Key result
Early conversion from calcineurin inhibitors to sirolimus in renal transplant recipients with allograft dysfunction improved 3-year event-free survival (P=0.024) and eGFR (+5.5 vs -6.4, P=0.011).
Why the study?
Does early conversion from calcineurin inhibitors to sirolimus improve survival, renal function, and cardiac hypertrophy in nondiabetic renal transplant recipients with allograft dysfunction?
Cohort (n=39)
Does early conversion from calcineurin inhibitors to sirolimus improve survival, renal function, and cardiac hypertrophy in nondiabetic renal transplant recipients with allograft dysfunction?
Absolute Event Rate: 5.5% vs -6.4%
p-value: p=0.011
Conversion from calcineurin inhibitors to sirolimus in renal transplant recipients with allograft dysfunction is associated with improved survival, renal function, and regression of left ventricular hypertrophy.
Should not yet change practice; leaves open need for RCTs to confirm benefit in allograft dysfunction.
BACKGROUND: Studies evaluating the effect of conversion from calcineurin inhibitor (CNI) to sirolimus (SRL) in renal transplant recipients (RTRs) have shown conflicting results, and only few short-term uncontrolled studies are available in patients with chronic allograft dysfunction. This is the first controlled study to evaluate long-term survival and both renal and cardiac outcomes in nondiabetic RTRs with allograft dysfunction who were converted from CNI to SRL. METHODS: We evaluated 13 RTRs with biopsy-proven allograft dysfunction who underwent early conversion from CNI to SRL, and 26 controls with normal graft function taking CNI. All continued both steroids and mycophenolate mofetil. SRL was titrated to trough levels of 4-8 ng/mL. Outcome measures included 3-year event-free survival, acute rejection rate and 3-year changes in Modification of Diet in Renal Disease (MDRD) Study equation estimated glomerular filtration rate (eGFR) and left ventricular mass index (LVMi) as assessed by echocardiography. RESULTS: Compared with controls, patients on SRL showed better 3-year event-free survival (p=0.024; log-rank test), significant eGFR increase (+5.5 ± 8.9 vs, -6.4 ± 14.7 ml/min per 1.73 m2, p=0.011), LVMi regression (-9.0 ± 7.6 g/m(2.7) vs. 1.0 ± 10.1 g/m(2.7), p=0.0038) and similar acute rejection rate. Three-year change in eGFR was the only significant predictor of event-free survival by Cox regression analysis (hazard ratio = 0.96; 95% confidence interval, 0.93-0.99; p=0.017), whereas SRL was the strongest predictor of both eGFR increase (beta coefficient, 0.342; p=0.01) and LVM reduction (beta coefficient, -0.609; p=0.0001) by multivariate regression analysis. CONCLUSIONS: Conversion from CNI to SRL in RTRs with allograft dysfunction proved to be associated with better survival, improved renal graft function and regression of cardiac hypertrophy.
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Paoletti et al. (2011) conducted a cohort in Renal transplant recipients with allograft dysfunction (n=39). Early conversion from calcineurin inhibitor (CNI) to sirolimus (SRL) vs. CNI continuation (controls with normal graft function) was evaluated on 3-year change in estimated glomerular filtration rate (eGFR) in ml/min per 1.73 m2 (p=0.011). Early conversion from calcineurin inhibitors to sirolimus in renal transplant recipients with allograft dysfunction improved 3-year event-free survival (P=0.024) and eGFR (+5.5 vs -6.4, P=0.011).
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