065095:Calcineurin Inhibitors; D003404:Creatinine / Q000097:blood; D016027:Heart Transplantation / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007668:Kidney / Q000503:physiopathology*; D008875:Middle Aged; D012189:Retrospective Studies; D020123:Sirolimus / Q000008:administration & dosage*
chemical_list: D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D003404:Creatinine; D020123:Sirolimus