Conversion from calcineurin inhibitors to sirolimus in kidney transplant recipients: a retrospective cohort study.
BACKGROUND
Replacing a calcineurin inhibitor (CNI) with sirolimus (SRL) may preserve kidney graft function. However, at the present time, only short follow-up after conversion is available. The aim of this study was to assess whether conversion from a CNI-based to an SRL-based maintenance regimen was safe and effective.


METHODS
We performed a retrospective cohort study among kidney graft patients whose CNI was withdrawn to be replaced by SRL. Two-tailed paired t tests were used to compare glomerular filtration rates (GFRs) and proteinuria levels before and up to 2 years after conversion. We used linear regression to determine the factors associated with changes in renal function after conversion.


RESULTS
The 193 study subjects had a mean GFR at conversion of 41 +/- 16 mL/min/1.73 m(2) a median proteinuria level of 0 g/L (interquartile range = 0-0.15). After conversion, the GFR was stable: at 1 year, the change was -0.34 mL/min/1.73 m(2) (95% confidence interval [CI] = -2.71, 2.03) and at 2 years, -0.96 mL/min/1.73 m(2) (95% CI = 4.26, 2.34). There was a small but significant increase in dipstick proteinuria at 1 year of +0.5 g/L, (95% CI = 0.20, 0.75). On multivariate analysis, proteinuria > or = 1 g/L at the time of conversion was the only predictor of deteriorating GFR at 1 year (beta: -7.91 mL/min/1.73 m(2); 95% CI = -14.10, -1.70). SRL had to be discontinued in 31% of patients.


CONCLUSIONS
Conversion from CNI to SRL resulted in stable graft function at 2 years and in a slight increase in proteinuria. Despite the relatively high reconversion rate, this strategy offers a reasonable alternative to CNIs for most patients.
Nephrology Department, Centre Hospitalier de l'Université de Montréal, Pavillon St-Luc, 1058 rue St-Denis, Montréal H2X 3J4, Canada. hcardinal@hotmail.com
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Cardinal
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Froidure
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Dandavino
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Daloze
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MJ
Hébert
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Colette
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Boucher
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D019703:Calcineurin / Q000627:therapeutic use; D065095:Calcineurin Inhibitors; D015331:Cohort Studies; D016572:Cyclosporine / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000453:epidemiology; D012044:Regression Analysis; D012189:Retrospective Studies; D020123:Sirolimus / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D017211:Treatment Failure; D016896:Treatment Outcome
D048868:Adaptor Proteins, Signal Transducing; C491861:CABIN1 protein, human; D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D019703:Calcineurin; D020123:Sirolimus