Purpose Although transition to sirolimus (SRL) as primary immunosuppression has been associated with an improvement in glomerular filtration rate (GFR), long term follow up has not been reported. The aim of this study was to evaluate GFR in SRL treated patients and to compare with patients remained on CNIs during 5 years follow-up (FU).

Methods and Materials The study population consisted of 85 cardiac transplant recipients with impaired renal function and/or cardiac allograft vasculopathy in whom CNIs were substituted with sirolimus (SRL group) and 86 cardiac transplant recipients maintained on CNI based immunosuppression (CNI group). Secondary immunosuppressants were not changed. GFR was measured by corrected iothalamate clearance.

Results Mean follow up was 5.3 (IQR 3.7, 6.1) years. GFR increased from 53.522.4 to 59.524.7 mL/min (p=0.03) 4 years after SRL initiation while in the CNI group, GFR declined from 57.021.8 to 53.120.6 mL/min (p=0.03) in the same period of FU. In multivariate logistic regression analysis, treatment with CNI (p=0.04), lower GFR at study entry (p=0.03), and ischaemic aetiology of cardiomyopathy prior to transplantation (p=0.04), were all associated with long term worsening of GFR. In the SRL group, improvement in GFR was significant in patients with GFR 40 mL/min prior to conversion but not in patients with GFR<40 mL/min. At the end of FU, 3 (4%) vs 6 (7%) (p=0.018), 3 (4%) vs 11 (13%) (p=0.33), and 7 (8%) vs 23 (28%) (p=0.001), in the SRL group vs the CNI group had kidney transplant, required haemodialysis, and died respectively.

Conclusions Substitution of CNIs with SRL in stable cardiac transplant recipients was associated with improved renal function, particularly in patients with GFR 40 mL/min prior to conversion, and survival. These results suggest that the initial improvement seen with substituting SRL for CNIs is sustained over a longer FU period and this strategy has the potential to improve long-term outcome in cardiac transplantation.